Anxiety and COMT: Study on the Role of Genetics in Anxiety Disorders

Background: Many studies have shown that anxiety disorders run in families and it is believed to be influenced by the interaction of several genes. However, little is known about the the genes that influences predisposition to anxiety.

Objective: The objective of this study is to determine if there is any association between certain genes and anxiety disorders. Subjects: 420 subjects from 10 clinical research sites in the United States. 210 diagnosed with anxiety disorders ICD9 code 300.00 (Anxiety state, unspecified), 300.02 (Generalized anxiety disorder), 300.09 (other anxiety states), and 210 controls with no diagnosis of anxiety disorders. Average age 52.

Methods: Subjects were genotyped with the proprietary Proove Narcotic Risk Genetics Profile using TaqMan SNP genotyping assays (Life Technologies, Carlsbad, CA). A panel of 12 SNPs (DRD1 -48A>G, DRD2 A1 allele, DRD4 -521C/T, DAT1, COMT Vall58Met, OPRK1 36G >T, OPRM1 A118G, DBH -1021 C/T, 5-HT2A -1438G/A, 5-HTTLPR, Gamma-Aminobutyric Acid (GABRA 6) (1519T>C GABA(A)gamma 2, and MTHFR C677T)

Results: Cross tab analysis using IBM SPSS Version 21 showed COMT as the only gene to show association with anxiety disorders (P=0.027). Further analysis with a multinomial logistic regression found COMT homozygous mutation to be associated with subjects with anxiety disorders compared to the controls who were associated with both normal and heterozygous COMT (P= 0.022 or 6.225). Also females were more prevalent in the anxiety disorders population compared to males (P= 0.042).

Conclusion: This study suggests that mutation in COMT may play a role in genetic predisposition to anxiety disorders. Findings in this study are in line with other study findings that have found women to have higher prevalence rates of anxiety disorders compared to men. This study will hopefully help improve understanding on the role of genetics in anxiety and stimulate further work in this area.