Working memory reflects vulnerability to early life adversity as a risk factor for substance use disorder in the FKBP5 cortisol cochaperone polymorphism, rs9296158

• Published in: PloS one Vol. 14; no. 6; p. e0218212
• Main Authors: Lovallo, William R, Acheson, Ashley, Cohoon, Andrew J, Sorocco, Kristen H, Vincent, Andrea S, Hodgkinson, Colin A, Goldman, David
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.06.2019; Public Library of Science (PLoS)
• Subjects: Adolescents; Adult; Alcoholism; Analysis; Behavior; Behavioral sciences; Biology and Life Sciences; Children; Cognitive ability; Cortisol; Decision making; Exposure; Female; Gene polymorphism; Genetic polymorphisms; Genotypes; Glucocorticoids; Health sciences; Hormones; Humans; Hydrocortisone; Impulsivity; Laboratories; Male; Medicine and Health Sciences; Memory; Memory, Short-Term; Nervous system; Polymorphism; Polymorphism, Genetic; Psychiatry; Psychopathology; Psychopharmacology; Risk analysis; Risk Factors; Shape memory; Short term memory; Signal transduction; Signaling; Social Sciences; Studies; Substance abuse; Substance use; Substance use disorder; Substance-related disorders; Substance-Related Disorders - genetics; Substance-Related Disorders - physiopathology; Tacrolimus Binding Proteins - genetics; Veterans; Vulnerability (Psychology); Young adults; United States > US; Oklahoma
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0218212

Early life adversity (ELA) negatively affects health behaviors in adulthood, but pathways from ELA exposure to behavioral outcomes are poorly understood. ELA in childhood and adolescence may translate into adult outcomes by way of modified glucocorticoid signaling. The cortisol cotransporter, FKBP5 has a G-to-A substitution (rs9296158) that hinders cortisol trafficking within target cells, and this impaired glucocorticoid signaling may shape the long-term response to ELA. We used performance on the Stroop test to assess working memory in 546 healthy young adults who had experienced 0, 1, or > 1 forms of ELA in childhood and adolescence and were genotyped for the FKBP5 rs9296158 G-to-A polymorphism. We observed a robust Gene x Environment interaction (F = 9.49, p < .0001) in which increased ELA exposure led to progressively greater Stroop interference in persons carrying AG and AA genotypes of FKBP5 with no such effect in GG carriers. Further work is needed to explore the modification of cognitive function resulting from ELA. Impairments in working memory illustrate how ELA may use glucocorticoid pathways to influence working memory with potential implications for decision-making and risky behavior including substance use disorders.