Department of Psychiatry and Psychological Medicine, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia.
Ruder Boskovic Institute, 10 000 Zagreb, Croatia.
Curr Issues Mol Biol. 2021 Jul 8;43(2):618-636. doi: 10.3390/cimb43020045.
Negative symptoms of schizophrenia, including anhedonia, represent a heavy burden on patients and their relatives. These symptoms are associated with cortical hypodopamynergia and impaired striatal dopamine release in response to reward stimuli. Catechol-O-methyltransferase (COMT) and monoamine oxidase type B (MAO-B) degrade dopamine and affect its neurotransmission. The study determined the association between rs4680 and rs4818, rs1799836 and rs6651806 polymorphisms, the severity of negative symptoms, and physical and social anhedonia in schizophrenia. Sex-dependent associations were detected in a research sample of 302 patients with schizophrenia. In female patients with schizophrenia, the presence of the G allele or GG genotype of rs4680 and rs4818, as well as GG haplotype rs4818-rs4680, which were all related to higher COMT activity, was associated with an increase in several dimensions of negative symptoms and anhedonia. In male patients with schizophrenia, carriers of the rs1799836 A allele, presumably associated with higher MAO-B activity, had a higher severity of alogia, while carriers of the A allele of the rs6651806 had a higher severity of negative symptoms. These findings suggest that higher dopamine degradation, associated with COMT and MAO-B genetic variants, is associated with a sex-specific increase in the severity of negative symptoms in schizophrenia patients.
精神分裂症的阴性症状，包括快感缺失，给患者及其亲属带来了沉重的负担。这些症状与皮质下多巴胺能减退和纹状体多巴胺释放对奖励刺激的反应受损有关。儿茶酚-O-甲基转移酶（COMT）和单胺氧化酶 B（MAO-B）降解多巴胺并影响其神经传递。该研究确定了 rs4680 和 rs4818、rs1799836 和 rs6651806 多态性与精神分裂症阴性症状严重程度以及身体和社交快感缺失之间的关系。在 302 名精神分裂症患者的研究样本中检测到了性别依赖性关联。在女性精神分裂症患者中，rs4680 和 rs4818 的 G 等位基因或 GG 基因型的存在，以及与 COMT 活性更高相关的 rs4818-rs4680 GG 单倍型，与阴性症状和快感缺失的多个维度的增加有关。在男性精神分裂症患者中，携带 rs1799836 A 等位基因的患者，可能与 MAO-B 活性更高有关，其言语贫乏的严重程度更高，而携带 rs6651806 A 等位基因的患者其阴性症状的严重程度更高。这些发现表明，与 COMT 和 MAO-B 遗传变异相关的多巴胺降解增加与精神分裂症患者阴性症状严重程度的性别特异性增加有关。
