These authors contributed equally to the manuscript.
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Original Article
Genetic Markers of Comorbid Depression and Alcoholism in Women
Article first published online: 27 DEC 2012
DOI: 10.1111/acer.12060
Copyright © 2012 by the Research Society on Alcoholism
Issue
Alcoholism: Clinical and Experimental Research
Early View (Online Version of Record published before inclusion in an issue)
Additional Information
How to Cite
Procopio, D. O., Saba, L. M., Walter, H., Lesch, O., Skala, K., Schlaff, G., Vanderlinden, L., Clapp, P., Hoffman, P. L. and Tabakoff, B. (2012), Genetic Markers of Comorbid Depression and Alcoholism in Women. Alcoholism: Clinical and Experimental Research. doi: 10.1111/acer.12060
- †
These authors contributed equally to the manuscript.
Publication History
- Article first published online: 27 DEC 2012
- Manuscript Accepted: 28 SEP 2012
- Manuscript Received: 30 MAR 2012
Funded by
- ONB-Jubilaeumsfonds. Grant Number: 13705
- Banbury Fund
- NIH/NIAAA. Grant Number: R24AA013162
- NIAAA. Grant Number: T32AA007464
- Abstract
- Article
- References
- Cited By
Keywords:
- Genetics;
- Alcoholism;
- Depression;
- Lesch Typology;
- Adenylyl Cyclases
Background
Alcohol dependence (AD) is often accompanied by comorbid depression. Recent clinical evidence supports the benefit of subtype-specific pharmacotherapy in treating the population of alcohol-dependent subjects with comorbid major depressive disorder (MDD). However, in many alcohol-dependent subjects, depression is a reactive response to chronic alcohol use and withdrawal and abates with a period of abstinence. Genetic markers may distinguish alcohol-dependent subjects with MDD not tied chronologically and etiologically to their alcohol consumption. In this work, we investigated the association of adenylyl cyclase genes (ADCY1–9), which are implicated in both AD and mood disorders, with alcoholism and comorbid depression.
Methods
Subjects from Vienna, Austria (n = 323) were genotyped, and single nucleotide polymorphisms (1,152) encompassing the genetic locations of the 9 ADCY genes were examined. The Vienna cohort contained alcohol-dependent subjects differentiated using the Lesch Alcoholism Typology. In this typology, subjects are segregated into 4 types. Type III alcoholism is distinguished by co-occurrence of symptoms of depression and by affecting predominantly females.
Results
We identified 4 haplotypes associated with the phenotype of Type III alcoholism in females. One haplotype was in a genomic area in proximity to ADCY2, but actually within a lincRNA gene, 2 haplotypes were within ADCY5, and 1 haplotype was within the coding region of ADCY8. Three of the 4 haplotypes contributed independently to Type III alcoholism and together generated a positive predictive value of 72% and a negative predictive value of 78% for distinguishing women with a Lesch Type III diagnosis versus women designated as Type I or II alcoholics.
Conclusions
Polymorphisms in ADCY8 and ADCY5 and within a lincRNA are associated with an alcohol-dependent phenotype in females, which is distinguished by comorbid signs of depression. Each of these genetic locations can rationally contribute to the polygenic etiology of the alcoholism/depression phenotype, and the use of these genetic markers may aid in choosing appropriate and beneficial treatment strategies.