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Glutamatergic and HPA-axis pathway genes in bipolar disorder comorbid with alcohol- and substance use disorders

Content Provider	Springer Nature Link
Author	Dalvie, Shareefa Fabbri, Chiara Ramesar, Raj Serretti, Alessandro Stein, Dan J.
Copyright Year	2015
Abstract	Glutamatergic neurotransmission has been shown to be dysregulated in bipolar disorder (BD), alcohol use disorder (AUD) and substance use disorder (SUD). Similarly, disruption in the hypothalamic-pituitary-adrenal (HPA)-axis has also been observed in these conditions. BD is often comorbid with AUD and SUD. The effects of the glutamatergic and HPA systems have not been extensively examined in individuals with BD-AUD and BD-SUD comorbidity. The aim of this investigation was to determine whether variants in the glutamatergic pathway and HPA-axis are associated with BD-AUD and BD-SUD comorbidity. The research cohort consisted of 498 individuals with BD type I from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). A subset of the cohort had comorbid current AUD and current SUD. A total of 1935 SNPs from both the glutamatergic and HPA pathways were selected from the STEP-BD genome-wide dataset. To identify population stratification, IBS clustering was performed using the program Plink 1.07. Single SNP association and gene-based association testing were conducted using logistic regression. A pathway analysis of glutamatergic and HPA genes was performed, after imputation using IMPUTE2. No single SNP was associated with BD-AUD or BD-SUD comorbidity after correction for multiple testing. However, from the gene-based analysis, the gene PRKCI was significantly associated with BD-AUD. The pathway analysis provided overall negative findings, although several genes including GRIN2B showed high percentage of associated SNPs for BD-AUD. Even though the glutamatergic and HPA pathways may not be involved in BD-AUD and BD-SUD comorbidity, PRKCI deserves further investigation in BD-AUD.
Starting Page	183
Ending Page	189
Page Count	7
File Format	PDF
ISSN	08857490
Journal	Metabolic Brain Disease
Volume Number	31
Issue Number	1
e-ISSN	15737365
Language	English
Publisher	Springer US
Publisher Date	2015-11-12
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Alcoholism Bipolar disorder Gene Polymorphism Pathway Sub-phenotype Neurosciences Neurology Metabolic Diseases Biochemistry Oncology
Content Type	Text
Resource Type	Article
Subject	Biochemistry Neurology (clinical) Cellular and Molecular Neuroscience

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