Dataset Information

Relationship between the serotonin transporter polymorphism and obsessive-compulsive alcohol craving in alcohol-dependent adults: a pilot study.

ABSTRACT: A serotonin deficiency state has been implicated in alcohol-dependent individuals' experience of obsessive-compulsive alcohol craving. Because the serotonin transporter (5-HTT) functions to remove serotonin from the synapse, it is thought that increased reuptake (indicated by the number of high-expressing L(A) alleles present in the 5-HTT gene-linked polymorphic region [5-HTTLPR] of the SLC6A4 gene) is associated with an increase in obsessive-compulsive alcohol craving. The current pilot investigation sought to explore this hypothesis by examining the extent to which obsessive-compulsive alcohol craving varies by 5-HTTLPR genotype among participants enrolled in an ongoing pharmacogenetics trial. All participants were screened with a semi-structured diagnostic interview, completed self-report measures of alcohol-related behavior, and underwent peripheral venous blood draw for DNA genotyping. Cross-sectional data obtained at baseline from 176 currently drinking alcohol-dependent individuals were analyzed using multiple regression. Preliminary findings suggest that 5-HTTLPR is not predictive of Obsessive Compulsive Drinking Scale total and factor scores. Although the 5-HTTLPR polymorphism was not related to obsessive-compulsive alcohol craving in this pilot study, additional research is needed to clarify the possible role of serotonergic mechanisms in alcohol craving.

SUBMITTER: Thompson RD

PROVIDER: S-EPMC2932830 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Relationship between the serotonin transporter polymorphism and obsessive-compulsive alcohol craving in alcohol-dependent adults: a pilot study.

Thompson Rachel D RD Heffner Jaimee L JL Strong Judith A JA Blom Thomas J TJ Anthenelli Robert M RM

Alcohol (Fayetteville, N.Y.) 20100703 5

A serotonin deficiency state has been implicated in alcohol-dependent individuals' experience of obsessive-compulsive alcohol craving. Because the serotonin transporter (5-HTT) functions to remove serotonin from the synapse, it is thought that increased reuptake (indicated by the number of high-expressing L(A) alleles present in the 5-HTT gene-linked polymorphic region [5-HTTLPR] of the SLC6A4 gene) is associated with an increase in obsessive-compulsive alcohol craving. The current pilot investi ...[more]

PMID: 20598843

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Project description:We previously have shown that cue-induced alcohol craving and propensity for higher drinking are modulated by allelic differences in SLC6A4 associated with serotonin transporter (5-HTT) expression level alterations. In an independent study, we characterized another polymorphism, SNP rs1042173, in 3'-untranslated region (3'-UTR) of the same gene, which also altered 5-HTT expression levels; the T allele of rs1042173 was associated with lower mRNA and protein levels. In subsequent analyses, the TT genotype was found to be associated with higher drinking intensity in alcohol-dependent (AD) individuals of Caucasian descent. Building upon these findings, we hypothesized that the low-expressing TT genotype associated with intense drinking would predict higher craving for alcohol in AD individuals. In this pilot study, we sought to test our hypothesis by examining 34 Hispanic AD volunteers (mean age, 34.8 years) for rs1042173 genotype-based [i.e., TT versus TG/GG (Gx)] differences in subjective response to alcohol. We employed a human laboratory paradigm and analyzed the data using a linear mixed-effects model (SAS® PROC MIXED) to assess treatment, cue procedures, and genotype main effects as well as the two-way interaction effects between them. On subjective "urge to drink" and "crave for a drink," we found a significant main effect of the cue experiment (p ≤ 0.01) and an interaction effect between genotype and cue effects (p < 0.05). TT genotype was associated with higher urge to drink (p = 0.002) and crave for a drink (p = 0.005) when exposed to alcohol cue. Our results not only support the hypothesis that rs1042173 is a genetic marker for cue-induced alcohol craving among AD males but also are suggestive of a neurobiological mechanism associated with the rs1042173-TT genotype that triggers a disproportionate craving in response to alcohol consumption, which in turn may lead to more intense drinking. Future studies with larger sample sizes are needed to characterize the interactive effects of the serotonin transporter-linked polymorphic region (5'-HTTLPR)-L-allele reported in our previous study and of the rs1042173-TT genotype on cue-induced alcohol craving.

Project description:Background: While the Yale-Brown Obsessive-Compulsive Scale Second Edition (Y-BOCS-II) is the gold-standard for measurement of obsessive-compulsive (OC) symptom severity, its factor structure is still a matter of debate and, most importantly, criterion validity for diagnosis of OC disorder (OCD) has not been tested. This study aimed to clarify factor structure and criterion validity of the Y-BOCS-II. Methods: We first validated and quantified the psychometric properties of a culturally adapted Portuguese translation of the Y-BOCS-II (PY-BOCS-II). The PY-BOCS-II and other psychometric instruments, including the OCD subscale of the Structured Clinical Interview for the DSM-IV, used to define OCD diagnosis, were administered to 187 participants (52 patients with OCD, 18 with other mood and anxiety disorders and 117 healthy subjects). In a subsample of 20 OCD patients and the 18 patients with other diagnoses, PY-BOCS-II was applied by clinicians blinded to diagnosis. Results: PY-BOCS-II had excellent internal consistency (Cronbach's α = 0.96) and very good test-retest reliability (Pearson's r = 0.94). Exploratory factor analysis revealed a two-factor structure with loadings consistent with the Obsessions and Compulsions subscales, and there was good to acceptable convergent and divergent validity. Importantly, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve suggested elevated accuracy in discriminating between patients with OCD and control subjects (AUC = 0.96; 95% confidence interval [CI]: 0.92-0.99), that was retained in comparisons with age, gender and education matched controls (AUC = 0.95; 95% CI: 0.91-0.99), as well as with patients with other mood and anxiety disorders (AUC = 0.93; 95% CI: 0.84-1). Additionally, a cut-off score of 13 had optimal discriminatory ability for the diagnosis of OCD, with sensitivity ranging between 85 and 90%, and specificity between 94 and 97%, respectively when all samples or only the clinical samples were considered. Conclusion: The PY-BOCS-II has excellent psychometric properties to assess the severity of obsessive-compulsive symptoms, reflecting obsessive, and compulsive dimensions, compatible with currently defined subscales. Furthermore, we found that a cut-off of 13 for the Y-BOCS-II total score has good to excellent sensitivity and specificity for the diagnosis of OCD.

Dataset Information

Relationship between the serotonin transporter polymorphism and obsessive-compulsive alcohol craving in alcohol-dependent adults: a pilot study.

Publications

Relationship between the serotonin transporter polymorphism and obsessive-compulsive alcohol craving in alcohol-dependent adults: a pilot study.

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