Gene-environment interplay in alcoholism and other substance abuse disorders: Expressions of heritability and factors influencing vulnerabilities

Abstract

Factors that confer predisposition and vulnerability for alcoholism and other substance abuse disorders may be described usefully within the gene-environment interplay framework. Thus, it is postulated that heritability provides a major contribution not only to alcohol but also to other substances of abuse. Studies of evoked potential amplitude reduction have provided a highly suitable and testable method for the assessment of both environmentally-determined and heritable characteristics pertaining to substance use and dependence. The different personal attributes that may co-exist with parental influence or exist in a shared, monozygotic relationship contribute to the final expression of addiction. In this connection, it appears that personality disorders are highly prevalent co-morbid conditions among addicted individuals, and, this co-morbidity is likely to be accounted for by multiple complex etiological relationships, not least in adolescent individuals. Co-morbidity associated with deficient executive functioning may be observed too in alcohol-related aggressiveness and crimes of violence. The successful intervention into alcohol dependence and craving brought about by baclofen in both human and animal studies elucidates glutamatergic mechanisms in alcoholism whereas the role of the dopamine transporter, in conjunction with both the noradrenergic and serotonergic transporters, are implicated in cocaine dependence and craving. The role of the cannabinoids in ontogeny through an influence upon the expression of key genes for the development of neurotransmitter systems must be considered. Finally, the particular form of behaviour/characteristic outcome due to childhood circumstance may lie with biological, gene-based determinants, for example individual characteristics of monoamine oxidase (MAO) activity levels, thereby rendering simple predictive measures both redundant and misguiding.

Perinatal kynurenine 3‐hydroxylase inhibition in rodents: Pathophysiological implications

“…In addition, abnormally high KYNA levels, leading to α7nACh and NMDA hypofunction during a critical period of brain development, may result in pathological changes later in life. This could be especially detrimental in individuals with a genetic vulnerability for brain diseases such as schizophrenia and substance abuse, which have been linked to such early neurochemical impairments (Palomo et al, 2004; Rapoport et al, 2005).…”

Treatment of substance use disorders in schizophrenia: A unifying neurobiological mechanism?

“…Numerous authors have proposed neural diathesis-stress models whereby some form of genetically-based neurobiological vulnerability interacts with environmental stressors to precipitate the onset of schizophrenia [65,66] or SUD [67]. Vulnerability to schizophrenia and SUDs may be related to each other in such models, with substance use serving as the environmental stressor precipitating onset of psychosis and relapse in vulnerable individuals [68].…”

Pairing mild stress with increased serotonin‐1B receptor expression in the nucleus accumbens increases susceptibility to amphetamine

“…Both genetic and environmental factors can have a huge impact on the effects of psychostimulant drugs but the way in which interactions between these factors influence addiction remains to be elucidated (Palomo et al. , 2004; Kreek et al.…”

“…This is not an easy task, however, as an individual’s initial response to psychostimulant drugs varies widely, as does susceptibility to addiction. Both genetic and environmental factors are thought to play essential roles in addiction vulnerability but how interactions between these components influence the development of addiction is not yet well understood (Palomo et al. , 2004; Kreek et al.…”