Effects of Family History of Alcohol Dependence on the Subjective Response to Alcohol Using the Intravenous Alcohol Clamp

Kerfoot, Karin; Pittman, Brian; Ralevski, Elizabeth; Limoncelli, Diana; Koretski, Julia; Newcomb, Jenelle; Arias, Albert J.; Petrakis, Ismene L.

doi:10.1111/acer.12199

Cited by 29 publications

(27 citation statements)

References 38 publications

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“…Participants were then given a light breakfast. See Kerfoot et al (2013) for further detail regarding procedures.…”

Section: Methodsmentioning

confidence: 99%

“…The present report is a secondary analysis of data from a study designed to compare the effects of two ethanol doses and placebo on subjective response to ethanol and cognitive function in non-alcohol-dependent, family history positive versus negative young adults (Kerfoot et al 2013). In the parent study, participants responded to IV ethanol administration with clamping technique in a dose-related, time-dependent manner on measures of subjective effects and showed impaired coordination and impaired performance on cognitive measures.…”

Section: Introductionmentioning

confidence: 99%

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Relationships between impulsivity and subjective response in an IV ethanol paradigm

et al. 2014

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Rationale: Impulsivity and individual differences in subjective response to alcohol are risk factors for alcohol problems and possibly endophenotypes for alcohol dependence. Few prior studies have addressed relationships between the two constructs. Objectives: To predict subjective responses to ethanol, we tested self-reported impulsiveness, ethanol dose condition (high dose, low dose or placebo) and time (7 timepoints) along with interactions among these variables. Methods: The present study is a secondary analysis of data from a within subject, placebo-controlled, dose-ranging ethanol administration study using IV infusion with a clamping technique to maintain steady-state breath alcohol concentration. The sample consisted of healthy, non-alcohol dependent social alcohol drinkers between the ages of 21-30 (N=105). Participants at varying levels of impulsivity were compared with regard to stimulant and subjective responses to three ethanol dose conditions over time. Results: Individuals with higher impulsivity reported stronger stimulant and weaker sedative response to alcohol, particularly at the higher dose. Higher impulsivity was associated with a steeper increase in stimulant effects during the first half of clamped ethanol infusion with the higher dose. Conclusions: These results suggest that impulsive individuals may experience enhanced reinforcing, stimulant effects and relatively muted aversive, sedative effects from alcohol. These subjective responses may relate to enhanced risk of alcohol problems among more impulsive individuals.

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“…Participants were then given a light breakfast. See Kerfoot et al (2013) for further detail regarding procedures.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Relationships between impulsivity and subjective response in an IV ethanol paradigm

et al. 2014

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“…Morzorati et al, 2002; Schuckit and Smith, 1996) though several studies have not (e.g. (Kerfoot et al, 2013; Wetherill et al, 2012). It is possible that in the present study, the genotypic effects of GABRA2 accounted for much of the variability in the acute adaptation of subjective perceptions, and that family history did not account for a substantial portion of the remaining variability.…”

Section: Discussionmentioning

confidence: 99%

Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking

Kosobud

Wetherill

Plawecki

et al. 2015

Alcoholism Clin & Exp Res

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Background Subjective perceptions of alcohol intoxication are associated with altered risk for alcohol abuse and dependence. Acute adaptation of these perceptions may influence such risk, and may involve genes associated with pleasant perceptions or the relief of anxiety. This study assessed the effect of variation in the GABAA receptor genes GABRG1 and GABRA2 and recent drinking history on the acute adaptation of subjective responses to alcohol. Methods 132 non-dependent moderate to heavy drinkers, aged 21–27, participated in 2 single-blind, counterbalanced sessions, approximately one week apart. One session was an intravenous alcohol “clamp”, during which breath alcohol concentration was held steady at 60 mg/dL (60 mg%) for 3 hours, and the other an identical session using saline infusion. Subjective perceptions of intoxication, enjoyment, stimulation, relaxation, anxiety, tiredness and estimated number of drinks were acquired before (baseline), and during the first and final 45 minutes of the clamp. A placebo-adjusted index of the subject’s acute adaptation to alcohol was calculated for each of the 7 subjective measures, and used in a principal component analysis to create a single aggregate estimate for each subject’s adaptive response to alcohol. Analysis of covariance tested if GABRA2 and GABRG1 single nucleotide polymorphism (SNP) genotypes, gender, placebo session, family history of alcoholism, recent drinking history, and the genotype x recent drinking history interaction significantly predicted the adaptive response. Results Recent drinking history (p=0.01), and recent drinking history x genotype interaction (p=0.01) were significantly associated with acute adaptation of the subjective responses to alcohol for the GABRA2 SNP rs279858. Conclusion Higher recent drinking was found to be associated with reduced acute tolerance to positive, stimulating effects of alcohol in carriers of the rs279858 risk allele. We postulate that the GABRA2 effect on alcohol dependence may, in part, be due to its effect on subjective responses to alcohol.

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“…Complete details of the intravenous alcohol procedures used were published previously as the participants were recruited in a previous study which had a primary purpose to examine the effects of family history on alcohol response in the lab (Kerfoot et al, 2013). The institutional review boards of the VA Connecticut Healthcare System and Yale University School of Medicine approved this study.…”

Section: Methodsmentioning

confidence: 99%

“…Subjects were between the ages of 21 and 30 years old, without DSM-IV psychiatric or substance use disorder diagnoses (excluding alcohol abuse) as measured by the Structured Clinical Interview for DSM-IV (SCID) (First, 2007). Subjects were required to have a negative urine toxicology for drugs of abuse on test days, and could not be alcohol naïve (for more details, see Kerfoot et al, 2013). Women were required to have a negative pregnancy test at screening and on every test day.…”

Section: Methodsmentioning

confidence: 99%

GRIK1 and GABRA2 Variants Have Distinct Effects on the Dose‐Related Subjective Response to Intravenous Alcohol in Healthy Social Drinkers

Yang

Arias

Feinn

et al. 2017

Alcoholism Clin & Exp Res

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Background The heritable risk for alcohol use disorder (AUD) is expressed partly through alterations in subjective alcohol response. In this study, we investigated the effects of two AUD risk-associated single nucleotide polymorphisms (SNPs), GABRA2 rs279858 and GRIK1 rs2832407, on the subjective response to alcohol administered intravenously to healthy social drinkers in a laboratory setting. Methods 93 self-identified European American social drinkers underwent three blinded lab sessions in which they received intravenous infusions of ethanol at three target blood alcohol levels (0.00mg%, 40mg%, 100mg%) using a “clamp” procedure. The self-reported Biphasic Alcohol Effects Scale (BAES) stimulation and sedation subscales were the primary outcome measures. We examined the effects of these two genetic variants on subjective response to alcohol. Results For the BAES stimulation subscale scores, adjusting for age, baseline scores, and time effects, individuals with two copies of the GABRA2 rs279858 C “risk” allele for AUD exhibited the greatest stimulant responses to high dose alcohol compared to the other risk allele counts (dose-by-allele count interaction effect, p=0.001, post-hoc contrast for C-allele p=0.012). For the BAES sedation subscale scores, adjusting for the same covariates, we detected a dose-by-allele count interaction effect (p=0.0044) such that subjects with two copies of the GRIK1 C “risk” allele reported the greatest sedative response to the higher alcohol dose. Conclusions This study suggests that gene variants contributing to the risk for AUD may alter features of the alcohol dose-response relationship in specific ways. GABRA2 rs279858*C enhances stimulant responses to higher levels of alcohol, while the GRIK1 rs2832407*C allele increases sedative responses. In summary, GRIK1 and GABRA2 variants have distinct effects on the dose-related subjective response to intravenous alcohol in humans.

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Effects of Family History of Alcohol Dependence on the Subjective Response to Alcohol Using the Intravenous Alcohol Clamp

Cited by 29 publications

References 38 publications

Relationships between impulsivity and subjective response in an IV ethanol paradigm

Relationships between impulsivity and subjective response in an IV ethanol paradigm

Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking

GRIK1 and GABRA2 Variants Have Distinct Effects on the Dose‐Related Subjective Response to Intravenous Alcohol in Healthy Social Drinkers

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