Larger amygdala volumes after childhood trauma associated with depression and cortisol response to psychosocial stress in adulthood

Abstract

Background: Childhood trauma is a major risk factor for the development of affective disorders later in life. We sought to determine whether this risk is linked to neurostructural changes in limbic brain regions after childhood trauma.Methods:We recruited 49 medically healthy adult women (28.2±7.1 years of age) from the Atlanta area to include women with/without childhood trauma and with/without major depression (MDD). Childhood trauma exposure was quantified using the Childhood Trauma Questionnaire (CTQ).Lifetime and current diagnoses of MDD and posttraumatic stress disorder (PTSD) were assessed using the Structured Clinical Interview for DSM-IV (SCID). Current depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAM-D). Magnetic resonance images were acquired, preprocessed, and registered into stereotactic space. Volume analyses of the left and right amygdala were performed using the interactive software package DISPLAY developed at the Brain Imaging Center of the Montreal Neurological Institute, and a standardized segmentation protocol was applied to outline the anatomical boundaries of the amygdala. Total plasma cortisol responses to the Trier Social Stress Test (TSST) were measured.Results: When stratifying groups by childhood trauma exposure and MDD, women with both childhood trauma and MDD had largest right amygdala volumes compared to all other groups (interaction effect: F=6.172, p= 0.017). Correlational analyses revealed that higher CTQ scores were associated with larger left (r=0.31, p<0.05) and right (r=0.31, p<0.05) amygdala volumes. These correlations remained significant when controlling for age, race, and lifetime diagnoses of MDD and PTSD. Higher CTQ scores were associated with current depression scores (r=0.30, p<0.05), which in turn were positively associated with the size of the right amygdala volume (r=0.32, p<0.05). Finally, the size of the left amygdala was associated with increased cortisol response to the TSST (15 min post TSST: r= 0.44, p< 0.05, 30 min post TSST: r= 0.436, p< 0.05). A similar trend was observed for the right amygdala.Conclusions: These findings add to the growing understanding of the neurobiological basis that may underlie the association between early adverse experience, stress vulnerability, and increased risk for affective disorders.