Hardee JE1, Cope LM1, Munier EC1, Zucker RA1, Heitzeg MM1
1 University of Michigan Addiction Research Center and Department of Psychiatry, Ann Arbor, MI
There is substantial evidence for sex differences in risk trajectories for alcohol use disorders (AUD), such that females tend toward negative emotionality and males tend toward behavioral undercontrol. Because the neural development of emotion circuitry across adolescence varies between males and females, it represents a potential mechanism by which underlying neurobiology contributes to risk for alcohol use and AUD. Longitudinal functional magnetic resonance imaging (fMRI) was conducted in males and females (n=18 each) with a family history of AUD starting at ages 8–13 years. Participants performed an emotional word task (negative, neutral, positive words) while being scanned at 1- to 2-year intervals, covering the age range of 8.5–17.6 years. Each participant had 3–4 fMRI scans. Significant age-related sex differences were found in the right amygdala and right precentral gyrus for the negative vs. neutral word contrast. Post-hoc tests revealed that activation significantly decreased with age in the right amygdala and right precentral gyrus in males, whereas activation in females persisted. Internalizing behaviors, as measured by the Youth Self Report, significantly increased with age for females but not for males. Taken together, these results reveal sex differences in the neural processing of emotion in at-risk adolescents, suggesting that females may be more vulnerable to risk for AUD through an amygdala-mediated, or emotion processing, pathway.