Faculty Collaboration Database

Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation. J Abnorm Psychol 2015 Nov;124(4):817-33

Date

11/26/2015

Pubmed ID

26595470

Pubmed Central ID

PMC4662045

DOI

10.1037/abn0000094

Scopus ID

2-s2.0-84973131594 (requires institutional sign-in at Scopus site)   99 Citations

Abstract

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology.

Author List

Pagliaccio D, Luby JL, Bogdan R, Agrawal A, Gaffrey MS, Belden AC, Botteron KN, Harms MP, Barch DM

Author

Michael S. Gaffrey PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Amygdala
Anxiety
Child
Emotions
Female
Gene-Environment Interaction
Humans
Hypothalamo-Hypophyseal System
Magnetic Resonance Imaging
Male
Nerve Net
Neuroimaging
Pituitary-Adrenal System
Polymorphism, Single Nucleotide
Receptors, Corticotropin-Releasing Hormone
Receptors, Glucocorticoid
Receptors, Mineralocorticoid
Stress, Psychological
Tacrolimus Binding Proteins