Research Letter: Childhood trauma and the rs1360780 SNP of FKBP5 gene in psychosis: a replication in two general population samples

• Published in: Psychological medicine 2016-01, Vol.46 (1), p.221-223
• Main Authors: Alemany, S, Moya, J, Ibáñez, M I, Villa, H, Mezquita, L, Ortet, G, Gastó, C, Fañanás, L, Arias, B
• Format: Article
• Language: English
• Subjects: Adult; Adult Survivors of Child Abuse; Age; Anxiety; Child abuse & neglect; Children; Female; Gene polymorphism; Genetic diversity; Humans; Hypothalamic-pituitary-adrenal axis; Hypothalamus; Male; Marijuana; Neurobiology; Pituitary; Polymorphism, Single Nucleotide; Population; Psychological Trauma - genetics; Psychology; Psychosis; Psychotic Disorders - genetics; Schizophrenia; Single-nucleotide polymorphism; Spain; Stress; Tacrolimus Binding Proteins - genetics; Trauma; Young Adult
• ISSN: 0033-2917; 1469-8978
• DOI: 10.1017/S0033291715001695

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been proposed as a neurobiological mechanism underlying the childhood adversity-psychosis link (Daskalakis & Binder, 2015). Therefore, genetic variation affecting HPA axis regulation may account for differential response to childhood adversity (Van Winkel et al. 2008). FKBP5 is a co-chaperone which regulates glucocorticoid receptor (GR) sensitivity (Binder, 2009). A single nucleotide polymorphism (SNP) in this gene, the rs1360780, is associated with differential up-regulation of FKBP5 and GR sensitivity (Binder et al. 2004). Specifically, the T allele is associated with enhanced expression following GR activation, leading to an increased GR resistance and decreased efficiency of the negative feedback of the stress hormone axis which results in a prolonged activation of this system. This dysregulated stress response may be a potential risk factor for stress-related psychiatric disorder (Binder et al. 2008; Binder, 2009; Zannas & Binder, 2014).