Sex differences in the development of emotion circuitry in adolescents at risk for substance abuse: a longitudinal fMRI study.
There is substantial evidence for behavioral sex differences in risk trajectories for alcohol and substance use, with internalizing factors such as negative affectivity contributing more to female risk. Because the neural development of emotion circuitry varies between males and females across adolescence, it represents a potential mechanism by which underlying neurobiology contributes to risk for substance use. Longitudinal functional magnetic resonance imaging was conducted in males and females (n = 18 each) with a family history of alcohol use disorders starting at ages 8-13 years. Participants performed an affective word task during functional magnetic resonance imaging at 1- to 2-year intervals, covering the age range of 8.5-17.6 years (3-4 scans per participant). Significant age-related sex differences were found in the right amygdala and right precentral gyrus for the negative vs neutral word condition. Males showed a significant decrease in both amygdala and precentral gyrus activation with age, whereas the response in females persisted. The subjective experience of internalizing symptomatology significantly increased with age for females but not for males. Taken together, these results reveal sex differences in negative affect processing in at-risk adolescents, and offer longitudinal neural evidence for female substance use risk through internalizing pathways.
Department of Psychiatry.|Addiction Center, University of Michigan, Ann Arbor, MI, USA.
Jillian E
JE
Hardee
Department of Psychiatry.|Addiction Center, University of Michigan, Ann Arbor, MI, USA.
Lora M
LM
Cope
Department of Psychiatry.|Addiction Center, University of Michigan, Ann Arbor, MI, USA.
Emily C
EC
Munier
Department of Psychiatry, University of Utah, Salt Lake City, UT, USA.
Robert C
RC
Welsh
Department of Psychiatry.|Addiction Center, University of Michigan, Ann Arbor, MI, USA.
Robert A
RA
Zucker
Department of Psychiatry.|Addiction Center, University of Michigan, Ann Arbor, MI, USA.
Mary M
MM
Heitzeg
D000293:Adolescent; D000437:Alcoholism / Q000000981:diagnostic imaging / Q000503:physiopathology; D000679:Amygdala / Q000000981:diagnostic imaging / Q000503:physiopathology; D002648:Child; D004644:Emotions; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D011446:Prospective Studies; D021641:Recognition, Psychology; D012306:Risk; D057566:Self Report; D012727:Sex Characteristics; D019966:Substance-Related Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology*
amygdala; emotion; fMRI; sex differences; substance use