Early‐Life Adversity and Blunted Stress Reactivity as Predictors of Alcohol and Drug use in Persons With COMT (rs4680) Val158Met Genotypes

Abstract

Background: Risk for alcoholism may be enhanced by exposure to early-life adversity (ELA) in persons with genetic vulnerabilities. We examined ELA in the presence of a common variant of the gene for the enzyme catechol-O-methyltransferase (COMT, Val158Met, rs4680) in relation to cortisol reactivity, the onset of early drinking, and experimentation with drugs.Methods: Saliva cortisol reactivity to speech and mental arithmetic stress was measured in 480 healthy young adults (23.5 years of age, 50% females) who experienced either 0, 1, or ≥ 2 forms of ELA during childhood and adolescence, provided information on use of alcohol and recreational drugs, and were genotyped for the Val158Met polymorphism.Results: ELA led to progressively smaller cortisol responses in the Met/Met and Val/Met allele groups but to progressively larger responses in Val homozygotes, F = 3.29, p = 0.011. ELA independently predicted earlier age at first drink, F = 14.2, p < 0.0001, with a larger effect in Met-allele carriers, F = 13.95, p < 0.00001, and a smaller effect in Val homozygotes, F = 4.14, p = 0.02. Similar effects were seen in recreational drug use. Cortisol reactivity was unrelated to drinking behavior or drug experimentation.Conclusions: ELA leads to blunted stress reactivity and, independently, contributes to potentially risky drinking and drug-use behaviors in persons carrying 1 or 2 copies of the COMT 158Met allele. The results reinforce the impact of early experience on the stress axis and on risky behaviors, and they point to the 158Met allele as conveying a vulnerability to the early environment.

Early Life Stress and Risks for Opioid Misuse: Review of Data Supporting Neurobiological Underpinnings

“…Early life stress is associated with deficits in emotion regulation and neuroendocrine responses to stress that persist into adulthood and are associated with the development of several forms of psychopathology [ 5 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 ]. Recently, it has been suggested that such deficits may be intermediaries in the pathway that links ELS with the development of OUD [ 90 , 103 , 119 , 120 , 121 ].…”

Dimensions of Craving Interact with COMT Genotype to Predict Relapse in Individuals with Alcohol Use Disorder Six Months after Treatment

“…This is an important issue in genetic research that should be investigated in the future. However, Lovallo et al [ 93 ] did include genetic ancestry in a model related to alcohol use disorder, and discovered these factors were not significant contributors in the relationship between COMT genotype and cortisol response. Recent publications [ 78 , 94 , 95 ] have also not included genetic ancestry, so although this does remain a limitation in the current study, our results merit further investigations regarding the relationship of COMT and AUD.…”

Effect of Catechol-O-Methyltransferase Genotype Polymorphism on Neurological and Psychiatric Disorders: Progressing Towards Personalized Medicine

“…Another study done in 2019 included 480 young adults to assess the likelihood of alcohol and drug use in people who experienced early-life adversity (ELA) in the presence of a COMT genotype. [24].…”

“…In addition, ELA predicted earlier age of first alcoholic drink with a greater effect in Met allele than in Val/Val genotype. The study concluded that people with Val/Met or Met/Met variant of COMT who had exposure to ELA are more vulnerable to risky drinking behavior [ 24 ].…”