Zhuo Chuanjun, Xu Yong, Zhang Li, Jing Rixing, Zhou Chunhua
Department of Psychiatric-Neuroimaging-Genetics and Comorbidity Laboratory (PNGC-Lab), Tianjin Mental Health Centre, Mental Health Teaching Hospital of Tianjin Medical University, Tianjin Anding Hospital, Tianjin, China.
Department of Psychiatry, College of Basic Medical Science, Tianjin Medical University, Tianjin, China.
Front Genet. 2019 Mar 6;10:92. doi: 10.3389/fgene.2019.00092. eCollection 2019.
Few studies have been conducted to explore the influence of the catechol-o-methyltransferase () 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 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 genotype or not. We found that -met genotype subjects' treatment response was better than that of -val subjects. Although -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 -met genotype subjects than in -val genotype subjects. This is the first study to report that Hi-AVH subjects' baseline brain functional features are influenced by their genotypes and that the -met genotype subjects exhibit better responses to dopamine antagonists but have more widespread GMV and gFCD reduction than subjects with the -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.
很少有研究探讨儿茶酚-O-甲基转移酶（COMT）基因型对患有幻听（AVH）的健康个体（Hi-AVH）中AVH症状严重程度和治疗效果的影响。我们假设多巴胺拮抗剂治疗Hi-AVH中AVH的疗效可能受其COMT基因型影响，并可能伴有相应的脑改变。为了在一项人工控制的初步研究中初步调查和检验我们的假设，我们招募了42名Hi-AVH作为受试者，并使用磁共振成像和基因方法来探索基础脑特征，以研究多巴胺拮抗剂治疗Hi-AVH受试者中AVH的疗效是否受其COMT基因型影响。我们发现COMT-Met基因型受试者的治疗反应优于COMT-Val受试者。虽然与COMT-Val基因型受试者相比，COMT-Met基因型受试者在基线时整体功能连接密度（gFCD）增加但灰质体积（GMV）无差异，但值得注意的是，我们发现两组在治疗后gFCD和GMV均降低，但COMT-Met基因型受试者的降低比COMT-Val基因型受试者更广泛。这是第一项报告Hi-AVH受试者的基线脑功能特征受其COMT基因型影响，且COMT-Met基因型受试者对多巴胺拮抗剂表现出更好反应，但与COMT-Val基因型受试者相比，GMV和gFCD降低更广泛的研究。尽管存在一些局限性，但这些发现可能为进一步解释AVH的机制提供辅助信息，并为学者进一步探索Hi-AVH受试者或精神分裂症患者中AVH的特定治疗靶点提供线索。
