Early life stress modulates amygdala-prefrontal functional connectivity: Implications for oxytocin effects

• Published in: Human brain mapping Vol. 35; no. 10; pp. 5328 - 5339
• Main Authors: Fan, Yan, Herrera-Melendez, Ana Lucia, Pestke, Karin, Feeser, Melanie, Aust, Sabine, Otte, Christian, Pruessner, Jens C., Böker, Heinz, Bajbouj, Malek, Grimm, Simone
• Format: Journal Article
• Language: English
• Published: New York, NY Blackwell Publishing Ltd 01.10.2014; Wiley-Liss; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: Adult; amygdala; Amygdala - blood supply; Amygdala - drug effects; Biological and medical sciences; Double-Blind Method; early life stress; Electrodiagnosis. Electric activity recording; Functional Laterality; Humans; Image Processing, Computer-Assisted; Investigative techniques, diagnostic techniques (general aspects); Magnetic Resonance Imaging; Male; Medical sciences; Nervous system; Neural Pathways - blood supply; Neural Pathways - drug effects; Oxygen - blood; oxytocin; Oxytocin - pharmacology; Prefrontal Cortex - blood supply; Prefrontal Cortex - drug effects; pregenual anterior cingulate cortex; Psychiatric Status Rating Scales; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Regression Analysis; Rest; resting-state functional connectivity; state anxiety; Stress, Psychological - diagnosis; Young Adult; Affect affectivity; Nervous system diseases; Amygdala; Oxytocin; Radiodiagnosis; Central nervous system; Stress; Encephalon; pregenual anterior cingulate cortex; state anxiety; Cingulate cortex; resting-state functional connectivity; Anxiety; early life stress; amygdala; oxytocin
• ISSN: 1065-9471; 1097-0193; 1097-0193
• DOI: 10.1002/hbm.22553

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. Hum Brain Mapp 35:5328–5339, 2014. © 2014 Wiley Periodicals, Inc.