title: Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence.
abstract: Early life stress (ELS) and function of the hypothalamic-pituitary-adrenal axis predict later psychopathology. Animal studies and cross-sectional human studies suggest that this process might operate through amygdala-ventromedial prefrontal cortex (vmPFC) circuitry implicated in the regulation of emotion. Here we prospectively investigated the roles of ELS and childhood basal cortisol amounts in the development of adolescent resting-state functional connectivity (rs-FC), assessed by functional connectivity magnetic resonance imaging (fcMRI), in the amygdala-PFC circuit. In females only, greater ELS predicted increased childhood cortisol levels, which predicted decreased amygdala-vmPFC rs-FC 14 years later. For females, adolescent amygdala-vmPFC functional connectivity was inversely correlated with concurrent anxiety symptoms but positively associated with depressive symptoms, suggesting differing pathways from childhood cortisol levels function through adolescent amygdala-vmPFC functional connectivity to anxiety and depression. These data highlight that, for females, the effects of ELS and early HPA-axis function may be detected much later in the intrinsic processing of emotion-related brain circuits.
authors.affiliation: Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, Wisconsin, USA. caburghy@wisc.edu
authors.forename: Cory A
authors.initials: CA
authors.lastname: Burghy
authors.forename: Diane E
authors.initials: DE
authors.lastname: Stodola
authors.forename: Paula L
authors.initials: PL
authors.lastname: Ruttle
authors.forename: Erin K
authors.initials: EK
authors.lastname: Molloy
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Armstrong
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Oler
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Fox
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Hayes
authors.forename: Ned H
authors.initials: NH
authors.lastname: Kalin
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Essex
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Davidson
authors.forename: Rasmus M
authors.initials: RM
authors.lastname: Birn
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior / Q000502:physiology* / Q000523:psychology; D000679:Amygdala / Q000254:growth & development*; D001007:Anxiety / Q000453:epidemiology / Q000378:metabolism* / Q000523:psychology; D003863:Depression / Q000453:epidemiology / Q000378:metabolism* / Q000523:psychology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D009434:Neural Pathways / Q000254:growth & development; D017397:Prefrontal Cortex / Q000254:growth & development*; D011446:Prospective Studies; D013315:Stress, Psychological / Q000453:epidemiology / Q000378:metabolism / Q000523:psychology
chemical_list: D006854:Hydrocortisone