Associations Between and Changes in Hippocampal Volume and the Cortisol Response Over Time: The Role of Childhood Maltreatment and Depression
Stress-related brain mechanisms, specifically HPA axis dysregulation and reductions in hippocampal volume, have long been associated with the pathology of major depressive disorder, especially within the context of a history of childhood maltreatment. However, investigations that examine the association between these two mechanisms are scarce. The aim of the current study was to (1) test the hypothesis that (1) cortisol reactivity and hippocampal volume are correlated mediators of the relation between childhood maltreatment; and (2) examine changes in, and associations between cortisol reactivity and hippocampal volume over time specifically within the context of childhood maltreatment and changes in depression symptomology. The current study included 144 adults (91 with a lifetime history of depressive disorders, 53 never-depressed), 64 of whom returned for a 6-month follow-up. At baseline, participants underwent both a gold-standard contextual interview to assess childhood maltreatment (i.e., Childhood Experiences of Care and Abuse; CECA) and a comprehensive diagnostic interview (Structured Clinical Interview for DSM-IV Axis I Disorders; SCID). At both time points participants completed a depression symptom inventory (i.e., Montgomery-Asberg Depression Rating scale; MADRS), a laboratory social-stress paradigm that specifically accounts for how individuals respond to stressors in their environment (Trier Social Stress Test; TSST), and neuroimaging in a magnetic resonance imaging scanner. Contrary to hypotheses, across both analyses cortisol reactivity and hippocampal volume were not significantly associated. However, cortisol reactivity but not hippocampal volume was found to mediate the relation between childhood maltreatment and depression. Hippocampal volume was also found to co-vary across time with depression symptom severity. Although these findings suggest that our current conceptualization of the relation between cortisol reactivity and hippocampal volume requires revision, the results indicate these stress-related neurobiological processes remain important targets in our understanding of depressive disorders.