COMT-Val158Met polymorphism modulates antipsychotic effects on auditory verbal hallucinations and temporal lobe gray matter volumes in healthy individuals-symptom relief accompanied by worrisome volume reductions.

Abstract	Investigation of auditory verbal hallucinations (AVHs) in schizophrenics is complicated by psychiatric symptoms. Investigating healthy individuals with AVHs (H-AVHs) can obviate such confounding factors. The objective of this study was to explore the effects of antipsychotic treatment on AVHs and gray matter volumes (GMVs) in H-AVH subjects and whether such are effects are influenced by COMT-Val158Met genotype. Magnetic resonance imaging (MRI) and genotyping studies were completed for 42 H-AVH subjects and 42 well-matched healthy controls (HCs). COMT-Met/Met homozygotes (158th codon) were identified as COMT-Met genotype; COMT-Met/Val heterozygotes and COMT-Val/Val homozygotes were identified as COMT-Val genotype. Data were compared across groups (H-AVH vs. HC, and between genotypes) with two-sample t-tests. The H-AVH COMT-Met group showed a stronger response to antipsychotic treatment than the H-AVH COMT-Val group (p < 0.001). Both H-AVH genotype groups exhibited temporal lobe GMV reductions after treatment, and relative to their respective genotype-matched HC groups. Antipsychotic treatment effects in H-AVH subjects were influenced by COMT-Val158Met genotype and associated with widespread GMV reductions. These findings provide clues for further exploration of treatment targets for AVHs. Treatment associated GMV reductions, however, raise concerns about use of antipsychotics in H-AVH subjects.
Authors	Chuanjun Zhuo, Langlang Cheng, Gongying Li, Yong Xu, Rixing Jing, Shen Li, Li Zhang, Xiaodong Lin, Chunhua Zhou
Journal	Brain imaging and behavior (Brain Imaging Behav) Vol. 14 Issue 5 Pg. 1373-1381 (Oct 2020) ISSN: 1931-7565 [Electronic] United States
PMID	30712251 (Publication Type: Journal Article)
Chemical References	Antipsychotic Agents COMT protein, human Catechol O-Methyltransferase
Topics	Antipsychotic Agents (therapeutic use) Catechol O-Methyltransferase (genetics) Genotype Gray Matter (diagnostic imaging, drug effects) Hallucinations (diagnostic imaging, drug therapy, genetics) Humans Magnetic Resonance Imaging Temporal Lobe

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