Linking an anxiety-related personality trait to brain white matter microstructure: diffusion tensor imaging and harm avoidance.

CONTEXT Emotional, cognitive, and behavioral response patterns underlying temperament and personality are established early and remain stable from childhood. Anxiety-related traits are associated with psychiatric disease and represent predisposing factors for various affective disorders, including depression and anxiety. Emotional processing relies on the structural and functional integrity of distributed neuronal circuits. Therefore, anxiety-related personality traits and associated increased risk of psychiatric disease might be rooted in structural variability in large-scale neuronal networks. OBJECTIVE To test the hypothesis that individuals with high scores on the harm avoidance (HA) subscale of the Temperament and Character Inventory show reduced white matter (WM) structural integrity in distributed brain areas, including corticolimbic pathways involved in emotional processing and reappraisal. DESIGN Healthy participants completed the Temperament and Character Inventory and underwent diffusion tensor imaging. Tract-based spatial statistics were used to examine the associations between HA and WM integrity across the brain. SETTING Center for the Study of Human Cognition, Department of Psychology, University of Oslo, Oslo, Norway. PARTICIPANTS A total of 263 healthy adults aged 20 to 85 years recruited through newspaper advertisements. MAIN OUTCOME MEASURE Neuroimaging diffusivity indexes of brain WM microstructure, including fractional anisotropy, mean and radial diffusivity, and their associations with HA. RESULTS In line with our hypothesis, increased HA was associated with decreased fractional anisotropy and increased mean and radial diffusivity in major WM tracts, including pathways connecting critical hubs in a corticolimbic circuit. There was no evidence of modulating effects of sex, degree of subclinical depression, alcohol consumption, general intellectual abilities, or years of education. CONCLUSIONS Increased HA is associated with decreased WM microstructure, implying that structural connectivity modulates anxiety-related aspects of personality. Decreased WM integrity reflects increased susceptibility to psychiatric disease and represents a promising biomarker that might ultimately facilitate targeted pharmacological and psychological interventions and treatment of disease.