Personality disorders and perceived stress in major depressive disorder
Introduction
Over the years, increasing attention has been devoted to investigating the comorbidity between major depressive disorder (MDD) and personality disorders (PDs). In general, the presence of PDs is assumed to have adverse effects on the course and treatment of MDD (for a recent review, see Newton-Howes et al., 2006). Consistent with this hypothesis, co-occurrence of MDD and PD has been associated with poorer response to treatment in most (Peselow et al., 1992, Sato et al., 1993) but not all (Fava et al., 1994, Fava et al., 1997) studies, and with higher risk of depressive recurrence (Ilardi et al., 1997, Hart et al., 2001). Moreover, compared with MDD subjects without PD, those with comorbid PD reported significantly greater impairments in social and emotional functioning and lower well-being (Skodol et al., 2005); higher levels of residual symptoms (Shea et al., 1990); slower recovery (Patience et al., 1995); higher levels of psychotropic utilization at a 1-year follow-up (Casey et al., 2004); and more frequent referral to psychiatric services (Moran et al., 2001).
On the other hand, others have failed to find a link between comorbid PD and poor treatment response (Fava et al., 1994, Fava et al., 1997, Fava et al., 2002, Russell et al., 2003, Mulder et al., 2003). Echoing these negative findings, a recent meta-analysis including findings from six randomized controlled trials with strict methodological criteria found that MDD subjects with comorbid PD had only a 3% lower remission rate compared to MDD subjects without PD, a difference that was not statistically significant (Kool et al., 2005). Taken together, these findings raise the possibility that comorbid personality pathology is not necessarily associated with poor treatment response, and that other intervening variables might be involved.
One possibility is that the three PD clusters based on the Diagnostic and Statistical Manual (DSM; American Psychiatric Association, 1987, American Psychiatric Association, 2000), Cluster A (paranoid, schizoid, schizotypal), Cluster B (borderline, histrionic, narcissistic, antisocial), and Cluster C (avoidant, dependent, obsessive–compulsive) may be differentially related to the course and outcome of depression. Sato et al. (1994), for example, found that only the presence of a Cluster A PD had a significant negative effect on short-term outcome in depression, while Fava et al. (1994) showed that the presence of Cluster B (but not Cluster A or C) PD in MDD was associated with a more favorable outcome following treatment with fluoxetine. Similarly, in a cohort of depressed patients undergoing a 6-month treatment, the presence of symptoms of avoidant, schizotypal, and schizoid, but no other, PD was associated with poorer outcome (Mulder et al., 2006).
A second, not mutually exclusive, possibility is that the presence of comorbid PD among MDD subjects is associated with higher occurrence of factors that increase the risk of depression, such as life stressors and poor social support (Pfohl et al., 1984). Consistent with this hypothesis, in a community sample, symptoms of Cluster A and B, but not Cluster C, disorders predicted interpersonal chronic stress and self-generated episodic stress over 2 years, which in turn increased the vulnerability for depressive symptoms (Daley et al., 1998). Thus, in the study of Daley et al., life stress mediated the relationship between personality pathology and later depression, even when controlling for initial depressive severity.
Findings of a possible mediating role of stress on the relationships between PD and depression are intriguing, particularly since stress has been implicated in the etiology and maintenance of depression (Kendler et al., 1999, Brown and Harris, 1989, Hammen, 2005), and has been associated with poorer treatment outcome and more frequent relapse (Tennant, 2002). Of note, research has suggested that risk for depression increases when individuals perceive stress as uncontrollable, unpredictable, and severe, and deem coping resources as insufficient (Cohen and Williamson, 1988, Hammen, 2005, Lazarus and Folkman, 1984). In addition, compared to pre-treatment levels, perceived stress markedly diminishes following antidepressant treatment, and the degree of stress reduction tends to be highly related to the degree of depressive symptom reduction (Fava et al., 1992).
In the present study, we evaluated 384 MDD outpatients enrolled in an 8-week open-label treatment with fluoxetine for the presence of Cluster A, B, or C PD, as defined by the DSM-III-R (American Psychiatric Association, 1987). To investigate whether PD was associated with elevated stress perception, a subgroup of these participants (n = 227) filled out before and after treatment the Perceived Stress Scale (PSS; Cohen et al., 1983), which assessed the degree to which participants appraised their daily life as unpredictable, uncontrollable, and overwhelming. Specifically, our goal was to test whether the presence of a given DSM-III-R-based PD cluster predicted levels of stress after 8-week antidepressant treatment with fluoxetine. We hypothesized that the presence of Cluster A or Cluster B PD comorbidity would predict elevated levels of perceived stress in MDD outpatients.
Section snippets
Participants
Data from the current study were derived from a larger study conducted at the Depression Clinical and Research Program (DCRP) at Massachusetts General Hospital (Fava et al., 2002, Farabaugh et al., 2002). The main goal of the parent study, which included 384 outpatients between the ages of 18 and 65, was to evaluate the efficacy of fluoxetine in the treatment of MDD. In order to be enrolled in an 8-week open treatment of fluoxetine 20 mg/day, subjects were required to meet criteria for MDD, as
Results
Three hundred eighty-four subjects were enrolled in the 8-week open treatment of fluoxetine 20 mg/day (Fava et al., 2002). In this sample, 54.7% of the subjects were female (n = 210), 33.6% were married (n = 129), 56.5% completed at least a college degree (n = 217), and 62.5% were currently employed (n = 240). The mean age of this sample was 39.8 (S.D.: 10.5), and the mean baseline HAMD-17 score was 19.7 (S.D.: 3.5). The mean age of onset of the first MDD and the mean duration of the current MDD
Discussion
Stress and major life events have been implicated in the etiology and maintenance of depression (Kendler et al., 1999, Brown and Harris, 1989, Hammen, 2005). Consistent with this hypothesis, prior studies have found that higher daily life stressors and perceived stress were associated with poorer outcome in major depressive disorder (Tennant, 2002). The main goal of this study was to investigate whether the presence of a stable PD comorbidity, specifically a DSM-III-R-based Cluster A, B or C
Acknowledgments
This work was supported by NIMH grant R01-MH-48-483-05. Dr. Fava has received research support from Abbott Laboratories, Lichtwer Pharma GmbH, Lorex Pharmaceuticals; as well as honoraria from EPIX Pharmaceuticals, Bayer AG, Compellis, Janssen Pharmaceutica, Knoll Pharmaceutical Company, Lundbeck, Dov Pharmaceuticals, Biovail Pharmaceuticals, Inc., BrainCells, Inc., Cypress Pharmaceuticals, Fabre-Kramer Pharmaceuticals, Inc., Grunenthal GmBH, MedAvante, Inc., Sepracor, and Somerset
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