Sulfur Amino Acid Metabolic Process Pathway may Modulate Bipolar Disorder with Alcohol Dependence Comorbidity

Abstract

Background: A relationship between alcohol use disorder and Bipolar Disorder (BD) has far been detected. A record of alcohol dependence may worsen the course of BD. Nevertheless, the genetic underpinnings of this comorbidity have not been completely elucidated. Authors investigated the impact of a set of genetic variations as possible risk factors for the pathological mood swings in bipolar patients with a record of alcohol dependence. Methods: A list of candidate genes identified as risk loci by GWAS studies in last 10 years were tested in a sample of 802 bipolar patients from the public available STEP-BD study. Variations harbored by these genes were checked for quality, imputed and pruned. A set of 260 genes embedded in 160 different pathways were analyzed as predictors of the frequency of severe (YMRS>11) manic events and depressive phases (MADRS>19) during the period of observation (1139 days for manic records and 1856 for depressive records). Their effect was tested in combination with alcohol comorbidity. Clinical and sociodemographic variables entered the study as covariates when significantly associated with the phenotypes. Results: We found an impact of alcohol dependence positive record with a higher frequency of severe manic (p=0.02) and depressive (p=0.0006) records. A positive association between a pathway related to the Sulfur amino acid metabolic process (GO:0000096) and an increased frequency of severe depressive records was detected for BD subjects with a record of alcohol dependence. Discussion: We found an association between GO: 0000096 (Sulfur amino acid metabolic process pathway) and severe depressive episodes in BD patients with a record of alcohol dependence in their clinical story.