Risk and protective effects of serotonin and BDNF genes on stress-related adult psychiatric symptoms

Paul G Nestor,Keira O'Donovan,Hannah E Lapp,Victoria Choate Hasler,Sara B Boodai,Richard Hunter

doi:10.1016/j.ynstr.2019.100186

Abstract

We focused on individual risk by examining childhood adversity and current psychiatric symptoms in a sample of 100 college students genotyped for both the serotonin transporter (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF). Naturally occurring allelic variation in 5-HTTLPR (short/long) and BDNF (valine/methionine) have been strongly implicated in stress-related psychiatric risk, but the combined effects of these alleles on psychological functioning have yet to be fully elucidated. Univariate analysis revealed gene-environment correlations linking heightened psychiatric risk with past childhood adversity for short but not long 5-HTTLPR allelic carriers and for valine (Val) but not methionine (Met) BDNF allelic carriers. Multivariate analyses revealed a significant gene x gene interaction with results showing that risk varied systematically depending on both 5-HTTLPR and BDNF alleles, independent of childhood adversity. Hierarchical regression analyses indicated that approximately 11% of the variance in symptoms of depression could be specifically accounted for by the epistatic interaction of 5-HTTLPR and BDNF val66Met polymorphisms. Allelic group analyses indicated lowest risk, as measured by depression and anxiety, for allelic carriers of 5-HTTLPR-short and BDNF Met, followed by 5-HTTLPR-long and BDNF-Val, 5-HTTLPR-short and BDNF-Val, and 5-HTTLPR-long and BDNF-Met. Results suggest that protective or risk-enhancing effects on stress-related psychiatric functioning may depend on specific allelic combinations of 5-HTTLPR and BDNF.

Highlights

The concept of risk originating from influential epidemiological studies of atherosclerotic disease of the 1960s (Dawber, 1980) has long played a central role in models of psychopathology
We examined individual differences in psychiatric risk in a sample of 100 college students who were genotyped for 5-HTTLPR and brain-derived neurotrophic factor (BDNF) polymorphisms and who completed measures of childhood adverse experiences and current psychiatric symptomatology
For participants who were homozygous for the HTTLPR long variant, the data revealed no evidence of gene-environment correlation with the sole exception of childhood adversity and obsessive compulsiveness

Summary

Introduction

The concept of risk originating from influential epidemiological studies of atherosclerotic disease of the 1960s (Dawber, 1980) has long played a central role in models of psychopathology. Understood in reference to specific and discrete mental illness, risk is often viewed trans-diagnostically, with the focus on elucidating general mechanisms and underlying etiological and pathophysiological processes and phenotypical precursors that may be common across different psychiatric disorders (Cuthbert and Insel, 2013). From this perspective, whether a particular form of mental illness is expressed depends on a combination of environmental, genetic, and temperamental factors. These effects, in turn, may be especially pronounced during late adolescence and early adulthood, a well-known developmental period of risk for mental illness (Hooley et al, 2017)

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Results

Conclusion