{"title":"精神分裂症和相关精神病的炎症亚型和翻译炎症相关基因发现:治疗分层和新疗法途径的视角","authors":"Jeffrey R Bishop, Lusi Zhang, Paulo Lizano","doi":"10.1097/HRP.0000000000000321","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>Dysregulation of immunological and inflammatory processes is frequently observed in psychotic disorders. Numerous studies have examined the complex components of innate and adaptive immune processes in schizophrenia and related psychoses. Elevated inflammation in these conditions is related to neurobiological phenotypes and associated with both genetics and environmental exposures. Recent studies have utilized multivariate cytokine approaches to identify what appears to be a subset of individuals with elevated inflammation. The degree to which these findings represent a general process of dysregulated inflammation or whether there are more refined subtypes remains unclear. Brain-imaging studies have attempted to establish the link between peripheral inflammation and gray matter disruption, white matter abnormalities, and neuropsychological phenotypes. However, the interplay between peripheral inflammation and neuroinflammation, as well as the consequences of this interplay, in the context of psychosis remains unclear and requires further investigation. This Perspectives article reviews the following elements of immune dysregulation and its clinical and therapeutic implications: (1) evidence supporting inflammation and immune dysregulation in schizophrenia and related psychoses; (2) recent advances in approaches to characterizing subgroups of patients with elevated inflammation; (3) relationships between peripheral inflammation and brain-imaging indicators of neuroinflammation; (4) convergence of large-scale genetic findings and peripheral inflammation findings; and (5) therapeutic implications: anti-inflammation interventions leveraging genetic findings for drug discovery and repurposing. We offer perspectives and examples of how multiomics technologies may be useful for constructing and studying immunogenetic signatures. Advancing research in this area will facilitate biomarker discovery, disease subtyping, and the development of etiological treatments for immune dysregulation in psychosis.</p>","PeriodicalId":12915,"journal":{"name":"Harvard Review of Psychiatry","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f5/53/hrp-30-59.PMC8746916.pdf","citationCount":"28","resultStr":"{\"title\":\"Inflammation Subtypes and Translating Inflammation-Related Genetic Findings in Schizophrenia and Related Psychoses: A Perspective on Pathways for Treatment Stratification and Novel Therapies.\",\"authors\":\"Jeffrey R Bishop, Lusi Zhang, Paulo Lizano\",\"doi\":\"10.1097/HRP.0000000000000321\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Abstract: </strong>Dysregulation of immunological and inflammatory processes is frequently observed in psychotic disorders. Numerous studies have examined the complex components of innate and adaptive immune processes in schizophrenia and related psychoses. Elevated inflammation in these conditions is related to neurobiological phenotypes and associated with both genetics and environmental exposures. Recent studies have utilized multivariate cytokine approaches to identify what appears to be a subset of individuals with elevated inflammation. The degree to which these findings represent a general process of dysregulated inflammation or whether there are more refined subtypes remains unclear. Brain-imaging studies have attempted to establish the link between peripheral inflammation and gray matter disruption, white matter abnormalities, and neuropsychological phenotypes. However, the interplay between peripheral inflammation and neuroinflammation, as well as the consequences of this interplay, in the context of psychosis remains unclear and requires further investigation. This Perspectives article reviews the following elements of immune dysregulation and its clinical and therapeutic implications: (1) evidence supporting inflammation and immune dysregulation in schizophrenia and related psychoses; (2) recent advances in approaches to characterizing subgroups of patients with elevated inflammation; (3) relationships between peripheral inflammation and brain-imaging indicators of neuroinflammation; (4) convergence of large-scale genetic findings and peripheral inflammation findings; and (5) therapeutic implications: anti-inflammation interventions leveraging genetic findings for drug discovery and repurposing. We offer perspectives and examples of how multiomics technologies may be useful for constructing and studying immunogenetic signatures. Advancing research in this area will facilitate biomarker discovery, disease subtyping, and the development of etiological treatments for immune dysregulation in psychosis.</p>\",\"PeriodicalId\":12915,\"journal\":{\"name\":\"Harvard Review of Psychiatry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f5/53/hrp-30-59.PMC8746916.pdf\",\"citationCount\":\"28\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Harvard Review of Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/HRP.0000000000000321\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Harvard Review of Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/HRP.0000000000000321","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Inflammation Subtypes and Translating Inflammation-Related Genetic Findings in Schizophrenia and Related Psychoses: A Perspective on Pathways for Treatment Stratification and Novel Therapies.
Abstract: Dysregulation of immunological and inflammatory processes is frequently observed in psychotic disorders. Numerous studies have examined the complex components of innate and adaptive immune processes in schizophrenia and related psychoses. Elevated inflammation in these conditions is related to neurobiological phenotypes and associated with both genetics and environmental exposures. Recent studies have utilized multivariate cytokine approaches to identify what appears to be a subset of individuals with elevated inflammation. The degree to which these findings represent a general process of dysregulated inflammation or whether there are more refined subtypes remains unclear. Brain-imaging studies have attempted to establish the link between peripheral inflammation and gray matter disruption, white matter abnormalities, and neuropsychological phenotypes. However, the interplay between peripheral inflammation and neuroinflammation, as well as the consequences of this interplay, in the context of psychosis remains unclear and requires further investigation. This Perspectives article reviews the following elements of immune dysregulation and its clinical and therapeutic implications: (1) evidence supporting inflammation and immune dysregulation in schizophrenia and related psychoses; (2) recent advances in approaches to characterizing subgroups of patients with elevated inflammation; (3) relationships between peripheral inflammation and brain-imaging indicators of neuroinflammation; (4) convergence of large-scale genetic findings and peripheral inflammation findings; and (5) therapeutic implications: anti-inflammation interventions leveraging genetic findings for drug discovery and repurposing. We offer perspectives and examples of how multiomics technologies may be useful for constructing and studying immunogenetic signatures. Advancing research in this area will facilitate biomarker discovery, disease subtyping, and the development of etiological treatments for immune dysregulation in psychosis.
期刊介绍:
The Harvard Review of Psychiatry is the authoritative source for scholarly reviews and perspectives on important topics in psychiatry. Founded by the Harvard Medical School''s Department of Psychiatry, the Harvard Review of Psychiatry features review papers that summarize and synthesize the key literature in a scholarly and clinically relevant manner. Topics covered include: Schizophrenia and related disorders; Mood disorders; Personality disorders; Substance use disorders; Anxiety; Neuroscience; Psychosocial aspects of psychiatry; Ethics; Psychiatric education; and much more.
In addition, a Clinical Challenges section presents a case with discussion from a panel of experts. Brief reviews are presented in topic-specific columns that include Cross-Cultural Psychiatry, History of Psychiatry, Ethics, and others.