De Simone Giuseppe, Mazza Benedetta, Vellucci Licia, Barone Annarita, Ciccarelli Mariateresa, de Bartolomeis Andrea
Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences, and Dentistry, University Medical School of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.
UNESCO Chair on Health Education and Sustainable Development, University of Naples "Federico II", 80131 Naples, Italy.
Antioxidants (Basel). 2023 Apr 21;12(4):975. doi: 10.3390/antiox12040975.
Schizophrenia is a worldwide mental illness characterized by alterations at dopaminergic and glutamatergic synapses resulting in global dysconnectivity within and between brain networks. Impairments in inflammatory processes, mitochondrial functions, energy expenditure, and oxidative stress have been extensively associated with schizophrenia pathophysiology. Antipsychotics, the mainstay of schizophrenia pharmacological treatment and all sharing the common feature of dopamine D2 receptor occupancy, may affect antioxidant pathways as well as mitochondrial protein levels and gene expression. Here, we systematically reviewed the available evidence on antioxidants' mechanisms in antipsychotic action and the impact of first- and second-generation compounds on mitochondrial functions and oxidative stress. We further focused on clinical trials addressing the efficacy and tolerability of antioxidants as an augmentation strategy of antipsychotic treatment. EMBASE, Scopus, and Medline/PubMed databases were interrogated. The selection process was conducted in respect of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Several mitochondrial proteins involved in cell viability, energy metabolism, and regulation of oxidative systems were reported to be significantly modified by antipsychotic treatment with differences between first- and second-generation drugs. Finally, antioxidants may affect cognitive and psychotic symptoms in patients with schizophrenia, and although the evidence is only preliminary, the results indicate that further studies are warranted.
精神分裂症是一种全球性精神疾病，其特征在于多巴胺能和谷氨酸能突触发生改变，导致脑网络内部及之间的整体连接障碍。炎症过程、线粒体功能、能量消耗和氧化应激的损害与精神分裂症的病理生理学密切相关。抗精神病药物是精神分裂症药物治疗的主要手段，都具有占据多巴胺D2受体这一共同特征，可能会影响抗氧化途径以及线粒体蛋白水平和基因表达。在此，我们系统地综述了关于抗氧化剂在抗精神病作用中的机制以及第一代和第二代化合物对线粒体功能和氧化应激影响的现有证据。我们还进一步关注了探讨抗氧化剂作为抗精神病治疗增效策略的疗效和耐受性的临床试验。我们检索了EMBASE、Scopus和Medline/PubMed数据库。选择过程遵循系统评价和Meta分析的首选报告项目（PRISMA）标准。据报道，几种参与细胞活力、能量代谢和氧化系统调节的线粒体蛋白在接受抗精神病药物治疗后有显著改变，第一代和第二代药物之间存在差异。最后，抗氧化剂可能会影响精神分裂症患者的认知和精神症状，尽管证据只是初步的，但结果表明有必要进行进一步研究。
