title: Early life stress modulates amygdala-prefrontal functional connectivity: implications for oxytocin effects.
abstract: Recent evidence suggests that early life stress (ELS) changes stress reactivity via reduced resting state functional connectivity (rs-FC) between amygdala and the prefrontal cortex. Oxytocin (OXT) modulates amygdala connectivity and attenuates responses to psychosocial stress, but its effect appears to be moderated by ELS. Here we first investigate the effect of ELS on amygdala-prefrontal rs-FC, and examine whether ELS-associated changes of rs-FC in this neural circuit predict its response to psychosocial stress. Secondly, we explore the joint effect of OXT and ELS on the amygdala-prefrontal circuit. Eighteen healthy young males participated in a resting-state fMRI study of OXT effects using a double-blind, randomized, placebo-controlled, within-subject crossover design. We measured the rs-FC to bilateral amygdalae and subsequently assessed changes of state anxiety and prefrontal responses to psychosocial stress. Multiple linear regressions showed that ELS, specifically emotional abuse, predicted reduced rs-FC between the right amygdala and pregenual anterior cingulate cortex (pgACC), which in turn predicted elevated state anxiety after psychosocial stress. In subjects with lower ELS scores, stronger pgACC-amygdala rs-FC predicted stronger pgACC deactivation during the psychosocial stress task, and this rest-task interaction was attenuated by OXT. In subjects with higher ELS scores however, the rest-task interaction was altered and OXT showed no significant effect. These findings highlight that ELS reduces pgACC-amygdala rs-FC and alters how rs-FC of this circuit predicts its stress responsiveness. Such changes in pgACC-amygdala functional dynamics may underlie the altered sensitivity to the effects of OXT after ELS.
authors.affiliation: Cluster of Excellence "Languages of Emotion",, Freie Universität Berlin, Berlin, Germany; Department of Psychiatry, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany; Dahlem Institute for Neuroimaging of Emotion, Freie Universität Berlin, Berlin, Germany.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fan
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Herrera-Melendez
authors.forename: Karin
authors.initials: K
authors.lastname: Pestke
authors.forename: Melanie
authors.initials: M
authors.lastname: Feeser
authors.forename: Sabine
authors.initials: S
authors.lastname: Aust
authors.forename: Christian
authors.initials: C
authors.lastname: Otte
authors.forename: Jens C
authors.initials: JC
authors.lastname: Pruessner
authors.forename: Heinz
authors.initials: H
authors.lastname: Böker
authors.forename: Malek
authors.initials: M
authors.lastname: Bajbouj
authors.forename: Simone
authors.initials: S
authors.lastname: Grimm
mesh_terms: D000328:Adult; D000679:Amygdala / Q000098:blood supply / Q000187:drug effects*; D004311:Double-Blind Method; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000098:blood supply / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D010121:Oxytocin / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000098:blood supply / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D012146:Rest; D013315:Stress, Psychological / Q000175:diagnosis; D055815:Young Adult
chemical_list: D010121:Oxytocin; D010100:Oxygen
keywords: amygdala; early life stress; oxytocin; pregenual anterior cingulate cortex; resting-state functional connectivity; state anxiety