Psychiatric symptoms in adolescents: FKBP5 genotype—early life adversity interaction effects

Abstract

Psychiatric disorders are multi-factorial and their symptoms overlap. Constitutional and environmental factors influence each other, and this contributes to risk and resilience in mental ill-health. We investigated functional genetic variation of stress responsiveness, assessed as FKBP5 genotype, in relation to early life adversity and mental health in two samples of adolescents. One population-based sample of 909 12-year-old adolescents (SESBiC) was assessed using the Life Incidence of Traumatic Events scale (LITE) and the Strengths and Difficulties Questionnaire (SDQ). One sample of 398 17-year-old adolescents, enriched for poly-victimized individuals (USSS), was assessed using the Juvenile Victimization Questionnaire (JVQ) and the Trauma Symptom Checklist for Children (TSCC). The FKBP5 rs1360780 and rs3800373 polymorphisms were genotyped using a fluorescence-based competitive allele-specific PCR.Most prominently among poly-victimized older male adolescents, the least common alleles of the polymorphisms, in interaction with adverse life events, were associated with psychiatric symptoms, after control of ethno-socio-economic factors. The interaction effect between rs3800373 and adverse life events on the TSCC sub-scales -anxiety, depression, anger, and dissociation -and with the rs1360780 on dissociation in the USSS cohort remained significant after Bonferroni correction.This pattern of associationis in line with the findings of clinical and neuroimaging studies, and implies interactive effects of FKBP5 polymorphisms and early life environment on several psychiatric symptoms. These correlates add up to provide constructs that are relevant to several psychiatric symptoms, and to identify early predictors of mental ill-health.

Genetics of resilience: Implications from genome‐wide association studies and candidate genes of the stress response system in posttraumatic stress disorder and depression

“…Elevated FKBP5 levels lead to a decreased negative feedback regulation of the HPA axis and glucocorticoid receptor resistance, which is probably responsible for a dysregulated stress response (Binder et al, ). In several association studies, genetic variations in the FKBP5 gene were associated with PTSD occurrence and severity, depending on the presence of childhood trauma (Binder et al, ; Buchmann et al, ; Comasco et al, ; Watkins et al, ). These results were substantiated in a recently published study showing a gene × environment interaction between FKBP5 polymorphisms and childhood abuse to predict the risk for PTSD (Tamman et al, ).…”

Association between resilience and posttraumatic stress disorder among Brazilian victims of urban violence: a cross-sectional case-control study

“…4 Resilience to stress is multifactorial and includes the individual's psychological and neurobiological profile, as well as environmental characteristics such as a personal history of trauma or a lack of social support. 5,6 Psychosocial factors correlated with resilience have been investigated in several studies. These include positive emotions and optimism, actively facing fear, cognitive flexibility, a moral guide based on values, spirituality, and social support.…”

Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol Drinking in Young Adult Rats and Humans

“…A functional polymorphism in the human FKBP5 gene has been identified, SNP rs1360780; homozygosity for the minor allele T has been associated with twice the amount of FKBP5 protein levels in lymphocytes, relative to the other genotypes [ 27 ]. Furthermore, differential stress responsivity, distinctive Amy overreactivity to emotional stimuli as well as psychiatric phenotypes characterized by an impaired stress response have been associated with the T allele or TT genotype, alone or in interaction with aversive environmental factors [ 9 , 28 ].…”