Amygdala-orbitofrontal structural and functional connectivity in females with anxiety disorders, with and without a history of conduct disorder

Abstract

Conduct disorder (CD) and anxiety disorders (ADs) are often comorbid and both are characterized by hyper-sensitivity to threat, and reduced structural and functional connectivity between the amygdala and orbitofrontal cortex (OFC). Previous studies of CD have not taken account of ADs nor directly compared connectivity in the two disorders. We examined three groups of young women: 23 presenting CD and lifetime AD; 30 presenting lifetime AD and not CD; and 17 with neither disorder (ND). Participants completed clinical assessments and diffusion-weighted and resting-state functional MRI scans. The uncinate fasciculus was reconstructed using tractography and manual dissection, and structural measures extracted. Correlations of resting-state activity between amygdala and OFC seeds were computed. The CD + AD and AD groups showed similarly reduced structural integrity of the left uncinate compared to ND, even after adjusting for IQ, psychiatric comorbidity, and childhood maltreatment. Uncinate integrity was associated with harm avoidance traits among AD-only women, and with the interaction of poor anger control and anxiety symptoms among CD + AD women. Groups did not differ in functional connectivity. Reduced uncinate integrity observed in CD + AD and AD-only women may reflect deficient emotion regulation in response to threat, common to both disorders, while other neural mechanisms determine the behavioral response.