Mood and anxiety disorders are the cause of much individual personal distress and also a major public health problem. A recent review of the epidemiological studies of mental disorder within the European Union demonstrated that when grouped together anxiety disorders and the principal mood disorders had an estimated 12-month prevalence rate of approximately 14% and 7.8%, respectively.¹ Using estimates to calculate the size of the population in the European Union that would be affected (69.1 million people), it was estimated that in 2010 anxiety disorders (excluding post-traumatic stress disorder) cost approximately 66 billion Euros and mood disorders (affecting 33.3 million people) cost approximately 113 billion Euros.² Furthermore, three anxiety disorders (panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder) and two mood disorders (unipolar depression and bipolar disorder) were among the major medical causes of disability.

Anxiety and mood disorders typically have an early onset and long-term course; are often co-morbid with schizophrenia, substance misuse and physical illness; and are associated with increased risks of attempted and completed suicide. Many patients with mood or anxiety disorders will not present for treatment or are not recognised; the standard of care they receive is often sub-optimal; and the effectiveness of pharmacological and psychological treatment interventions in real-world clinical practice can be disappointing.³ It has been argued that increasing the rate of current treatment approaches in patients who are in contact with health services than who are not being treated would be cost-effective, as the increased direct cost of providing treatment would be more than that offset by the reduced indirect costs of lost employment—due to the return of people to paid work.

As in other areas of medicine, many patients with long-term conditions are disappointed by the effectiveness or acceptability of current treatments; hence there is a need to consider additional approaches to the management of depressive and anxiety symptoms, particularly treatments which may be relatively inexpensive when compared to current approaches. The tradition of yoga has been established over centuries in India and is been described in detail in a number of ancient Indian scriptures (Upanishads, Vedas). The most influential text is the “Patanjali Yoga Sutra” written in Sanskrit approximately in 400 BC, and archaeological evidences suggests that the Yoga practices and methods described in that text were being practiced as early as 3000 BC.⁴ The word “yoga” is derived from the Sanskrit word “Yuj” which means to unite or join and indicates that the purpose of yoga is to unite ourselves with our highest nature (Bhole).⁵ According to Sage Patanjali, yoga practices have been divided into eight types: Yama, Niyama, Asana, Pranayama, Pratyahara, Dharana, Dhyana and Samadhi (Table 1).

Yogic Breathing (Pranayam)

“Pranayam” or breath control is an important type of yogic practice that includes changing the rate and depth of breathing, holding the breath, breathing through the mouth, or breathing through one or both nostrils. These regulated breathing techniques are classed as “Pranayama” in Sanskrit.⁷ The word Pranayama is formed from two words: “Prana,” meaning life force or energy (also refers to the breath); and “Ayam,” meaning control or regulation. Several techniques of Pranayama are described and have been classified differently by various yogic scholars. One classification is based on breathing from one or both nostrils.⁸ Left nostril breathing Pranayama is called Chandra anuloma-viloma Pranayama (Chandra means Moon) whereas right nostril breathing Pranayama is called Surya anuloma-viloma Pranayama (Surya means Sun). Breathing through alternate nostrils is called Nadisuddhi. There are various forms of Pranayama of which one alters the depth of breathing, like Bhastrika (meaning “bellows”); another alters the rate of breathing, like Kapal Bhati; another involves breathing through the mouth, and includes Sadanta and Sitkari; and others like Kumbhak involve a period of breath holding, and Bhramari involves exhaling with the production of sound. The most recommended forms for daily use are Bhastrika, Kapal Bhati, Bahaya, Anulom-vilom, Bhramari, Udgeeth and Pranav Pranayama.⁹

LITERATURE SEARCH

We searched the online databases Medline, Psychinfo, EMBASE and AMED via the NHS Evidence web site. The first search was performed using the keywords yogic breathing and Pranayama and had 330 hits. Separate searches were also performed with keywords anxiety, OCD/obsessive compulsive disorder, panic disorder, post-traumatic stress disorder, phobia, depression and physical health problems and had 320 228, 30 545, 25 648, 42 600, 18 475, 549 867 and 185 861 hits respectively. Each of these searches were then combined with the first search, resulting in 45 hits for anxiety, 2 for OCD, 6 for PTSD, 0 for panic disorder, 40 for depression, and 22 for physical health problems. All of these final hits were carefully screened and five studies were selected. The references from these articles were checked to find any other potentially relevant articles. Furthermore the “Google Scholar” site was searched for the keywords Yogic breathing and Pranayama, and had 807 hits. These articles were also screened to identify any more potentially relevant articles (Table 2) the trial dataset of relevant studies is summarised in Table 3.

RESULTS

Effects in Physically Ill Patients

In a controlled trial involving healthy volunteers, Pranayama has been associated with a reduction in heart rate, the lowering of systolic and diastolic blood pressure, an increase in peak expiratory flow rate and improvement in problem-solving skills.¹⁰ In an uncontrolled open study involving healthy volunteers, it was associated with a reduction in mean arterial pressure and systolic blood pressure.¹¹ A pilot study¹² of haemodynamic variables associated with a yogic breathing technique found that it induced dramatic shifts in all variables, both during the exercise and in the subsequent resting period, with long-term practice. This effect may possibly be due to “resetting” of the cardio-respiratory pacemaker, because a controlled trial in healthy volunteers showed that three months of Pranayama training modulates ventricular performance by increasing parasympathetic activity and decreasing sympathetic activity.¹³ A randomised controlled trial in healthy volunteers found beneficial effects of Hatha Yoga and Omkar meditation (two types of yogic breathing practice) on cardio-respiratory performance and psychological status and an increase in melatonin levels after three months of continuous practice.¹⁴ A further investigation found that unilateral nostril yoga breathing practices (eg, right, left and alternate nasal breathing) appeared to influence blood pressure in different ways.¹⁵

Beneficial effects of Pranayama have also been seen in the area of metabolic diseases, where a reduction in blood glucose and improvement in lipid profile and serum insulin levels were reported in a randomised controlled trial involving patients with Type 2 diabetes mellitus¹⁶; and in a range of respiratory diseases. A recent uncontrolled open study found a marked improvement in clinical manifestations in patients with chronic naso-bronchial allergies, who were advised to do regular breathing, Kapal Bhati and Anulome-velome Pranayam.¹⁷ A systematic review to determine the effectiveness of breathing retraining in the management of asthma found evidence for a possible role in overall patient management.¹⁸

Yoga and Pranayama have been found to exert psychological benefits in patients with established physical health problems. For example, adoption of yogic breathing techniques was found to improve well-being in a randomised controlled trial involving patients living with HIV/AIDS.¹⁹ A recent case-control study²⁰ about the effects of breathing rate on self-reported pain and emotion following thermal pain stimuli in women with fibromyalgia syndrome found that slow breathing decreased negative affect ratings following painful stimuli, both in patients with fibromyalgia and in a control group of healthy women. Yoga therapy was reported to improve quality of life in an open uncontrolled study in patients with migraine.²¹ Tibetan yoga (which incorporates controlled breathing and visualization, mindfulness techniques, and low-impact postures) was found to significantly improve sleep-related outcomes in patients with lymphoma.²² Yoga intervention was found to enhance the health of patients with chronic back pain, with improvements in measures of pain, depression and energy-fatigue, and on the Short Form-12 Mental Health Scale.²³ Stress reduction interventions such as yoga may be helpful in complementing conventional anti-emetic drugs in the management of chemotherapy-related nausea and emesis.²⁴ Yoga practice has also been reported to assist cancer patients in managing symptoms such as depression, anxiety, insomnia, pain and fatigue.²⁵ A controlled pilot trial suggests that adult populations may improve their overall “wellness,” through practicing yogic breathing exercises.²⁶

Effects on Neuropsychological Function and Well-Being

In some studies, yogic breathing has been found to affect neuropsychological performance—for example, a significant improvement in a task involving Letter Cancellation Task scores was observed in participants who practiced three yoga breathing techniques over four sessions.²⁷ Another study found a marked reduction in visual and auditory reaction times in participants who practiced one type of yogic breathing technique,²⁸ indicating an improvement in sensory-motor performance and suggesting an enhanced processing ability.

An “antidepressant” effect of yogic breathing was reported following a randomised controlled trial involving alcohol-dependent subjects,²⁹ and it also appears effective in reducing stress, anxiety and depression.^30,31 For example, Sudarshan Kriya yoga (which combines various breathing exercises and postures) was reported to be a beneficial, low-risk, low-cost adjunct in the treatment of stress, anxiety, post-traumatic stress disorder, depression, stress-related medical illnesses, substance abuse and in the rehabilitation of criminal offenders.³⁰ Instruction in yogic breathing techniques, both alone and when combined with giving “testimony,” was found to significantly reduce intensity of depression in abused women.³² A small uncontrolled study in patients with the diagnosis of obsessive-compulsive disorder found yogic therapy to be beneficial,³³ and the combination of yoga postures and breathing techniques was found to reduce distress symptoms in an uncontrolled investigation involving Tsunami survivors.³⁴ In addition, yoga based interventions may prove useful to relieve distress following mass disasters.³⁵ A two-year longitudinal study³⁶ involving medical students who participated in deep breathing exercises found reductions in examination anxiety, nervousness, self-doubt and concentration problems. An unpublished compendium of four studies reported significant improvement in post-traumatic and depressive symptoms after augmentation with a specific yogic breathing technique.³⁷

Presumed Mechanism of Action of Pranayama

The exact physiological mechanisms underlying the effects of Pranayama remain unclear, but models have been proposed based on the findings of previous investigations. Diaphragmatic breathing is thought to form the basis of breathing exercises in general and Pranayama in particular. Adoption of slow deep breathing is one of the more common relaxation techniques and forms an important component in the management of many patients with anxiety disorders.³⁸ Varieties of breathing techniques and patterns have been used for relaxation, stress management and improved control of psychophysiological states and to improve autonomic function.³⁹

Observations of individual breathing patterns have shown “under-functioning” of the diaphragm and over-activity of muscles in the chest wall and upper thorax; appearing that “chest breathing” is natural and involuntary for the majority of population.⁴⁰ This form of breathing is well noted in the flight/fight response during stress and anxiety-provoking situations.⁴¹ It is also known that the breath becomes more shallow and “jerky” in stressful situations, and reflects variations in the prevailing mental state. Changes in breathing patterns have been described in certain emotional states and in those with anxious personality traits.^42,43 Poor pulmonary function has been found to be associated with negative emotional states and a more rapid rate of their decline.⁴⁴

During rapid and shallow breathing, the lower lobes of lungs are not adequately ventilated, although they are better perfused. As a result, there is an inadequate gas exchange in the lower lobes, resulting in a ventilation–perfusion mismatch. This imbalance can be corrected by diaphragmatic breathing, which is both deeper and more regular. It increases suction pressure in the thoracic cavity and improves the venous return of blood; subsequently it reduces the work load on the heart and has positive effects on circulatory functions. Rhythmic diaphragmatic breathing can improve ventilation of the lungs⁴¹ and hence may enhance oxygen transfer into blood. Increased venous return to the lungs increases blood supply to the pulmonary alveoli. This form of breathing prolongs the process of inhalation, which in turn is associated with increased passage of nutrients and enzymes into air sacs, thereby increasing metabolic functions in the alveoli and offering more protection to lungs. The metabolic products have the capacity to further slow the breathing rate resulting in increased parasympathetic activity and release of acetylcholine and nitric oxide, which are considered to have protective effects on other tissues and organs.

A close association between emotional state and functioning of the autonomic nervous system (ANS) has been observed in previous studies.^45,46 Some investigations have highlighted “negative affect” as the common pathway between depression, anxiety, anger and impairments in cardiac autonomic function.⁴⁷ The association between certain emotional disorders and ANS activity has been noted through the findings of studies in a range of conditions; for example, in attention deficit/hyperactivity disorder,⁴⁸ in autism,⁴⁹ in adults with anxiety disorders⁵⁰ and in post-traumatic stress disorder.⁵¹

Many studies have found that ANS activity can be influenced by voluntary breath regulation. One of three known methods for selectively activating one aspect of the ANS is by unilateral forced nostril breathing (UFNB) itself one of the types of Pranayama.⁵² UFNB selectively activates the ipsilateral branch of the sympathetic nervous system with a possible compensatory effect leading to contra-lateral vagus nerve stimulation.⁵² The second method works by stimulation of an autonomic reflex point on the fifth inter-costal space near the axilla, and the third employs unilateral vagus nerve stimulation via the mid cervical branch and requires surgical implantation of a wire and pacemaker. Three months of Pranayama training has been shown to increase parasympathetic activity and to decrease sympathetic activity in young volunteers¹³; and these findings have been replicated in other studies.^40,53

One hypothesis⁵⁴ suggests that slow pranayamic breathing generates inhibitory signals and a hyperpolarising current within neural and non-neural tissue, by mechanically stretching pulmonary tissues during breath inhalation and retention. Inhibitory impulses, along with a hyperpolarisation current, may initiate the synchronisation of neural elements in the central nervous system (CNS), peripheral nervous system and surrounding tissues causing a shift in the balance of autonomic activity towards parasympathetic dominance.

In contrast, Pranayama can also cause CNS excitation. A recent study found the presence of paroxysmal gamma waves (PGW) in subjects practicing in Bhramari Pranayam, and these epileptiform-like waves were considered to represent a non-epileptic hyper-synchrony.⁵⁵ Another study observed decreased chemoreflex sensitivity through voluntary breath regulation.⁵⁶ Furthermore, markers of neuroendocrine function, such as prolactin and possibly of vasopressin and oxytocin, can also be affected by yogic breathing.⁵⁷

A neurophysiological unifying model postulates that yogic breathing exerts its influences by strengthening, balancing and stabilising the autonomic and stress response system, decreasing chemoreflex sensitivity, improving the baroreflex response, shifting to parasympathetic dominance via vagal stimulation, balancing of cortical areas by thalamic activity, inhibiting cortical areas involved in executive functions (for example, those underlying anticipation, planning and worrying), activation of the limbic system and through increased release of prolactin and oxytocin, thereby enhancing feelings of calmness and bonding.⁵⁸

CONCLUSION

Anxiety and depressive disorders are common, distressing, impairing and burdensome conditions for which a range of pharmacological and psychosocial interventions are available, though none of them can be considered “ideal.” As with other long-term medical conditions, many affected individuals are disappointed by the lack of effectiveness or poor acceptability of conventional treatments, and hope that alternative or complementary approaches may prove beneficial. Unfortunately many alternative approaches have not been subject to rigorous evaluation, using randomised controlled trial designs.

Yogic breathing (Pranayam) involves control of the rate, depth and type of breathing and is considered to be an important component of yogic practice. “Breathing exercises” are sometimes recommended as part of the overall management plan for patients with anxiety disorders.⁶⁰ There are many reports of benefit being derived from the use of yogic breathing techniques in healthy volunteers, patients with physical health problems and patients with mental disorders including obsessive-compulsive disorder and post-traumatic stress disorder; and a number of physiological studies suggest that yogic breathing techniques may produce beneficial effects in cardio-respiratory parameters.

However, this systematic review and the subsequent appraisal of identified studies reveals only limited evidence for the efficacy of yogic breathing arising from adequately designed and sufficiently powered randomised controlled trials in patients with well-defined anxiety disorders. As such, there is a persistent need for a large randomised controlled trials in strictly defined clinical samples, in which assessments of potential efficacy in acute treatment are accompanied by investigations of possible changes in neuropsychological autonomic nervous system functioning, which might underlie any effects in reducing measures of anxiety; furthermore, there is a need to establish whether any potential benefits seen during acute treatment are maintained over longer periods.

Acknowledgements: We are grateful to Steph Carey-Kent, for help with the formatting of tables and references.

Disclosure: The authors declare no conflict of interest

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Depression and cardiovascular disease are very common, and often, they coexist, being the prevalence of depression in various cardiac disorders ranges from 15% to 20%.¹

Major depression is considered a primary risk factor for the development of cardiovascular diseases, including coronary artery disease (CAD), myocardial infarction (MI),^1–10 and congestive heart failure (CHF).^11–13 An emerging literature suggests also that depression might contribute to hypertension.^14–16 The risk of developing these cardiovascular disorders increases when the depressive disorder is severe.^7,14,17 Nonetheless, the so-called “minor” or “subthreshold” forms of depression, currently included in the realm of “mood spectrum disorders,”^{18, 19} have been also recently investigated as conditions potentially related with a higher risk to develop a cardiovascular disease.^11,20–22 Vice versa, according to clinical and epidemiological studies, patients with cardiovascular diseases show a twofold to fourfold increased risk to develop a depressive disorder.^11,20,21

Moreover, major and minor forms of depression, isolated depressive symptoms or clusters of depressive signs and symptoms, might be considered secondary risk factors for cardiovascular diseases, being reliable predictors of poor outcome, worse prognosis,^23–25 and increased mortality.^20,24–27

Despite the large amount of evidence linking cardiovascular disorders and depressive disorders, many aspects of their relationship are still unclear. Several observations are concordant with the hypothesis of a bidirectional relationship between the cardiac and the spectrum of depressive disorders.^{20,21,28–30} Following this hypothesis, these disorders should be considered as a risk factor for each other. The primary aim of this article in fact is to systematically review the clinical evidence of their bidirectional relationship. The secondary aim is to evaluate the possible explanation of their potential common psychoorganic background.

METHODS

Search Strategy

We performed a systematic search of MEDLINE and PsychINFO. Initial search was conducted in November 2009 with a final search in December 2011. The search strategies used MeSH headings and keywords for “cardiac disease” or “hypertension” or “coronary artery disease” or “myocardial infarction” or “congestive heart failure” and “depression” or “major depression” or “depressive symptoms” or “minor depression” and “primary risk” or “secondary risk.” The searches were limited to the English Language and adults. Studies of children were excluded from the analysis.

Inclusion and Exclusion Criteria

Studies were included if (1) they involved adult participants aged older than 18 years; (2) they were prospective studies, cross-sectional, studies with control group; (3) they systemic review or meta-analyses; (4) they analyzed the relationship between spectrum of depressive disorders and cardiac disease; and (5) the publication date from 1937 to December 2011. Studies were excluded if (1) they did not control for any confounding factors in the relationship between depressive spectrum disorders and cardiac disease (age, sex, education, cigarette smoking, body mass index, alcohol use, history of diabetes, stroke, or coronary heart disease, antidepressant use, lifestyle factors, and stressful events) and analyzing data stratified by race and age, (2) they were not available in full text; or (3) they were not available in English.

RESULTS

Clinical Evidences of a Bidirectional Relationship

Depressive spectrum disorders: primary risk factor for cardiovascular diseases

Hypertension. Depressive spectrum disorders might contribute to hypertension. ^{14–16,31–34} In a prospective study, the National Health and Nutrition Examination Survey Epidemiologic Study (NHANES), a cohort of almost 3000 adult men and women, normotensive at baseline, were followed up for 7 to 16 years. After adjusting for hypertension risk factors (age, sex, education, cigarette smoking, body mass index, alcohol use, history of diabetes, stroke, or coronary heart disease, and baseline systolic blood pressure) and analyzing data stratified by race and age, results showed that depressive symptoms were significant predictors of hypertension onset (Table 1).³¹ For white individuals aged 45 to 64 years and for black individuals aged 25 to 64 years, high depression scores remained independent predictors of incident hypertension (Table 1). Moreover, depressive symptoms were predictive of later hypertension incidence in young adults, and especially, young blacks with depressive symptoms were at high risk of developing hypertension. In another prospective population study, a cohort of 3343 young adults (aged 23–35 years) from the Coronary Artery Risk Development in Young Adults (CARDIA), normotensive at baseline, have been followed up for 5 years. After adjusting for hypertension risk factors (age, sex, education, cigarette smoking, body mass index, alcohol use, history of diabetes, stroke, or coronary heart disease, and baseline systolic blood pressure) and analyzing data stratified by race, subjects with higher scores (16) on the Center for Epidemiological Studies Depression Scale (CES-D) were at significant risk for hypertension incidence compared with those with low CES-D scores (7). Those with intermediate depressive symptoms (CES-D scores 8–15) were also at significant risk.³¹ These associations were significant in blacks alone but were not found in whites, which had a lower hypertension incidence (Table 1).³² The prospective data in the Baltimore Epidemiologic Catchment Area (ECA) follow-up study, a longitudinal population-based study in East Baltimore on normotensive subjects, showed that individuals with a major depressive episode, measured at baseline by the Diagnostic Interview Schedule (DIS), had increased risk for hypertension onset compared to those who reported never having depressive symptoms. This risk is increased after adjustment for age, gender, race, body mass index, Nam-Powers socioeconomic score, alcohol usage, smoking, exercise, and diabetes status. Even though the data are based on self-reported hypertension, which might constitute a misdiagnosis of hypertension, and some confounding factor have not been considered (ie, salt intake), these findings suggest that depression may be an independent risk factor for hypertension, particularly for those with recurrent episodes or a long-term history of the disease (Table 1). Also, the Canadian National Population Health Survey study, in which 12 270 subjects were followed up for about 2 years, showed that the risk of developing hypertension was elevated in those with major depression, both men and women, and increased to 9.5% (95%CI: 7.4–9.7) with age (Table 1).¹⁵ On the contrary, depressive symptoms, such as dysthymia and dysphoria, did not statistically increase the risk for hypertension (Table 1).³¹ Data from the male twins of the Vietnam Era Twin Registry (VET) show that hypertension was significantly associated with one to four symptoms and five or more symptoms of depression.¹⁴ A CAPO Among depressive symptoms, hopelessness was associated with increased incidence of hypertension in 616 initially normotensive men, in a 4-year follow-up prospective study³⁵. Men reporting high levels of hopelessness at baseline were three times more likely to become hypertensive than men who were not hopeless.³⁵ However, several cross-sectional and prospective studies reported no relation between depression and hypertension.^39–41 Indeed, the latter studies were characterized by short follow-up period (1–3 years), which may not have been sufficient to detect the relations seen in studies with longer follow-up.^16,41

In summary, prospective studies have found that, after adjusting for hypertension risk factors, major depression, severe or moderate pictures of depression, and symptoms of depression might act as independent risk factors for incident hypertension in both men and women.^{14,15,31–36} With respect to age and race, young black and old (>66 years) white individuals with depression might be at high risk of developing hypertension. Severity of depression seems to increase risk, and especially, major recurrent or long-term history depression might favor the development of hypertension. Among depressive symptoms, hopelessness might increase the risk of hypertension especially if severe, instead other symptoms such as dysphoria or dysthymia might not increase risk of hypertension. Further research is needed to study the role of other aspects of depressive spectrum disorders such as depressed mood and the cognitive and emotive symptoms.

Coronary artery disease and myocardial infarction. The hypothesis of a specific relationship between affective disorders and cardiac diseases was emphasized in the 1980s and 1990s, with a large amount of clinical studies on psychosomatic disorders, anxiety, depression, and MI and CAD.^{1–3,5,7–11,42–44} During the last 10 years, several prospective cohort studies enrolling healthy subjects have confirmed that depressive disorders are independent relevant risk factors for the development of CAD (Table 2 ).^{3–5,8,10,11} Recently, four systematic reviews and two important meta-analyses have resumed the most important prospective studies in this field (Table 3). Going into detail, a meta-analysis of 11 prospective studies showed that major depression was associated with a 2.7-fold relative risk for the development of CAD, whereas depressed mood was associated with a 1.5-fold relative risk.³³ The most recent meta-analysis, involving 21 prospective studies, found an almost twofold relative risk for CAD among subjects “depressed” at baseline.⁷ The risk for cardiovascular disease has been related to severity of affective disorders.^7,45 Nonetheless, even minor forms of depression,^11,22 subsyndromal forms of depression,¹¹ or isolated depressive symptoms^11,21 such as hopelessness,^21,46,47 fatigue-sadness, and irritability^{48, 49} have been demonstrated to constitute an independent risk for CAD. Dysthymia has also been indicated as an independent risk factor for CAD¹¹ with an increased 2.5-fold risk in the long term.²²

Depressive spectrum disorders might constitute an independent risk factor for acute MI too (Tables 3 and 4 ).^{1–3,50–52} The incidence of acute MI is twofold to fourfold increased in depressed subjects as compared to non-depressed subjects.^2,3,8 For major forms of depression, a 1.6-fold increased risk for MI has been described⁸ Nonetheless, minor forms of depression or isolated depressive symptoms such as decreasing energy, excessive fatigue, feelings of demoralization, increased irritability,^{22,46,48–51,53} hopelessness,^1,48,54 and dysthymia²² also constitute as a risk factor for MI (Tables  3 and 4 ).

In summary, prospective studies have found that, after adjusting for confounding factors, major depression, severe or moderate pictures of depression, and symptoms of depression might act as independent risk factors for CAD and MI in both men and women, black and white, adults and elderly. Among depressive symptoms, especially, not only hopelessness seems to increase the risk for CAD and MI but also other symptoms such as fatigue, demoralization, and irritability might increase the risk of CAD and MI. Further research is needed to study the role of depressed mood, anhedonia, and somatic-affective aspect of the depressive spectrum disorders in the etiology of CAD and MI.

Congestive heart failure The possible influence of depression on the development of heart failure in patients with CAD or MI is less established. A 14-year follow-up on elderly depressed women without heart disease at baseline showed that risk of having CHF was 1.5 times higher than non-depressed women.¹³ In a sample of old depressed patients with isolated systolic hypertension, the risk of having CHF was twofold higher than in patients without depression.¹² Depression was associated then with an increased incidence of CHF also in a sample of depressed post-CAD subjects.^55,57 In summary, depression might act as an independent risk factor for heart failure, especially among elderly women but not elderly men. Indeed, this field needs further studies as the possible influence of depression or depressive symptoms in the development of CHF have not been fully addressed to date.

Depressive spectrum disorders: secondary risk factor for cardiovascular diseases

Increased prevalence of depressive spectrum disorders of different severity was demonstrated in patients with established cardiovascular disease although it is difficult to identify whether depressive symptoms where already present before the onset of an event or if the development of a severe pathological condition is rather the cause of the depression. This dilemma can be hardly solved. However, increasing evidence suggests that the comorbidity between cardiovascular and depressive conditions is associated with a worse cardiovascular prognosis. Spectrum of depressive disorders might act as a secondary risk factor.

Hypertension Symptoms of depression might impair the management and prognosis of hypertension,^{58, 60} but it has been not fully address to date. Severe depressive symptoms seem to increase the risk of cardiovascular-related death in older adults, especially women, with diagnosed hypertension in the Established Populations for Epidemiologic Studies of the Elderly.⁶⁰ Among elderly persons, a significant risk of MI or death was associated with worsening depressive symptoms over time (Table 5).⁵⁸ In summary, depression and depressive symptoms seems to act as a secondary risk factor for hypertension especially in women, increasing the risk of fatal and not fatal cardiac events. Indeed, studies at this time are very few and include only elderly population. Further research is needed to study the role of depression and depressive disorders in the prognosis of hypertensive patients.

Coronary artery disease and myocardial infarction Major and minor forms of depression^23,24 and the presence of isolated depressive symptoms increase the risk for rehospitalization, reinfarction, and CHF in patients with known CAD,^{23,53,55,62–64} thus negatively affecting CAD prognosis.^{26,53,64–68} Moreover, CAD patients with depression generally show mortality rates for cardiac events 1.5 to 3.4 times higher than patients without depression.^{1,24–26,46,53,63–65, 69} Among depressive symptoms, anhedonia seems to be the most tightly related to increased risk of fatal and non-fatal major cardiac events.^70,71

The presence of depressive symptoms after an acute MI predict a later return to activity, worse social readaptation, lower likelihood of returning to work, and poorer quality of life.⁷². Depression negatively influences the course of cardiac diseases, in particular the number of rehospitalizations,^27,73 the quality of life, and mortality rates^10,72–78 of MI patients. Early onset of depression within 5 to 15 days following MI is associated with more than a fourfold increased risk of mortality during the following 6 months,⁷⁹ with a threefold increased risk in the following 12–18 months^{80, 81} and within 5 years.⁸² Presence and severity of depression are associated with a higher risk of sudden cardiac death, independently from classical cardiovascular risk factors.^83–85

According to recent observations, subsyndromic depressive manifestations also increase the risk of adverse cardiac events.^{86, 87} Among them, somatic-affective symptoms of depression, as well as anhedonia, are associated with a worse cardiac prognosis, increasing rehospitalization and mortality rates.^71,88–91 On the other side, cognitive depressive dimensions were only marginally related to health status (Table 6).^76,88,89

In summary, prospective studies have found that, after adjusting for confounding factors, major depression, severe or moderate pictures of depression, and symptoms of depression might be independent secondary risk factors for CAD and MI in both men and women adults. Depression, especially if severe, increases the risk of fatal and non-fatal cardiac events in CAD and MI subjects. Among depressive symptoms, particularly anhedonia and somatic-affective symptoms seem to increase the risk for fatal and non-fatal cardiac events in CAD and MI patients.

Congestive heart failure Recent studies show that, also in HF patients, comorbid mild-to-moderate clinical features of depression are associated with adverse outcomes and worse prognosis.^92–104 Comorbid depression in CHF is one of the strongest predictors for low levels of treatment compliance^{94,102,106,95,101,103,97,98,100–109} regardless of HF etiology,⁹⁵ and a higher incidence of cardiac events such as myocardial infarction or sudden cardiac death.^{95, 98} and 3-times higher after 5 years.¹¹⁰ Also, in this case, fatigue and somatic-affective, but not cognitive symptoms of depression, predict poor outcome in chronic HF (Table 7).¹¹¹

In summary, prospective studies have found that, after adjusting for confounding factors, major depression, severe or moderate pictures of depression, and symptoms of depression might act as independent secondary risk factors for CHF in both men and women adults. Depression and depressive symptoms might increase the risk of fatal and non-fatal cardiac events in CHF patients. Fatigue and somatic-affective, but not cognitive symptoms, seem to predict poor outcome in CHF patients. Indeed, further research is needed to study the relationship between other aspects of depressive spectrum disorders and CHF prognosis.

Cardiovascular diseases: risk factors for depressive disorders

Some evidences suggest that also cardiac diseases might constitute a risk factor for the onset of depressive disorders involving hypertension, CAD, MI, and CHF.

Hypertension. Hypertension has been proposed as a risk factor for the development of depression, and a “vascular depression” hypothesis has been developed.^{112, 113} However, this hypothesis is based only on cross-sectional studies, and to date, it is not confirmed by prospective studies. Indeed, increased prevalence of depression has been described in hypertensive patients as well. Rabkin et al. found a threefold higher prevalence of major depression in patients with hypertension (Table 8).^{114, 115}

Coronary artery disease and myocardial infarction CAD. is traditionally considered a risk factor for the onset of affective disorders.^{11, 21, 116} Depressive disorders prevalence rates are usually higher in CAD patients than in the general population and range from 16% to 27%.^11,116–118

High rates of depression in patients with acute MI have been documented since the late 1960s. Early studies described the so-called post-MI “catastrophic reaction” in patients in coronary care unit119¹²⁰ and considered the “depressive reaction” as a psychological response to physical illness. Given that, a stereotyped post-MI course was described, with an anxious response for the first 2 days post-MI, followed by a depressive response.¹²⁰

Prevalence rates for depressive disorders after an acute MI range from 10% to 87%.^{78, 79}119 ^120–125 This wide variability was mainly due to the differences in study design, to the evolution of inclusion and exclusion criteria, to the number of days considered after the acute event, and to heterogeneity of age range of patients enrolled. Thus, according to Research Diagnostic Criteria (RDC),⁷⁰ only 18% of patients with MI might fulfill the diagnosis of major depression when evaluated within 8–10 days from the acute event, reaching the 27% if minor depression was also considered. Prevalence of major depression increased to 20%–45% when the Dimensional Rating Instrument was utilized (Table 8).^{80, 86} More than 80% of patients who develop a major depression after an acute MI show a major or minor type of depression after 3 months from the cardiac event.⁷⁰

In summary, CAD and MI might increase the risk of developing depressive disorders and are associated with higher prevalence rates of affective disorders than general population.

Congestive heart failure. CHF seems to be a risk factor for the onset of mood disorders,^{20, 95} especially in the elderly.^{12, 20, 95} Furthermore, subthreshold forms of depression or isolated depressive symptoms have been described in 24%–85% of CHF patients^{94, 95,128–131} and major form of depression in 14%–26% of CHF patients.^{95, 129}

A large number of studies have focused on demographic characteristics of CHF patients with depression: in particular, older Caucasian females seem to be at the highest risk to develop depression^{127, 131, 20, 129}

In summary CHF might increase the risk of developing depressive disorders and is associated with higher prevalence of affective disorders than general population.

Comments on causality

There are sufficient evidences to suggest that depression and depressive spectrum disorders might constitute primary and secondary risk factors for cardiac disease. Among depressive symptoms, especially demoralization, irritability, somatic symptoms, fatigue, anhedonia, and hopelessness, have been described as possible primary and secondary risk factor for cardiac disease. Vice versa cardiac disease might act as risk factors for depression and depressive spectrum disorders. Thus, we hypothesized that they might be related by a bidirectional relationship.

Psychobiological Evidence of a Common Etiological Background

It has been hypothesized that depressive symptoms might predispose to cardiac disease and vice versa, through common neuroendocrine pathways, involving the hypothalamic-pituitary-adrenal (HPA) cortical axis, autonomic nervous system,^30,133–139 activation of inflammation mediators, platelet activation, and endothelial function,^72,81 raising the question of a genetic vulnerability common to both cardiovascular diseases and mood disorders.^140,141

Autonomic system dysregulation

Neurohormonal dysregulation, namely increased levels of norepinephrine, renin, angiotensin-II, aldosterone, arginine, vasopressin, and endothelin-1, is present in cardiovascular diseases as well as in mood disorders.^40,81 Sympathetic nervous system activation as well as overstimulation of the HPA axis⁹ are commonly observed among patients with major depression: such alterations may play a role in sustaining blood pressure elevation over time.^32,40 Patients with depression frequently show hypercortisolemia and adrenomedullary dysfunction, demonstrated by means of corticotropic hormone-releasing factor challenge and cortisol non-suppression dexamethasone tests.^9,142,85,139 worsening in parallel with depression severity.^144,144 In particular, HRV patterns are directly correlated with the presence and severity of somatic symptoms but not with cognitive symptoms of depression.¹⁴⁴ Increased resting HR and low HRV are known to be associated with cardiovascular mortality in patients with depression,¹⁴⁴ as well as in patients with cardiovascular disease regardless of the presence of mood disorders. Conversely, the presence of two or more depressive symptoms among patients with cardiovascular diseases is associated with reduced HRV after an acute coronary event, affecting recovery,¹⁴⁶ independently from antidepressants treatment that are not able to influence HRV.¹⁴⁷ Recently, increased adrenergic tone was demonstrated in subjects with moderate-to-severe depression by microneurography, a technique able to record directly and quantify sympathetic nerve traffic from a peripheral nerve.¹⁴⁸

Inflammation

Cytokines, such as the tumor necrosis factor (TNF), interleukins (IL-1 and IL-6), and the C-reactive protein, are involved in all stages of atherosclerosis^20,27,150 and an increase in mortality rates.^151,151 At the same time, there is a growing body of literature showing that both major and subthreshold forms of depression¹⁵³ influence inflammatory processes in subjects with CAD.¹⁵⁴ For example, depressive symptoms are correlated with an increase in the secretion of specific cytokines (eg, IL-1β and TNF) among patients with CAD or CHF.^9,155 Moreover, inflammation mediators release seems to be increased among depressed than non-depressed patients with cardiovascular disease.^156,157

Hypercoagulability

Platelet activity and aggregation are key components of acute myocardial ischemia. CHF patients often show coagulation abnormalities.¹⁵⁸ The association between hypercoagulability and depressive symptoms is controversial, although patients with depression show higher fibrinogen levels.¹⁵⁹ Moreover, platelet aggregation is altered in depression,¹⁶⁰ with a negative correlation with the enhanced density of platelet serotonin (5-HT2A) receptors.⁴¹

Endothelial Dysfunction

Endothelial dysfunction is the first step of atherosclerotic process: it is present in patients with cardiovascular risk factors, and it is an independent predictor of cardiovascular event. ^167–169 A reduced endothelium-dependent vasodilatation of the brachial artery was demonstrated in patients with established CAD with depressive symptoms as compared to patients with the same heart affection but no symptoms of depression.¹⁷⁰ In a recent study, hopelessness and other depressive symptoms have been correlated with circulating biomarkers of endothelial dysfunction, including e-selectin, p-selectin, and soluble intercellular adhesion molecule-1 in a sample of general population, even after adjustment for other risk factors.¹⁷¹ According to these studies, depressive symptoms may have a negative impact on cardiovascular system, mediated by endothelial dysfunction.¹⁷³ Since inflammation mediators and sympathetic activation critically influence endothelial function, it may represent a link between depression and cardiovascular disease.

Common Genetic Vulnerability

The predisposition to coronary artery diseases is hereditary, as recently reviewed by Musunuru and Kathiresan,^{96, 173} Some studies have suggested that a shared genetic vulnerability could explain the relationship between depression and hypertension. Grewen et al.¹⁷⁴ investigated whether parental history of hypertension enhances the impact on ambulatory blood pressure (ABP) of depressed mood as indexed by the Beck Depression Inventory (BDI) (n=314). Higher BDI scores were significantly associated with higher 24-hour ABP in these subjects but not in participants without parental history of hypertension. Relationships were significantly stronger in those with two hypertensive parents vs those with one vs and those with no hypertensive parents. In contrast, interaction was least predictive of BP levels during sleep, suggesting that the influence of depression on BP is manifested during responses to everyday stresses and strains.¹⁷⁴ In several disease-association studies, the C825T polymorphism of the gene encoding for the ?3 subunit of G proteins could be linked to both hypertension and depression, possibly identifying a common genetic background for the two conditions.¹⁷⁵ The Vietnam Era Twin Registry Study showed that the association between depression, hypertension, and CAD might be mediated by genetic factors, especially in men.¹⁷⁶ Conversely, the Swedish Twin Registry study showed a genetic predisposition to both CAD and major depression episodes in women, while, in men, “environmental factors” seem to play a more important role.¹⁷⁷ These studies of covariation strongly suggest common genetic influences across depression and CAD, as summarized in a recent review.¹⁷⁸ Moreover, the genetic variability of inflammatory pathways is important both for depression and CAD development.¹⁷⁸ Two variants within the serotonin pathway have been examined in relation to CAD and depression, although the results are not conclusive.¹⁷⁸ The l allele at the 5-HT promoter site has been shown to increase risk for CAD^{179, 180} while a TT genotype at position 102 in the 5-HT2 gene was associated with risk for MI.¹⁸¹ Variation in serotonin metabolism has been implicated in multiple mood disorders, too,¹⁸² and genetic variability in two serotonin-related polymorphisms, in turn, has been linked to alterations in serotonin levels.¹⁸³ The 5HTTLPR is an insertion/deletion polymorphism in the 5? flanking regulatory region of the serotonin transporter gene, characterized by either long (L) or short (S) alleles, associated with differential transcriptional efficiencies.¹⁸⁴ Reduced serotonin transporter transcription, expression, and function have been reported in S allele carriers compared to L allele homozygotes¹⁸² and have been related to depression, with some studies reporting that the S allele is associated with depressive symptoms and increased risk of new cardiac events in MI patients,¹⁸⁵ whereas others have indicated that the L/L genotype is associated with susceptibility to MI¹⁸⁰ and increased incidence of adverse cardiac events.¹⁸⁶ Most available studies have so far dealt with the impact of polymorphisms in relation to either depression or cardiovascular disease. A few recent studies have now examined the effects of gene-gene or gene-environment interactions and are investigating the impact of “depression-related” variants on cardiac response to stress. The first promising results were obtained with the serotonin transporter. Among patients with CAD, carriers of the S allele of 5-HTTLPR are more vulnerable to depression, perceived stress, and high norepinephrine secretion. These factors may contribute to worse cardiovascular outcomes in these patients.¹⁸⁷ Recently, autonomic dysregulation in depression has been studied also in bivariate genetic modeling and revealed significant genetic correlations between depressive symptoms and HRV. Of the total covariance between depressive symptoms and HRV indices, over 80% was due to the same genetic factors. In conclusion, depressive symptoms are associated with decreased HRV and this association is due, in large part, to a shared genetic effect. These results suggest that a common neurobiological dysfunction links depression and autonomic dysregulation.¹⁴¹

CONCLUSIONS

Spectrum of depressive disorders might act as independent risk factor for the development of cardiovascular diseases, as well as negative prognostic factors in patients with established cardiovascular disease. The systematic assessment of the overall spectrum of depressive disorders should be taken into account in cardiovascular patients, considering the impact of depressive spectrum symptomatology on clinical outcome of cardiovascular diseases. In fact, in addition to major and minor forms of depression, also subsyndromal aspects of depression, including cluster of depressive symptoms, demoralization, irritability, somatic symptoms, fatigue, anhedonia, and hopelessness, need to be evaluated in patients with cardiovascular disease. On the other hand, cognitive aspects of depression seem not to affect both the development and the prognosis of cardiac disease. Therefore, further research is needed to study systematically spectrum of depressive disorders including depressed mood, anhedonia, and somatic-affective aspects of depression and their role as primary and secondary factors in hypertension and cardiovascular diseases, particularly HF. Cardiovascular disease might act as a risk factor for depression and depressive spectrum disorders; thus, a bidirectional relationship has been hypothesized. A common pathophysiological background, involving autonomic system dysregulation, inflammatory mediators, hypercoagulability, and endothelial dysfunction, as well as a common genetic vulnerability, might be responsible of the association between cardiovascular disease and depressive spectrum disorders. Nonetheless, further research is needed to study the multifactorial relationship between the realm of cardiovascular diseases and the realm of depressive spectrum disorders.

Disclosure: The authors declare no conflict of interest.

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Attention deficit and hyperactivity disorder (ADHD) affects a significant proportion of children and adolescents and causes impairments in school performance and other areas of functioning.¹ The relationship between sleep and attention deficit/hyperactivity disorder (ADHD) is complex.² Sleep problems are common in children and adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD), even in the absence of treatment with stimulant medications.³ Gau and Chiang showed that adolescents with a childhood diagnosis of ADHD were more likely to have current and lifetime sleep problems and sleep disorders.⁴ Sleep problems are relevant to the management of children with ADHD. Such problems can cause a significant distress for these children and their parents. ^5–8 These sleep problems may also worsen symptoms of ADHD.⁹ They may pose a challenge to the clinician. Therefore, appropriate assessment and treatment of sleep problems in children with ADHD is important. In addition to clinical improvement it may also improve the quality of life of these children and their families and reduce associated impairments of ADHD. However, to appropriately manage sleep complaints in patients with ADHD, it is necessary to better characterize them and understand the specific sleep alterations underlying these complaints. The commonly occurring sleep disorders in children include delayed sleep phase disorder (DSPD), poor sleep hygiene, insomnia, narcolepsy and restless leg syndrome/periodic limb movements in sleep.¹⁰

DSPD is characterized by habitual sleep-wake times that are delayed, usually more than two hours, relative to conventional or socially acceptable times. Affected individuals complain of difficulty falling asleep at socially acceptable times, but once asleep, sleep is sleep is reported to be normal. Diagnostic criteria for DSPD per International Classification of Sleep Disorders (ICSD):

• There is a delay in the phase of major sleep phase period in relation to the desired sleep time and wake-up time, as evidenced by a chronic or recurrent complaint of inability to fall asleep at a desired conventional clock time together with the inability to awaken at a desired and socially acceptable time.

• When allowed to choose their preferred schedule, patients will exhibit normal sleep quality and duration for age and maintain a delayed, but stable, phase of entrainment to the 24-hour sleep-wake pattern

• Sleep log or actigraphy monitoring (including sleep diary) for at least 7 days demonstrates a stable delay in the timing of the habitual sleep period

• The disturbance is not better explained by another sleep disorder, medical or neurological disorder, mental disorder, medication use, or substance use disorder.¹¹

Therapeutic interventions for DSPD consist of behavioral and pharmacological interventions. Phototherapy involving timed light exposure at wake times resulting in advancing sleep-wake cycle is used to treat DSPD. In chronotherapy, bed times and wake times are progressively delayed until sleep-wake cycle has rotated around the clock and neared the desired schedule. Timed melatonin administration is also helpful in treatment of DSPD. Pharmacological interventions including use of benzodiazepine receptor agonists, stimulants and melatonin agonists have not been studied in the treatment of children with DSPD and are not recommended by AASM practice parameters.¹²

The relationship between DSPD and ADHD in children and adolescents is not clearly elucidated. This article summarizes the available evidence about the relationship between ADHD and DSPD in children and adolescents. It also postulates the possible neurobiological underpinnings of these two disorders.

The relationship between ADHD and DSPD is complex and may range from underlying neural mechanisms to common causally related sleep disturbances. The neural basis might involve the same brain areas and mechanisms. Sleep regulation involves prefrontal cortex and thalamic regions. These brain areas are also involved in mediation of attentional functions, working memory and behavioral inhibition. ^13–15

DSPD causes insufficient sleep and consequent excessive daytime sleepiness. This sleep loss may manifest as behavioral dyscontrol in the form of impulsivity, hyperactivity and inattentiveness. Sleep disturbance caused by DSPD may impact the functioning of prefrontal cortex and associated neural areas resulting in attentional impairments and behavior disinhibition.¹⁶

ADHD and its associated symptoms and co-morbidities may result in these children having delayed sleep onset and consequent impairments related insufficient sleep. Studies have shown that children with ADHD have more bed-time refusal and sleep onset insomnia. ADHD and DSPD may share common neural mechanism that leads to both ADHD symptoms and DSPD. A significant number of children with ADHD have sleep onset insomnia akin to DSPD. Children with ADHD may have a circadian disruption associated with timing of melatonin secretion and response to environmental cues that regulate sleep onset.¹⁷

DSPD in Children and Adolescents Diagnosed with ADHD

• Dahl et al in 1991 described a case of a 10-year-old girl diagnosed with ADD who had a 5-year history of sleep difficulties. Chronotherapy combined with behavior modification program resulted in increase in sleep from 7.2 to 9.2 hours per night. This treatment resulted in significant improvement in positive interraction with peers, increased productivity on a timed arithmetic task and increased percentage of assigned seatwork completed.¹⁸

• Gruber et al (2000) studied 28 children with ADHD with actigraphs and sleep diaries for five consecutive nights. They found that these children often had evidence of sleep onset insomnia suggestive of DSPD.¹⁹

• 3.Vander Heijden(2005) studied 87 children between ages of 6–12 years diagnosed with ADHD and chronic idiopathic sleep onset insomnia and compared them with 33 children with ADHD symptoms without sleep onset insomnia. These children were evaluated on actigraphic sleep estimates, circadian-rest activity rhythm and dim light melatonin onset (DLMO). It was found that children with ADHD and chronic idiopathic sleep-onset insomnia showed a delayed sleep phase and delayed DLMO compared to the control group suggesting that this type of insomnia is a circadian sleep rhythm disorder, DSPD.¹⁷

• Rybak et al (2006) treated 29 adults who met DSM-IV criteria for ADHD with bright light therapy in the morning. Bright light therapy resulted in significant improvement in both subjective and objective improvement in core ADHD symptoms. They found that improvements were strongly correlated with phase advance in circadian preference. This study shows that delayed sleep phase may contribute significantly to ADHD symptoms and needs to be addressed in treatment.²⁰

These studies are summarized in the Table 1:

ADHD Symptoms in Children and Adolescents Diagnosed with DSPD

• Walters et al (2008) did not find ADHD symptoms in a preliminary study of five adults with DSPD. They concluded that this relationship needs to be explored further. They hypothesized that sleep disruption caused by delayed sleep onset in DSPD may not enough to cause daytime inattention and hyperactivity.²¹

• We described a case of 17-year-old male who had presented with comorbid ADHD symptoms and DSPD. His DSPD symptoms preceded diagnosis of ADHD.ADHD symptoms were not adequately treated with stimulant medications. He did show significant improvement in ADHD symptoms and psychosocial functioning after directing treatment at DSPD.²²

The available evidence reveals that delayed sleep phase and DSPD is commonly seen in children with ADHD with and without treatment. There is not enough evidence for or against presence of ADHD symptoms in children and adolescents with a primary diagnosis of DSPD. The relationship between ADHD and DSPD does seem to be bi-directional. Treatment directed at delayed sleep phase does seem to help improve ADHD symptoms. This article underscores the need for further studies to elucidate the relationship between DSPD and ADHD. It also highlights the importance of being aware of the relationship between ADHD and DSPD with its implications upon the treatment of children and adolescents with ADHD.

Disclosure: The author declares no conflict of interest

REFERENCES

1. American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders, A Text Revision. DSM-IV-TR. Arlington, VA: APA; 2000.
2. Owens JA. Epidemiology of sleep disorders during childhood. In: Sheldon SH, Ferber R, Kryger MH, eds. Principles and Practice of Pediatric Sleep Medicine. Philadelphia, PA: Elsevier Saunders; 2005:27–33.
3. Stein MA. Unravelling sleep problems in treated and untreated children with ADHD. J Child Adolesc Psychopharmacol. 1999;9:157–168.
4. Gau SS, Chiang H. Sleep problems and disorders among adolescents with persistent and subthreshold attention-deficit/hyperactivity disorders. Sleep. 2009;32(5):671–679.
5. Owens JA. Sleep disorders and attention deficit/hyperactivity disorder. Current Psychiatry Rep. 2008;Oct(5):439–444.
6. Corkum P, Tannock R, Moldofsky H. Sleep disturbances in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1998;37:637–646.
7. Hvolby A, Jorgensen J, Bilenberg N. Actigraphic and parental reports of sleep difficulties in children with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med. 2008;162:323–329.
8. Owens J. The ADHD and sleep conundrum: a review. J Dev Behav Pediatr. 2005;26:312–322.
9. Owens J, Sangal RB, Sutton VK, Bakken R, Allen AJ, Kelsey D. Subjective and objective measures of sleep in children with attention deficit/ hyperactivity disorder. Sleep Med. 2009;10:446–456.
10. Meltzer LJ, Mindell JA. Sleep and sleep disorders in children and adolescents. Psychiatr Clin North Am. 2006;29:1059–1076.
11. American Academy of Sleep Medicine (AASM). The International Classification of Sleep Disorders, Diagnostic and Coding Manual. 2nd ed. Diagnostic and coding manual. Westchester, Illinois: American Academy of Sleep Medicine, 2005: 118–120.
12. Morganthlaer TI, Lee-Chiong T, Alessi C, et al. Practice parameters for clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine Report. Sleep. 2007;30: 1445–1459.
13. Dahl RE. The regulation of sleep and arousal: development and psychopathology. Dev Psychopathol. 1996;8:3–27.
14. Dahl RE. The impact of inadequate sleep on children’s daytime cognitive function. Semin Pediatr Neurol. 1996;3:44–50.
15. Barkley RA. Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull. 1997; 121:65–94.
16. Horne JA. Human sleep loss and behavioral implications for the prefrontal cortex and psychiatric disorders. Br J Psychiatry. 1993;162: 413–419.
17. Van der Heijden KB, Smits MG, Van Someren EJ, Gunning WB. Idiopathic chronic sleep onset insomnia in attention deficit/hyperactivity disorder: a circadian rhythm sleep disorder. Chronobiol Int. 2005;22(3): 559–570.
18. Dahl RE, Pelham WE, Wierson M. The role of sleep disturbances in attention deficit disorder symptoms: a case study. J Pediatr Psychol. 1991; 16:229–239.
19. Gruber R, Xi T, Frenette S, et al. Sleep disturbances in prepubertal children with Attention deficit hyperactivity disorder: a home polysomnography study. Sleep. 2009;32:343–350.
20. Rybak YE, McNeely HE, Mackenzie BE, et al. An open trial of light therapy in adult attention deficit/hyperactivity disorder. J Clin Psychiatry. 2006;67(10):1527–1535.
21. Walters AS, Silvestri R, Zucconi M, Chandrashekariah R, Konofal E. Review of possible relationship and hypothetical links between attention deficit hyperactivity disorder (ADHD) and simple sleep related movement disorders, parasomnias, hypersomnias, and circadian rhythm disorders. J Clin Sleep Med. 2008;4:591–600.
22. Khurshid KA, Khan A. Delayed sleep phase disorder and attention deficit hyperactivity disorder symptoms in a teenager. Atten Def Hyperact Disord. 2009;192:211–213.

Una serie di studi condotti tra varie culture in tutto il mondo ha dimostrato che i pazienti affetti da schizofrenia sono vittime di grave stigma e discriminazione sociale. Malgrado gli sforzi di numerose società regionali e internazionali, i pazienti affetti da schizofrenia sono spesso considerati imprevedibili, incompetenti e pericolosi per la società e persino responsabili della propria malattia. ^1–4 A seconda dei sistemi sociali e culturali, tale discriminazione deriva dal pubblico in generale con tendenze a stigmatizzare e discriminare, dal paziente stesso con atteggiamenti auto-stigmatizzanti e da istituzioni con discriminazione strutturale intenzionale o involontaria.⁵

I sistemi di supporto culturali e sociali hanno un impatto importante sulle disabilità del mondo reale dei pazienti schizofrenici. Uno studio condotto da Harvey, et al ha dimostrato che i risultati nel mondo reale sono migliori presso i pazienti schizofrenici che hanno ricevuto un supporto sociale adeguato rispetto a quelli con un supporto culturale e sociale scarso, pur possedendo analoghi risultati alle misure di performance delle abilità della vita quotidiana. Pertanto è stato dimostrato che i sistemi di supporto culturali e sociali possono produrre risultati divergenti nel mondo reale, persino tra individui con gli stessi livelli di abilità e potenziale.⁶ Il supporto sociale è della massima importanza nelle malattie psichiatriche come la schizofrenia, in quanto i pazienti hanno pi[ugrave] probabilità di anticipare lo stigma sociale, nascondendo la malattia e ignorando gli appuntamenti medici rispetto a pazienti affetti da altre condizioni croniche. Questo è ciò che deriva dalla paura di essere ufficialmente "etichettato" come una persona affetta da malattia mentale, il che scatena meccanismi controproduttivi di fronteggiamento, tra cui rinviare l'inizio del trattamento, fattore che conduce a sua volta a un ritardo nella ricerca di aiuto, una maggiore durata di psicosi non trattate (DUP) e maggiore morbilità.^{2, 7} I dati provenienti da 200 pazienti arruolati nel programma "Early Psychosis Program" hanno dimostrato che il 20% dei pazienti ha aderito parzialmente o inadeguatamente alle terapie antipsicotiche, mentre il 39% non ha aderito affatto alle cure mediche (assunzione di medicine) nel primo anno del programma. È stato dimostrato inoltre che i pazienti non aderenti manifestano pi[ugrave] sintomi positivi, pi[ugrave] recidive, maggiore uso di alcol e cannabis, percezioni ridotte e una qualità di vita inferiore. Costoro appartenevano a un gruppo di età pi[ugrave] giovane, con un inizio della malattia pi[ugrave] precoce e minori probabilità di avere un membro della famiglia coinvolto nel trattamento.⁸ La non aderenza al trattamento può essere associata anche a una maggiore propensione alla violenza, arresti correlati, vittimizzazioni, abuso di sostanze stupefacenti e problemi legati all'alcol, fattori che nel complesso contribuiscono a creare un grave livello di insoddisfazione personale.⁹ Inoltre l'aderenza parziale ai farmaci antipsicotici rappresenta un grande ostacolo per il raggiungimento di risultati ottimali nella schizofrenia e in questi pazienti può essere dannosa quanto la completa non aderenza, con esiti negativi come un maggior numero di sintomi psicotici, un rischio di recidiva e di riospedalizzazione pi[ugrave] elevato e percentuali di suicidio pi[ugrave] alti.¹⁰

Questa review intende illustrare la letteratura pubblicata sulla discriminazione verso i pazienti affetti da schizofrenia, in termini di ineguaglianza ed esclusione sociale.

Metodi

E’ stata condotta una ricerca sistematica della letteratura pubblicata su MEDLINE, "Cochrane Library of Systematic reviews” and “BiomedCentral Databases", utilizzando combinazioni di parole chiave come schizofrenia, ineguaglianza, stigma, discriminazione, patologia concomitante, occupazione e social network. Abbiamo limitato le nostre analisi alle pubblicazioni apparse a partire dal 2001, che si concentrano su schizofrenia, disturbi mentali e sugli indicatori di discriminazione sociale associati. Per questa analisi sono stati selezionati articoli corrispondenti a tali requisiti. Le bibliografie delle pubblicazioni esaminate sono state ulteriormente analizzate per identificare altri articoli rilevanti. Infine è stato selezionato un totale di 25 articoli ed è stata condotta un'analisi delle informazioni relativamente agli argomenti rilevanti.

Schizofrenia ed esclusione sociale

The International Study of Discrimination and Outcomes (INDIGO) è un'indagine condotta presso centri affiliati in diversi paesi, pubblicato nel 2009. Lo studio mirava a descrivere natura, direzione e gravità dell'autodiscriminazione e della discriminazione sociale a cui sono soggetti i pazienti schizofrenici. In totale, sono stati coinvolti e intervistati tramite colloqui diretti "faccia a faccia" 732 pazienti affetti da schizofrenia, 453 uomini e 279 donne, da 27 paesi di tutto il mondo, è lo studio è stato condotto con l'aiuto della World Psychiatric Association (WPA) e altre organizzazioni associate. La discriminazione è stata misurata utilizzando una nuova scala di misurazione (DISC-Discrimination and stigma scale) che produce punteggi tipo: discriminazione vissuta positiva, discriminazione vissuta negativa e discriminazione anticipata. La discriminazione positiva e quella negativa indicano la discriminazione sociale e la discriminazione anticipata indica l'autodiscriminazione. I risultati di questa indagine sono estremamente importanti per comprendere le sfide che i pazienti affetti da schizofrenia devono affrontare a causa dello stigma sociale derivante da conoscenze, atteggiamenti e comportamenti altrui. I risultati dello studio hanno dimostrato che circa il 49% dei pazienti affetti da schizofrenia percepisce la malattia come un effettivo svantaggio sociale. Le categorie principali riguardavano stringere amicizie e mantenerle, trattamento da parte dei familiari, trovare o mantenere un impiego, rapporti con i vicini, rapporti intimi e sessuali, sicurezza personale, privacy e appuntamenti galanti. Mentre è stata rilevata una grave discriminazione negativa in questi settori, le percentuali di vantaggio positivo erano irrilevanti. ¹¹ (Figure 1).

Un altro studio condotto da Switaj, et al ha dimostrato che la maggioranza dei pazienti affetti da schizofrenia (86%) nasconde la malattia e il tipo di trattamento ai parenti prossimi, mentre il 59% è convinto che le persone lo considerino meno competente. Circa il 63% dei pazienti è risultato turbato dalle opinioni negative altrui e un significativo 69% ha riportato commenti offensivi da parte della gente riguardo persone affette da disturbi mentali.¹²

Un'altra conclusione importante dello studio INDIGO sono state le percentuali molto elevate di autodiscriminazione da parte dei pazienti affetti da schizofrenia. Infatti, pi[ugrave] di un terzo dei partecipanti ha anticipato un atteggiamento di discriminazione nella ricerca di un impiego e nei rapporti personali intimi, quando in realtà non ne sussisteva la condizione (Figure 2).¹¹

Lo studio conclude chele percentuali di discriminazione anticipata e vissuta dai pazienti affetti da schizofrenia sono ripetutamente elevati in ogni paese. Inoltre gli autori hanno affermato che aldilà della discriminazione sociale, l'autodiscriminazione dovuta a scarsa autostima è un grave motivo di preoccupazione tra i pazienti schizofrenici. Pertanto, il gruppo di studio ha auspicato che è necessario implementare interventi atti a migliorare l'autostima dei pazienti affetti da schizofrenia, per aumentare l'efficacia delle misure mirate a ridurre la discriminazione sociale, quali le legislazioni contro la discriminazione per disabilità.¹¹ Altri studi hanno riconosciuto la gravità della discriminazione anticipatoria (stigma interiorizzato) nella schizofrenia. Nel 2010, uno studio condotto da Yanos, et al comprendente 78 pazienti affetti da schizofrenia o disturbi schizoaffettivi, ha dimostrato che lo stigma interiorizzato ha una forte correlazione negativa con i risultati vocazionali dei pazienti affetti da malattie mentali gravi.¹³ Un altro studio pubblicato nel 2010 e condotto da Brohan, et al, comprendente 1229 i pazienti con malattie mentali gravi, ha dimostrato una forte incidenza dell'autostigma. Circa il 42% dei pazienti ha riportato livelli da moderati ad alti di autostigma, mentre circa il 70% ha riportato livelli da moderati ad alti di discriminazione percepita.¹⁴

Schizofrenia e ineguaglianza nelle opportunità di impiego

Sono stati condotti diversi studi di ricerca sui motivi per i quali i pazienti affetti da schizofrenia si trovano ad affrontare ostacoli considerevoli nell'ottenere o mantenere un impiego. Ciò è di grande rilevanza attualmente, in quanto la disoccupazione tra i malati mentali gravi è associata a un maggiore onere economico. Inoltre l'occupazione influisce sull'esito della malattia, in quanto il lavoro è correlato a risultati positivi del funzionamento sociale, della gravità sintomatologica, della qualità di vita e dell'autostima nei pazienti schizofrenici.¹⁵ Benché l'ottenimento di un impiego sia un obiettivo menzionato frequentemente dai pazienti schizofrenici, le percentuali di occupazione sono spesso insoddisfacenti; in Europa, le percentuali sono solo dell’ 8% a causa di numerosi fattori: individuali, relativi alla malattia e sociali.¹⁶ Alcuni sondaggi effettuati in Europa e negli Stati Uniti hanno confermato questa allarmante situazione. Le percentuali di occupazione riportate da questi studi variano dal 10% al 20%, mentre le percentuali abituali per la popolazione normale sono molto pi[ugrave] elevate (Table 1).^{15, 16}

Sono stati attribuite diverse cause alle basse percentuali di occupazione tra i pazienti schizofrenici. Si possono sommariamente suddividere in personali, relative alla malattia e sociali. I fattori personali includono problematiche quali una bassa percentuale di occupazione nel passato. Inoltre è emerso che i fattori relativi alla malattia, quali la gravità della malattia, e i fattori sociali quali la discriminazione nell'impiego e le legislazioni a tutela del benessere sociale, rivestono un ruolo importante nelle percentuali di disoccupazione pi[ugrave] elevate. ^15–17 Un sondaggio condotto nel Regno Unito, in Francia e in Germania ha dimostrato che una durata maggiore della malattia, l'abuso di alcol e sintomi psicotici negativi o positivi pi[ugrave] gravi hanno ridottole percentuali di occupazione, mentre l'accesso alla formazione professionale ha migliorato le opportunità di impiego tra i pazienti schizofrenici.¹⁸

I pazienti affetti da schizofrenia possono riscontrare particolari difficoltà nel mantenere l'impiego, qualora riescano ad arrivare a una posizione competitiva in una qualsiasi società o azienda, a causa dell'indifferenza dimostrata loro sul posto di lavoro. Uno studio condotto da Nithsdale, et al ha dimostrato che i pazienti affetti da schizofrenia e disturbi schizoaffettivi percepiscono una mancanza di supporto interpersonale da parte dei colleghi e subiscono l'amara realtà della discriminazione sociale.¹⁹ Analogamente, un sondaggio condotto nell'area Nord di Londra ha dimostrato che addirittura molti medici ritengono che i pazienti affetti da schizofrenia non siano idonei a impieghi che comportano livelli superiori di competenza tecnica. Infatti, benché ritengano che le percentuali di occupazione attuali siano molto inferiori rispetto al potenziale effettivo, essi considerano circa due terzi dei pazienti affetti da disturbi psichiatrici incapaci di lavorare o di svolgere unicamente un impiego volontario o sociale. Considerano inoltre che, anche quando sussista un'inclinazione a fornire supporto a tali pazienti, le risorse disponibili sono scarse.²⁰ Tuttavia, l'esperienza con il modello Individual Placement and Support (IPS), implementato dallo Psychiatric Research Centre di Dartmouth, dà un quadro della situazione diverso.²¹ In una relazione pubblicata in Psychiatric Services, i fondatori di IPS hanno dichiarato che la percentuale di occupazione con il modello IPS è del 71%, con il 67% degli impiegati che ha un profilo lavorativo competitivo.²²

Schizofrenia e associazione con mortalità e morbilità eccessive

Le persone affette da schizofrenia sono soggette a pi[ugrave] alti rischi di morbilità e mortalità rispetto alla popolazione generale.^{23, 24} Uno studio condotto da Brown, et al ha dimostrato che le persone affette da schizofrenia hanno un rischio di mortalità da due a tre volte maggiore rispetto a quello della popolazione generale. Lo studio ha rivelato anche un'incidenza di mortalità cardiovascolare pi[ugrave] elevata tra questi pazienti rispetto a quella della popolazione generale. La maggior parte dell'elevato numero di decessi è stato attribuito a cause naturali. ²³ Tuttavia queste elevate percentuali di mortalità possono derivare anche da patologie concomitanti che, come è stato dimostrato, sono presenti in maggior misura presso i pazienti schizofrenici; oltre il 50% degli individui affetti da schizofrenia possiede una o pi[ugrave] condizioni psichiatriche o mediche generali concomitanti. Uno studio condotto da Weber, et al ha dimostrato che i pazienti affetti da schizofrenia hanno percentuali di morbilità fino a tre volte pi[ugrave] elevati rispetto alla popolazione generale. Pertanto, per ridurre l'elevata incidenza di morbilità e mortalità associati alla schizofrenia sono auspicabili un'attenzione maggiore alla prevenzione, una diagnosi e un trattamento precoci delle patologie concomitanti.²⁴ Oltre ai fattori summenzionati, le abitudini personali dei pazienti possono avere un forte impatto sulle percentuali di morbilità e mortalità; è infatti risaputo che i pazienti affetti da schizofrenia seguono diete alimentari inadeguate, esercitano una scarsa attività fisica e vi sono percentuali di fumatori pi[ugrave] elevate rispetto alla popolazione generale.²⁵ Le pressioni finanziarie possono giocare un ruolo importante nell'esito finale dei pazienti schizofrenici. Un recente studio condotto da Mattsson, et al ha dimostrato che i pazienti con primo episodio psicotico possono trarre beneficio da interventi che riducono la pressione finanziaria, facilitando in tal modo le attività quotidiane e il funzionamento sociale.²⁶

Un altro aspetto che può avere un impatto significativo sulle percentuali di morbilità e mortalità riguarda le ineguaglianze nella qualità dell'assistenza fornita per le patologie concomitanti nei pazienti schizofrenici. ^27–29 Uno studio condotto tra i pazienti con malattie cardiovascolari ha dimostrato che i pazienti affetti da schizofrenia hanno meno probabilità di ricevere terapie basate su linee guida specifiche per cardiopatie coronariche o ictus (rapporto di probabilità rettificato [OR] di 0,35, 0,82 e 0,51 per trapianti coronarici, beta-bloccanti e statine, rispettivamente), anche se è stato dimostrato che hanno percentuali di mortalità pi[ugrave] elevate rispetto alla popolazione generale.²⁷ Attualmente, diverse società scientifiche stanno cercando di affrontare questo problema pubblicando linee guida per la gestione delle patologie concomitanti nei pazienti affetti da disturbi psichiatrici. Le linee guida della European Psychiatric Association (EPA), supportata dalla European Association for the Study of Diabetes (EASD) e la European Society of Cardiology (ESC), per il trattamento delle malattie cardiovascolari e del diabete nei pazienti psichiatrici, sono solo un esempio. Si spera che queste misure diano inizio alla collaborazione tra operatori sanitari di diversi settori e che aumentino la consapevolezza di psichiatri e medici di base sulla necessità di gestire i pazienti affetti da malattie mentali gravi con terapie basate su linee guida specifiche. ³⁰

Conclusione

In ambito psichiatrico vengono impiegati considerevoli sforzi per migliorare gli esiti complessivi dei pazienti affetti da malattie mentali gravi. La ricerca continua a indagare nuovi metodi che possano avere un impatto positivo sugli esiti a lungo termine nei pazienti schizofrenici. Tuttavia, malgrado i progressi scientifici nella gestione di questo complesso disturbo, una grossa proporzione di pazienti deve ancora affrontare il fardello causato da sintomi persistenti e il progressivo declino del funzionamento sociale. Circa il 50% dei pazienti soffre di discriminazione sociale e fino al 72% dei pazienti anticipa la discriminazione e si distanzia dalla società. I pazienti affetti da schizofrenia sono inoltre soggetti a discriminazione intenzionale o involontaria da parte delle istituzioni. La schizofrenia ha anche un notevole impatto a livello finanziario, in quanto la maggioranza dei pazienti non ha impiego o deve affrontare numerose difficoltà pratiche per mantenere l'impiego. Fino al 90% dei pazienti in Europa e Stati Uniti non ha un impiego, un numero considerevolmente pi[ugrave] elevato rispetto alla popolazione generale. Per l'esiguo gruppo di pazienti che riesce a ottenere un impiego, risulta particolarmente difficile mantenerlo, a causa dei complessi rapporti interpersonali sul posto di lavoro. Oltretutto, i medici che avrebbero il compito di incoraggiare i pazienti affetti da malattie mentali gravi, condividono l'opinione che questi non siano in grado di svolgere professioni con livelli di competenza elevati. Qualora siano invece pronti ad offrire il loro supporto, la mancanza di risorse disponibili è un fattore molto limitante per la riabilitazione di questi soggetti. I pazienti affetti da schizofrenia soffrono di maggiore incidenza di morbilità e mortalità a causa delle mediocri abitudini personali e della presenza di patologie concomitanti. È stato stimato che i pazienti affetti da schizofrenia hanno un rischio di morbilità e mortalità da due a tre volte maggiore rispetto alla popolazione generale. Purtroppo, la maggior parte dei pazienti affetti da schizofrenia non riceve adeguate terapie basate su linee guida specifiche per le patologie concomitanti, anche se è stato chiaramente dimostrato che il rischio di mortalità è sensibilmente maggiore. È fondamentale che i medici curanti prevedano la non aderenza e l'aderenza parziale ai farmaci prescritti nei pazienti schizofrenici e che intraprendano misure correttive proattive per favorire la continuazione del trattamento e ottenere migliori risultati a lungo termine. Sono indispensabili nuove opzioni farmacoterapeutiche che migliorino l'aderenza al trattamento unite a un adeguato supporto sociale e a servizi di assistenza psicologica. Tanto i pazienti quanto la società e i medici devono essere educati per assicurare che vengano impiegati sforzi coesivi efficaci per eliminare i problemi socioeconomici attuali associati alla schizofrenia.

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Medically unexplained symptoms (MUS) are symptoms without any objective physical or pathological cause. Several terms have been used to describe these symptoms such as psychosomatic syndromes and symptoms, conversion disorders, somatoform disorders, functional somatic syndromes, and symptoms.¹ These symptoms might include: fatigue (without physical stimulation), tension headaches, low back pain, facial pain, dizziness, heart palpitations, indigestion, abdominal bloating or cramping, constipation or diarrhea, pain while urinating, loss of voice, shortness of breath (without physical stimulation), trouble swallowing, or nausea.² No specific cause can be found by health care providers and usually the management is complex.³ MUS are presented in different anatomical regions of the body and due to this there are variations in presentation and reporting among individuals. However, several previous researchers have demonstrated the overlap of medically unexplained conditions meaning that patients who present one group of MUS may present symptoms across other domains as well.^{4, 5} It is quite common that patients with a diagnosis for one of the functional syndromes to meet the diagnostic criteria for one or more of the other functional syndromes. These MUS patients present multiple medically unexplained physical symptoms and usually they are termed as polysymptomatic somatizers. These particular individuals mainly are chronic patients and refractory to treatment.²

Medically unexplained symptoms (MUS) can be split into several diagnostic categories or syndromes such as irritable bowel syndrome (IBS), chronic widespread pain, temporomandibular joint dysfunction, atypical facial pain, chronic fatigue syndrome (CFS), fibromyalgia.¹ The two main subgroups of MUS are CFS and IBS.

Chronic fatigue syndrome is an illness characterized by severe, disabling fatigue. According to the US Center for Disease Control and Prevention (CDC), which constitutes the current criteria for CFS, its definition requires the presence of a persistent or relapsing chronic fatigue that: (1) is of new or definite onset, (2) has remained unexplained after clinical evaluation, (3) is not the result of ongoing exertion, (4) is not substantially alleviated by rest, and (5) produces significant reduction in previous levels of occupational and social activities. Additionally, four or more of the following symptoms must occur with fatigue for at least 6 months: impaired memory or concentration, sore throat, tender cervical or auxiliary lymph nodes, muscle pain, multijoint pain, new headaches, unrefreshing sleep, or postexertion malaise.⁶

The IBS is a chronic gastrointestinal disorder, accompanied by abdominal pain associated with altered bowel function (diarrhea, constipation, or both), feeling of distention, heartburn, nausea, dyspepsia, or early satiety.⁷ IBS is diagnosed using the Rome III diagnostic criteria, which has provided uniformity in epidemiological studies of IBS.⁷ These criteria include the presence of abdominal pain and/or discomfort, associated with altered stool habit and 3 days of pain or discomfort per month in the last 3 months, associated either with improvement when defecating or with a change in the frequency form of stool (symptom frequency and duration criterion).⁸

The CFS and IBS are chronic diseases that share certain features such as pain and disability, and in addition, these two diagnoses commonly occur simultaneously within many individuals. According to Aaron and Buchwald, 58% to 92% of patients with CFS also have IBS.⁹ In both conditions, the presented symptoms are disproportionate to physical findings and have an apparent association with “stress” and psychosocial factors.⁴ Both CFS and IBS are diseases that are not life threatening, but result in altered daily activity and functionality.¹⁰ In both of these conditions, the patients are often ill for some time before a diagnosis is made. Also, both CFS and IBS are two times more common among women than among men. Finally, among MUS patients, reported rates of depression and anxiety compared to the general population are increased.¹⁰

METHODOLOGY

The following study conducted by an extensive search of Cochrane library Medline (1971–2010), and EMBASE (1980–2010) to identify pharmacological, nonpharmacological, psychological, and other interventions using the search terms “MUS,” “somatisation,” “somatization,” “somatoform disorders,” “psychological therapies,” “cognitive behavior therapy,” “pharmacological therapies,” “management,” “therapy,” “drug therapy,” and “antidepressants” with Boolean operators AND and OR on the entire text.

Etiology of MUS

The relation among anxiety, depression, MUS, and what are the strongest predictors of the new onset of MUS at a follow-up phase has been the interest of several studies. The role of symptoms, previous infections, and mood disorders are each thought to be involved in the etiology of MUS, which is multifaceted. For example, Katon et al. suggested that the number of MUS is positively correlated to the patient's degree of psychopathology and physical deconditioning.¹¹

The Role of Infection in MUS

The etiology of MUS, specifically IBS and CFS, was examined by Moss-Morris and Petrie. The authors examined the possible important differences in the etiology or precipitating factors that could be related to IBS and CFS, after an infection such as Campylobacter gastroenteritis and infectious mononucleosis. They found that the strongest predictors of CFS were the premorbid levels of distress, particularly depression, whereas the strongest predictor of IBS was the nature of the precipitating infection.¹² The finding that high levels of distress at the time of infection predict CFS and IBS agrees with several other studies.¹³

In another study, White et al. examined the predictors of fatigue syndromes and mood disorders after infectious mononucleosis. Some of the findings suggested that this type of infection, its consequent immune reaction, and physical deconditioning may be important for the onset of CFS. In contrast, the mood disorders that accompany CFS were predicted by a history of mood disorders and an emotional personality, and not the particular infection.¹⁴ Furthermore, White et al. examined the incidence, risk, and prognosis of acute and CFSs and psychiatric disorders after glandular fever. The results showed that glandular fever has a central role as a risk factor on the onset and development of both acute and CFSs. Moreover, at the onset of the CFS, the prevalence of psychiatric morbidity had increased significantly from premorbid levels. The most frequent new diagnosis at the onset of CFS was the major depressive disorder. Nevertheless, it must be mentioned that the study's findings suggested that there was a significant increase of psychiatric morbidity at the onset of the disease but not significant excess after 6 months.¹⁵

Hormonal Disturbances in MUS

Small adrenal glands and adrenocortical hormone abnormalities present in some patients with MUS during stressful episodes may be an important event of MUS.<refrange text="16–19"> ^16–19 </refrange> The effects of stressors on adrenal development of the fetus, in other species, seem to depend both on the timing and magnitude of exposure to products of the maternal stress response in relation to the stages of development that determine the maturation of the various body systems during gestation and early postnatal development.²⁰ If exposed before initiation of a developmental stage, there may be no effect. During the critical period while the adrenocortical maturation program is running however, studies in rodents,^{21, 22} carnivores,²³ and primates^{24, 25} all have found maternal stressors to reduce adrenal size in the affected offspring. If a sufficiently severe stress response occurs after the critical period of adrenocortical development, adrenal size and subsequent adrenocortical responses to stress may be increased.²⁶

Genetic Background in MUS

?he progress in investigating the molecular basis of many psychological conditions such as MUS revealed that genetic, epigenetic factors may contribute to the pathogenesis. In addition to epigenetic alterations in gene expression, a variety of genetic polymorphisms that affect stress responsiveness also have been identified in humans,²⁷ including the catechol-O-methyltransferase,²⁸ serotonin transporter,²⁹ and α₂-adrenergic receptor genes.³⁰ Once pregnant, exposure of mothers carrying such polymorphisms to significant salient stressors may increase the risk for exposure of a developing fetus to products of the stress response, enhancing the chances of sensitizing the stress response system of these offspring. Such a mechanism has been identified in other disorders.

Recently Beversdorf et al.³¹ reported that a history of prenatal stress peaking at 25-28 weeks gestation was associated with an increased risk for development of autism. Such studies are needed in patients with MUS to test the relevance of these provocative findings to this category of disorders. Cognitive function too is influenced by both genetic³² and epigenetic³³ factors. Many studies have also shown that cognitive factors such as classical and operational conditioning, attentional bias, and memory can influence the onset, development, and maintenance of MUS.

Anxiety and Depression

The experience of psychological distress, especially anxiety and depression, has been considered to be an important factor in the development of MUS as mentioned above. Empirical research has demonstrated a high degree of comorbidity between the presentation of MUS, and anxiety and depression, both on a symptom and syndrome level.^{34, 35}

Henningsen reports that the association among anxiety, depression, and MUS might represent a reactive increase of anxiety and depression in patients who suffer from chronic bodily symptomatology; physical and psychological symptoms relate to each other but have different expressions of common distress and the bodily symptoms per se or the awareness for them could be a result of depression and anxiety, representing a primary psychological phenomenon.³⁶ Additionally, it is suggested that functional somatic syndromes such as IBS and CFS are related to depression and anxiety, although they are not fully dependent on them.³⁶

The relationship among anxiety, depression, and MUS could be described as cyclical.⁷ In particular, anxiety and depression increase and intensify the somatic symptoms in the majority of MUS patients and vice versa and they can be associated with a vicious cycle. Worsening of symptoms with regard to severity, intensity, and frequency could be a result of: (1) the effects of living with chronic symptoms, which can be painful and disabling; (2) the nature of these chronic diseases is poorly understood, which provokes patients’ frustration as they present symptoms for which no physical or pathological change can be found; and (3) being misunderstood by the significant others such as close family members, social network, and physicians. Then, the worsening of somatic symptoms results in increased levels of anxiety or depression, as the patients find “evidence” to believe that they have a more serious disease that has not yet been diagnosed or that their condition cannot be improved through treatment.⁷

Specifically for CFS, current literature suggests that among CFS patients, a majority meet criteria for depression and up to 85% report depressed mood as a key symptom. This percentage is significantly higher compared to the prevalence of depression in patients with a range of medical illnesses including rheumatoid arthritis, multiple sclerosis, neuromuscular disorders, and myopathies.<refrange text="37–39"> ^37–39 </refrange> In addition, generalized anxiety disorder seems to be more prevalent among patients with CFS than in general population.³⁰,⁴⁰

Regarding IBS, several studies have examined the presence of psychiatric disorders in patients with IBS. The findings demonstrated that the presence of one or more Axis I psychiatric diagnosis is so common in clinical IBS patients that it might be considered to be a typical characteristic. Patients with IBS also suffer more frequently from anxiety disorders (panic and generalized anxiety disorder) and mood disorders (major depression and dysthymic disorder) than members of the general population.⁴¹ In addition, IBS patients are more neurotic and anxious in personality, in comparison with healthy controls or patients with organic bowel disorders such as Crohn's disease and inflammatory bowel disease.⁷

Treatment

Neurologists and general practitioners frequently encounter patients with inexplicable, unintentionally produced somatic complaints with excessive somatic preoccupation is difficult to diagnose or categorize reliably due to rigid diagnostic criteria that often overlap with several psychiatric disorders. Management of patients with dysfunctional somatoform disorders is complex and challenging, particularly when initiated in a neurology outpatient or inpatient setting.³

However, treatment options are not clarified yet. It can be seen that the competition between physical and psychological schools of thoughts has long been a feature of thinking about MUS. A skirmish in this ongoing battle involved an epidemic of unexplained symptoms that occurred at the Royal Free Hospital in 1955. It was initially interpreted as a purely neurological encephalomyelitis (ME).⁴² Later, it was interpreted as being more consistent with the purely psychological mechanism of epidemic hysteria. The debate was acrimonious and, despite important clinical differences between this epidemic of illness, polarized thinking has continued to dominate and even distort the etiological debate.⁴²

Many treatments have been proposed over the years with most being based on the advocate's own particular etiological theory. Despite brief enthusiasms, however, few of these treatments have been systematically and none generally accepted as effective.⁴²

Sumathipala presented a comprehensive literature search for MUS. Studies were carried out in primary, secondary, and tertiary care settings. The therapists ranged from medical specialists, psychiatrists, and psychologists to primary care physicians. Three types of interventions (antidepressant medication, cognitive behavioral therapy [CBT], and other nonspecific interventions) were supported by evidence on the efficacy of treatment for patients with MUS.⁴³ There is more level I evidence for CBT compared with the amount for other approaches. Only one study reported from the developing world. CBT is efficacious for either symptom syndromes or for the broader category of MUS, reducing physical symptoms, psychological distress, and disability.⁴³

Cognitive Behavioral Therapy

An important advantage of the cognitive behavioral approach describe below is that it can transcend such dualistic thinking and integrate psychological, social, and physical factors into coherent model and a rational treatment. The modern cognitive behavioral approach to MUS is based on: (1) An expansion of the medical perspective to include not only the patients’ somatic symptoms and psychological state, but also factors including cognitions, mood, behavior, and circumstances; and (2) The adoption of a model in which the factors identified interact to perpetuate the illness. A cognitive behavioral model according to clinical characteristics (see Table 1) of CFS is presented in Fig. 1.⁴²

According to that model, the treatment plan is implemented in five stages taking place in the following order: (1) assessment and formulation, (2) experiment of increase activity and re-evaluation of illness beliefs, (3) reviewing unhelpful attitudes, (4) problem solving practical difficulties, and (5) review and planning for the future.⁴³

The cognitive behavioral conceptualization offers several important advantages. First, the factors important in perpetuating the illness is, for the most part, apparent from clinical assessment and do not require complex investigation. Second, the formulation can be individualized to cope with the heterogeneity among patients with MUS. Third, it integrates physical, psychological, and social factors into a single model.⁴²

During the therapeutic process the aim of the therapist, after goals’ setting, is to work with the patient in a collaborative way in order to help him/her to attain a more realistic and useful formulation of his/her illness and to develop ways of coping most conductive to recovery. As far as possible, therapeutic interventions are based on and guided by the formulation. It is often useful to start with a focus on coping behavior and then move on to cognitive aspects of the problem. The other components of the cognitive model (physiology, mood, and social environment) do not always require any direct intervention. Sometimes, however, additional interventions in these realms may also be necessary.⁴²

Behavioral interventions can be used as a part of a cognitive behavioral approach. This strategy is intended not only to change behavior but also to influence other components of the model. Thus, a planned increase in activity can be used to evaluate beliefs that the patient may hold about the illness such as “activity always makes me worst” (CFS). By increasing the patient's confidence and range of activities, mood can also be improved. Behavioral change is an important means by which the effects of inactivity on physiological functioning can be reversed. Moreover the principal cognitive interventions are designed both to enable patients to see that improvement can be achieved by their own efforts and to build confidence in their ability to function.⁴²

In order to achieve patient compliance the therapy should address illness beliefs in a collaborative manner, and in order to reduce disability it should be intensive and aim toward rehabilitation. Intensive CBT that incorporates these aspects can be an acceptable and effective therapy for patients.⁴² The ultimate value of this conceptualization, however, is whether it leads to an effective treatment. A recent study carried out by Arnold et al. demonstrates that after 6- and 12-month follow-ups, the cognitive-behavioral intervention by trained family physicians was not more effective than care-as-usual.⁴⁴ The aim of this study was to assess the effectiveness of a cognitive-behavioral intervention by the family physician. In a controlled design with detailed information on patient selection, there were 6409 patients that were screened on somatoform disorder, and 65 participants were allocated to care-as-usual or the experimental condition. The authors mention the possibility that the intensity of treatment was insufficient for the severe and persistent symptoms that were encountered in primary care.⁴⁴

Relatively small numbers of studies were carried out in primary care, but the trend has been changing over the last decade.⁴³ No studies have compared pharmacological and psychological treatments.⁴³ Most trials assessed only short-term outcomes. Use of divergent selection procedures, interventions, outcome measures, instruments, and other methodological differences observed in these studies hamper the ability to compare treatment effects across studies.⁴³

Burton back in 2003 reviewed published research on MUS in primary care. A literature review and qualitative comparison of information was carried out. Four questions were addressed: what is the prevalence of MUS, to what extent do MUS overlap with psychiatric disorder, which psychological processes are important in patients with MUS, and what interventions are beneficial? Neither somatized mental distress nor somatisation disorders based on symptom counts adequately account for most patients seen with MUS.⁴⁵ There is substantial overlap between different symptoms and syndromes, suggesting they have much in common. Patients with MUS may best be viewed as having complex adaptive systems in which cognitive and physiological processes interact with each other and with their environment. Cognitive behavioral therapy and antidepressant drugs are both effective treatments, but their effects may be greatest when the patient feels empowered by their doctor to tackle their problem.⁴⁵

At this point we may introduce another perspective; psychosomatic medicine may be defined as a comprehensive, interdisciplinary framework for the assessment of psychological factors affecting individual vulnerability as well as course and outcome of illness and the biopsychosocial consideration of patient care in clinical practice.⁴⁶ Current advances in the field have practical implications for medical research and practice, with particular reference to the role of lifestyle, the challenge of MUS, the psychosocial needs entailed by chronic illness, the appraisal of therapy beyond pharmaceutical reductionism, and the function of the patient actively contributing to his/her health.⁴⁶

CONCLUSIONS

Literature provides the interaction and correlation among anxiety, depression, and MUS. Anxiety and depression are more prevalent among patients reporting MUS, and have been linked cross-sectionally to the development of MUS. However, it is unclear whether MUS occur in response to elevated anxiety/depression or whether the reverse is true. According to Burton, the notion that most MUS are the result of a single process of somatisation (particularly the somatisation of mental distress), or are due to a somatisation disorder that can be defined primarily in terms of numbers of symptoms, is no longer supported by the evidence.⁴⁵

Actually, if existing psychiatric classification such as DSM–IV or CDI-10, are applied to patients meeting criteria for MUS most can be accommodated into one or another of the diagnostic categories. Many patients meet criteria for depression and anxiety syndromes, some report a sufficient number of syndromes to meet criteria for somatization disorder, and others express sufficient concern about the cause of their illness to suggest a diagnosis of hypochondriasis. However, the fit of the patients’ symptoms to the diagnostic criteria for these syndromes is often poor and the validity of the diagnoses therefore uncertain.⁴²

For example, the category of CFS has the advantage of describing patients according to their predominant complaint. Although most can be given an alternative syndromal diagnosis, it is less certain how useful it is to do this. Therefore, it remains a reasonable strategy to describe patients whose clinical presentation is dominated by the complaint of chronic disabling fatigue as suffering from CFS and also specify any other diagnostic criteria they meet. This way of approaching the problem is analogous to that used in the management and study of patients with chronic unexplained pain.⁴²

For MUS, once the broad category has been defined, patients can be further described according to a number of clinically relevant factors including illness beliefs, mood, coping behavior, psychological state, and social situation. This approach may provide the basis for a more useful subclassification of fatigue states.⁴²

There is now good evidence that physiology, personality, life experiences, health cognitions, and interaction with health care professionals are all important and any new paradigm needs to include them.⁴⁵ If further progress is to be made, a useful subclassification of the syndrome will be needed. One approach would be to define subcategories or dimensions that specify beliefs, mood disturbance, and behavior, as well as physiological findings.⁴²

A better understanding of MUS is needed and, of course, the performance of more efficient treatments. We probably need a brief treatment for more widespread use in primary care and a more effective treatment for resistant cases. We also need predictors of response to brief therapy. For patients who never cope well or who are in difficult occupational circumstances “schema” therapies may be appropriate. All this issues require empirical evaluation and further research.

Disclosure: The authors declare no conflict of interest.

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Bipolar disorder (BD) in its broadest sense has a community lifetime prevalence of 4% and is a severely impairing illness that impacts several aspects of patients’ lives. In particular, patients with BD have high rates of disability and higher rates of mortality than individuals without BD.¹ Furthermore, also in a young age it is becoming a very serious disease for the society, with an estimated one million individuals under the age of 18 years who suffer from BD in the United States.²

Current treatment for BD include lithium and both first- and second-generation antipsychotics in the treatment of acute mania. Quetiapine and the olanzapine–fluoxetine combination are also effective for treating bipolar depression, while olanzapine, quetiapine, and aripiprazole are effective during the maintenance phase. Anticonvulsants particularly valproate and carbamazepine have antimanic properties, whereas lamotrigine may be preferably effective in the treatment of depression but not mania.³ Furthermore, during the past decade, there has been a substantial increase in the prescribing of antipsychotics to children and adolescents with BD.⁴

Bipolar disorder may be considered a multifactorial disorder resulting from interaction between genetic and nongenetic factors and many studies demonstrate that environmental factors play an important role in the etiopatogenesis and in the development of BD. The nongenetic factors include early childhood trauma, stressful life events, virus infections, cannabis use, obstetric complications, and even very distant environmental factors such as solar cycles. Childhood traumatic events are probably the most promising environmental determinant to have been investigated.⁵

CHILDHOOD TRAUMA

Recently, an epidemiological World Health Organization (WHO) survey in 21 countries investigated the prevalence and associations of retrospectively reported childhood adversities with first onset of a wide variety of mental disorders across the life course. It was found high rates of any childhood adversities in high-income (38.4%), high–middle-income (38.9%), and low/lower-middle-income (39.1%) countries. Parental death was the most common childhood adversity (11.0–14.8%). Other common childhood adversities included physical abuse (5.3–10.8%), family violence (4.2–7.8%), and parental mental illness (5.3–6.7%). Multiple childhood adversities were common among respondents with any childhood adversities (59.3–66.2%), with mean childhood adversities among respondents with two or more of 2.5–2.9.⁶ Data from the US National Comorbidity Survey Replication (NCS-R) show that childhood adverse events explain (in a predictive sense) 32.4% of all mental disorders, 32.4% of anxiety disorders, 26.2% of mood disorders, 41.2% of disruptive behavior disorders, and 21.0% of substance disorders. Some 53.4% of NCS-R respondents reported having at least one childhood adverse events. The most common were parental divorce (17.5%), family violence (14.0%), family economic adversity (10.6%), and parental mental illness (10.3%). Multiple childhood adverse events were the norm among respondents with each childhood adverse events, from 51.2% among those with death of a parent to 95.1% among those with parental neglect and a mean of 3.2 childhood adverse events among respondents with more than one.⁷ Furthermore, data from the US NCS-R provided evidence for the role of childhood adverse events in predicting greater impairment related to anxiety disorders and increased days out of role for mood, anxiety, and disruptive behavior disorders.⁸

Several other studies have investigated the prevalence of childhood traumatic events in BD. In two recent studies, trauma experiences were collected with The Childhood Trauma Questionnaire, a self-report measure yielding a total score and five subscores (emotional and physical neglect, emotional, physical, and sexual abuse). In both of them, a high prevalence of childhood trauma was found (65% and 54.4%, respectively). Interestingly, having suffered two or more types of trauma was associated with a tripling in the risk of BD (odds ratio [OR] = 3.14 [95% CI 1.52–6.47], p=.001).^9,10

In a recent work¹¹ 30 patients with unipolar disorder and 30 patients with BD were compared to 60 matched healthy controls in regard to the rate of stressful life events assessed with the Childhood Life Events List and the Adult Life Events Questionnaire. The results reported that the entire sample of affective patients had more stressful life events assessed in general as compared with normal controls. A significant relationship was found between childhood stressful life events and the development of affective disorders in adulthood, with patients with unipolar disorder exhibiting less positive and achievement stressful life events but no significant differences were found across mood spectrum disorders on rate of childhood stressful life events.

Interestingly, a possible neurobiological basis underlying the association between childhood trauma and the course of BD has been studied. There is a correlation between brain-derived neurotrophic factor (BDNF) levels and childhood trauma in BD showing that bipolar patients who were exposed to a traumatic event or events have lower BDNF levels.¹² There is also the evidence of a neurobiological effect of life stress: it's been proven that exposure to trauma in early life induces long-lived hyper(re)activity of corticotropin-releasing factor (CRF) systems as well as alterations in other neurotransmitter systems, resulting in increased stress responsiveness and these mechanisms may underlie the increased risk of psychopathology.¹³

Childhood Trauma and Outcomes

Many researchers suggest that childhood trauma not only predisposes subjects to BD but also modulates the clinical expression and the course of the disease. In particular, it has been demonstrated that childhood trauma is related to a more severe prognosis and more severe clinical expression.

A study conducted in the Bipolar Disorders Research Clinic of the New York Presbyterian Hospital reported histories of severe childhood abuse in about half of the sample. They were associated with early age at illness onset, with lifetime substance misuse comorbidity and past-year rapid cycling.¹⁴ A cohort study of 651 bipolar patients also showed positive significant correlations between early childhood trauma, greater number of subsequent manic or depressive episodes, and faster cycling pattern.¹⁵

Childhood trauma may also have a more insidious influence on the interepisode affective functioning of bipolar patients, which in turn may affect the overall prognosis of the disease. In particular, the CTQ total score is associated with Affective Lability Scale (ALS) and the Affect Intensity Measure (AIM) scores. The ALS is a self-report scale measuring subjects’ perception of their ability to shift from what they consider to be their normal (euthymic) mood state to anger, depression, elation, and/or anxiety. It also assesses their tendency to oscillate between states of depression and elation and between states of anxiety and depression. The AIM is a self-report scale measuring individual differences in the intensity of response to a given level of emotion-provoking stimulation.¹⁰ Similarly, other studies have investigated a significant association between lifetime suicide attempts and severe childhood sexual abuse. In particular, multiple forms of abuse showed a graded increase in risk for suicide attempts.^14,16,17 In particular, it has been demonstrated that suicidal bipolar patients more frequently report emotional and sexual abuses. Having suffered both types of abuse is associated with a doubled risk of suicide attempt among bipolar patients.¹⁰ Finally, several studies have shown that there is the evidence that childhood trauma is associated with comorbid substance misuse^14–16 and hallucinations in people with bipolar affective disorder.¹⁸

Childhood Physical Abuse

The prevalence of childhood physical abuse in patients with BD is variable. In a sample of 254 adults with mood disorders, physical abuse, and exposure to domestic violence is considered as the most common types of adverse childhood experience.¹⁹

In the most recent study on this topic, the prevalence is 16.1% in a sample of 118 patients.²⁰ In the largest study involving 631 bipolar outpatients, a history of early physical abuse is reported in 64 patients (19.5%). Furthermore, early physical abuse is associated with a higher incidence of early illness, faster cycling frequencies, and lifetime Axis I and Axis II disorders including a lifetime history of alcohol and substance abuse.¹⁶ Interestingly, patients (49 men, 41 women) with co-occurring bipolar I and substance use disorders (92% alcohol, 42% drug) reported a prevalence of 43% of childhood physical abuse.²¹

A recent study has shown that after adjusting for significant differences in demographic (age, sex, race, and living situation) among the three abuse subgroups (emotional, physical, and sexual abuse), physical abuse is independently associated with longer duration of BD illness and greater prevalence of first-degree family history of a mood disorder.²² Similarly, BD individuals with a familial liability for suicidal behavior and exposed to physical and/or sexual abuse during the childhood are at a greater risk to have a more impaired course of bipolar illness and greater suicidality compared to those subjects with either only one or none of these risk factors.²³

Childhood Sexual Abuse

Childhood sexual abuse has an impact on the later symptom profile of patients with bipolar affective disorder, increasing their vulnerability to experience hallucinations.²⁴ Several works have recently assessed the prevalence and correlates of childhood and adolescent sexual abuse. In 118 patients with bipolar I disorder treated for a first episode of psychotic mania, a total of 80% of patients had been exposed to stressful life events during childhood and adolescence and 15.3%, to sexual abuse; in particular, 29.8% of female patients had been exposed to sexual abuse and 5.6% of male patients.²⁰

In the study of Leverich et al, 631 consecutive patients were enrolled. Of 377 female patients, 185 (49%) reported having experienced early abuse in childhood or adolescence; sexual abuse was reported in 43.4% of the women. Of 274 male patients, 99 (36%) reported ever having been abused in childhood or adolescence and 21.2% reported sexual abuse. Of the patient group who reported physical abuse, 52% also reported sexual abuse and 50% of patients who reported sexual abuse also reported physical abuse.¹⁵

Other Traumas

There are many works that have reported the prevalence of emotional trauma among BD patients. Garno et al identified histories of severe childhood abuse in 51% of a cohort of 100 adults with BD, with emotional abuse being the most frequent type of trauma. In a retrospective study, the severity and frequency of childhood trauma were compared between bipolar patients and control subjects and emotional abuse was the only subtype of trauma more frequent in the bipolar patient group than in the control group.¹⁰ Similarly, it was found that the percentage of emotional abuse in the sample of 52 patients affected by BD was 25% and the percentage of emotional neglect was 21.2%²⁵ and another study demonstrated that only emotional abuse is associated with BD with a suggestive dose-effect.⁵

Other risk factors are linked to BD. In particular, several studies investigated the importance for the development of BD of family history of depression,²⁶ parental suicide,²⁷ early parental loss.²⁸ Interestingly, with respect to early parental loss, no significant difference was observed between schizophrenia and BD patients, while a lower rate was observed for unipolar depression patients.

CONCLUSIONS

This review shows how an unacceptably large number of children in our society are subjected to early adverse experiences, exposing these children to an increased risk for the development of BD that may persist throughout adulthood. However, while there is a great amount of studies on childhood trauma in patients with BD type I, we can't say the same for BD type II.

Findings from preclinical and clinical studies suggest that early life stress induces long-lived hyperactivity and sensitization of CNS, in particular CRF and other neurotransmitter systems, resulting in enhanced endocrine, autonomic, and behavioral stress responsiveness.¹³ With repeated exposure to life stress, this vulnerability may result in symptoms of BDs, as well as in other physiologic abnormalities frequently observed in adult survivors of abuse.

The identification of childhood trauma as a potential risk factor and/or course disease modifier in BD (not only in terms of comorbid conditions, but also in terms of affective functioning) may improve our understanding of the complex interactions between genetic susceptibility factors and the environment. Currently, there are no specific investigations of the interaction between candidate genes and childhood trauma in the susceptibility to BD per se.⁵

In particular, longitudinal studies have revealed that maltreatment risk factors—particularly neglect, physical,and/or sexual abuse; multiple subtypes; and earlier onset—are related to emotion dysregulation that contribute to later internalizing and externalizing symptomatology directly as well as indirectly through negative peer relations.²⁹

Nonetheless, not all individuals who have been abused and neglected succumb to the extreme adversity in their lives. Investigation of how some maltreated individuals cope adaptively despite experiencing significant stress and trauma offers an opportunity to discover processes at multiple levels of analysis.³⁰

Following this line of research, discovering how maltreated children develop and function resiliently despite experiencing a multitude of stressors may offer considerable promise for elucidating developmental theories of coping and for prevention and intervention.

To reach a more complete understanding of the role of environmental adversities in risk for psychiatric disorders, it has been hypothesized an interaction between early and current adversity. In particular, there is a growing interest in those early familiar experiences that sensitize individuals to the impact of subsequent environmental stressors, ie, that family psychopathology might increase the likelihood of having adverse experiences since early in life.³¹

In conclusion, we may consider the development of BD as the result of the addition of genetic to environmental vulnerability including familiar psychopathology.

Disclosure: The authors declare no conflict of interest.

REFERENCES

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3. Fountoulakis KN, Vieta E. Treatment of bipolar disorder: a systematic review of available data and clinical perspectives. Int J Neuropsychopharmacol. 2008;11(7):999–1029.
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6. Kessler RC, McLaughlin KA, Green JG, et al. Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. Br J Psychiatry. 2010;197:378–385.
7. Kessler RC, Green JG, Adler LA, et al. Structure and diagnosis of adult attention-deficit/hyperactivity disorder: analysis of expanded symptom criteria from the Adult ADHD Clinical Diagnostic Scale. Arch Gen Psychiatry. 2010;67(11):1168–1178.
8. Alonso J, Vilagut G, Chatterji S, et al. Including information about comorbidity in estimates of disease burden: results from the World Health Organization World Mental Health Surveys. Psychol Med. 2010;16:1–14.
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11. Horesh N, Iancu I. A comparison of life events in patients with unipolar disorder or bipolar disorder and controls. Compr Psychiatry. 2010;51:157– 164.
12. Kauer-Sant’Anna M, Tramontina J, Andreazza AC, et al. Traumatic life events in bipolar disorder: impact on BDNF levels and psychopathology. Bipolar Disord. 2007;9(suppl 1):128–135.
13. Heim C, Nemeroff CB. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry. 2001;49:1023–1039.
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15. Leverich GS, McElroy SL, Suppes T, et al. Early physical and sexual abuse associated with an adverse course of bipolar illness. Biol Psychiatry. 2002;51(4):288–297.
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Adolescent school-based bullying is a widespread problem throughout Europe and North America, affecting on average 11% of students at least weekly^1,2 while a higher proportion of students are thought to suffer from victimization at least occasionally.^3,4 No consensus has been reached regarding a specific definition for bullying, however, many studies utilize Olweus's (2000)⁵ guidelines: “An individual is being victimized when [they are] exposed, repeatedly and over time to negative actions. It is a negative action by which someone intentionally [causes] or attempts to [cause] harm or discomfort [to another person]” [pp. 487–489]. Additionally, bullying situations reflect an imbalance of power between the victim and the bully, with bullies being stronger than their chosen victim.⁵

The psychological effects of victimization are known to be wide ranging, with a vast literature outlining both the physiological and mental-health consequences of peer victimization. Victims have been shown to report increased psychosomatic complaints such as headaches and stomachaches^6,7 as well as showing risk for longer-term mental health risks such as psychotic-like experiences, ^8–10 anxiety and depression, and lowered self esteem. ^11–13

In addition to associated emotional problems (such as anxiety, depression, and lowered self-esteem), adolescent victimization from bullying presents an additional risk toward the development of harmful externalizing behaviors such as aggression, delinquency, and alcohol misuse. ^14–16 While a broad literature has documented associations between other forms of victimization (eg maltreatment from parents) and externalizing behavior problems such as risky alcohol use, ^17–19 most published studies to-date that have investigated adolescent bullying victimization, have focused upon victimization and internalizing problems, leaving relatively little known about any related externalizing behavior problems such as increased consumption of alcohol use and alcohol-related problems.

In order to prevent against the adverse consequences of adolescent bullying, it is imperative to understand all of the associated risks. Justification for a link between this form of peer victimization and externalizing behaviors, in particular alcohol use, can be seen within the extensive literature, which consistently associates other forms of childhood and adolescent victimization (including sexual and physical abuse) with the development of alcohol and substance use disorders,^20,21 alcohol-related problem behaviours²² and an earlier initiation of alcohol use.^23,24 Evidence has been shown empirically, for example in a study that investigated groups of alcoholic women. Results showed that between 24% and 85% suffered some form of childhood abuse.²² The adverse effects of childhood abuse in relation to the uptake of risky alcohol drinking are known to endure into adulthood, with abuse suffered before the age of 18 associated with persistent alcohol-related problems.²³ Further, it has been shown that up to 81% of adult women treated for drug dependency report experiencing childhood abuse or neglect.²⁵ Additionally, violent or traumatic attacks have also been linked to alcohol misuse. Berenson et al (2001)²⁶ showed that victims of violent attacks (such as rape), were up to four times more likely to experiment with alcohol and marijuana.

The effects of childhood victimization are thought to not only influence an increased consumption of alcohol, but also to affect the style of drinking adopted. Using a national sample of 4008 adult women, Duncan and colleagues²⁷ showed that those women with a history of child abuse were more likely to report alcohol-related problems (including problems with friends and family members and driving while intoxicated), in addition to showing an increased risk for the use of illicit drugs such as cocaine, heroin, and marijuana.

Further, other forms of victimization, such as assault and child maltreatment have been shown to lower the age of initiation of alcohol use.^28,29 In a longitudinal study conducted over 16 months, 593 adolescents (with an average age of 11.8 years) reported whether they had witnessed, been threatened with or suffered from actual physical violence, or violence involving a weapon. Results showed that witnessing violence or experiencing lower levels of actual violence, led to an earlier age of alcohol use initiation, which was predictive of future victimization after 16 months. Within this study of preadolescents, the direct experience of victimization had an inverse relationship with the age of initiation of use, suggesting that some forms of victimization deter children from engaging with alcohol, potentially as a protective factor to protect them from situations in which victimization is more likely.³⁰

Acts of victimization, which have been perpetrated by peers, but which would not be defined as bullying, have been associated with earlier initiation of alcohol use. In a cross-sectional study of 856 seventh-grade students in the United States, logistic regression analyses showed a significant association between preadolescent alcohol use and dating violence (this result remained significant over and above other indicators of alcohol use such as the effects of peer delinquency, depression, impulsivity, binge drinking, and other substance use).³¹ Further, Brady and colleagues (2008)³² interviewed 247 adolescents aged 16 to 20 years. Participants reported whether or not they had experienced one or more of 10 violent acts, perpetrated by a peer (including physical fights, being threatened or attacked with a weapon, and being stabbed with a knife or shot with a gun). Regression analyses showed that those adolescents who had experienced violent forms of victimization reported greater substance use (alcohol or tobacco). This relationship was moderated by the use of positive coping skills, such that those victims who utilized these styles of coping (such as focusing on positive aspects of life) reported lower levels of substance use, while victims who did not engage such skills reported elevated substance use levels.

The existing literature outlined above suggests that victimization of various forms is associated with alcohol use and misuse within adolescence. Fewer studies have examined the association between adolescent school-based victimization from bullying and alcohol use. Different motivations are thought to underlie the consumption of alcohol,^24,33 with negative internal motivations (such as drinking to cope or to “escape from” a stressful life event), associated with alcohol misuse and related problems.³⁴ Alcohol use is a more prevalent behavior within adolescence, being more readily available than illicit drugs and has been described as a “gateway” drug toward other illicit substances.³⁵ For these reasons, the relationship between adolescent school-based victimization and alcohol use is the specific focus of this systematic review in order to assess the current state of the literature and any apparent gaps. Studies that focus upon illicit drug use are considered beyond the scope of this article. This review will focus upon (1) methodological considerations of currently published peer-reviewed articles and (2) the alcohol use outcomes that have been investigated in accordance with bullying victimization.

METHOD

An electronic search was conducted of the Psychinfo, Scopus, and PubMed databases, which includes a wide range of life science journals. The search terms utilized were: bullying victimization OR victimization OR bullying AND adolescent AND alcohol use OR alcohol misuse OR alcohol. Any article available online, which had undergone a peer review process and was either published or currently in press was considered for review within this article. This electronic list was supplemented by manual searching of the reference list from each included paper to obtain all potentially relevant publications. In order to be considered appropriate for inclusion, papers had to investigate bullying from the perspective of the victim. The bullying had to have been perpetrated within adolescent peer groups. Studies that focused upon other forms of peer victimization (eg assault), but that did not meet criteria for bullying victimization, were considered beyond the scope of this review. To be considered as “bullying” the victimization had to meet the Olweus (2000)⁵ definition for bullying (ie repeated negative actions over time against an individual). Alcohol use included any measurement of consumption (including quantity, frequency, and problematic drinking styles such as binge drinking). Studies that included victimization and/or alcohol use as part of a larger investigation were considered for inclusion within this review. Additionally, the study had to also investigate the relationship between bullying victimization and alcohol use. Studies were excluded if they only investigated the use of drugs in accordance with bullying victimization. Any study that utilized a latent variable of “substance-use” composed of both alcohol and other drug use was considered for inclusion within this review.

FINDINGS

In total the electronic searches from three databases in addition to manually searching the reference list of all relevant studies yielded 49 articles. Only eight studies fulfilled all criteria. One study was excluded from the review as no definition of bullying was provided for the participants, nor was information reported about frequency of victimization, or whether the victimization actions were repeated over time. As such it was not felt possible to compare the results of this study with the other seven studies on bullying and alcohol use. All of the seven included articles were published online between 2001 and 2010 or are currently in press. Two studies investigated alcohol use as part of a latent variable assessing “substance use.” Only two studies were longitudinal, with a maximum time period of 12 months.

Methodological Considerations

All studies included within this review were published in the past 10 years allowing for a current understanding of the effects of victimization from bullying upon alcohol use, accordingly, this also narrows the scope of the available literature and our subsequent understanding of this important relationship. Only two studies examined this association longitudinally,^36,37 however, the longest period assessed was over 12-months. This lack of longer-term longitudinal studies, with the majority of articles based upon cross-sectional designs, allows for only a snap-shot into the association between adolescent bullying victimization and alcohol misuse. The state of the literature is therefore severely limited when trying to understand the developmental consequences of bullying victimization in terms of its association with alcohol misuse.

A further impediment to the literature is the definition of bullying victimization used within studies. Out of the seven included studies, only four provided participants with a definition for bullying victimization, with all of these based upon the Olweus definition of bullying.^1,2,36,38 Within a further two studies, while no definition was provided for participants, the questions asked were detailed and covered different types of bullying victimization (ie physical, verbal, and/or relational victimization).^37,39 While the final study did not provide a definition for bullying and asked participants to answer detailed questions covering relational and physical victimization, this study did not use the term “bullying” to describe the victimization.⁴⁰

Additionally, the studies varied on what form of bullying victimization was examined. Two studies examined two types of victimization as separate concepts (mental/ relational and physical)^37,40; one study examined three types of victimization as a composite score (ie physical victimization, including hitting and kicking; relational victimization, including social exclusion and rumor mongering; and verbal victimization, including name calling and teasing)³⁶; and a further study examined four types of victimization as a composite score (physical, relational, verbal and cyber-based victimization using computer-based technologies).³⁹ The final three studies did not use detailed questions in addition to their definition of bullying and therefore received no information about the types of victimization.^1,2,38 Taking into account the differences between studies in terms of definitions and questions used, as well as the types of victimization measured, it is difficult to compare and contrast the results from the different studies, as participants understanding of bullying may have differed between studies, depending upon the style of questioning used and whether or not a definition of bullying was provided.

Sample Characteristics

The age of participants between the different studies ranged from 11 to 16 years old. This difference in ages may have had an effect on whether or not an association was found between victimization and alcohol use; the two studies that reported no relationship included participants aged between 11 and 16.^1,2 Adolescence marks the development of different coping mechanisms with emotion-specific coping strategies becoming increasingly prevalent.⁴¹ The use of alcohol in order to escape or cope with the trauma associated with victimization may, therefore, not be adopted as a behavior until later in adolescence, once alcohol has become more readily available and a more prevalent behavior amongst the peer group. Further, victimization has been shown to decline during adolescence,^42,43 therefore, adolescents who remain as victims aged 16 may have a different or more homogeneous profile than those victimized aged 11. Subsequently, it is difficult to compare studies showing a differential age range in terms of externalizing behaviors.

Study Design

As aforementioned, only two out of the seven studies included within this review used longitudinal designs (both of these studies used two time points over 10 months and 12 months, which asked for retrospective reporting on victimization over the past 12 months and 6 months, respectively).^36,37 The remaining five cross-sectional studies asked participants about their experiences of victimization ranging from the past 30 days to within the current school term (ie a maximum 3 months; see Table 1). As aforementioned, bullying victimization is a developmental phenomenon that changes during adolescence.⁴³ The lack of studies spanning a greater proportion of the adolescent period represents a big gap of knowledge within the literature. This aspect, in addition to the short time span reported on within the cross-sectional studies, further impedes our understanding into both bullying victimization and its association with alcohol use and related problems.

Findings from the Literature

The included studies are summarized within Table 1. Taking the various methodological limitations into account, the seven studies show an interesting array of outcomes with respect to the relationship between victimization and alcohol use. Five out of the seven studies report a significant and positive association between victimization and alcohol use, ^36–40 with four of these studies investigating gender specific relationships. ^37–40 Both Sullivan and colleagues as well as Tharp-Taylor and colleagues investigated the relationship between physical and relational (or mental) victimization and alcohol use separately for girls and boys, yet report contrasting results.^37,40 The study conducted by Sullivan and colleagues⁴⁰ reported a positive association between relational victimization and both the frequency of alcohol use (defined as the number of times within the past 30 days that the participant had drunk beer, wine, or liquor) and advanced alcohol use (defined as “being drunk” from alcohol use). In terms of gender effects, a significant positive association that was specific to boys was reported between physical victimization and both an increased frequency of alcohol use and advanced alcohol use,⁴⁰ with no gender specific effects shown for relational victimization. Similarly to Sullivan and colleagues,⁴⁰ the study by Tharp-Taylor and colleagues³⁷ reported predictive associations between physical and relational (or mental) victimization and alcohol use (defined as the number of drinking days over a 30-day period) over a 10-month period. On reporting gender specific effects, Tharp-Taylor and colleagues³⁷ showed the same relationship between physical victimization and increased alcohol use to be specific to girls. These contrasting gender effects reflect the sensitivity of this association to study design, with methodological differences between these two studies seen in average age (14.5 years compared to 12.5 years), sample size (276 compared to 926), demographic constitution (majority African American compared to ethnically diverse), sampling timeframe (cross-sectional compared to longitudinal over 10 months), as well as the definitions used for measuring alcohol frequency.

A third study examined gender differences in 1,495 adolescents (average age of 16 years) in the relationship between bullying victimization (a composite score taken from four different types of victimization) and alcohol use. Results showed a direct relationship for boys between frequency of victimization and a latent “substance use” variable (including frequency of alcohol use, drinking to get drunk, tobacco and marijuana use within the past 30 days). An indirect relationship was shown, which was specific for girls, through heightened levels of depression.³⁹ This study supported a previously published article that showed that bullying victimization for girls was associated with solitary “risky single occasion drinking” (ie, binge drinking) and that this co-occurred with increased depression, lower general life satisfaction, and lower self-esteem.³⁸

To show a positive association between bullying victimization and alcohol use, the fifth study examined mediating mechanisms that help to explain the association between bullying victimization and alcohol-related problems. Results showed that the development of coping motives for drinking partially explained the relationship between victimization and alcohol related problems (such as fighting, noticing changes in personality, etc.) over a 12-month period.³⁶ As aforementioned, two studies (which were taken from the same dataset), showed no relationship between victimization and an increase in frequency of alcohol use.^1,2 The results from these two cross-sectional studies, which benefited from large sample sizes (15 686 and 113 200, respectively) must be taken into account when interpreting any risk posed by bullying victimization upon the development of alcohol use disorders.

CONCLUSIONS

This review has highlighted the paucity of research, as well as the conflicting results and study designs within the investigation of the effect of being victimized by bullying upon adolescent alcohol use. It is clear that further research is needed before any strong conclusions can be drawn. The wide research base that has consistently shown developmental associations between other forms of victimization in adolescence (such as parental abuse) and alcohol use disorders, both within adolescence and adulthood, should be taken as justification for further research into the area of peer-based bullying victimization. Importantly, two of the seven studies reviewed above investigated underlying mechanisms within this association, showing that coping drinking motives and levels of depression mediate the relationship between victimization and alcohol use,^36,38 suggesting that both emotional symptoms (such as low mood) and coping styles can help to explain this relationship. These findings support other studies that show an increased risk for avoidance drinking due to adverse childhood experiences (including abuse, parental divorce, assault, or familial mental illness).^20,26 This research also suggests that positive coping skills can protect individuals from the behavioral problems associated with victimization.

As aforementioned, victimization from bullying has been associated with adverse mental health outcomes including anxiety, depression, and psychotic symptoms.^8,10,12 It would be important for future studies to investigate the mechanisms through which the development of these mental health problems may either help to explain an increase in alcohol use, or conversely, whether increases in avoidant behaviors (such as alcohol use and other harmful behaviors) may influence the onset and development of mental health disorders. It is therefore imperative that future studies attempt to strengthen the knowledge base for the effects of adolescent bullying victimization, as well as to investigate the potential mechanisms so that prevention and intervention programs can be tailored toward those victims prone toward a maladaptive or avoidant coping style that could lead toward alcohol misuse as well as related problems.

The Preventure and Adventure trials^44,45 have successfully administered and replicated personality targeted coping skills-based interventions to high school students throughout Greater London, UK. These trials have been shown to be successful in reducing both risk taking behavior (such as alcohol and drug use), as well as adverse mental health outcomes over a 2-year period for higher risk adolescents showing vulnerable characteristics based upon their personality. It would therefore be interesting to assess the outcomes of these trials in terms of adolescent victims of bullying and their specific risk for alcohol use and related problems.

Acknowledgements: Lauren Topper is supported by the IMAGEN project and the Alcohol Education Research Council, UK. IMAGEN receives research funding from the European Community's Sixth Framework Program (LSHM-CT-2007-037286). This paper reflects only the author's views and the Community is not liable for any use that may be made of the information contained therein.

Disclosure: The authors declare no conflict of interest.

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9. Campbell MLC, Morrison AP. The relationship between bullying, psychotic-like experiences and appraisals in 14–16-year olds. Behav Res Ther. 2007;45:1579–1591.
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11. Arseneault L, Milne BJ, Taylor A, et al. Being bullied as an environmentally mediated contributing factor to children’s internalizing problems. Arch Pediatr Adolesc Med. 2008;162:145–150.
12. Hawker DSJ, Boulton MJ. Twenty years’ research on peer victimization and psychosocial maladjustment: a meta-analytic review of crosssectional studies. J Child Psychol Psychiatry. 2000;41:441–455.
13. Ivarsson T, Broberg AG, Arvidsson T, Gillberg C. Bullying in adolescence: psychiatric problems in victims and bullies as measured by the Youth Self Report (YSR) and the Depression Self-Rating Scale (DSRS). Nord J Psychiatry. 2005;59:365–373.
14. Khatri P, Kupersmidt JB, Patterson C. Aggression and peer victimization as predictors of self-reported behavioral and emotional adjustment. Aggress Behav. 2000;26:345–358.
15. Laird RD, Jordan KY, Dodge KA, Pettit GS, Bates JE. Peer rejection in childhood, involvement with antisocial peers in early adolescence, and the development of externalizing behavior problems. Dev Psychopathol. 2001;13:337–354.
16. Hanish LD, Guerra NG. A longitudinal analysis of patterns of adjustment following peer victimization. Dev Psychopathol. 2002;14:69–89.
17. Arseneault L, Bowes L, Shakoor S. Bullying victimization in youths and mental health problems: ‘‘much ado about nothing’’? Psych Med. 2010;40:717–729.
18. Butt S, Chou S, Browne K. A rapid systematic review on the association between childhood physical and sexual abuse and illicit drug use among males. Child Abuse Review. 2011;20:6–38.
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21. Bensley LS, Spieker SJ, Van Eenwyk J, Schoder J. Self-reported abuse history and adolescent problem behaviors. II. Alcohol and drug use. J Adolescent Health. 1999;24:173–180.
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Forensic psychiatrists deal with some of the most difficult patients in psychiatry. They are concerned with the assessment of complex cases including risk assessment and with the treatment of mentally disordered offenders, typically in secure settings such as secure hospitals or prisons. Furthermore, forensic psychiatrists act as expert witness in court commenting, for example, on issues of criminal responsibility and competency to stand trial.

Forensic psychiatry is a subspecialty of clinical psychiatry, which requires special legal and criminological knowledge and experience in the treatment of mentally disordered offenders. Forensic psychiatrists should have solid psychiatric training as well as practical experience in dealing with mentally disordered offenders. The double knowledge in psychiatry and law defines the subspeciality of forensic psychiatry and provides the ethical foundations for its practitioners.¹

The core concern underlying all the ethics-related precepts is the relationship between the psychiatrist and the evaluee.² In psychiatric ethics, the dual-role dilemma refers to the tension between psychiatrists’ obligations of beneficence toward their patients and conflicting obligations to the community, third parties, other health care workers, or the pursuit of knowledge in the field. These conflicting obligations present a conflict of interest in that the expectations of the psychiatrist, other than those related to patients’ best interests, are so compelling.

Forensic psychiatry operates within a certain legal and societal context that undergoes constant evolution. Laws are rules that guide human behavior and as such are man-made. This means that concepts such as responsibility or competence are normative rather than clinical issues³ that differ from country to country, sometimes significantly.⁴ Therefore, while the ethical issues facing forensic psychiatrists might be similar across cultures, they do also depend on the specific legal system and service provision within each country.⁵

FORENSIC PSYCHIATRIST AS EXPERT WITNESS

Forensic psychiatrists as well as forensic psychologists appear in court as expert witnesses, giving their opinion on specific issues as requested by lawyers or a judge. As such they have to act within the law but also have to accept the authority of the legal profession. Psychiatrists in court only provide an opinion while decisions are made by the judge or jury, a situation that differs from that encountered by the highly skilled forensic psychiatrist in his or her other work context and one that can cause discomfort or even resentfulness. Difficulties met by the psychiatric expert witness include harassment by the different parties involved in the trial,⁶ public criticism, difficulties in keeping one's dates, low reward, poor relationships with the legal profession partly due to unfounded attacks, loss of dignity, and status as a consequence of the confrontation with sharp-shooting lawyers amongst others. Some psychiatrists avoid expert witness duties altogether because of the number of frustrations they are confronted with in court. They are glad that there are “masochistic” colleagues who are prepared to be available to act as expert witness.⁷

Taking on duties as an expert witness is not only associated with external frustrations but has caused grave soul searching when accepting duties that originally are not core tasks of the psychiatrist.⁸ The terms “criminal responsibility” or “guilt” in legal thinking do not exist as an empirical entity in psychiatry. Even if a medical expert does not comment directly on criminal responsibility—and he should not as a matter of fact—his expert opinion aims at enabling this finding. Helping to determine the criminal irresponsible has a serious side effect⁹: the forensic psychiatrist legitimates the punishment of individuals labeled as responsible. The psychiatrist, at first sight, takes on the humanitarian act of treating those who are not punished due to their mental disorder. This action, however, becomes problematic as the psychiatrist does not only undertake treatment but also custodial functions. The forensic psychiatrist is “changing sides,”¹⁰ he moves from protector of the ill individual to being protector of the society.¹¹

In cases of psychiatric reports on refugees facing deportation, which bear considerable diagnostic and prognostic difficulties, the psychiatrist has a major impact on an individual's life that can have grave consequences including deterioration of existing mental disorders.⁵ The most severe role conflict for psychiatrists exists in countries with capital punishment where forensic experts are used to assess the “competency to be executed,” which could be achieved by treating the mental illness. Keane¹² argues in this context that physicians may be causing harm to co-victims, respectively, murder victims’ relatives when they delay, halt, or advocate against an execution.

An alternative to the difficult and sometimes reluctant engagement in legal work could be the total refusal, the retreat from the forensic field. But to go on a “total strike” is certainly not the ideal way to achieve important changes in legal practice.⁸ Given the reality of expert witness work, some authors have questioned whether it is justified to speak of humanitarian engagement of psychiatrists in this field.¹³ Besides the mentioned possibilities to cooperate half willingly or to refuse expert witness duties, there is also the option of willing adaptation and overadaptation. This is what Robert Musil described in his novel Der Mann ohne Eigenschaften (The Man Without Qualities) some decades ago (1952): the tendency of doctors to conform and to adapt to the expectations of the legal profession.

The forensic psychiatrist is indeed confronted with a double dilemma: Either he is legitimating punishment by labeling only a fraction of the accused as disordered and in need of treatment; in this case he might be called a servant of justice. Alternatively, if he is offering treatment for a large number of offenders he might be accused of brain washing and treatment tyranny. Psychiatry has been criticized for therapeutic nihilism and revenge; on the other hand, when progressive institutions were developed for the treatment of disordered offenders, therapists were criticized for applying too lengthy treatments based on unclear criteria with doubtful success. In public consciousness, outsiders of the society are treated either too softly—as currently in many European countries—or too harshly. Forensic psychiatry, acting on behalf of society with the doubly stigmatized, is subjected to double reproach.⁷ There is probably no subspeciality of psychiatry that has been more criticized than forensic psychiatry.

Despite discomfort, contradictions, and resistance, psychiatrists should not retreat from the forensic field. Psychiatrists can continue to work on humanizing the management of law breakers facilitating suitable treatment for those in need. This also means that cooperation with the legal system should not be refused as this allows a contribution of experiences that may be helpful for the further development of the law. It is, however, always important to be watchful regarding attempts to instrumentalize psychiatry. In this context, the forensic psychiatrist has to adhere to role clarity: As a physician, he is primarily obligated to the treatment and well-being of the (incarcerated) patients and is not exclusively an agent of social control. Moreover, the general conditions in a therapeutic setting (eg, dealing with medical confidentiality) have to be clear and transparent to the patients. This clearness and transparency should also found the situation of Independent Medical Examinations (IMEs) as described by the Scientific Section Forensic Psychiatry of the World Psychiatric Association.¹⁴

PRACTICAL ASPECTS OF FORENSIC-PSYCHIATRIC ASSESSMENTS

When asked to provide an opinion on an offender, the forensic psychiatrist should obtain the consent of the examinee to provide the report to the requesting body. This means he has to ensure the examinee has the capacity to consent and understands the purpose of the report and that any relevant information will be included. He should also state whether the assessment is compulsory or not and provide information about possible consequences of both cooperation and noncooperation. The information on probably negative consequences of noncooperation can be (mis)understood by the examinee as enforcing his/her pseudo-voluntary consent. The forensic psychiatrist should explain the purpose of the consultation clearly and note that it is not a therapeutic consultation and that no help, suggestions, treatment, and possibly not even feedback will be offered, with the exception of intervention if the examinee is at immediate and serious risk. The relationship is one of evaluation, and the fact that the evaluator is in no position to reassure the person on matters of confidentiality or privacy could mean that negative findings will endanger the interests and cause harm to the person being evaluated, regardless of this person's health and the evaluator being a physician.¹⁴ Because of this, forensic psychiatrists may even be implicated in the criminalization of mentally ill persons.¹

If the examinee discloses confidential information that could jeopardize his social position (eg, Case Report No 36 in Carmi et al),¹⁵ one option for the examiner is to inform the judge privately about the material assembled so not to fail the expert duty in concealing pertinent information. How this material will be used, however, is for the judge to determine.

The compilation of third party information through interviewing family or friends, as is common practice in general psychiatry, can easily be construed as inadmissible investigation activity in forensic psychiatry, particularly if it happens without consultation with the examinee and the court and without explaining the right to refuse the evaluation.

Prison physicians have a responsibility to request from the appropriate authorities (eg, courts) a forensic-psychiatric assessment in cases where they suspect a disorder such as a psychotic disorder, a severe personality disorder, or markedly reduced intelligence that may affect the prisoner's criminal responsibility, competence to stand trial, or fitness to be detained. In this context, forensic psychiatrists should not, as a matter of principle and in order to avoid a conflict of roles, assess their own patients.¹⁶ They contribute to humanizing legal procedures by providing expert information and their special view on the development of delinquent behavior in order so that justice can be done to the accused, while at the same time providing objective information. Forensic psychiatrists should present their specialist knowledge in such a manner that it is readily understandable to the legal client and, thus, provide a basis for independent decision making.

In dealing with deviant behavior, criminology and psychiatry have developed two parallel approaches that partly give different definitions of terms in their own specialist language, for example, of the term psychopathy. The resulting communication problems, especially translating psychiatric findings and conclusions into the legal coordinate system, are an internationally familiar phenomenon.⁵ The forensic psychiatrist should avoid overstepping competences and venturing into normative evaluation that is reserved for the courts. An uncontrolled (over)identification with the offender based on unrecognized counter-transference can lead to adoption of an exaggerated helper role. On the other hand, assuming the role of a prosecutor or judge can turn the evaluation situation into a cross-examination and lead to incorrect evaluation findings. What is required from the forensic psychiatrist is the psychopathological analysis of the mental condition of a perpetrator and his personality performed on the basis of empirical knowledge and competent specialist examination. The expectations an offender has of the forensic-psychiatric expert may involve not only the hope of a favorable outcome of the trial but also the need for exploration of the self and the delinquent acts in question. Thus, the expert gets assigned therapeutic functions, if only as a communication partner, which makes the completely neutral attitude of his role appear fictitious.

CONDUCT OF THE EXAMINATION

In conducting an IME, forensic psychiatrists should ensure they have the qualifications and expertise to perform the assessment and provide the expert opinion. The assessment should be undertaken in person and in a setting that provides the greatest practical confidentiality. The forensic psychiatrist should clearly explain the purpose of the consultation and note that it is not a therapeutic consultation and that no help, suggestions, treatment, or even feedback will be offered, with the exception that intervention is appropriate if the examinee is at immediate and serious medical risk. The consent of the examinee should be sought prior to an interview being recorded and a copy of any recording should be offered to the examinee. If interpreters are required, they should be professionally trained and consideration should be given to religious, gender, and cultural compatibility. Questions should be asked in a way that indicates the forensic psychiatrist is not biased. The use of rapport building in a forensic evaluation is an ethical issue in itself but will assist information gathering.¹⁴

CONTENT OF REPORT

The report should be written in plain language. The use of psychiatric terminology should be avoided in an effort to make the information comprehensible for nonmedically trained readers. Fact and opinion should be clearly distinguished. The following information should be included¹⁴:

1. Qualifications and experience of the IFP

2. A statement about who commissioned the report.

3. A statement regarding the examinee's consent to the release of information.

4. Demographic data including the name and date of birth of the examinee, the domestic situation, marital status, and number of children.

5. Personal history including developmental, educational, occupational, sexual and relationship, substance use, and forensic history.

6. A description of the examinee's personality, interests, hobbies, and coping style.

7. History of the present complaint as presented by the examinee and reports from informants.

8. Past psychiatric history

9. Family history of psychiatric illness

10. Medical history

11. Mental State Examination should include a description of appearance and behavior; emotional tone; speech; thought stream, form, and content; orientation and sensory perception; higher mental functioning; insight; and judgment.

12. Tests and investigations

13. A summary and formulation, or synthesis of the case, and diagnosis should be recorded. The formulation should take the form of a biopsychosocial explanation of the presumptive causative factors in the examinee's condition. Inconsistencies between reported symptoms and observed mental state or physical examination should be noted. Indications of malingering should be noted, but its determination and weight, however, is best left to the decision-making body to make.

14. Finally, an opinion is offered, in relation to questions posed by the requesting body. The report itself should clearly demonstrate how conclusions were reached. Limitations to the examination should be explained in the report and mention made of investigations or other data that are required to reach a conclusive opinion.

15. Comments on special issues may be required including prognosis, management, impairment, disability, and legal concepts such as competency.

RISK ASSESSMENT

Forensic psychiatrists as well as forensic psychologists are crucially involved in the assessment of risk, particularly the risk of future (violent) re-offending but also the risk of institutional violence. These assessments might determine whether an individual is going to be released or the level of security he will be treated in. In some countries (eg, Germany) the law allows preventive detention, for example, detention for the protection of others after serving a time-limited prison sentence. According to the law, two independent forensic experts have to provide a legal prognosis. In cases of prisoners serving a life sentence or in cases of preventive detention, release is only possible if there is no risk that the dangerousness of the offender persists. Therefore, risk assessments have major ethical implications for forensic practitioners.⁵

The science of assessing risk has boomed in recent years with an increasing number of structured instruments being available to fulfill this task. It is generally accepted that structured risk assessment instruments increase the accuracy of prediction compared to unaided clinical judgment alone. Two main approaches of risk assessment tools have been described¹⁷: actuarial methods and structured clinical judgment. In actuarial assessments, prediction is based on coding of mainly historical items that have been shown to be associated with future violence in a predetermined way. Findings are often presented as probability estimate of the future event of interest (eg, violent re-offending). The appeal of such instruments (eg, Violence Risk Appraisal Guide VRAG)¹⁸ is the ease of their administration and the perceived (but deceptive) clarity of the outcome. Limitations of actuarial assessments are that they do not allow taking into account more sophisticated and detailed information specific to the individual including dynamic variables and protective factors. Structured clinical judgment instruments (eg, the HCR-20)¹⁹ serve as an aide memoir, providing a structure for the assessment while also relying on clinical expertise. They are based on a review of the literature with regards to factors relevant to future risk but are, unlike actuarial tools, not sample-specific.

For example, probability risk estimates using actuarial assessment tools have been developed in a specific population and might not be valid in other groups. Therefore, an instrument validated in male offenders released from a high secure prison in Canada may not be valid in women treated in the community of a European setting and it should, therefore, be used with caution in such a population, if at all. Furthermore, all risk assessment instruments produce indications about groups of individuals but are limited in what they state about the individual. They generally do not differentiate the severity of violent reoccurrence or the timeframe in which to expect such an event.⁵

No matter how sophisticated risk assessment instruments are, future behavior cannot be predicted with any certainty, giving rise to particular challenges in balancing the civil liberties of the patient and the protection of the public from potential future harm by that patient. Buchanan and Leese,²⁰ reviewing studies in which risk assessments were validated by follow-up of actual future violence, concluded that six people would have to be detained for 1 year to prevent one person from acting violent during this time period. However, the question of how much risk is acceptable to the society is not a psychiatric one. Society must decide how many it will restrain unnecessarily to protect us from the one person who might hurt us. This is purely a moral and political issue that must be left to the conscience of the community.²¹ In an increasingly risk-aversive society, public pressure demands reducing false negative predictions with the expectation of eliminating risk. However, reducing false negative risk prediction will lead to an increase in false positives, which means that even more patients might be subjected to severe restrictions of their liberties, many of whom might never have gone on to commit a (further) violent offense.

While forensic psychiatrists will probably always be expected to make predictions about future risk, they should not lose sight of their primary duty as clinicians that are toward their patients. In the context of risk assessment, this does not mean that they should withhold information regarding risk from relevant agencies, but rather that they should focus on the clinical task of treatment. This means managing rather than merely predicting risk. They also should educate policy makers and the population as a whole on what can realistically be expected in terms of risk reduction and the means necessary to achieve this task.

Keywords

forensic psychiatry, independent medical examinations, ethics

Disclosure: The authors declare no conflict of interest.

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11. Leyrie J. Manuel de psychiatrie légale et de criminologie clinique. In: Librairie Philosophique. Paris: Vrin; 1977.
12. Keane M. The ethical ‘‘elephant’’ in the death penalty ‘‘room’’. Am J Bioeth. 2008;8(10):45–50.
13. Hallek SL. A troubled view of current trends in forensic psychiatry. J Psychiatry Law. 1974;2:135–157.
14. World Psychiatric Association. Scientific Section Forensic Psychiatry’s consensus paper on guidelines for Independent Medical Examination. 2010. Submitted to World Psychiatry—under editorial review.
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16. Reid WH. The treatment-forensic interface. J Psychiatr Pract. 2008;14:122– 125.
17. Dolan M, Doyle M. Violence risk prediction. Br J Psychiatry. 2000;177:303– 311.
18. Webster CD, Harris GT, Rice ME, Cormier C, Quinsey VL. The violence prediction scheme: assessing dangerousness in high risk men. Toronto: University of Toronto, Centre of Criminology; 1994.
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21. Halleck SL. The ethical dilemmas of forensic psychiatry: a utilitarian approach. Bullet Am Acad Psychiatry Law. 1984;12:279–288.

Exposure to trauma such as childhood abuse, physical and sexual assault, natural disaster, and other traumatic experiences substantially increases risk for major depressive disorder, posttraumatic stress disorder, substance use disorder, suicide attempts, or comorbidity of these.^1–6 Interestingly, there are individuals who cope successfully and report few or no adverse psychiatric sequelae despite these trauma exposures, whose outcomes exemplify resilience.^7–9 Resilience is the relative resistance to environmental risk experiences.^{10, 11} It is the ability to cope and adapt successfully to stress, adversity, or trauma.¹⁰ Although there have been a number of studies on relationships between adverse childhood experiences and negative mental health outcomes in adulthood, our knowledge of relationships between nurturing childhood family environment and resilience and between resilience and positive and negative affect are limited. Hence, in this study, we examined (1) association between retrospective perception of nurturing quality of developmental family environment and resilience, measured with the Connor–Davidson Resilience Scale (CDRISC) and (2) association between resilience and positive and negative affect.

METHODS

This is a cross-sectional study of an urban, predominantly African-American community sample. Inclusion criteria included being 18 or older, understanding English, and ability to give informed consent. Members of the research team approached adult patients waiting for their appointments at the primary care clinic, obstetrical-gynecological clinic, or pharmacy of Grady Memorial Hospital in Atlanta, GA, to solicit study participation. Participants gave informed consent and completed a battery of self-report measures. The study was approved by the institutional review boards of Emory University School of Medicine and Grady Memorial Hospital.

We collected sociodemographic information including age, sex, race, education, income, and marital status. We also obtained retrospective self-reported perception of developmental family environment and assessed for lifetime history of trauma exposure (categorized as childhood abuse/neglect or other trauma), resilience, and positive and negative affect, as detailed below.

Sociodemographic Characteristics

Marital status was classified as “being married” or “other” (single/never married, separated, divorced, or widowed). Race was categorized into African American or other. Education consisted of three levels: (1) high school or below, (2) some college or technical school, and (3) college graduate or graduate school. Monthly income was categorized into three groups: (1) <$1000 per month, (2) $1000–$2000 per month, and (3) ≥$ 2000 a month.

Developmental Family Environment

Self-reported perception of nurturing quality of family environment during upbringing was assessed retrospectively with a question from the Clinical Data Form,¹² “How warm and nurturing was your family when you were growing up?” Response was based on a 5-point Likert scale, with 1=cold; 2=somewhat unpleasant; 3=fine, 4=quite warm, and 5=warm and nurturing. Higher score reflects more nurturing family environments.

Childhood abuse/neglect was assessed retrospectively with the psychometrically validated Childhood Trauma Questionnaire (CTQ).^{13, 14} This scale performed equivalently across four diverse populations – adult substance abusing inpatients, adolescent psychiatric inpatients, substance abusing individuals from a southwest Texas community, and individuals from a normative community sample – with different maltreatment histories, supporting the measurement invariance of the scale. The CTQ also had good convergent and discriminant validity.¹⁴ Scores from the CTQ were extracted for the categories of emotional, physical, and sexual abuse, and emotional and physical neglect. Following Bernstein and Fink's score ranges for none, mild, moderate, and severe levels of abuse, we classified each type of abuse into (1) none/mild range and (2) moderate/severe range.¹³ Consistent with prior research on the impact of adverse childhood experiences,^15–17 we used the total number of types of abuse in the moderate/severe range as the index for childhood abuse that ranged from 0 to 5 for each participant.

Other trauma was assessed retrospectively using the Traumatic Events Inventory.^{18, 19} This instrument measures lifetime exposure to different categories of trauma, including natural disaster, serious accident or injury, sudden life-threatening illness, military combat, physical assault, and sexual assault. For each category, having had the exposure was scored “1” and no exposure “0.” The childhood abuse items in this inventory were excluded to avoid overlap with the information collected with the CTQ. Score can range from 0 to 14, with higher scores reflecting exposure to more types of trauma.

Resilience was measured with the psychometrically validated, 25-item, self-rated CDRISC. Total score ranges from 0 to 100, with higher score reflecting greater resilience. The CDRISC demonstrated good psychometric properties in a community sample and in samples of primary care outpatients and general psychiatric outpatients.²⁰ It has high internal consistency (Cronbach's α=0.89), high test–retest reliability, and good convergent validity. The CDRISC scale has five loading factors, where factor 1 reflects personal competence, high standards, and tenacity. Factor 2 corresponds to trust in one's instincts, tolerance of negative affect, and strengthening effects of stress. Factor 3 relates to one's positive acceptance of changes and secure relationships. Factor 4 reflects self-control. Factor 5 represents spiritual influences.²⁰

Positive and negative affect were measured with the Positive and Negative Affect Scale (PANAS)²¹. This scale consists of 10 items representing positive affect (enthusiastic, interested, determined, excited, inspired, alert, active, strong, proud, and attentive) and 10 items descriptive of negative affect (scared, afraid, upset, distressed, jittery, nervous, ashamed, guilty, irritable, and hostile). Response to each item is a 5-point Likert scale (1–5), with 1=very slightly or not at all, 2=a little, 3=moderately, 4=quite a bit, and 5=extremely true. The positive affect score ranges from 10 to 50, with a higher score reflecting more positive affect. Likewise, the negative affect score ranges from 10 to 50, with a higher score reflecting more negative affect. The PANAS has high-internal consistency (Cronbach's α=0.84–0.90), excellent convergence (0.76 ≤ r ≤ 0.90), and discriminant correlation with measures of mood factors, and significant stability over a 2-month time period.²¹

Statistical Analyses

Analyses were performed using SAS Software (version 9.2^© of 2008; SAS Institute, Cary, NC, USA). Association between developmental family environment and resilience was examined with multiple linear regression, adjusting for potential confounding factors such as age, sex, race, childhood abuse/neglect, other trauma exposure, education, income, and marital status. Likewise, associations between resilience and positive and negative affect were assessed with multiple linear regression, also adjusting for the aforementioned potential confounders.

RESULTS

A total of 1321 individuals were assessed, of whom 64.6% were women and 92.3% were African American. The average age was 38, and 9.7% were married. Most participants had a high school education or below (68.2%), whereas 25.3% had some college or technical school education, and 6.4% were college graduates or attended graduate school. 11.1% of participants had a monthly income of ≥$2000, whereas the majority had a monthly income of <$1000 (Table 1).

Association Between Perception of Developmental Family Environment and Resilience

A more nurturing family environment during upbringing was associated with higher level of resilience in adulthood (β=2.28; p <0.0001; Table 2), after adjusting for history of childhood abuse and neglect, other trauma exposure, sex, age, race, education, income, and marital status. Particularly, one point higher on the nurturing scale of developmental family environment was associated with 2.28 points higher on the resilience scale (Table 2). Age, sex, and race were not significant factors in the multiple regression model for resilience and were thus removed from the model. As expected, more childhood abuse was associated with lower score on the resilience scale (β=−2.20; p <0.0001; Table 2). The association between other trauma exposure that happened mostly during adulthood and resilience was only nominally significant (β=0.32; p=0.053; Table 2). Higher education was associated with more resilience in this model (p=0.042; Table 2). Specifically, compared to individuals with an educational level of high school or below, those with some college or technical school, on average, had 2.25 points higher on their resilience scale (β=2.25; p=0.034; Table 2), and those graduating from college or attending graduate school had 3.22 points higher on their resilience scale (β=3.22; p=0.087; Table 2). The latter comparison only trended toward significance, possibly due to the small sample size of the college graduate/graduate school group (6.4%, Table 1).

As expected, having a higher income level was associated with a higher score on the resilience scale, after adjusting for confounding factors (p<0.0001; Table 2). Specifically, compared to individuals making <$1000 a month, those with income between $1000 and $2000 a month had, on average, 2.52 points higher on their resilience scale (β=2.52; p=0.020; Table 2), and those with a household income of greater than $2000 had 6.48 points higher on the resilience scale (β=6.48; p<0.0001; Table 2). Lastly, being married was associated with higher level of resilience than being divorced, single, widowed, or separated (β=3.25; p=0.032; Table 2).

Association Between Resilience and Positive Affect

In the multiple regression model for positive affect, resilience influences positive affect both as a main effect and an interaction term with childhood abuse, after adjusting for confounding factors of history of childhood abuse/neglect, other trauma exposure, age, sex, race, marital status, income, and education level (Table 3). As a main effect, higher resilience score was associated with greater positive affect (β=0.30; p<0.0001; Table 3). As an interaction term, resilience mitigates the adverse effect of childhood abuse/neglect on positive affect score (β=0.02; p=0.006; Table 3). Race, sex, marital status, income, and education level were not significant factors for positive affect and were removed from the model. As expected, childhood abuse/neglect was negatively associated with resilience (β=–1.43; p=0.006; Table 3), as was other trauma exposure (β=–0.16; p=0.016; Table 3).

Association Between Resilience and Negative Affect

In the multiple regression model, resilience influences negative affect as a main effect, and no interaction between resilience and childhood abuse was observed (Table 4). Higher level of resilience was associated with lower negative affect, after controlling for history of childhood abuse/neglect, other trauma exposure, age, sex, race, education level, income, and marital status (β=–0.17; p<0.0001; Table 4). Age, race, and marital status were not significant factors and thus were removed from the model. Childhood abuse/neglect was positively associated with negative affect (β=1.34; p<0.0001; Table 4); likewise, other trauma exposure was positively associated with negative affect (β=0.33; p=0.0005; Table 4). Higher educational attainment was associated with low negative affect score (p=0.038 and p=0.034; Table 4). Higher income level was also associated with lower negative affect score (β=–1.95; p=0.014; Table 4). Lastly, being female was associated with higher negative affect score (β=1.23; p=0.021; Table 4).

DISCUSSION

In this cross-sectional study of 1321 adults, we examined the relationship between self-reported perception of developmental family environment and resilience, assessed with the CDRISC. We found that having a more nurturing developmental family environment was associated with higher resilience scores after controlling for potential confounding factors such as history of childhood abuse/neglect, other trauma exposure, age, sex, race, education, income, and marital status. In this multiple linear model for resilience, we also observed that higher education, higher income, and being married were associated with higher score of resilience.

In addition, we examined the association between resilience and positive and negative affect. We found that resilience was associated with positive affect both as a main effect and an interaction term with childhood abuse, after adjusting for age, sex, race, other trauma exposure, education, income, and marital status. Higher level of resilience was not only associated with higher positive affect score but also mitigated the adverse effect of childhood abuse on positive affect. The multiple linear regression model for positive affect also suggests that childhood abuse/neglect and other trauma exposure were negatively associated with positive affect. Furthermore, resilience was negatively associated with negative affect after adjusting for confounding factors. We did not observe an interaction between resilience and childhood abuse/neglect on the outcome of negative affect. Lastly, the multiple regression model for negative affect suggested that higher education, higher income level, and male sex were negatively associated with negative affect.

Our finding of the positive association between nurturing developmental family environment and resilience is consistent with results from three other studies. In a prospective study of 43 adolescents, Collishaw and colleagues found that retrospective perception of high level of parental care was associated with resilience in individuals exposed to childhood physical or sexual abuse.⁸ In a second study, Wyman and colleagues reported that higher level of resilience in urban children exposed to major life stress was associated with more nurturing developmental family environment, reported not by the study participants but by their parents.²² In the third study, Bowes and colleagues observed that high level of maternal warmth and of positive home atmosphere promoted resilience in children after their exposure to bullying.²³

Our secondary finding that higher education and higher income were associated with greater resilience is consistent with results published by Campbell and colleagues, who observed that higher education and income levels predicted higher resilience measured with the CDRISC.²⁴ Lastly, our result of significant and positive association between resilience and positive affect is consistent with observations by Burns and colleagues.²⁵ Furthermore, these findings are in line with recent models of factors contributing to happiness and life satisfaction, in which positive emotions lead to increased resilience and life satisfaction.²⁶

The observed association between a more nurturing childhood family environment and greater resilience in adulthood is probably due to the fact that a more sensitive, caring, and safe home environment, we speculate, can promote adaptive emotional and behavioral development, including positive self-image, personal mastery, adaptive coping skills, competent interpersonal skills, and greater optimism. These characteristics, in turn, are likely to help with adaptive coping in the face of adversity in adulthood and foster more positive affect and less negative affect.

These results should be interpreted in light of our study's limitations. First, developmental family environment and trauma exposure were assessed retrospectively and are thus susceptible to recall bias. Second, since this is a cross-sectional study using a primary care clinic sample, the association between nurturing developmental family environment and resilience cannot be interpreted as a causal association. Future prospective studies are needed to thoroughly understand the causal relationship between family environment and resilience. Third, nurturing family environment was assessed using a self-report measure. A more fine-grained and objective assessment of the nurturing quality of developmental family environment is needed to obtain a more accurate measure of this construct. We chose to use the total number of types of childhood abuse in the moderate to severe range rather than either the total CTQ score or CTQ subscale scores in order to capture the impact of being exposed to multiple types of childhood abuse. In other words, a severe childhood physical abuse score might have been equivalent to a moderate physical abuse score combined with a moderate emotional abuse score. Exposure to multiple types of abuse has been demonstrated to be associated with increased risk for multiple negative mental and physical health outcomes.^{15, 27, 28}

In conclusion, this study adds to our understanding of the environmental factors contributing to resilience and the influence of resilience on positive and negative affect. Psychiatric and psychological approaches have primarily focused on pathological responses to stressful traumatic events. The concept of resilience may offer a broad array of new approaches, both for understanding the psychology and neurobiology of trauma response as well as for developing prevention and treatment strategies through the enhancement of resilience traits.

Keywords

Resilience, developmental family environment, positive affect, negative affect, childhood abuse

Disclosure: The author declares no conflict of interest.

Acknowledgements

Support was received from the Emory and Grady Memorial Hospital General Clinical Research Center, NIH National Centers for Research Resources (M01RR00039), and NIH MH071537. We thank the participants who graciously shared their stories and their time, and our colleagues Allen Graham, India Karapanou, Angelo Brown, Lauren Sands, Daniel Crain, and Asante Kamkwalala for their excellent assistance and support.

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Professor Tom Burns (UK) presented results of research, highlighting the importance of addressing treatment outcomes most relevant to patients. He described the patient–psychiatrist therapeutic alliance as an integral part of treatment,¹ and discussed the levels of coercion used in both the UK and USA.^{2, 3} Data showed that 35% of patients using mental health services in the UK have experienced leverage or informal coercion.³ Dr Cecilia Brain (Sweden) further emphasised the impact of stigma on patients with schizophrenia and the stigmatisation experienced by not only people with mental illness, but also their family and psychiatric care service providers.

Several presenters reported the benefits of continuous medication on long-term outcomes in schizophrenia, including reduced relapse⁴ and re-hospitalisation rates.⁵ Professor Robin Emsley (South Africa) discussed the consequences of relapse, including effects on personal relationships, employment/education status and contribution to stigma.⁶ Further data demonstrated benefits on measures of quality of life and functioning in patients receiving continuous medication.^{7, 8} He also presented data highlighting the benefits of early initiation of treatment in schizophrenia. Early treatment with risperidone long-acting injectable (RLAI) reduced relapse rate, improved remission rate and increased effects on Positive and Negative Syndrome Scale (PANSS) total scores compared with oral antipsychotics.⁹ Professor Fernando Cañas (Spain) presented data demonstrating that treatment with paliperidone palmitate, a long-acting injectable (LAI) antipsychotic, reduced relapse rates compared with placebo (10% vs. 34%, respectively),¹⁰ and also decreased hospitalisation rates.¹¹ Data from a recent naturalistic study showed that use of RLAI is associated with lower risk of hospitalisation compared with non-use of RLAI or with the use of injectable formulations of first-generation antipsychotics.¹²

The relevance of addressing factors beyond symptom control was also discussed. Professor Philip Gorwood (France) presented data from an extensive survey of 3610 psychiatrists, who perceived that a majority of patients have impaired functioning. Forty-one per cent of psychiatrists assessed functioning according to their patient's involvement in personal and social relationships, whilst 35% used engagement in work or study as a marker.¹³

Dr Andreas Schreiner (Janssen, Germany) discussed the challenges of treating patients in an acute hospital setting. He emphasised the importance of establishing a therapeutic alliance at this stage, with the prevention of harm to self or others being an important short-term goal.¹⁴ Data showed that paliperidone palmitate may be a suitable treatment option for patients with schizophrenia in this setting. Results demonstrated an early onset of symptom control,^{15, 16} without oral supplementation,¹⁷ and reduced risk of relapse and readmission to hospital.^{10, 11} Moreover, paliperidone palmitate was efficacious in acutely exacerbated patients, reducing PANSS scores and improving functioning.¹⁵

Dr Husseini Manji (Johnson & Johnson, USA) delivered a wide-ranging keynote lecture, which considered the huge financial burden that mental illness poses to the health system and the need for effective treatments. He also discussed the roles of synaptic and neural plasticity^{18, 19} in psychiatric disorders and potential new directions for treatment.

Day 1 concluded with a lively interactive panel discussion on the topic of long-term outcomes in schizophrenia. A panel consisting of a patient representative (Paul Arteel, Global Alliance of Mental Illness Advocacy Networks [GAMIAN], Belgium), family carer (Inger Nilsson, EUropean Federation of Associations of families of people with Mental Illness [EUFAMI], Sweden), nurse (Professor Richard Gray, UK) and psychiatrist (Professor Robin Emsley, South Africa) highlighted the views of each of these different stakeholders. Paul Arteel provided information regarding the work of the patient group, GAMIAN. Inger Nilsson provided a heartfelt and emotional testament of her own experiences as a family carer, and expressed her sense of isolation and exclusion from the decision-making process. Professor Richard Gray emphasised the importance of illustrating the link between medication adherences and achieving treatment goals. Professor Robin Emsley discussed patient- and treatment-related barriers in achieving optimal long-term outcomes and discussed that psychiatrists consider lack of insight as the most important reason why patients discontinue their medication.

In the opening session of Day 2, speakers addressed the challenges of a differential diagnosis of SCA in an engaging panel discussion. The panel consisted of Professor Eduard Vieta (Spain), Professor Mauro Mauri (Italy) and Professor Andrea Fagiolini (Italy), with presentations given by Professors Vieta and Mauri. Discussions between the panel and delegates revolved around whether SCA was a valid, reliable and specific diagnostic category and considered the usefulness of the diagnosis.

This session was followed by a presentation reviewing further elements of the treatment and management of SCA. Professor Vieta pointed to a previous lack of clinical trials of antipsychotics specifically assessing their efficacy in patients with SCA. He discussed recent trials with second-generation antipsychotics, including paliperidone extended release and their effectiveness in reducing symptoms in patients with SCA.^20–22

Professor Andrea Fagiolini reviewed the issues around, and reasons for, polypharmacy in the treatment of schizophrenia and the impact of pharmacokinetic or pharmacodynamic interactions. In particular, he reviewed the interaction of antipsychotics as well as other commonly prescribed drugs (metabolised by cytochrome P450 enzymes)²³ and how these can influence treatment effectiveness.

A keynote lecture was delivered by Dr Stephen Stahl (USA), which addressed the issue of switching antipsychotic medications, and discussed which variables should be considered when switching to ‘-pines’ (including olanzapine, clozapine and quetiapine) or ‘-dones’ (including risperidone, paliperidone and ziprasidone). He emphasised the importance of considering pharmacokinetic and pharmacodynamic profiles to ensure antipsychotic coverage was maintained during the switching process. Dr Stahl also shared with the delegates some common errors and specific case studies.

The meeting was brought to a close by Professor Eric Constant (Belgium), who presented a poignant and informative view of the life of composer Ravel, his work and psychological state of mind.

This 2-day medical education meeting was approved for Continuing Medical Education (CME) credits by the European Accreditation Committee in CNS and was funded by a grant from Janssen Pharmaceutica, NV.

ABOUT JANSSEN

Janssen Pharmaceutical Companies of Johnson & Johnson are dedicated to addressing and solving the most important unmet medical needs of our time, including oncology (e.g. multiple myeloma and prostate cancer), immunology (e.g. psoriasis), neuroscience (e.g. schizophrenia, dementia and pain), infectious disease (e.g. HIV/AIDS, hepatitis C and tuberculosis) and cardiovascular and metabolic diseases (e.g. diabetes). Driven by our commitment to patients, we develop sustainable, integrated healthcare solutions by working side-by-side with healthcare stakeholders, based on partnerships of trust and transparency. More information can be found at http://www.janssen-emea.com/.

ABOUT JANSSEN MEDICAL EDUCATION IN PSYCHIATRY

Through its website, the Psychiatry Medical Education Portal (www.PsyAcademy.com), Janssen strengthens its partnerships with healthcare professionals within the mental health community. The website, regularly updated with new content, contains a host of medical education materials and includes presentation slide decks from recent meetings, CME accredited webcasts and various educational tools that can be utilised by healthcare professionals in everyday clinical practice.

ABOUT SAN LUCAS MEDICAL

San Lucas Medical (www.sanlucasmedical.com) is a publisher of premier medical publications in Europe and Asia. Located in London, UK, San Lucas publishes magazines in the medical specialties of mind and brain, oncology, haematology, neurology, dermatology, cardiology and numerous other subjects. San Lucas representatives attended this meeting in Copenhagen to report on its presentations and outcomes. San Lucas Medical is also the primary funding agent for MDSNe, the European online social network for medical doctors. www.mdsne.com

Contact: Dayan Gunesekera, San Lucas Medical

E-mail: dayang@sanlucasmedical.com

Tel: 44-(0)7957 441160

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