AUTHOR=Zhuo Chuanjun , Xu Yong , Zhang Li , Jing Rixing , Zhou Chunhua 

TITLE=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

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.00092

DOI=10.3389/fgene.2019.00092

ISSN=1664-8021

ABSTRACT=<p>Few studies have been conducted to explore the influence of the catechol-o-methyltransferase (<italic>COMT</italic>) 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 <italic>COMT</italic> 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 <italic>COMT</italic> genotype or not. We found that <italic>COMT</italic>-met genotype subjects’ treatment response was better than that of <italic>COMT</italic>-val subjects. Although <italic>COMT</italic>-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 <italic>COMT</italic>-met genotype subjects than in <italic>COMT</italic>-val genotype subjects. This is the first study to report that Hi-AVH subjects’ baseline brain functional features are influenced by their <italic>COMT</italic> genotypes and that the <italic>COMT</italic>-met genotype subjects exhibit better responses to dopamine antagonists but have more widespread GMV and gFCD reduction than subjects with the <italic>COMT</italic>-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.</p>