Published online by Cambridge University Press: 22 November 2017
Early life stress (ELS) is a significant risk factor for the emergence of internalizing problems in adolescence. Beginning in adolescence, females are twice as likely as males to experience internalizing disorders. The present study was designed to examine sex differences in the association between ELS and internalizing problems in early pubertal adolescents, and whether and how corticolimbic function and connectivity may underlie these associations. Fifty-nine early pubertal males and 78 early pubertal females, ages 9–13 years (all Tanner Stage 3 or below) underwent functional magnetic resonance imaging as they performed an emotion label task that robustly interrogates corticolimbic function. Participants were also interviewed about their experience of ELS. Females exhibited a positive association between ELS and internalizing problems, whereas males exhibited no such association. Whole-brain and amygdala region of interest analyses indicated that whereas females exhibited a positive association between ELS and the ventrolateral prefrontal cortex during implicit emotion regulation, males showed no such association. Activation in these regions was positively associated with internalizing problems in females but not males; however, activation in these regions did not mediate the association between ELS and internalizing problems. Finally, both boys and girls exhibited an association between ELS and increased negative connectivity between the right ventrolateral prefrontal cortex and bilateral amygdala. Using a carefully characterized sample of early pubertal adolescents, the current study highlights important sex differences in the development of corticolimbic circuitry during a critical period of brain development. These sex differences may play a significant role in subsequent risk for internalizing problems.
We thank Holly Pham, Isabella Lazzareschi, Cat Camacho, Monica Ellwood-Lowe, Sophie Schouboe, Maddie Pollak, and Morgan Popolizio for their assistance in scheduling and running the participants. We also thank the adolescents and families who participated in our study. This work was supported by NIMH Grants R01MH101495 (to I.H.G.), K01MH106805 (to S.J.O.), and F32MH107129 (to K.L.H.N.); the Brain & Behavior Research Foundation Young Investigator Awards 23583 (to S.J.O.) 23819 (to K.L.H.); the Klingenstein Third Generation Foundation Fellowship Awards (to S.J.O. and K.L.H.); the National Science Foundation Graduate Fellowship Awards (to N.L.C. and L.S.K.); and the Stanford University Gerald J. Lieberman Graduate Fellowship (to N.L.C.).
Full text views reflects PDF downloads, PDFs sent to Google Drive, Dropbox and Kindle and HTML full text views.