Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Behav Brain Res. 2021 Mar 26;402:113101. doi: 10.1016/j.bbr.2020.113101. Epub 2021 Jan 14.
Schizophrenia is a debilitating psychiatric illness that remains poorly understood. While the bulk of symptomatology has classically been associated with disrupted brain functioning, accumulating evidence demonstrates that schizophrenia is characterized by systemic inflammation and disturbances in metabolism. Indeed, metabolic disease is a major determinant of the high mortality rate associated with schizophrenia. Antipsychotic drugs (APDs) have revolutionized management of psychosis, making it possible to rapidly control psychotic symptoms. This has ultimately reduced relapse rates of psychotic episodes and improved overall quality of life for people with schizophrenia. However, long-term APD use has also been associated with significant metabolic disturbances including weight gain, dysglycemia, and worsening of the underlying cardiometabolic disease intrinsic to schizophrenia. While the mechanisms for these intrinsic and medication-induced metabolic effects remain unclear, inflammation appears to play a key role. Here, we review the evidence for roles of inflammatory mechanisms in the disease features of schizophrenia and how these mechanisms interact with APD treatment. We also discuss the effects of common inflammatory mediators on metabolic disease. Then, we review the evidence of intrinsic and APD-mediated effects on systemic inflammation in schizophrenia. Finally, we speculate about possible treatment strategies. Developing an improved understanding of inflammatory processes in schizophrenia may therefore introduce new, more effective options for treating not only schizophrenia but also primary metabolic disorders.
精神分裂症是一种使人衰弱的精神疾病，目前仍未被很好地了解。虽然大部分症状通常与大脑功能障碍有关，但越来越多的证据表明，精神分裂症的特征是系统性炎症和代谢紊乱。事实上，代谢疾病是与精神分裂症相关的高死亡率的主要决定因素。抗精神病药物 (APD) 彻底改变了精神疾病的管理方式，使其能够快速控制精神病症状。这最终降低了精神病发作的复发率，并提高了精神分裂症患者的整体生活质量。然而，长期使用 APD 也与明显的代谢紊乱有关，包括体重增加、血糖异常和精神分裂症内在的潜在心血管代谢疾病恶化。虽然这些内在和药物引起的代谢作用的机制仍不清楚，但炎症似乎起着关键作用。在这里，我们回顾了炎症机制在精神分裂症疾病特征中的作用的证据，以及这些机制如何与 APD 治疗相互作用。我们还讨论了常见炎症介质对代谢疾病的影响。然后，我们回顾了精神分裂症中固有和 APD 介导的全身炎症的证据。最后，我们推测了可能的治疗策略。因此，对精神分裂症中炎症过程的深入了解，可能会为治疗精神分裂症和主要代谢疾病带来新的、更有效的选择。
