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Few studies have been conducted to explore the influence of the catechol-o-methyltransferase ( COMT ) genotype on the severity of and treatment efficacy on auditory verbal hallucination (AVH) symptoms in healthy individuals with AVHs (Hi-AVHs). We hypothesized that the efficacy of dopamine antagonist treatment on AVHs in Hi-AVHs may be influenced by their  COMT  genotype and may be accompanied by corresponding brain alterations. To preliminarily investigate and test our hypothesis in an artificially controlled pilot study, we enrolled 42 Hi-AVHs as subjects and used magnetic resonance imaging and genetic methods to explore the basis brain features to investigate whether the efficacy of dopamine antagonist treatment on AVHs in Hi-AVH subjects was influenced by their  COMT  genotype or not. We found that  COMT -met genotype subjects’ treatment response was better than that of  COMT -val subjects. Although  COMT -met genotype subjects demonstrated an increase in global functional connectivity density (gFCD) but no difference on gray matter volume (GMV) compared to COMT-val genotype subjects at baseline, notably, we found that both groups demonstrated gFCD and GMV reduction after treatment, but the reduction was more widespread in  COMT -met genotype subjects than in  COMT -val genotype subjects. This is the first study to report that Hi-AVH subjects’ baseline brain functional features are influenced by their  COMT  genotypes and that the  COMT -met genotype subjects exhibit better responses to dopamine antagonists but have more widespread GMV and gFCD reduction than subjects with the  COMT -val genotype. Despite several limitations, these findings may provide auxiliary information to further explain the mechanisms of AVHs and provide a clue for scholars to further explore specific treatment targets for AVHs in Hi-AVH subjects or in schizophrenia patients.

frontiers in genetics

The Effect of Dopamine Antagonist Treatment on Auditory Verbal Hallucinations in Healthy Individuals Is Clearly Influenced by COMT Genotype and Accompanied by Corresponding Brain Structural and Functional Alterations: An Artificially Controlled Pilot Study