Extraversion modulates cortisol responses to acute social stress in chronic major depression.

BACKGROUND: Chronic Major Depressive Disorder (CMDD) is a common, disabling illness that is often complicated by high reactivity to social stress. To further elucidate the nature of this reactivity, the current study evaluated whether the personality dimensions of neuroticism and extraversion influenced cortisol responses to a social challenge in CMDD patients vs. controls. METHODS: Fifty participants with CMDD and 58 healthy controls completed the Trier Social Stress Test (TSST) using a standard protocol. Neuroticism and extraversion were measured using the Revised NEO Personality Inventory. Hierarchical linear regressions assessed associations between independent variables neuroticism and extraversion and dependent variable cortisol area-under-the-curve increase (AUCi) in response to the TSST in the two study groups. RESULTS: The extraversion-by-group interaction was a significant predictor of cortisol AUCi, while no significant findings related to neuroticism were found. Simple slopes analysis revealed a significant negative association between extraversion and AUCi in the CMDD group, but not in healthy controls. Post-hoc analysis of the raw cortisol data over time found that CMDD participants with higher extraversion scores had significantly higher pre-challenge cortisol levels than did other study participants, however this did not explain or confound the AUCi results. CONCLUSIONS: In participants with CMDD but not in controls, higher levels of extraversion were associated with higher pre-challenge cortisol levels and decreased cortisol reactivity during the TSST, however these two findings were statistically independent. These findings underline the importance of considering personality factors when studying stress biology in CMDD patients. Extraversion may prove to be an important intermediate target for both research and clinical work in this complex, heterogenous and often treatment-resistant population.

High reactivity of the cortisol awakening response predicts positive treatment outcome in heterogeneous depressed patients completing an alternate milieu inpatient program.

OBJECTIVE: Delineating clinically meaningful subgroups within heterogeneous depressed populations is a major challenge. As outlined in the Research Domain Criteria Strategy, biomarkers may help to empirically classify such patients. Following this basic strategy, the current pilot study examined whether the cortisol awakening response (CAR) following admission to hospital predicts treatment response in heterogeneous depressed patients completing a 4-week alternate milieu inpatient program. METHODS: The Alternate Inpatient Milieu program at the Centre for Addiction and Mental Health is composed of both individual-based and group-based programming designed to promote a recovery-oriented, collaborative treatment environment. The current sample consisted of 25 consecutive patients with various forms of complex/chronic depression who completed the full program. Saliva samples were collected at 0, 30 and 60 min after awakening on 2 consecutive days following admission. Linear regressions controlling for baseline depression scores were used to assess whether the CAR AUCg (area under the curve ground) and/or AUCi (area under the curve increase) at admission predicted the change in depression scores from admission to discharge based on the Quick Inventory of Depressive Symptoms scale. RESULTS: The CAR AUCi, but not the CAR AUCg, at admission significantly predicted treatment response over the 4-week hospital stay. In these naturalistic patients with major depressive disorder, high CAR reactivity as assessed using the AUCi was associated with a better treatment response (t=2.20; df=2,24; P=.039). The CAR was easy to implement and well accepted by patients and staff. CONCLUSION: This pilot study suggests that CAR reactivity at admission may help to identify a subgroup of depressed patients most likely to respond clinically to a 4-week alternate milieu inpatient program.

Summary cortisol reactivity indicators: Interrelations and meaning.

Research on the hypothalamic pituitary adrenal (HPA) axis has involved a proliferation of cortisol indices. We surveyed recently published HPA-related articles and identified 15 such indices. We sought to clarify their biometric properties, specifically, how they interrelate and what they mean, because such information is rarely offered in the articles themselves. In the present article, the primary samples consist of community mothers and their infants (N = 297), who participated in two challenges, the Toy Frustration Paradigm and the Strange Situation Procedure. We sought to cross-validate findings from each of these samples against the other, and also against a clinically depressed sample (N = 48) and a sample of healthy older adults (N = 51) who participated in the Trier Social Stress Test. Cortisol was collected from all participants once before and twice after the challenges. These heterogenous samples were chosen to obtain the greatest possible range in cortisol levels and stress response regulation. Using these data, we computed the 15 summary cortisol indices identified in our literature survey. We assessed inter-relations amongst indices and determined their underlying dimensions via principal component analysis (PCA). The PCAs consistently extracted two components, accounting for 79%-93% of the variance. These components represent "total cortisol production" and "change in cortisol levels." The components were highly congruent across challenge, time, and sample. High variable loadings and explained factor variance suggest that all indices represent their underlying dimensions very well. Thus the abundance of summary cortisol indices currently represented in the literature appears superfluous.

A novel examination of atypical major depressive disorder based on attachment theory.

OBJECTIVE: While a large body of descriptive work has thoroughly investigated the clinical correlates of atypical depression, little is known about its fundamental origins. This study examined atypical depression from an attachment theory framework. Our hypothesis was that, compared to adults with melancholic depression, those with atypical depression would report more anxious-ambivalent attachment and less secure attachment. As gender has been an important consideration in prior work on atypical depression, this same hypothesis was further tested in female subjects only. METHOD: One hundred ninety-nine consecutive adults presenting to a tertiary mood disorders clinic with major depressive disorder with either atypical or melancholic features according to the Structured Clinical Interview for DSM-IV Axis-I Disorders were administered a self-report adult attachment questionnaire to assess the core dimensions of secure, anxious-ambivalent, and avoidant attachment. Attachment scores were compared across the 2 depressed groups defined by atypical and melancholic features using multivariate analysis of variance. The study was conducted between 1999 and 2004. RESULTS: When men and women were considered together, the multivariate test comparing attachment scores by depressive group was statistically significant at p < .05. Between-subjects testing indicated that atypical depression was associated with significantly lower secure attachment scores, with a trend toward higher anxious-ambivalent attachment scores, than was melancholia. When women were analyzed separately, the multivariate test was statistically significant at p < .01, with both secure and anxious-ambivalent attachment scores differing significantly across depressive groups. CONCLUSION: These preliminary findings suggest that attachment theory, and insecure and anxious-ambivalent attachment in particular, may be a useful framework from which to study the origins, clinical correlates, and treatment of atypical depression. Gender may be an important consideration when considering atypical depression from an attachment perspective.

Sex differences in hormonal responses to a social stressor in chronic major depression.

BACKGROUND: Acute depression has been associated with increased hypothalamic-pituitary-adrenal (HPA) reactivity. While chronicity of depressive illness influences symptoms, course and outcome, its effect on the HPA axis has not been extensively evaluated. The current study evaluated cortisol stress responses to a social challenge in chronic major depressive disorder (CMDD). METHODS: Cortisol stress responses to the Trier Social Stress Test (TSST) were compared in 26 participants with CMDD and 28 healthy controls using repeated measures analysis of variance (RANOVA). In addition, group differences in area under the curve (AUC) and peak percentage change in cortisol were examined. RESULTS: The RANOVA indicated a significant sex by condition interaction in cortisol responses to the social challenge. Post-hoc testing of pair-wise group differences revealed that in females, CMDD subjects had greater cortisol levels in response to the TSST than did controls. Similarly, AUC was greater in females with CMDD than in female controls. Neither of these differences was significant in males. However, male CMDD subjects exhibited a significantly decreased peak percentage change in cortisol in response to the TSST than did male controls. CONCLUSIONS: Males and females with CMDD exhibited unique differences in cortisol responses to the social challenge relative to controls. In females, CMDD subjects had greater overall secretion of cortisol whereas in males, CMDD subjects had a blunted peak response to the social stressor. Sex differences are an important consideration in future work in this population.

A dimensional approach to personality in atypical depression.

The current study addresses the relationship of personality and atypical depression using the Five-Factor Model (FFM), a dimensional approach to personality. The aim of the study was to help clarify which personality traits are more characteristic of atypical depression than of other depressive subtypes. Outpatients (n=160) with non-psychotic major depression were characterized as having atypical (n=26), or non-atypical depression (n=134) based on DSM-IV criteria. To limit the effect of state depression, personality was assessed after subjects received a minimum of 14 weeks of antidepressant treatment. The Revised NEO Personality Inventory, which generates data based on the FFM, was the primary assessment measure. Post-treatment, relative to the non-atypical comparison group, the atypical group had significantly higher scores on the dimension of Neuroticism, the facets of Impulsivity and Anger-Hostility, and a significantly lower score on the facet of Deliberation. In sum, the FFM provides a new understanding of which unique personality characteristics may be associated with atypical depression.