Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Psychiatry, Czech Republic.
Prog Neuropsychopharmacol Biol Psychiatry. 2023 Jan 10;120:110626. doi: 10.1016/j.pnpbp.2022.110626. Epub 2022 Aug 31.
Both the discovery of biomarkers of schizophrenia and the verification of biological hypotheses of schizophrenia are an essential part of the process of understanding the etiology of this mental disorder. Schizophrenia has long been considered a neurodevelopmental disease whose symptoms are caused by impaired synaptic signal transduction and brain neuroplasticity. Both the onset and chronic course of schizophrenia are associated with risk factors-induced disruption of brain function and the establishment of a new homeostatic setpoint characterized by biomarkers. Different risk factors and biomarkers can converge to the same symptoms of schizophrenia, suggesting that the primary cause of the disease can be highly individual. Schizophrenia-related biomarkers include measurable biochemical changes induced by stress (elevated allostatic load), mitochondrial dysfunction, neuroinflammation, oxidative and nitrosative stress, and circadian rhythm disturbances. Here is a summary of selected valid biological hypotheses of schizophrenia formulated based on risk factors and biomarkers, neurodevelopment, neuroplasticity, brain chemistry, and antipsychotic medication. The integrative neurodevelopmental-vulnerability-neurochemical model is based on current knowledge of the neurobiology of the onset and progression of the disease and the effects of antipsychotics and psychotomimetics and reflects the complex and multifactorial nature of schizophrenia.
精神分裂症生物标志物的发现和精神分裂症生物学假设的验证是理解这种精神障碍病因的过程中的重要组成部分。精神分裂症长期以来一直被认为是一种神经发育疾病，其症状是由突触信号转导受损和大脑神经可塑性引起的。精神分裂症的发病和慢性病程都与风险因素诱导的大脑功能障碍以及以生物标志物为特征的新的平衡状态的建立有关。不同的风险因素和生物标志物可以汇聚到相同的精神分裂症症状上，这表明疾病的主要原因可能高度个体化。与精神分裂症相关的生物标志物包括应激诱导的可测量生化变化（升高的全身适应负荷）、线粒体功能障碍、神经炎症、氧化和硝化应激以及昼夜节律紊乱。这里总结了一些基于风险因素和生物标志物、神经发育、神经可塑性、大脑化学和抗精神病药物制定的有效的精神分裂症生物学假设。综合神经发育-易损性-神经化学模型基于疾病发病和进展的神经生物学以及抗精神病药物和致幻剂的作用的现有知识，并反映了精神分裂症的复杂性和多因素性质。
