To Each His Own Fear: Gender-Related Association of Anxiety, Substance Use, and Eating Disorders in a Representative Birth Cohort Sample of Young Adults with Either COMT Val158Met allele

Introduction: The role of catechol-O-methyltransferase (COMT) in catecholamine neurotransmitter metabolism has led to the investigation of variants of the corresponding gene in the etiology of different psychiatric disorders, but the results are inconclusive. Methods: We have examined the relationship between COMT Val158Met single nucleotide polymorphism (rs4680) and the occurrence of psychiatric disorders in a highly representative birth cohort sample of young adults in the Estonian Children Personality Behaviour and Health Study (original n = 1,238). The lifetime occurrence of psychiatric disorders at the age of 25 years was assessed with the Mini-International Neuropsychiatric Interview. Results: Both Val- and Met-alleles of the COMT Val158Met were associated with specific psychiatric disorders. Met-allele carriers had a significantly higher occurrence of agoraphobia (3.2% vs. 0.5%; chi(2) = 4.10; p < 0.05) compared to Val/Val homozygotes. Also, the occurrence of panic disorder was significantly higher in female Met-allele carriers than in Val/Val homozygote females (10.2% vs. 3.6%; chi(2) = 4.62 p = 0.03). In contrast, the occurrence of generalized anxiety disorder was higher in Val/Val females when compared to Met-allele carriers (12.7% vs. 6.8%; chi(2) = 4.16; p = 0.04). Also, female Val/Val homozygotes (15.5%) had a higher occurrence of eating disorders than Met-allele carriers (6.1%) of the COMT Val158Met polymorphism (chi(2) = 10.39; p = 0.002). In the whole sample, Met-allele homozygotes had a higher occurrence of alcohol use and substance use disorders than Val-allele carriers (chi(2) = 3.62 and 3.68, respectively; p < 0.05). Conclusion: In a regional highly birth cohort representative sample, either COMT rs4680 variant was observed in association with specific psychiatric disorders.