Background
Alcohol Dependence (AD) is often accompanied by co-morbid depression. Recent clinical evidence supports the benefit of subtype specific pharmacotherapy in treating the population of AD subjects with co-morbid major depressive disorder (MDD). However, in many AD 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 co-morbid depression.
Methods
Subjects from Vienna, Austria (n = 323) were genotyped and SNPs (1,152) encompassing the genetic locations of the nine ADCY genes were examined. The Vienna cohort contained alcohol dependent subjects differentiated using the Lesch Alcoholism Typology. In this typology subjects are segregated into four types. Type III alcoholism is distinguished by co-occurrence of symptoms of depression and by affecting predominantly females.
Results
We identified four 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, two haplotypes were within ADCY5, and one haplotype was within the coding region of ADCY8. Three of the four 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 AD phenotype in females, which is distinguished by co-morbid 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.
The psychodynamic instruments introduced in this study proved to be effective in measuring personality pathology in psychiatric inpatients and in helping clinicians throughout the indication and recommendation process during transition from inpatient to outpatient treatment. Since components of such assessment methods are being considered for DSM 5, their practical utility is shown in this study.
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