Apathy is associated with a single-nucleotide polymorphism in a dopamine-related gene

• We focused on 4 functional SNPs in dopamine transmission.
• The relationship between the 4 SNPs and apathy was analyzed.
• We selected 963 neurologically normal subjects as participants.
• A SNP in the COMT gene is associated with a lower risk of apathy.
• Dopaminergic neurotransmission is important in the pathogenesis of apathy.

Dopaminergic neurotransmission is an important factor in the pathogenesis of apathy. In addition, the contribution of genetic factors to the regulation of brain dopaminergic activity is widely acknowledged. Therefore, we hypothesized that genes associated with brain dopaminergic activity may have some effects on apathy. In the current study, we evaluated the association between four functional single-nucleotide polymorphisms (SNPs) in specific genes related to dopaminergic neurotransmission and apathy in a general population. Participants in the health examination at the Shimane Institute of Health Science were recruited for this study (n = 963). Apathy was assessed using the Japanese version of the apathy scale. SNPs were genotyped using the TaqMan method. In our population, 22.1% had apathy. We confirmed that apathy was associated with decreased cognitive function and depressive state. A significant association was found between an SNP in the catechol-O-methyltransferase (COMT) gene (rs4680) encoding the low-activity Met allele and apathy. This relationship was still significant after adjustment for confounding factors. Our study indicates an association between rs4680, an SNP in the COMT gene, and lower risk of apathy. Considering the function of rs4680, the current study suggests the importance of dopaminergic neurotransmission in the pathogenesis of apathy in a general population.