Structural Brain Patterns Associated with Traumatic Stress Resilience and Susceptibility to Mood and Anxiety Symptoms in Youths

Understanding biological mechanisms underlying traumatic stress resilience is critical and can advance preventive psychiatry. Brain phenotypes of stress resilience have been investigated in animals, but such data in humans is scarce. Here we characterize cross-sectional brain correlates of traumatic stress resilience and susceptibility to mood and anxiety psychopathology (MAP) in community youth with substantial trauma exposure. Philadelphia Neurodevelopmental Cohort youths with high-quality structural neuroimaging data were included (N = 1392, mean age similar to 15). MAP was quantified using a dimensional factor score. Resilience and susceptibility were ascertained retrospectively and defined as low/high MAP (respectively) in relation to trauma exposure. This resilience-susceptibility construct was operationalized as the interaction term between trauma exposure and MAP. Clinical functioning level was quantified with the Children Global Assessment Scale. Statistical models examined association of volume, cortical thickness, and gray matter density with resilience, covarying for age, sex, race, socioeconomic status, and image quality. Resilience was associated with better clinical functioning and with specific neural correlates, such that in extensive traumatic stress exposure, smaller brain volume was associated with low MAP; while in low trauma exposure, smaller volumes were correlated with higher MAP. This pattern was evident in total brain volume (trauma by MAP interaction, F(1, 1383), p < .05), and in volumes of white matter, parietal lobe, basal ganglia, and within basal ganglia (nucleus accumbens, globus pallidus, and putamen) (all FDR corrected p's < .05). Exploratory analyses revealed no such interaction in the hippocampus or amygdala. Findings suggest that in substantial childhood/adolescent life trauma exposure, larger brain volume, usually considered protective, is inversely associated with resilience.