Genetic and Environmental Predictors of Early Alcohol Use

Kaufman, Joan; Yang, Bao Zhu; Douglas‐Palumberi, Heather; Crouse-Artus, Mindy; Lipschitz, Deborah S.; Krystal, John H.; Gelernter, Joel

doi:10.1016/j.biopsych.2006.06.039

Cited by 186 publications

(162 citation statements)

References 43 publications

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“…One answer comes from childhood studies showing that the same genotype is associated with vulnerability to adversity and with benefit from positive environmental factors (social support). 31,152 These results suggest that the 5-HTTLPR short allele confers a general sensitivity to both positive and negative aspects of environment. It remains to be established whether this sensitivity extends to adolescence and adulthood and what are the underlying neural and psychological mechanisms.…”

Section: Interpreting the Resultsmentioning

confidence: 84%

“…The studies summarised above reported that 5-HTTLPR genotype moderates the effect of environmental adversity on the onset of diagnosed depression, 11,15,32,35,37 on a continuous measure of depressive symptoms, 29,31,34,[40][41][42] on severity of depression within a group of diagnosed patients 36 and on suicidality. 11,47 Additional recent studies have found similar relationship for alcohol and drug use 43,59,152 and for violent criminal behaviour. 153 Evidence from animal studies also supports the 5-HTTLPR G Â E in the genesis of alcohol dependence.…”

Section: Genetic Control Of the Environmentmentioning

confidence: 73%

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The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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Section: Interpreting the Resultsmentioning

confidence: 84%

Section: Genetic Control Of the Environmentmentioning

confidence: 73%

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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“…This report adds to the growing literature documenting specific examples of gene-by-environment interaction involving the 5-HTTLPR variant at the SLC6A4 locus; we now add AS to previously studied phenotypes that already include depression and alcohol use (Kaufman et al, 2006a). These results are surprising in their consistency (although, as noted above, some studies have not been consistent), and together, they suggest that this one variant plays a very substantive role in modulating an individual's stress sensitivity or resilience.…”

Section: Discussionmentioning

confidence: 79%

Gene-by-Environment (Serotonin Transporter and Childhood Maltreatment) Interaction for Anxiety Sensitivity, an Intermediate Phenotype for Anxiety Disorders

Stein

Schork

Gelernter

2007

Neuropsychopharmacol

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202

146

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Anxiety sensitivity (AS) is a dispositional characteristic that predisposes to the development of anxiety disorders (eg, panic and posttraumatic stress disorder) and major depression. AS is subject to genetic and environmental influences, the former as yet unidentified and the latter known to include childhood maltreatment. The serotonin transporter gene (SLC6A4) promoter polymorphism (5-HTTLPR) has been associated with depression, but most consistently in the context of environmental stress. We tested the hypothesis that 5-HTTLPR genotype and childhood maltreatment would interact to increase susceptibility to AS in young adults. Subjects were European-American college undergraduates (N ¼ 150, median age 18 years) characterized on a measures of AS (Anxiety Sensitivity Index) and retrospective childhood maltreatment (Childhood Trauma Questionnaire [CTQ]). 5-HTTLPR genotypes were obtained from blood-derived DNA. Linear regression was used to model relationships between 5-HTTLPR, childhood emotional abuse, and AS; covariates such as sex, neuroticism, and ancestral proportion scores were incorporated into some models in a larger, ethnically heterogenous sample (N ¼ 247) to evaluate robustness of the findings to model assumptions. A statistically signficant interaction was observed between levels of childhood emotional (or physical) maltreatment and 5-HTTLPR genotype. Specifically, S/S individuals with higher levels of maltreatment had significantly higher levels of AS than subjects in other groups. No such relationship was found for neuroticism, attesting to the possible specificity of the findings for AS. Findings were consistently robust to the inclusion of covariates, and were not confounded by population stratification. In conclusion, these results provide evidence of a specific genetic influence on anxiety sensitivityFan intermediate phenotype for anxiety (and depressive) disorders; this effect is modified by severity of childhood maltreatment. These findings are consistent with the notion that 5-HTTLPR operates broadly to moderate emotional responsivity to stress.

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“…Ten studies estimating the associations of an interaction between the 5-HTTLPR genotype and an environmental factor with alcohol use and misuse were found, two that examined rhesus monkeys [28,30] and eight that examined humans [29,[31][32][33][34][35][36][37]. Descriptions of the studies are presented in Tables 1 and 2.…”

Section: Resultsmentioning

confidence: 99%

“…Studies recruited participants through flyers, advertisements, emails [34,36], questionnaires on youth psychosocial health [29,31,33,35], and from treatment programs [32,37]. Four of the eight studies of humans were longitudinal [31][32][33]35], and four cross-sectional [29,34,36,37].…”

Section: Recruitment and Designsmentioning

confidence: 99%

Serotonin transporter genotype by environment: Studies on alcohol use and misuse in non-human and human primates

Todkar

Nilsson

Oreland

et al. 2013

Translational Neuroscience

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Much evidence indicates that gene-by-environment interactions (GxE) play a role in alcohol misuse. It has been proposed that interactions between serotonin and stress confer vulnerability for alcohol misuse. The present review examined studies of the interaction between the serotonin transporter linked polymorphic region (5-HTTLPR) genotype and stressful life events and alcohol-related phenotypes, in rhesus monkeys and humans. Ten studies were found that had investigated the interaction of 5-HTTLPR and various measures of stress and alcohol use or misuse, two studies of rhesus monkeys, and eight of humans. The results are contradictory. Important differences were reported in study samples, experimental designs, measures used to assess environmental variables, definitions and measurements of alcohol-related phenotypes, and in the statistical analyses. These differences may explain the contradictory results. Guidelines for future studies are suggested. Results are discussed in light of findings from molecular, non-human animal, and clinical studies. The review highlights the need for future studies examining associations of interactions between the serotonin transporter gene and environmental factors and alcohol misuse, especially in samples followed over time.

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Genetic and Environmental Predictors of Early Alcohol Use

Cited by 186 publications

References 43 publications

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

Gene-by-Environment (Serotonin Transporter and Childhood Maltreatment) Interaction for Anxiety Sensitivity, an Intermediate Phenotype for Anxiety Disorders

Serotonin transporter genotype by environment: Studies on alcohol use and misuse in non-human and human primates

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