Comorbidity of PTSD and Depression: Linked orSeparate Incidence

In this issue ofBiological Psychiatry,Breslau and col-leagues (2000) investigate the relationship between expo-sure to trauma, posttraumatic stress disorder (PTSD), andmajor depression disorder. The primary question focuseson whether exposure to trauma leads to major depression,independent of the development of PTSD.

The possibility that PTSD and depression are indepen-dent consequences of trauma exposure, with separatepathways leading to distinct psychiatric consequences, ishighly intriguing from a clinical treatment perspective,since in treated samples of trauma victims the co-occur-rence of PTSD, depression, anxiety, and, often, substance-related symptoms is the rule rather than the exception. Thecomplex clinical picture following trauma influences thenature of both psychoeducational and pharmacologic treat-ment strategies.

Since the appearance of PTSD in DSM-III in 1980,depression was found to be highly comorbid with thisdisorder. A large body of clinical and epidemiologicresearch has identified various links between extremestress, depression, and PTSD symptomatology. Specifi-cally, as shown in Figure 1, pre-exposure depression hasbeen found to be a risk factor for extreme stress (link 1;e.g., Breslau et al 1997; Bromet et al 1998), for PTSD(link 2; e.g., Breslau et al 1997; Bromet et al 1998), andfor postexposure depression (link 3; e.g., Bromet et al1982; Shalev et al 1998). In addition, depression wasfound to be a consequence of exposure (link 4; e.g.,Bromet et al 1982; Brown and Harris 1978; Kendler et al1999; Neria et al 2000). Finally, depression has also beenassociated with PTSD itself either concurrently (link 5;e.g., Shalev et al 1998) or following PTSD (link 6; Kessleret al 1995).

If there are different psychiatric outcomes emanatingfrom trauma exposure, an important question is whatpredicts them. Clinical studies have found that PTSD isassociated with changes in hypothalamic–pituitary–adre-nal (HPA) axis function (for a review, see Bremner et al1999) and that patients with PTSD differ from those withdepression with respect to cortisol response. It was alsoknown that stress exposure may have long-term effects onthe corticotropin-releasing factor/HPA axis (Bremner et al1999). This is consistent with epidemiologic studies thatshow that PTSD and depression are often chronic andenduring conditions.

In addressing the relationship of PTSD and depression

using epidemiologic methods, Breslau and colleaguesutilize a sophisticated statistical strategy, in analyzingresponses from two community-based large samples: ayoung adult cohort drawn from a health maintenanceorganization in southeast Michigan (N 5 1007) inter-viewed prospectively at four points in time, and a nation-ally representative sample included in the cross-sectionalNational Comorbidity Survey (N 5 5877).

The authors hypothesize that if trauma exposure in-creases the risk for major depression independently fromPTSD, the results will show that persons exposed totrauma without developing PTSD will have a higherincidence of major depression than persons who were notexposed to trauma. In addition, if persons with PTSD havea higher risk of depression than exposed people withoutPTSD, the authors hypothesize that the relationship be-tween PTSD and major depression is either causal or dueto a shared underlying vulnerability. Toward this end, theauthors examine whether differences in types of traumamight account for differences in the risk for major depres-sion, since high-impact events, like rape and combatexposure, confer a higher likelihood of PTSD than lessthreatening events (e.g., Kessler et al 1995).

The findings suggest several important links betweentrauma exposure, PTSD, and depression. First, they con-firm that pre-existing major depression is a risk factor forboth trauma exposure and PTSD. Second, the risk of(postexposure) major depression is higher in persons whodevelop PTSD than in people who do not. Third, theauthors conclude that the differences in rates of majordepression between exposed persons with and withoutPTSD could not be explained by the type of the exposure.

The findings extend previous work by showing that theincidence of PTSD significantly increases the risk forfirst-onset major depression. Thus, they do not support thehypothesis that postexposure depression has a pathwayseparate from that of PTSD. Moreover, as noted by theauthors, these findings suggest that the PTSD–depressionco-occurrence in trauma victims might be due to commonrisk factors or vulnerabilities. This conclusion is consistentwith previous reports that several risk factors for PTSD,such as female gender, family history of major depression,childhood trauma, and pre-existing anxiety and depres-sion, are also risk factors for major depression (Bremner etal 1993; Bromet et al 1998; Kessler et al 1995).

A central limitation in examining whether victims to

© 2000 Society of Biological Psychiatry 0006-3223/00/$20.00PII S0006-3223(00)01012-X

trauma are at risk for psychiatric disorders other thanPTSD is the current methodology applied in most of theinvestigations to date. Although the current DSM ac-knowledges that major depressive episodes can occur “inresponse to a psychosocial stress,” only PTSD and adjust-ment disorder require stress as a condition for receivingthe diagnosis. Structured interview schedules, such as theDiagnostic Interview Schedule administered by Breslau etal (2000) and the Composite International DiagnosticInterview administered by Kessler et al (1995), weredesigned to follow DSM criteria and specifically inquireabout PTSD symptoms in relation to traumatic exposures,but not about any other psychiatric symptoms. Thus, otherdisorders that are known to be outcomes of traumatic lifeevents, such as major depression, are assessed separately,without being linked to an etiologic event as an essentialpart of the diagnostic procedure. This procedural differ-ence will inevitably reduce the strength of the relation-ships found between extreme stress and these psychiatricdisorders relative to PTSD.

Moreover, in most studies only limited attention hasbeen given to the contributions of predisposing factors orenvironmental consequences, such as postexposure stress-ful events and changes in social support. In contrast to thedirect model of stress and its consequences found in muchof the trauma literature, a number of comprehensiveconceptual models of the stress-response process havebeen developed in parallel (e.g., Dohrenwend 1998; Kend-ler et al 1999). The findings from studies testing theadverse effects of stressful life events using these moreinclusive models underscore the importance of personalpredispositions, other concurrent situational factors andpersonal resources, social support, and coping abilities forunderstanding the impact of stressful experiences, includ-ing life threatening events.

Methodologically, the most powerful design to test thehypothesis of separate occurrence of PTSD and otherpsychiatric disorders is a prospective cohort study that

carefully and reliably assesses the exposure, the onset, andoffset of PTSD and other disorders (such as depression,anxiety, and substance abuse disorders), as well as longi-tudinal, including pre-exposure, measures of putative bi-ological markers. Thus, future studies should include largerepresentative samples, independent ratings of exposureseverity, ratings of mental health that are done indepen-dently of exposure, and reliable information on the timingof the onset and offset of disorders. Instruments havinggood congruence with clinical evaluation also need furtherdevelopment.

In conclusion, despite much progress, there still remainsthe need for a more comprehensive research agenda on thepsychiatric outcomes of trauma and extreme stress. Ap-plying recent comprehensive conceptual models will pro-mote a better understanding of the nature of the stress-response process that occurs in the wake of traumaticevents.

Yuval NeriaEvelyn J. Bromet

State University of New York—Stony BrookPutnam Hall—South CampusStony Brook NY 11794-8790

References

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Bromet EJ, Parkinson DK, Schulberg HC, Dunn LO, Gondek PC(1982): Mental health of residents near the Three Mile Islandreactor: A comparative study of selected groups.J PreventivePsychiatry1:225–276.

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Figure 1. Putative links between depression, trauma exposure,and posttraumatic stress disorder (PTSD).

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