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 Our knowledge of the mechanisms involved in the persistence of depression symptoms is incomplete. Both clinical and psychosocial factors may be of importance. Clinical variables consistently associated with poorer outcome in major depression include severity of illness (1–3), presence of anxiety symptoms or disorders (4–6), longer duration of illness or comorbid dysthymia (7–9), prior episodes of depression (1,10,11), and older age (1,3,12). In their review of psychosocial determinants of chronic depression (13), Riso and colleagues concluded that developmental factors, chronic stressors, and personality factors, particularly neuroticism, had the greatest empirical support. In a review of the psychological literature, Lara and Klein identified 3 major theoretical perspectives on the persistence of depression (14). These included responses to depression symptoms (or coping style), interpersonal behaviours and events, and childhood adversity. The following paragraphs briefly review the psychosocial factors that have been empirically and theoretically implicated in the persistence of depression. Responses to Depression SymptomsHow a person responds to depression symptoms has been hypothesized to play a role in either amplifying and perpetuating or alleviating depression. Rumination (that is, emotion-focused thinking that focuses attention on depressive symptoms) may result in depression persistence by increasing awareness of depressed mood and interfering with adaptive behaviours or problem solving (15–17). Rumination is conceptually related to coping style (14,18). Emotion-focused coping would be expected to perpetuate depression symptoms, whereas task-focused coping or social distraction might be expected to help alleviate depression (15,19). Preliminary evidence for the role of rumination in the maintenance of depression has been presented (20–23), but to date, evidence supporting the role of coping style in samples of patients with clinical depression has not been reported. Life EventsInterpersonal factors have been theoretically and empirically linked to the perpetuation of depression symptoms. Lewinsohn (24) and Coyne (25) have emphasized the role of negative interpersonal events that occur partly as a consequence of depression patients’ interpersonal behaviour. Preliminary evidence in support of this model has been reported (14). The well-demonstrated efficacy of interpersonal therapy in major depression provides indirect evidence of the importance of interpersonal factors in the maintenance of depression (26,27). Achievement-related life events (such as work or financial failures) might also be expected to contribute to the persistence of depression, whether or not such events occur as a consequence of patients’ depressive illness. However, achievement life events have not been specifically investigated in relation to the persistence of depression symptoms. Developmental FactorsNumerous studies have reported an association between such childhood adversities as abuse or negative parental bonding experiences (especially lack of care) and adult mental disorders, including depression (28,29). Empirical studies have also demonstrated that poor early relationships with one’s parents and traumatic childhood experiences including sexual abuse are associated with a greater likelihood of a chronic course of depression (30–34), although the mechanism of this association is not clear. Childhood adversities may represent an antecedent to personality dimensions, cognitive styles, or neurobiological changes that are associated with enduring vulnerability to depression symptoms. However, since almost all studies have relied on retrospectively recalled childhood experiences, it is also possible that recall biases account for the observed association. PersonalitySeveral different personality factors, including both personality dimensions and personality disorders, have been studied as putative predictors of persisting depression symptoms. Although different personality factors have been found to predict persisting depression, neuroticism has received the greatest empirical support (2,7,35,36). Neuroticism is a broad, higher-order personality factor that refers to proneness to negative affects, emotional instability, and vulnerability to stress (37,38). Accordingly, neuroticism might be expected to predict persisting depression, either as a main effect or via an interaction with stressful life events. However, the interaction between neuroticism and stressful life events in the maintenance of depression has not yet been investigated. The existing literature on the persistence of major depression has several limitations. First, few studies have evaluated whether responses to depression symptoms (rumination or coping style) are predictive of depression persistence in samples of patients with clinical depression. Second, relatively few studies have demonstrated that psychosocial factors have predictive validity beyond the effect of known clinical predictors of outcome. Third, although diathesis–stress models have frequently been used in studies of the onset of depressive episodes, studies to date have rarely considered possible interactions between psychological vulnerabilities (personality or responses to depression) and life events in predicting depression persistence. Accordingly, we conducted the present study to evaluate a range of psychosocial factors as potential predictors of persistent major depression symptoms in a mood disorders clinic. Specific hypotheses were as follows: 1. Clinical variables, including depression severity at Time 1, anxiety severity, recurrent depression, depressive episode duration, and older age, would be associated with nonremission and nonimprovement at Time 2. 2. Psychosocial factors, including neuroticism, rumination, emotion-focused coping, interpersonal and achievement life events, sexual abuse history, and parental lack of care and overprotection, would be associated with nonremission and nonimprovement at Time 2. Psychosocial factors would remain significantly associated with Time 2 outcome after controlling for the effects of clinical variables. 3. Task-focused and avoidance coping (which includes social diversion and distraction) would be associated with better outcome (remission and improvement) at Time 2, and these associations would remain significant after controlling for the effects of clinical variables. 4. Neuroticism, rumination, and emotion-focused coping would interact with achievement and interpersonal life events to predict nonremission and nonimprovement at Time 2. Task-oriented coping and avoidance coping were expected to interact with life events as resilience factors (that is, factors providing protection against persistent depression). MethodParticipants Study participants were a consecutive series of depression patients who had been referred for a psychiatric assessment to the Mood Disorders Program of the Health Sciences Centre in Winnipeg. The Health Sciences Centre is a university-affiliated teaching hospital in a city with a population of about 650 000. All patients had a primary diagnosis of MDD and a current major depressive episode at Time 1, despite at least one trial of antidepressant treatment. Patients with an active substance use disorder were excluded. Participants provided informed written consent to participate. A total of 287 patients with a current episode of MDD at the time of their initial assessment completed the baseline (Time 1) measures, and 179 (62.4%) of these completed the 1-year follow-up (Time 2) assessment. Eight patients were eliminated because of incomplete data. The present report is based on 171 patients (61 men) whose mean age was 41.8 years, SD 10.9. Common comorbid diagnoses included dysthymia (30%), social phobia (32%), panic disorder (34%), and prior history of alcohol abuse (38%). The 171 patients who completed the Time 2 assessment were not significantly different from the patients who did not complete the Time 2 assessment with regard to age, sex, education, marital status, depression symptom severity, episode duration, or number of depressive episodes. Procedure Experienced psychiatrists in the Mood Disorders Program diagnosed all patients according to DSM-IV criteria, on the basis of a 90-minute diagnostic interview designed to elicit phenomenological information. Hospital records and collateral information from the referring physician and from a family member were also considered when they were available. Patients completed a package of self-report measures prior to their Time 1 assessment interview. Twelve months after their initial assessment, patients were sent a second self-report assessment package, which they returned by mail. Patients were treated naturalistically (predominantly by general physicians) in the 12-month interval between Time 1 and Time 2. The treatments used between assessments included antidepressant medications (87%), individual psychotherapy (62%), and CBT (22%). Almost all patients (94%) received at least one of these forms of treatment between Time 1 and Time 2 Measures All 9 study measures listed below were completed at Time 1 only, with the exception of the depression measure (completed at Time 1 and at Time 2) and the life events measure (completed at Time 2 only). 1. The BDI (39) was used at the Time 1 and Time 2 assessments to measure depression severity. The BDI has been extensively studied and is a valid and reliable measure of depression (40). In the present study, the internal consistency of the BDI was a = 0.80. Scores on the BDI were used to classify patients as “in remission” at Time 2 (BDI < 10) (41) or as “improved” (50% reduction in BDI score by Time 2). 2. We used the Anxiety subscale of the DASS (42) as a continuous measure of general anxiety symptoms. The DASS is a well-validated measure of distress and has been shown to effectively discriminate anxiety from depression (43). In the present study, the internal consistency of the DASS-Anxiety scale was a = 0.89. 3. The PAQ (44) is a reliable and valid measure of a history of panic attacks. The PAQ was scored dichotomously (0 = no panic attacks in the past year; 1 = history of panic attacks in the past year). 4. The PBI (45) is a reliable and valid 25-item self-report measure of an individual’s experiences of being parented until age 16 years. The PBI has 2 subscales—Care and Overprotection. Patients completed a separate PBI for each parent. Care and Overprotection scores were computed as the average of mother and father scores. Internal consistencies for the PBI scales in the present study were as follows: mother care a = 0.94, mother overprotection a = 0.87, father care a = 0.93, and father overprotection a = 0.74. 5. The DMQ (46) assesses a range of developmental experiences implicated in the development of adult psychopathology. For the purposes of this study, a single DMQ item assessing history of sexual abuse (rape or incest) was used. 6. The NEO-FFI (38) is an extensively validated 60-item self-report measure assessing 5 higher-order personality factors. We used only the Neuroticism scale (12 items) in this study. The internal consistency of the Neuroticism scale was a = 0.76. 7. The RSQ (15) is a 21-item measure of ruminative responses to depression symptoms that are thought to increase the duration of depressive episodes. Patients respond to the questionnaire by indicating how often they engage in particular behaviours when they feel depressed. The internal consistency of the Rumination scale was a = 0.88. Sample items included “Think about how hard it is to concentrate” and “Isolate yourself and think about the reasons you feel sad.” 8. The CISS (19) is a 40-item measure of coping styles including Emotion-Oriented coping, Task-Oriented coping, and Avoidance coping scales. Subjects respond to the CISS by indicating how often they engage in specific activities when they encounter difficult, stressful, or upsetting situations. Internal consistencies for the CISS subscales were as follows: Emotion-Oriented coping a = 0.83, Task- Oriented coping a = 0.91, and Avoidance coping a = 0.71. Sample items included “worry about what I am going to do” (Emotion-Oriented coping), “focus on the problem and see how I can solve it” (Task-Oriented coping), and “take time off and get away from the situation” (Avoidance). 9. The LEI (47) is a life events measure that generates a total score for the number of stressful life events experienced over a specified time period. In this study, respondents completed the LEI at Time 2 to indicate which life events they experienced over the previous 12 months. Scores were generated for achievement life events (for example, work or financial problems) and interpersonal life events (for example, relationship discord or death of a loved one), using the item assignments of Hewitt and colleagues (48). The number of depressive episodes (single or recurrent) and the duration of the index depressive episode (months) were recorded during the Time 1 clinical interview. The Time 2 assessment also included a single self-report question that asked patients to indicate whether they had experienced a period of recovery from their depression over the previous year. Statistical Analyses We initially compared patients meeting and not meeting criteria for remission and improvement at Time 2, using univariate analyses (t tests for continuous variables and chi-square tests for categorical variables). We entered the variables that were significantly associated with outcome in the univariate analyses in multivariate logistic regression analyses. We then used logistic regression analyses to evaluate 10 possible interactions between psychological factors (neuroticism, rumination, emotion-focused coping, task oriented coping, and avoidance) and life stresses (interpersonal and achievement life events). Each of these regression analyses controlled for Time 1 symptoms and the main effects of the psychological factors and life stresses (49). Statistically significant interaction terms from these analyses were entered into final logistic regression models predicting Time 2 outcomes. In all logistic regression equations described above, remission (BDI < 10) was coded as 0, and nonremission was coded as 1. Similarly, improvement (that is, a 50% decrease in BDI score) was coded as 0, and nonimprovement was coded as 1. Using a sample size of 171 and alpha of 0.05 and assuming an event proportion (that is, remission or improvement) of 0.30, the present study had a power of 80% to detect an OR of 1.6 for individual continuous covariates (50). ResultsOverall Outcomes The mean BDI score of patients at Time 1 was 31.2, SD 8.4, and at Time 2 it was 22.9, SD 13.5. The rate of remission of depression symptoms at Time 2 was 22.8% (39/171). Improvement of 50% or greater in BDI scores was observed in 30.4% of patients (52/171). Univariate Analyses Comparisons of remitting and nonremitting patients are shown in Table 1. Statistically significant differences between the groups were found for the following variables: BDI score (t = 4.30, P < 0.001), DASS anxiety (t = 3.44, P = 0.001), panic attacks (c2 = 5.03, P = 0.025), neuroticism (t = 2.56, P = 0.011), rumination (t = 2.02, P = 0.045), interpersonal life events (t = 3.97, P < 0.001), achievement life events (t = 2.68, P = 0.008), avoidance coping (t = 3.34, P = 0.001) and sexual abuse history (c2 = 4.38, P = 0.036).
Comparisons of improved and unimproved patients are shown in Table 2. Statistically significant differences between the groups were found for the following variables: DASS anxiety (t = 3.11, P = 0.002), panic attacks (c2 = 4.01, P = 0.045), episode duration (t = 2.77, P = 0.006), older age (t = 2.03, P = 0.044), interpersonal life events (t = 4.27, P < 0.001), achievement life events (t = 2.18, P = 0.031), avoidance coping (t = 2.34, P = 0.020) and sexual abuse history (c2 = 4.32, P = 0.038).
Multivariate Analyses We entered statistically significant variables from the univariate analyses into multivariate logistic regressions. The regression models for remission and improvement are shown in Table 3. The significant variables in the model predicting nonremission included BDI score, DASS anxiety, interpersonal life events, and avoidance (negative association). The significant variables in the model predicting nonimprovement included DASS anxiety, episode duration, age, interpersonal life events, and avoidance coping (negative predictor).
Interaction Effects We evaluated 10 interactions between psychological factors and life events as predictors of nonremission and nonimprovement. In the final multivariate models including all significant clinical and psychosocial variables, avoidance coping interacted with interpersonal life events to predict nonremission (R2 change = 0.05, Wald = 11.22, P = 0.001) and nonimprovement (R2 change = 0.04, Wald = 8.93, P = 0.003). These interactions remained significant after controlling for multiple comparisons with a Bonefferoni correction (adjusted a = 0.05/10 = 0.005). None of the other interaction terms tested were significant predictors of outcome (all P values > 0.05). Among the patients with persisting depression symptoms at Time 2, 32 subjects reported that they had had a period of recovery from depression in between the Time 1 and Time 2 assessments. Because the predictors of unremitting or nonimproving depression may differ from the predictors of improvement followed by relapse, these 32 subjects were removed from the data set, and the analyses described above were repeated with the remaining 139 subjects. The identical variables were significant predictors in the final multivariate models. DiscussionSeveral important findings emerged in the study. A unique aspect of the study was the evaluation of both coping style and rumination in the perpetuation of depression. The main findings in univariate analyses were that rumination was associated with nonremission of depression, and avoidance coping was associated with both improvement and remission of depression at Time 2. Although this finding with regard to rumination is in keeping with Nolen–Hoeksema’s model (15), the association between rumination and 1-year outcome was small and was not significant in multivariate analyses. Conversely, the association between avoidance coping and favourable outcome at Time 2 was larger and remained significant in multivariate analyses. An association between avoidance coping and favourable outcome of depression may seem counterintuitive. However, the construct of avoidance coping measured by the CISS does not explicitly reflect pathological avoidance behaviour. Instead, the CISS Avoidance coping scale measures the tendency to engage in task-focused distraction and social diversion (19). Thus, in contrast to emotion-oriented coping, avoidance coping may result in opportunities for positive social interaction, engagement in pleasurable activity, and some alleviation of dysphoric mood. Several other psychosocial factors emerged as significant predictors of outcome in the study. As anticipated, based on previous studies, neuroticism, sexual abuse history, and life events were significant predictors of persisting depression in univariate analyses; however, the effects of neuroticism and sexual abuse history were not evident in multivariate analyses. Interpersonal life events had a more robust association with outcome than did achievement-related life events, and in multivariate analyses, interpersonal life events were significantly associated with nonremission and lack of improvement, whereas achievement events were not. Another unique aspect of the study was the evaluation of interactions between psychological vulnerabilities and life events in predicting persisting depression. Although 10 different possible interactions were evaluated, only 1 statistically significant interaction term was identified for remission and improvement. In each case, avoidance coping interacted with interpersonal life events to predict poorer outcome. Thus while the direct effect of avoidance coping on outcome was favourable, this relation was moderated by the occurrence of negative interpersonal life events. That is, if patients with depression do not encounter negative life events, distraction and social diversion may help alleviate depression symptoms, but in the context of interpersonal life events, avoidance is associated with persistent depression symptoms. Avoidance coping may result in failure to resolve interpersonal conflicts or problems, which in turn results in perpetuation of depression. This possibility warrants investigation. The significant effect of interpersonal life events observed in the study is in keeping with the hypothesized central role of interpersonal processes in the onset and perpetuation of depression (51). Clinically, these observations suggest that psychotherapeutic treatments emphasizing interpersonal processes are likely to be of particular value in this patient population. To date, evidence for the effectiveness of interpersonal therapy in chronic depression is modest (52); however, the cognitive-behavioural analysis system of psychotherapy, which emphasizes many interpersonal aspects of depression, has been found to be effective in chronic depression (53), and adaptations of CBT with a focus on early life adversity and poor social skills have been proposed for chronic depression (54). The most robust clinical predictors of outcome in the study included markers of illness severity (depression and anxiety symptoms), as well as duration of illness and age (for improvement, but not for remission). Anxiety severity was a robust predictor of outcome, even after controlling for initial depression symptom severity. This observation is in keeping with earlier studies of the impact of anxiety on the outcome of depression (4–6). Other forms of anxiety that were not assessed in the study (for example, social anxiety) may also have had an impact on outcome. Diagnostic and treatment efforts directed toward comorbid anxiety symptoms or disorders may be particularly important in this population of depression patients. The overall outcome of depression patients seen in consultation in this Mood Disorders Program was not encouraging, with just 22.8% of patients meeting criteria for remission and only 30.4% of patients showing a 50% improvement of BDI scores at Time 2. The poor outcome observed in the present study is likely attributable to the nature of the study population, which included patients referred for consultation following unsuccessful initial treatment and a lengthy mean illness duration over 19 months. The use of the BDI as an outcome measure might also have affected this result, because effect sizes on the BDI for improvement during active treatment tend to be smaller than the corresponding effect sizes for the Hamilton rating scale (55), and the criteria for defining remission are clearer for the Hamilton scale than for the BDI (56). Our study results should be considered in light of several limitations. First, depression symptoms and most of the psychosocial variables in this study were assessed with self-report measures, which may have increased their association with outcome as a result of method invariance. The baseline assessments relied on clinical diagnoses rather than on structured diagnostic interviews. The response rate in the study was 62%. Although the patients completing and not completing the Time 2 assessment were comparable on a range of clinical and demographic variables, it is not possible to rule out a response bias. The Time 2 evaluation was a cross-sectional assessment providing limited information on the course of depression symptoms and treatments received in the intervening period. However, it was reassuring that the observed predictors of outcome were unchanged when patients reporting a period of recovery followed by relapse were eliminated. A relatively large number of independent variables were assessed with a moderate sample size. Finally, since patients completed the life events measure concurrently with the Time 2 depression measure, it is possible that depressive symptoms at Time 2 influenced the recall or reporting of life events. Several potentially important clinical and research implications arise from the study. Patients with more severe depression and anxiety symptoms, as well as older patients and those with lengthy episodes of depression, are at high risk for persisting depression symptoms. Patients who encounter interpersonal life events, particularly when they have an avoidant coping style, are at risk for continued symptoms. Careful clinical attention to anxiety symptoms, effective management of interpersonal difficulties, and supportive treatments emphasizing effective coping styles may be appropriate interventions. From a research perspective, additional attention to the potential role of responses to depression symptoms and further investigation of the role of interactions between individual vulnerabilities and life events in the perpetuation of depression are warranted. Funding and SupportThis study was supported by an operating grant from the Social Sciences and Humanities Research Council of Canada, awarded to Dr Cox and Dr Enns. Dr Cox is supported by the Canada Research Chairs Program. References1. Sargeant JK, Bruce ML, Florio LP, Weissman MM. Factors associated with 1-year outcome of major depression in the community. Arch Gen Psychiatry 1990;47:519–26. 2. 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The interactional nature of depression. Washington (DC): American Psychological Association; 1999. 52. Markowitz JC. Interpersonal psychotherapy for chronic depression. J Clin Psychol 2003;59:847–58. 53. Keller MB, McCullough JP, Klein DN, Arnow B, Dunner DL, Gelenberg AJ, and others. A comparison of nefazodone, the cognitive behavioral analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med 2000;342:1462–70. 54. Riso LP, Newman CF. Cognitive therapy for chronic depression. J Clin Psychol 2003;59:817–31. 55. Lambert MJ, Hatch DR, Kingston MD, Edwards BC. Zung, Beck, and Hamilton rating scales as measures of treatment outcome: a meta-analytic comparison. J Consult Clin Psychol 1986;54:54–9. 56. Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori PW, and others. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse and recurrence. Arch Gen Psychiatry 1991;48:851–5. Author(s)Manuscript received August 2004, revised, and accepted March 2005. 1. Professor, Department of Psychiatry, University of Manitoba, Winnipeg, Manitoba. Address for correspondence: Dr M Enns, PZ430 771 Bannatyne Ave, Winnipeg, MB R3E 3N4 e-mail: menns@hsc.mb.ca
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