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Comorbid mood and anxiety disorders in victims of violence with posttraumatic stress disorder

Abstracts

OBJECTIVE: To review studies that have evaluated the comorbidity between posttraumatic stress disorder and mood disorders, as well as between posttraumatic stress disorder and other anxiety disorders. METHOD: We searched Medline for studies, published in English through April, 2009, using the following keywords: "posttraumatic stress disorder", "PTSD", "mood disorder", "major depressive disorder", "major depression", "bipolar disorder", "dysthymia", "anxiety disorder", "generalized anxiety disorder", "agoraphobia", "obsessive-compulsive disorder", "panic disorder", "social phobia", and "comorbidity". RESULTS: Major depression is one of the most frequent comorbid conditions in posttraumatic stress disorder individuals, but individuals with posttraumatic stress disorder are also more likely to present with bipolar disorder, other anxiety disorders and suicidal behaviors. These comorbid conditions are associated with greater clinical severity, functional impairment, and impaired quality of life in already compromised individuals with posttraumatic stress disorder. Depression symptoms also mediate the association between posttraumatic stress disorder and severity of pain among patients with chronic pain. CONCLUSION: Available studies suggest that individuals with posttraumatic stress disorder are at increased risk of developing affective disorders compared with trauma-exposed individuals who do not develop posttraumatic stress disorder. Conversely, pre-existing affective disorders increase a person's vulnerability to the posttraumatic stress disorder--inducing effects of traumatic events. Also, common genetic vulnerabilities can help to explain these comorbidity patterns. However, because the studies addressing this issue are few in number, heterogeneous and based on a limited sample, more studies are needed in order to adequately evaluate these comorbidities, as well as their clinical and therapeutic implications.

Comorbidity; Stress disorders, post-traumatic; Anxiety disorders; Mood disorders; Violence


OBJETIVO: Buscar estudos que avaliem a comorbidade entre transtorno de estresse pós-traumático e transtornos do humor, bem como entre transtorno de estresse pós-traumático e outros transtornos de ansiedade. MÉTODO: Revisamos a base de dados do Medline em busca de estudos publicados em inglês até abril de 2009, com as seguintes palavras-chave: "transtorno de estresse pós-traumático", "TEPT", "transtorno de humor", "transtorno depressivo maior", "depressão maior", "transtorno bipolar", "distimia", "transtorno de ansiedade", "transtorno de ansiedade generalizada", agorafobia", "transtorno obsessivo-compulsivo", "transtorno de pânico", "fobia social" e "comorbidade". RESULTADOS: Depressão maior é uma das condições comórbidas mais frequentes em indivíduos com transtorno de estresse pós-traumático, mas eles também apresentam transtorno bipolar e outros transtornos ansiosos. Essas comorbidades impõem um prejuízo clínico adicional e comprometem a qualidade de vida desses indivíduos. Comportamento suicida em pacientes com transtorno de estresse pós-traumático, com ou sem depressão maior comórbida, é também uma questão relevante, e sintomas depressivos mediam a gravidade da dor em sujeitos com transtorno de estresse pós-traumático e dor crônica. CONCLUSÃO: Os estudos disponíveis sugerem que pacientes com transtorno de estresse pós-traumático têm um risco maior de desenvolver transtornos afetivos e, por outro lado, transtornos afetivos pré-existentes aumentam a propensão ao transtorno de estresse pós-traumático após eventos traumáticos. Além disso, vulnerabilidades genéticas em comum podem ajudar a explicar esse padrão de comorbidades. No entanto, diante dos poucos estudos encontrados, mais trabalhos são necessários para avaliar adequadamente essas comorbidades e suas implicações clínicas e terapêuticas.

Comorbidade; Transtorno de estresse pós-traumático; Transtornos de ansiedade; Transtornos do humor; Violência


ARTICLES

Comorbid mood and anxiety disorders in victims of violence with posttraumatic stress disorder

Lucas C. QuarantiniI,II,*; Liana R. NettoI,*; Monica Andrade-NascimentoI,III,*; Amanda Galvão-de AlmeidaI,IV; Aline S. SampaioV; Angela Miranda-ScippaI; Rodrigo A. BressanIV; Karestan C. KoenenII,VI

ITeaching Hospital, Psychiatry Service, Universidade Federal da Bahia (UFBA), Salvador (BA), Brazil

IIHarvard School of Public Health, Department of Society, Human Development, and Health, Boston (MA), USA

IIIHealth Department, Universidade Estadual de Feira de Santana (UEFS), Feira de Santana (BA), Brazil

IVDepartment of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brazil

VUniversidade de São Paulo (USP), São Paulo (SP), Brazil

VIHarvard School of Public Health, Department of Epidemiology, Boston, MA, USA

Correspondence

ABSTRACT

OBJECTIVE: To review studies that have evaluated the comorbidity between posttraumatic stress disorder and mood disorders, as well as between posttraumatic stress disorder and other anxiety disorders.

METHOD: We searched Medline for studies, published in English through April, 2009, using the following keywords: "posttraumatic stress disorder", "PTSD", "mood disorder", "major depressive disorder", "major depression", "bipolar disorder", "dysthymia", "anxiety disorder", "generalized anxiety disorder", "agoraphobia", "obsessive-compulsive disorder", "panic disorder", "social phobia", and "comorbidity".

RESULTS: Major depression is one of the most frequent comorbid conditions in posttraumatic stress disorder individuals, but individuals with posttraumatic stress disorder are also more likely to present with bipolar disorder, other anxiety disorders and suicidal behaviors. These comorbid conditions are associated with greater clinical severity, functional impairment, and impaired quality of life in already compromised individuals with posttraumatic stress disorder. Depression symptoms also mediate the association between posttraumatic stress disorder and severity of pain among patients with chronic pain.

CONCLUSION: Available studies suggest that individuals with posttraumatic stress disorder are at increased risk of developing affective disorders compared with trauma-exposed individuals who do not develop posttraumatic stress disorder. Conversely, pre-existing affective disorders increase a person's vulnerability to the posttraumatic stress disorder--inducing effects of traumatic events. Also, common genetic vulnerabilities can help to explain these comorbidity patterns. However, because the studies addressing this issue are few in number, heterogeneous and based on a limited sample, more studies are needed in order to adequately evaluate these comorbidities, as well as their clinical and therapeutic implications.

Descriptors: Comorbidity; Stress disorders, post-traumatic; Anxiety disorders; Mood disorders; Violence

Introduction

Victims of violence commonly develop posttraumatic stress disorder (PTSD), an often chronic condition, associated with severe morbidity and psychosocial impairment. The description of PTSD in DSM-III and in subsequent DSM editions (American Psychiatric Association 1980, 1987, 1994) defines a syndrome that develops in response to a specific class of stressors, which is catastrophic or traumatic events which are distinguished from normal stressful life events, such as loss of job or marital discord. On the other hand, any psychological stressors, either those that meet the requirements for the definition of PTSD and those that do not, might precipitate major depression. Additionally, unlike PTSD, a major depression can occur regardless of stressors, and does not require an etiologic event as an essentialfactor.1

Data from the National Comorbidity Survey in the United States of America2 have demonstrated that PTSD is associated with unemployment or educational impairment, and commonly cooccurs with other psychiatric disorders, pointing out that 88.3% of men and 79.0% of women with PTSD also meet criteria for at least one other psychiatric diagnosis. For example, comorbid major depressions have been reported in 30% to 50% of people diagnosed with PTSD.2-4 In addition, PTSD is not the only psychopathological consequence of violence. Dutra et al. have reported that childhood abuse and chronic interpersonal trauma have frequently been associated with a risk of developing a wide range of psychiatric disorders, including mood, dissociative, addictive, eating and personality disorders.5 According to Brady, PTSD is especially likely to overlap with mood disorders, other anxiety disorders, somatization, substance abuse and dissociative disorders, and she concluded that individuals with PTSD should always be screened for psychiatric comorbidity.6

A longitudinal study examining the developmental mental health histories of adults with PTSD has observed that almost all the adults diagnosed with PTSD were diagnosed previously with another mental disorder. Most of these PTSD individuals had received another mental-disorder diagnosis by the age of 15 and these rates of lifetime comorbidity were higher than those observed for many other common mental disorders.7 Besides common environmental risk factors, genetic influences on PTSD overlap with those on other psychiatric disorders.8 The limited data available suggest that the majority of genes that affect risk for PTSD are also associated with other psychiatric disorders.

It is common knowledge that overlapping psychiatric disorders may be associated with additional social and occupational disability. In fact, Olfson et al. have carried out a cross-sectional study to assess disability associated with several mental disorders in outpatients, and have shown that, compared with patients who had a single mental disorder, patients with co-occurring disorders reported significantly more disability in social and occupational functioning.9 It is still controversial whether PTSD has a single effect on disability and quality of life after adjusting for other common mental disorders. Nevertheless, Sareen et al., studying the impact of PTSD on comorbidity, disability, and suicidality in a large sample of the general population, concluded that PTSD was not only associated with significant comorbidity with mental and physical health conditions but was also related to higher disability and suicidality, even when the influence of comorbidities was controlled.10

This paper aims to conduct a review of studies which evaluated comorbidity between PTSD and mood disorders (major depressive disorder and bipolar disorder), as well as between PTSD and anxiety disorders.

Method

We conducted a bibliographic research study of articles investigating mood and anxiety disorder comorbidity in victims of violence with PTSD, published in English up to April 2009 (excluding specific phobias). Articles were searched on Medline databases, with the following keywords: "posttraumatic stress disorder," "PTSD," "mood disorder," "major depressive disorder," "major depression," "bipolar disorder," "dysthymia," "anxiety disorder," "generalized anxiety disorder," "agoraphobia," "obsessive-compulsive disorder," "panic disorder," "social phobia" and "comorbidity." Relevant studies in the references of the articles were also obtained.

Results

To examine the comorbidity between PTSD and depression and, PTSD and anxiety disorders in victims of violence, we summarized the literature (26 articles).

1. Comorbid PTSD with mood disorders

1) Major depressive disorder

Although some stressors might precipitate major depressive disorder (MDD), this affective disorder occurs in the absence of stressors and, unlike PTSD, does not demand an etiologic event as an essential factor.1 Depression is one of the most common comorbid conditions associated with PTSD, and is typically present in 30-50% of PTSD cases. Individuals with both PTSD and comorbid depression usually have worse outcomes following treatment than individuals without PTSD 2,11-17

Salcioglu et al. achieved a reasonably clear separation between PTSD and depression symptoms, except for the symptoms shared by both disorders (loss of interest, memory and concentration problems, irritability and sleep disturbance).18 The compositions of the two groups of symptoms were very similar to those observed in previous studies.19-21 The authors grouped together the symptoms of reexperiencing, cognitive and behavioral avoidance, and hypervigilance, whereas the numbing and depressive symptoms were loaded on a separate factor, together with emotional numbing, detachment, sense of a foreshortened future, sleep difficulties, irritability, and memory and concentration difficulties. These symptoms are very reminiscent of depression, and based on studies with other trauma populations,22-24 Salcioglu et al. suggested that numbing symptoms should not be classified with avoidance symptoms in DSM-V.18

Enduring grief-related reactions (Complicated Grief -CG) are a controversial and multidimensional disorder that has been conceptualized as a more involved combination of depression and PTSD,25,26 especially when bereavement follows a violent death, such as by homicide or terrorist attack. In the current edition of the Diagnostic and Statistical Manual of Mental Disorders (2000), grief-related reactions are diagnosed as depression, posttraumatic stress disorder, or another anxiety disorder.27

In sharp contrast to this view, there is a growing movement among some bereavement researchers and theorists to elevate CG to a separate and unique diagnostic entity,28,29 arguing that existing treatments for either depression or PTSD are not efficacious for cases of severe, lasting grief reactions,30 and that, in general, CG and PTSD symptoms exhibited opposite reactions to heart rate and autonomic reactivity response:31 PTSD heightened autonomic response to cues that served as reminders of the traumatic event, whereas intense grief reactions were associated with reduced autonomic reactivity to cues of the loss.32

Animal studies have shown that infants separated from their mother exhibit an initial spike in arousal followed by a similar prolonged pattern of cardiovascular inhibition.33,34 The same type of autonomic pattern appears to characterize human separation responses.35,36 Pairing this response with CG symptoms may suggest that the absence of cardiovascular responsivity could be a consequence of acute separation distress and preoccupation with the loss.32,37 Instead of being an opposite reaction, the lack of cardiovascular responsiveness could be understood as an effect of a chronic and cumulative autonomic stress.38

In an experiment with Norway rats, Richter observed that the first response to stress was an increased heart rate, followed by slowing of heart rate and death, due to intense vagal discharge, when the stress situation was sustained.39

There was no agreement in the reviewed literature as to the best explanation for the association between PTSD and MDD. Prospective studies have supported several alternative explanations: 1) preexisting MDD increases a person's propensity to the PTSD-inducing effects of traumatic events;40,41 2) PTSD increases the risk of the first onset of MDD;2,40 3) MDD increases the risk of exposure to traumatic events,40 as it does for exposure to ordinary stressful life events;42 4) PTSD and MDD share genetic or environmental vulnerabilities.

Regarding environmental shared vulnerabilities, traumatic events leading to PTSD might also amplify the risk for major depression.4 In addition to traumatic events, other factors have been associated with increased risk of both PTSD and MDD. For example, psychological aggression has been significantly related to depressive symptoms.14,43-45 PTSD is highly prevalent in women exposed to intimate partner violence (IPV). This condition is associated with dysfunction resulting in problems in self maintenance, and difficulty in leaving home. Astin et al. reported prevalence rates of PTSD among battered women of up to 58%.46 Johnson et al. have conducted a cross-sectional study with a sample of 177 battered women from a refuge to investigate the contribution of IPV severity and IPV-related PTSD severity on these women's psychiatric morbidity (i.e., comorbidity and psychiatric severity) and social damage. Their results were consistent with other studies, and IPV severity was related to several indices of impairment as well as to PTSD severity. However, when controlling for IPV severity, PTSD severity was significantly related to a higher degree of psychiatric morbidity and higher levels of social dysfunction. PTSD severity also significantly mediated the relationship between IPV severity and the severity of psychiatric disorders, as well as loss of resources.47

This finding is not surprising, given the probable effect of psychological aggression on an individual's sense of self, particularly on beliefs regarding self-esteem, competence, and worth. Intense threat or fear-provoking language may create intense and immobilizing shame, with a consequent schema that undermines the use of social networks and support to ameliorate psychological pain. Nixon et al. support the belief that cognitions and schemata may play an important role in understanding why depression that develops in the context of PTSD is more critical than a general negative cognitive style, since it is directly related to trauma.14 Dunmore et al. suggest that depression precedes dysfunctional schemata, as a cognitive vulnerability that is manifested through maladaptive interpretation,48 sometimes evidenced even before the onset of depression.49 This creates a sense of helplessness that accounts for the higher scores on depression and somatic symptom scales.

Figure 1


Individuals with comorbid PTSD and MDD seem to have more maladaptive depressogenic cognitive styles than individuals with PTSD alone.14 Trauma-related guilt, particularly observed in the context of rape victims,50,51 Vietnam veterans52 and victims of intimate partner violence,53 has been observed to be more strongly associated with depressive symptomatology than is PTSD, and excessive or inappropriate guilt is a symptom of depression.54 Andrews suggests that shame brings about abusive experiences, then guilt and later, depression.55

The findings of Vranceanu et al., in a sample of children suffering multiple forms of abuse and neglect, suggest again that MDD and PTSD may have two different developmental mechanisms, where stress plays a central role in the development of depression, as the lack of social support does in the development of PTSD.56 Nonetheless, there is a high correlation between stress and social support, which highlights the vulnerability that one disorder creates, allowing the development of the other. People with a history of childhood maltreatment are more susceptible to the effects of daily stressors,57 and these individuals report more stress when compared to their non-maltreated counterparts.58 Moreover, survivors of maltreatment may perceive life events as more stressful because of their predisposition to a pervasive sense of helplessness59 and to decreased coping resources.60,61 Usually they have smaller support networks, which they find unsatisfactory.58,62 One potential explanation for these effects is that maltreatment causes distortions in children's cognitions regarding themselves and others. These distortions become internalized, leading to unhealthy adult relationships.63 It is also likely that maltreated children have less actual support in adulthood because their potential family support is limited; their parents and siblings may have been the perpetrators, or may themselves have suffered maltreatment experiences,64 and thus may be ineffectual as support providers.65 In addition, often children who have been maltreated grew up in dysfunctional family environments, and may have poor scripts for healthy adult relationships.64

The role of social resources in psychological adjustment to trauma/stressful events/bereavement is further demonstrated by Holohan et al. via two longitudinal studies conducted on victims of natural disasters. They found that losses of interpersonal and personality resources were directly predictive of depressive symptoms over the course of an extended period of years.66,67 Basoglu, Salcioglu and Livanou showed that a behavioral intervention designed to enhance a sense of control over fear reduces both PTSD and depressive symptoms.68 However, depression resulting from resource loss might require social support and compensation forlosses before there is any improvement.

Livanou et al. amplify the connection between loss and depression, postulating that, while depression might be due to bereavement, it might be secondary to PTSD in other stressful events.20 The fact that 24% of non-bereaved individuals in the traumatized sample of Salcioglu et al. had depression supports this hypothesis.18 From this perspective, secondary depression might be related to helplessness generated by symptoms of chronic PTSD, exposure to numerous unpredictable and uncontrollable aftershocks, and anticipatory fear of a future traumatic experience,69 which creates the sense of losing management and control.

Imported data from natural-disaster studies can help to clarify the relationship between trauma and depression. Salcioglu et al., in their study of earthquake survivors in Turkey, showed through linear regression analyses that depression was especially related to loss (of family members), while PTSD was strongly related to fear during the earthquake.18

As we can see, social support and stress are inversely correlated. This would suggest that victims of maltreatment may not only suffer impairment in their ability to develop basic social support structures, but also may become more vulnerable to stressors and additional losses (e.g., material or personal losses).

Besides the environmental vulnerabilities shared by PTSD and MDD, data from the Vietnam Era Twin Registry suggests that MDD is the psychiatric disorder with the largest overlap with genetic influences associated with PTSD. Genetic influences on major depression account for 100% of the genetic variance in PTSD.70 The serotonin transporter promoter S/S polymorphism is implicated in both disorders.71 Polymorphisms in FKBP5, a glucocorticoid-regulating cochaperone of stress proteins, which were associated with recurrence of major depressive episodes and response to antidepressant treatment72 have also been associated with peritraumatic dissociation73 (a risk factor for PTSD) and depression in medically injured children.

2) PTSD, depression and chronic pain

Depression as a possible mediator for chronic pain in PTSD was the focus of the Poundja et al. study with male veterans.74 High co-occurrence rates of pain and PTSD have been found in samples of war veterans treated in PTSD clinics,75,76 with a striking 80% rate of chronic pain, and the Poundja et al. study suggests that 89.5% of the effect of PTSD on pain is mediated by depression.74

3) Suicidal behavior

Both PTSD and major depressive episodes are individually associated with a risk of suicidal behavior. Lifetime prevalence of suicide attempts in a sample with major depressive episodes is approximately 16%.77 In a community survey, patients with PTSD were 14.9 times more likely to attempt suicide than subjects without PTSD.3,78 There is no study evaluating the prevalence of suicidal behaviors in a sample with comorbid PTSD and MDD. PTSD Individuals with comorbid BD also present an additional risk, and must be carefully evaluated for suicide risk by mental health professionals.79,80

4) Bipolar disorder

Several studies have shown that bipolar disorder (BD) subjects are at high risk for experiencing traumatic events. This may be due to disruptive behavior during mania or to increased childhood trauma history.81-83 As a result, BD patients usually report high rates of lifetime PTSD ranging from 16% to 39% in BD-I patients evaluated in the National Comorbidity Survey-Replication 84,85

Moreover, if the traumatic event occurs during manic or hypomanic phases, there is a higher probability of PTSD symptoms developing afterwards.86 Recent studies suggested that a history of trauma may be related to BD's etiology and prognosis.84 For example, early parental loss has been identified as a risk factor for BD.87 High-impact trauma has been associated with poor BD prognosis.88

Little is known about the quality of life (QoL) impairment and clinical consequences imposed by PTSD on bipolar patients. It is hypothesized that characteristics of PTSD have a substantial impact on the course of BD due to its nature, which contributes to raising the emotional instability in BD patients' lives.84 At the baseline evaluation for a study, bipolar patients with comorbid PTSD were less likely to be found in recovery (relative euthymia).89 Also, BD patients with PTSD frequently have sleep impairment, with consequent chronic over-arousal. It has a direct impact on the course of BD,82 and is indicative of poorer coping with PTSD symptoms.90

Higher rates of comorbidity with anxiety disorders, specifically with PTSD,89,91 have been found to be an important factor associated with poorer QoL among BD patients.92 Overall, the magnitude of BD's impact on QoL seems to be similar to the impact of chronic diseases (e.g., chronic renal disease or rheumatoid arthritis).93 Despite the fact that lower QoL scores are likely to be found during the depressive phase in BD patients,94-97 some factors such as manic symptoms,98 being of the female gender,99 and affective conditions such as cyclothymia,100 can influence the self-perception of QoL. Additionally, even BD patients in remission show impaired selfreportiing of QoL,101-103 indicating that other factors besides mood symptoms may influence QoL in BD patients.97

2. Comorbid PTSD with other anxiety disorders

Following the same lines as for MDD comorbidity, the explanation for the comorbidity between PTSD and other anxiety disorders is still unclear. Traumatic events can be a shared environmental trigger for other anxiety disorders besides PTSD. Brady has reported that exposure to family violence is associated with symptoms of posttraumatic stress and anxiety among youth.104 Kar and Bastia have conducted a study aimed at finding the prevalence of post-traumatic psychiatric disorders such as PTSD, major depressive disorder, generalized anxiety disorder and possible comorbidities in a group of adolescent students in rural areas, 14 months after a natural disaster. They also studied the association of these morbidities with sociodemographic factors, and their impact on school performance. The study demonstrated that adolescents exposed to a natural disaster exhibited a mix of PTSD, depression and anxiety symptoms and high comorbidity of diagnoses. Nevertheless, Kar and Bastia did not succeed in proving any association between these morbidities and impairment of performance in school.105

Moreover, genetic influences common to generalized anxiety disorder and panic disorder symptoms account for approximately 60% of the genetic variance in PTSD.106

It is also possible that pre-existent anxiety disorders increase the risk for trauma exposure, and subsequently, PTSD. Silver et al. carried out a study to examine the association between victimization of people with and without a mental disorder. Compared with people with no mental disorder, people with anxiety disorders experienced more sexual assaults.107 These findings were controlled for psychiatric comorbidity, demographic characteristics, and for participants showing violent behavior.

On the other hand, Marshall et al. conducted a study with the National Screening Day for Anxiety Disorders sample to investigate the relationship between PTSD symptoms, level of disability, and comorbid anxiety or depressive disorders. They observed that functional impairment, number of anxiety disorders, rates of comorbid major depressive disorder, and current suicidal ideation increased linearly and significantly with a higher number of subthreshold PTSD symptoms.108

Discussion

There is a high comorbidity rate between PTSD and other anxiety or mood disorders.

An explanation for the link between PTSD and unipolar MDD/other anxiety disorders may be related to gender. Many studies have demonstrated that female gender is an important risk factor for the development of PTSD.109 Data from the National Comorbidity Survey2 have shown that lifetime prevalence of PTSD is more than double in women in comparison with men (10.4% vs. 5.0%; p < 0.05).

Complementarily, some arguments focus on differences in types of exposure. When the violence is performed by the intimate partner, it contributes significantly to the emergence of PTSD in the female population.110 Edwards et al. found that lower scores on the mental health domain of the SF-36 quality of life questionnaire were associated with more categories of abuse (sexual, physical and emotional abuse), which is exactly the type of traumatic experience most frequently found in women.111 Oquendo et al. found that among 156 inpatients with major depression, those with comorbid lifetime PTSD were more likely to have attempted suicide than those without comorbid PTSD (75% vs. 54%; p < 0.01), and among the group with PTSD, the risk of a suicide attempt was higher among women.112

Besides this, pre-existing MDD or another anxiety disorder was found to predict trauma exposure.113 The likelihood of developing PTSD after traumatic exposure also seems to be significantly higher in this population.114

Psychiatric disorders also have been understood as a vulnerability factor for developing another psychiatric disorder after exposure to violence. Several studies were conducted aimed at identifying risk factors for trauma vulnerability and developing psychiatric disorders. Breslau reviewed epidemiological studies of PTSD in the general population and identified pre-existing psychiatric disorders, family history of disorders and childhood abuse as risk factors for PTSD in adults.115 Gabriel et al. carried out a cross-sectional study to assess the prevalence of PTSD, major depression and other anxiety disorders after a terrorist attack, among three groups with different levels of exposure: people injured in the attacks, city residents not injured, and police officers involved in the rescue effort. The proportion of patients who had a current psychiatric disorder was: 5% among the injured and 9% among the non-injured individuals. Those who had a comorbid mental disorder were 8% among the injured group, and 22% among the non-injured group. The most frequent comorbid mental disorder with PTSD was depression, followed by agoraphobia. After multivariate analyses, the use of psychoactive medications before the attack was a significant predictor of PTSD and depression among the injured individuals; history of psychiatric disorder and female gender, among the non-injured ones.116 The Gabriel et al. study provides strong evidence of an association between previous psychiatric disorder (major depression and anxiety disorder), or previous use of psychoactive medications, and subsequent psychopathology.

Table 1

On the other hand, traumatic experiences and PTSD may have a higher impact on the development and course of other psychiatric disorders. A case report describes how a patient with no psychiatric history developed PTSD, depression and obsessive-compulsive disorder (OCD) after a serious work accident.117 Additionally, according to McFarlane & Bookless, patients with a lifetime history of PTSD have eight times the risk for anxiety disorders compared to those without such history.118 The question of whether traumatic events increase the risk for MDD, independently of their PTSD effects, would be clarified if a significantly higher incidence were found of major depression in individuals who were exposed to trauma but did not develop PTSD, as compared with people who were not exposed. Such evidence would suggest that the depressive consequence of traumatic events might have a distinct pathway, separate from that of PTSD.

On the other hand, evidence of an increased risk of the subsequent onset of MDD in exposed persons with PTSD, but not in exposed persons who did not develop PTSD, would suggest that PTSD might cause major depression or that the two disorders share a common underlying vulnerability.1

Are those two risk factors for PTSD (female gender and preexistent anxiety/depression disorder) related? Kessler et al. found, in the data from the National Comorbidity Survey, that while men showed a predominance of alcohol or substance abuse/dependence in comorbidity with PTSD, women presented a predominance of comorbid anxiety disorders.2

PTSD also shares genetic vulnerabilities with other anxiety disorders and MDD. A family history of psychiatric disorders is a consistent risk factor for developing PTSD.115 Pre-existing psychiatric disorders, particularly conduct disorders, major depression and nicotine dependence, also increase PTSD risk.119 At the same time, PTSD increases the risk of first-onset major depression1 as well as alcohol, drug, and nicotine dependence.115 The incidence of other psychiatric disorders is no higher in individuals who experience trauma but do not develop PTSD. This fact has led to the suggestion that PTSD represents a generalized vulnerability to psychopathology following trauma.115

Finally, in terms of screening, preventive approaches through the assessment of the personal history of trauma in high-risk populations is fundamental to the investigation of the impact of violence on children's neurodevelopment and the profound negative functional consequences of trauma in the child's brain. Since violence can permanently alter neurogenesis, migration synaptogenesis, and neurochemical differentiation, the course of development of the brain over time is the key to grasping the relationship between exposure to violence in infancy and the emergence of the symptoms. This fact has implications for psychopathological outcomes, clinical assessment, research, intervention and prevention. Therefore, more research is needed into designing new treatment interventions,120 not only focused on treating symptoms but also on restoring the child's mental health during puberty, when the brain still has a degree of plasticity.121

Conclusion

Available studies suggest that PTSD patients have a higher risk of developing affective disorders and, conversely, that pre-existing affective disorders increase a person's propensity to the PTSD-inducing effects of traumatic events. Considering the broad variety of disorders related to PTSD and its high rates of co-occurrence, one question arises about whether they constitute a single wide phenotype with the same etiology or whether there are different classes of disorders with different etiologies. However, there are only a few studies addressing this issue, and most of them have worked with small sample sizes and different methodologies, which may limit the generalizability of the results.

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References

  • 1. Breslau N, Davis GC, Peterson EL, Schultz LR. A second look at comorbidity in victims of trauma: the posttraumatic stress disorder-major depression connection. Biol Psychiatry 2000;48(9):902-9.
  • 2. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995;52(12):1048-60.
  • 3. Davidson JR, Hughes D, Blazer DG, George LK. Post-traumatic stress disorder in the community: an epidemiological study. Psychol Med 1991;21(3):713-21.
  • 4. McFarlane AC, Papay P. Multiple diagnoses in posttraumatic stress disorder in the victims of a natural disaster. J Nerv Ment Dis 1992;180(8):498-504.
  • 5. Dutra L, Callahan K, Forman E, Mendelsohn M, Herman J. Core schemas and suicidality in a chronically traumatized population. J Nerv Ment Dis 2008;196(1):71-4.
  • 6. Brady KT. Posttraumatic stress disorder and comorbidity: recognizing the many faces of PTSD. J Clin Psychiatry 1997;58(Suppl 9):12-5.
  • 7. Koenen KC, Moffitt TE, Caspi A, Gregory A, Harrington H, Poulton R. The developmental mental-disorder histories of adults with posttraumatic stress disorder: a prospective longitudinal birth cohort study. J Abnorm Psychol 2008;117(2):460-6.
  • 8. Koenen KC, Fu QJ, Lyons MJ, Toomey R, Goldberg J, Eisen SA, True W, Tsuang M. Juvenile conduct disorder as a risk factor for trauma exposure and posttraumatic stress disorder. J Trauma Stress. 2005;18(1):23-32.
  • 9. Olfson M, Fireman B, Weissman MM, Leon AC, Sheehan DV, Kathol RG, Hoven C, Farber L. Mental disorders and disability among patients in a primary care group practice. Am J Psychiatry 1997;154(12):1734-40.
  • 10. Sareen J, Cox BJ, Stein MB, Afifi TO, Fleet C, Asmundson GJ. Physical and mental comorbidity, disability, and suicidal behavior associated with posttraumatic stress disorder in a large community sample. Psychosomc Med 2007;69(3):242-8.
  • 11. Blanchard EB, Buckley TC, Hickling EJ, Taylor AE. Posttraumatic stress disorder and comorbid major depression: is the correlation an illusion? J Anxiety Disord 1998;12(1):21-37.
  • 12. Boudreaux E, Kilpatrick DG, Resnick HS, Best CL, Saunders BE. Criminal victimization, posttraumatic stress disorder, and comorbid psychopathology among a community sample of women. J Trauma Stress 1998;11(4):665-78.
  • 13. Cascardi M, O'Leary KD, Schlee KA. Co-occurrence and correlates of posttraumatic stress disorder and major depression in physically abused women. J Fam Violence 1999;14(3):227-49.
  • 14. Nixon RD, Resick PA, Nishith P. An exploration of comorbid depression among female victims of intimate partner violence with posttraumatic stress disorder. J Affect Disord. 2004;82(2):315-20.
  • 15. Stein MB, Kennedy C. Major depressive and post-traumatic stress disorder comorbidity in female victims of intimate partner violence. J Affect Disord. 2001;66(2-3):133-8.
  • 16. Shalev AY, Freedman S, Peri T, Brandes D, Sahar T, Orr SP, Pitman RK. Prospective study of post-traumatic stress disorder and depression following trauma. Am J Psychiatry. 1998;155(5):630-7.
  • 17. Breslau N, Kessler RC, Chilcoat HD, Schultz LR, Davis GC, Andreski P. Trauma and post-traumatic stress disorder in the community. Arch Gen Psychiatry 1998;55(7):626-32.
  • 18. Salcioglu E, Basoglu M, Livanou M. Post-traumatic stress disorder and comorbid depression among survivors of the 1999 earthquake in Turkey. Disasters. 2007;31(2):115-29.
  • 19. Basoglu M, Salcioglu E, Livanou M. Traumatic stress responses in earthquake survivors in Turkey. J Trauma Stress. 2002;15(4):269-76.
  • 20. Livanou M, Basoglu M, Salcioglu E, Kalendar D. Traumatic stress responses in treatment-seeking earthquake survivors in Turkey. J Nerv Ment Dis. 2002;190(12):816-23.
  • 21. Salcioglu E, Basoglu M, Livanou M. Long-term psychological outcome in non-treatment seeking earthquake survivors in Turkey. J Nerv Ment Dis. 2003;191(13):154-60.
  • 22. Buckley TC, Blanchard EB, Hickling EJ. A confirmatory factor analysis of posttraumatic stress symptoms. Behav Res Ther. 1998;36(11):1091-9.
  • 23. Foa EB, Riggs DS, Gershuny BS. Arousal, numbing and intrusion: Symptom structure of PTSD following assault. Am J Psychiatry. 1995;152(1):116-20.
  • 24. Taylor S, Kuch K, Koch WJ, Crockett DJ, Passey G. The structure of posttraumatic stress symptoms. J Abnorm Psychol. 1998;107(1):154-60.
  • 25. Kaltman S, Bonanno GA. Trauma and bereavement: examining the impact of sudden and violent deaths. J Anxiety Disord. 2003;17(2):131-47.
  • 26. Zisook S, Chentsova-Dutton Y, Shuchter SR. PTSD following bereavement. Ann Clin Psychiatry. 1998;10(4):157-63.
  • 27. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th ed., rev. Washington, DC: American Psychiatric Association; 2000.
  • 28. Jacobs S, Mazure C, Prigerson H. Diagnostic criteria for traumatic grief. Death Stud. 2000;24(3):185-99.
  • 29. Lichtenthal WG, Cruess DG, Prigerson HG. A case for establishing complicated grief as a distinct mental disorder in DSM-V. Clin Psychol Rev. 2004;24(6):637-62.
  • 30. Shear K, Frank E, Houck PR, Reynolds CF 3rd. Treatment of complicated grief: a randomized controlled trial. JAMA. 2005;293(21):2601-8.
  • 31. Bonanno GA, Neria Y, Mancini A, Coifman KG, Litz B, Insel B. Is there more to complicated grief than depression and posttraumatic stress disorder? A test of incremental validity. J Abnorm Psychol 2007;116(2)342-51.
  • 32. Bonanno GA, Keltner D, Holen A, Horowitz MJ. When avoiding unpleasant emotions might not be such a bad thing: verbal- autonomic response dissociation and midlife conjugal bereavement. J Pers Soc Psychol. 1995;69(5):975-89.
  • 33. Hofer MA. The effects of brief maternal separations on behavior and heart rate of two week old rat pups. Physiol Behav. 1973;10(3):423-7.
  • 34. Reite M, Snyder DS. Physiology of maternal separation in a bonnet macaque infant. Am J Primatol. 1982;2(1):115-20.
  • 35. Field T, Reite M. Children's response to separation from mother during the birth of another child. Child Dev. 1984;55(4):1308-16.
  • 36. Hollenbeck AR, Susman EJ, Nannis ED, Strope BE, Hersh SP, Levine AS, Pizzo PA. Children with serious illness: behavioral correlates of separation and isolation. Child Psychiatry Hum Dev. 1980;11(1): 3-11.
  • 37. Fowles DC. The three arousal model: implications of gray's two-factor learning theory for heart rate, electrodermal activity, and psychopathy. Psychophysiology. 1980;17(2):87-104.
  • 38. Levine P. Accumulated Stress Reserve Capacity and Disease [thesis]. Ann Arbor, Michigan: Dept of medical biophysics University, Microfilm 77-15-760. UC Berkeley; 1977.
  • 39. Richter CD. On the phenomenon of sudden death in animals and man. Psychosomc Med 1957;19(3):191-8.
  • 40. Breslau N, Davis GC, Peterson EL, Schultz L. Psychiatric sequelae of posttraumatic stress disorder in women. Arch Gen Psychiatry 1997;54(1):81-7.
  • 41. Bromet E, Sonnega A, Kessler RC. Risk factors for DSM-III-R posttraumatic stress disorder: findings from the National Comorbidity Survey. Am J Epidemiol 1998;147(4):353-61.
  • 42. Kendler KS, Kessler RC, Neale MC, Heath AC, Eaves LJ. The prediction of major depression in women: toward an integrated etiologic model. Am J Psychiatry 1993;150(8):1139-48.
  • 43. Arias I, Pape KT. Psychological abuse: implications for adjustment and commitment to leave violent partners. Violence Vict 1999;14(1): 55-67.
  • 44. Street AE, Arias I. Psychological abuse and posttraumatic stress disorder in battered women: examining the roles of shame and guilt. Violence Vict 2001;16(1):65-78.
  • 45. Varma D, Chandra PS, Thomas T, Carey MP. Intimate partner violence and sexual coercion among pregnant women in India: relationship with depression and post-traumatic stress disorder. J Affect Disord 2007;102(1-3):227-35.
  • 46. Astin MC, Ogland-Hand SM, Coleman EM, Foy DS. Posttraumatic stress disorder and childhood abuse in battered women: Comparisons with maritally distressed women. J Consult Clin Psychology 1995;63(2):308-12.
  • 47. Johnson DM, Zlotnick C, Perez S. The relative contribution of abuse severity and PTSD severity on the psychiatric and social morbidity of battered women in shelters. Behav Ther 2008;39(3):232-41.
  • 48. Dunmore E, Clark DM, Ehlers A. Cognitive factors involved in the onset and maintenance of posttraumatic stress disorder (PTSD) after physical or sexual assault. Behav Res Ther 1999;37(9):809-29.
  • 49. Alloy LB, Abramson LY, Whitehouse WG, Hogan ME, Tashman NA, Steinberg DL, Rose DT, Donovan P. Depressogenic cognitive styles: predictive validity, information processing and personality characteristics, and developmental origins. Behav Res Ther 1999;37(6):503-31.
  • 50. Bennice JA, Grubaugh AL, Resick PA. Guilt, depression and PTSD among female rape victims Poster presented at the 17th Annual Meeting of the International Society for Traumatic Stress Studies: New Orleans, USA; 2001.
  • 51. Nishith P, Nixon RD, Resick PA. Resolution of trauma-related guilt following treatment of PTSD in female rape victims: a result of cognitive processing therapy targeting comorbid depression? J Affect Disord 2005;86(2-3):259-65.
  • 52. Cascardi M, O'Leary KD. Depressive symptomatology, self-esteem, and self-blame in battered women. J Fam Violence 1992;7(4): 249-59.
  • 53. Kubany ES, Abueg FR, Owens JA, Brennan JM, Kaplan AS, Watson SB. Initial examination of a multidimensional model of trauma-related guilt: applications to combat veterans and battered women. J Psychopathol Behav Assess 1995;17(4):353-76.
  • 54. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th ed. Washington, DC: American Psychiatric Association;1994.
  • 55. Andrews B. Bodily shame as a mediator between abusive experiences and depression. J Abnorm Psychology 1995;104(2):277-85.
  • 56. Vranceanu AM, Hobfoll SE, Johnson RJ. Child multi-type maltreatment and associated depression and PTSD symptoms: the role of social support and stress. Child Abuse Negl 2007;31(1): 71-84.
  • 57. Thakkar RR, McCanne TR. The effects of daily stressors on physical health in women with and without a childhood history of sexual abuse. Child Abuse Negl. 2000;24(2):209-21.
  • 58. Harmer AL, Sanderson J, Mertin P. Influence of negative childhood experiences on psychological functioning, social support, and parenting for mothers recovering from addiction. Child Abuse Negl. 1999;23(5):421-33.
  • 59. Seligman ME. Helplessness: on depression, development, and death In: Freeman WH, editor. Oxford; England; 1975.
  • 60. Cole PM, Putnam FW. Effect of incest on self and social functioning: a developmental psychopathology perspective. J Consult Clin Psychol 1992;60(2):174-84.
  • 61. Davis JL, Petretic-Jackson PA, Ting L. Intimacy dysfunction and trauma symptomatology: Long-term correlates of different types of child abuse. J Trauma Stress 2001;14(1):63-79.
  • 62. Gibson RL, Harthorne TS. Childhood sexual and adult loneliness and network orientation. Child Abuse Negl 1996;20(11):1087-93.
  • 63. Briere J, Berliner L, Bulkey JA, Jenny C, Reid T, editors. The APSAC handbook on child maltreatment 2nd ed. Newbury Park, CA: Sage Publication; 1996.
  • 64. Browne A, Finkelhore D. The impact of child sexual abuse: a review of the research. Psychol Bull 1986;99(1):66-77.
  • 65. Elliott AN, Carnes CN. Reactions of nonoffending parents to the sexual abuse of their child: a review of the literature. Child Maltreat 2001;6(4):314-31.
  • 66. Holahan CJ, Moos RH, Holahan CK, Cronkite RC. Resource loss, resource gain, and depressive symptoms: a 10-year model. J Pers Soc Psychol 1999;77(3):620-9.
  • 67. Holahan CJ, Moos RH, Holahan CK, Cronkite RC. Long-term posttreatment functioning among patients with unipolar depression: An integrative model. J Consult Clin Psychol 2000;68(2):226-32.
  • 68. Basoglu M, Salcioglu E, Livanou M. A randomized controlled study of single-session behavioural treatment of earthquake-related post-traumatic stress disorder using an earthquake simulator. Psychol Med. 2007;37(2):203-13.
  • 69. Basoglu M, Kilic C, Salcioglu E, Livanou M. Prevalence of posttraumatic stress disorder in earthquake survivors in Turkey: An epidemiological study. J Trauma Stress. 2004;17(2):133-41.
  • 70. Fu Q, Heath AC, Bucholz KK, Nelson EC, Glowinski AL, Goldberg J, Lyons MJ, Tsuang MT, Jacob T, True MR, Eisen SA. A twin study of genetic and environmental influences on suicidality in men. Psychol Med 2002; 32(1):11-24.
  • 71. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003;301(5631):386-9.
  • 72. Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Pütz B, Papiol S, Seaman S, Lucae S, Kohli MA, Nickel T, Künzel HE, Fuchs B, Majer M, Pfennig A, Kern N, Brunner J, Modell S, Baghai T, Deiml T, Zill P, Bondy B, Rupprecht R, Messer T, Köhnlein O, Dabitz H, Brückl T, Müller N, Pfister H, Lieb R, Mueller JC, Lõhmussaar E, Strom TM, Bettecken T, Meitinger T, Uhr M, Rein T, Holsboer F, Muller-Myhsok B. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet 2004;36(12):1319-25.
  • 73. Koenen KC, Saxe G,Purcell S, Smoller JW, Bartholomew D, Miller A, Hall E, Kaplow J, Bosquet M, Moulton S, Baldwin C. Polymorphisms in FKBP5 are associated with peritraumatic dissociation in medically injured children. Mol Psychiatry 2005;10(12):1058-9.
  • 74. Poundja J, Fikretoglu D, Brunet A. The Co-occurrence of posttraumatic stress disorder symptoms and pain: is depression a mediator? J Traum Stress 2006;19(5):747-51.
  • 75. Asmundson GJ, Coons MJ, Taylor S, Katz J. PTSD and the experience of pain: research and clinical implications of shared vulnerability and mutual maintenance models. Can J Psychiatry 2002;47(10):930-7.
  • 76. Beckham JC, Crawford AL, Feldman ME, Kirby AC, Hertzberg MA, Davidson JR, Moore SD. Chronic posttraumatic stress disorder and chronic pain in Vietnam combat veterans. J Psychosom Res 1997;43(4):379-89.
  • 77. Chen YW, Dilsaver SC. Lifetime rates of suicide attempts among subjects with bipolar and unipolar disorders relative to subjects with other Axis I disorders. Biol Psychiatry 1996;39(10):896-9.
  • 78. Oquendo M, Brent DA, Birmaher B, Greenhill L, Kolko D, Stanley B, Zelazny J, Burke AK, Firinciogullari S, Ellis SP, Mann JJ. Posttraumatic stress disorder comorbid with major depression: factors mediating the association with suicidal behavior. Am J Psychiatry. 2005;162(3):560-6.
  • 79. Simon NM, Pollack MH, Ostacher MJ, Zalta AK, Chow CW, Fischmann D, Demopulos CM, Nierenberg AA, Otto MW. Understanding the link between anxiety symptoms and suicidal ideation and behaviors in outpatients with bipolar disorder. J Affect Disord 2007;97(1-3): 91-9.
  • 80. Carballo JJ, Harkavy-Friedman J, Burke AK, Sher L, Baca-Garcia E, Sullivan GM, Grunebaum MF, Parsey RV, Mann JJ, Oquendo MA. Family history of suicidal behavior and early traumatic experiences: Additive effect on suicidality and course of bipolar illness? J Affect Disord 2008;109(1-2):57-63.
  • 81. Brown GR, McBride L, Bauer MS, Williford WO, Cooperative Studies Program 430 Study Team. Impact of childhood abuse on the course of bipolar disorder: a replication study in U.S. veterans. J Affect Disord 2005;89(1-3):57-67.
  • 82. Goldberg JF, Garno JL. Development of posttraumatic stress disorder in adult bipolar patients with histories of severe childhood abuse. J Psychiatr Res 2005;39(6):595-601.
  • 83. Romero S, Birmaher B, Axelson D, Goldstein T, Goldstein BI, Gill MK, Iosif AM, Strober MA, Hunt J, Esposito-Smythers C, Ryan ND, Leonard H, Keller M. Prevalence and correlates of physical and sexual abuse in children and adolescents with bipolar disorder. J Affect Disord 2009;112(1-3):144-50.
  • 84. Otto MW, Perlman CA, Wernicke R, Reese HE, Bauer MS, Pollack MH. Posttraumatic stress disorder in patients with bipolar disorder: a review of prevalence, correlates, and treatment strategies. Bipolar Disord 2004;6(6):470-9.
  • 85. Merikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RM, Petukhova M, Kessler RC. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry 2007;64(5):543-52.
  • 86. Kennedy BL, Dhaliwal N, Pedley L, Sahner C, Greenberg R, Manshadi MS. Post-traumatic stress disorder in subjects with schizophrenia and bipolar disorder. J Ky Med Assoc. 2002;100(9):395-9.
  • 87. Mortensen PB, Pedersen CB, Melbye M, Mors O, Ewald H. Individual and familial risk factors for bipolar affective disorders in Denmark. Arch Gen Psychiatry 2003;60(12):1209-15.
  • 88. Neria Y, Bromet EJ, Sievers S, Lavelle J, Fochtmann LJ. Trauma exposure and posttraumatic stress disorder in psychosis: findings from a first-admission cohort. J Consult Clin Psychol 2002;70(1): 246-51.
  • 89. Simon NM, Otto MW, Wisniewski SR, Fossey M, Sagduyu K, Frank E, Sachs GS, Nierenberg AA, Thase ME, Pollack MH. Anxiety disorder comorbidity in bipolar disorder patients: data from the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry 2004;161(12): 2222-9.
  • 90. Rothbaum BO, Mellman TA. Dreams and exposure therapy in PTSD. J Trauma Stress 2001;14(3):481-90.
  • 91. Kauer-Sant'Anna M, Frey BN, Andreazza AC, Ceresér KM, Gazalle FK, Tramontina J, da Costa SC, Santin A, Kapczinski F. Anxiety comorbidity and quality of life in bipolar disorder patients. Can J Psychiatry 2007;52(3):175-81.
  • 92. Neria Y, Olfson M, Gameroff MJ, Wickramaratne P, Pilowsky D, Verdeli H, Gross R, Manetti-Cusa J, Marshall RD, Lantigua R, Shea S, Weissman MM. Trauma exposure and posttraumatic stress disorder among primary care patients with bipolar spectrum disorder. Bipolar Disord 2008;10(4):503-10.
  • 93. Gutiérrez-Rojas L, Gurpegui M, Ayuso-Mateos JL, Gutiérrez-Ariza JA, Ruiz-Veguilla M, Jurado D. Quality of life in bipolar disorder patients: a comparison with a general population sample. Bipolar Disord 2008;10(5):625-34.
  • 94. Vojta C, Kinosian B, Glick H, Altshuler L, Bauer MS. Self-reported quality of life across mood states in bipolar disorder. Compr Psychiatry 2001;42(3):190-5.
  • 95. Yatham LN, Lecrubier Y, Fieve RR, Davis KH, Harris SD, Krishnan AA. Quality of life in patients with bipolar I depression: data from 920 patients. Bipolar Disord 2004;6(5):379-85.
  • 96. Gazalle FK, Andreazza AC, Hallal PC, Kauer-Sant'anna M, Ceresér KM, Soares JC, Santin A, Kapczinski F. Bipolar depression: the importance of being in remission. Rev Bras Psiquiatr 2006;28(2):93-6.
  • 97. Dias VV, Brissos S, Frey BN, Kapczinski F. Insight, quality of life and cognitive functioning in euthymic patients with bipolar disorder. J Affect Disord 2008;110(1-2):75-83.
  • 98. Gazalle FK, Hallal PC, Andreazza AC, Frey BN, Kauer-Sant'Anna M, Weyne F, da Costa SC, Santin A, Kapczinski F. Manic symptoms and quality of life in bipolar disorder. Psychiatry Res 2007;153(1):33-8.
  • 99. Robb JC, Young LT, Cooke RG, Joffe RT. Gender differences in patients with bipolar disorder influence outcome in the medical outcomes survey (SF-20) subscale scores. J Affect Disord 1998;49(3):189-93.
  • 100. Vázquez GH, Kahn C, Schiavo CE, Goldchluk A, Herbst L, Piccione M, Saidman N, Ruggeri H, Silva A, Leal J, Bonetto GG, Zaratiegui R, Padilla E, Vilapriño JJ, Calvó M, Guerrero G, Strejilevich SA, Cetkovich-Bakmas MG, Akiskal KK, Akiskal HS. Bipolar disorders and affective temperaments: a national family study testing the "endophenotype" and "subaffective" theses using the TEMPS-A Buenos Aires. J Affect Disord. 2008;108(1-2):25-32.
  • 101. Michalak EE, Yatham LN, Wan DD, Lam RW. Perceived quality of life in patients with bipolar disorder. Does group psychoeducation have an impact? Can J Psychiatry 2005;50(2):95-100.
  • 102. Sierra P, Livianos L, Rojo L. Quality of life for patients with bipolar disorder: relationship with clinical and demographic variables. Bipolar Disord 2005;7(2):159-65.
  • 103. Gazalle FK, Frey BN, Hallal PC, Andreazza AC, Cunha AB, Santin A, Kapczinski F. Mismatch between self-reported quality of life and functional assessment in acute mania: a matter of unawareness of illness? J Affect Disord 2007;103(1-3):247-52.
  • 104. Brady SS. Lifetime family violence exposure is associated with current symptoms of eating disorders among both young men and women. J Trauma Stress 2008;21(3):347-51.
  • 105. Kar N, Bastia BK. Post-traumatic stress disorder, depression and generalised anxiety disorder in adolescents after a natural disaster: a study of comorbidity. Clin Pract Epidemiol Ment Health 2006;2:17.
  • 106. Chantarujikapong SI, Scherrer JF, Xian H, Eisen SA, Lyons MJ, Goldberg J, Tsuang M, True WR. A twin study of generalized anxiety disorder symptoms, panic disorder symptoms and post-traumatic stress disorder in men. Psychiatry Res 2001;103(2-3):133-45.
  • 107. Silver E, Arseneault L, Langley J, Caspi A, Moffitt TE. Mental disorder and violent victimization in a total birth cohort. Am J Public Health 2005;95(11):2015-21.
  • 108. Marshall RD, Olfson M, Hellman F, Blanco C, Guardino M, Struening EL. Comorbidity, impairment, and suicidality in subthreshold PTSD. Am J Psychiatry. 2001;158(9):1467-73.
  • 109. Stein MB. A 46-year-old man with anxiety and nightmares after a motor vehicle collision. JAMA 2002;288(12):1513-22.
  • 110. Nemeroff CB, Bremner JD, Foa EB, Mayberg HS, North CS, Stein MB. Posttraumatic stress disorder: a state-of-the-science review. J Psychiatr Res 2006;40(1):1-21.
  • 111. Edwards VJ, Holden GW, Felitti VJ, Anda RF. Relationship between multiple forms of childhood maltreatment and adult mental health in community respondents: results from the adverse childhood experiences study. Am J Psychiatry. 2003;160(8):1453-60.
  • 112. Oquendo MA, Friend JM, Halberstam B, Brodsky BS, Burke AK, Grunebaum MF, Malone KM, Mann JJ. Association of comorbid posttraumatic stress disorder and major depression with greater risk for suicidal behavior. Am J Psychiatry 2003;160(3):580-2.
  • 113. Perkonigg A, Kessler RC, Storz S, Wittchen HU. Traumatic events and post-traumatic stress disorder in the community: prevalence, risk factors and comorbidity. Acta Psychiatr Scand 2000;101(1):46-59.
  • 114. Floen SK, Elklit A. Psychiatric diagnoses, trauma, and suicidiality. Ann Genl Psychiatry 2007;6:12.
  • 115. Breslau N. Epidemiologic studies of trauma, posttraumatic stress disorder, and other psychiatric disorders. Can J Psychiatry. 2002;47(10):923-9.
  • 116. Gabriel R, Ferrando L, Cortón ES, Mingote C, García-Camba E, Liria AF, Galea S. Psychopathological consequences after a terrorist attack: an epidemiological study among victims, the general population, and police officers. Eur Psychiatry 2007;22(6):339-46.
  • 117. Moraes EC Jr, Torresan RC, Trench EV, Torres AR. A possible case of posttraumatic obsessive-compulsive disorder. Rev Bras Psiquiatr 2008;30(3):291.
  • 118. McFarlane AC, Bookless C, Air T. Posttraumatic stress disorder in a general psychiatric inpatient population. J Trauma Stress 2001;14(4):633-45.
  • 119. Koenen KC, Hitsman B, Lyons MJ, Niaura R, McCaffery J, Goldberg J, Eisen SA, True W, Tsuang M. A twin registry study of the relationship between posttraumatic stress disorder and nicotine dependence in men. Arch Gen Psychiatry 2005;62(11):1258-65.
  • 120. Mello MF, Costa MC, Schoedl AF, Fiks JP. Aripiprazole in the treatment of posttraumatic stress disorder: an open-label trial. Rev Bras Psiquiatr 2008;30(4):358-61.
  • 121. Mari JJ, de Mello MF, Figueira I. The impact of urban violence on mental health. Rev Bras Psiquiatr 2008;30(3):183-4.
  • Correspondência:
    Lucas Quarantini Hospital das Clínicas
    Serviço de Psiquiatria
    Rua Augusto Viana, SN
    40110-909 Salvador, BA, Brasil
    E-mail:
  • *
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  • Publication Dates

    • Publication in this collection
      24 Nov 2009
    • Date of issue
      Oct 2009
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