Networks of blood proteins in the neuroimmunology of schizophrenia
| Autor: | Margot Fournier, Ming T. Tsuang, Thomas H. McGlashan, Jean Addington, Daniel H. Mathalon, Elaine F. Walker, Clark D. Jeffries, Carrie E. Bearden, Diana O. Perkins, Enrico Domenici, Scott W. Woods, Michel Cuenod, Kristin S. Cadenhead, Larry J. Seidman, Tyrone D. Cannon, Kim Q. Do, Barbara A. Cornblatt, Ines Khadimallah |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Correlation Adolescent Adult Biomarkers Blood Proteins Female Humans Longitudinal Studies Matrix Metalloproteinase 9 Neuroimmunomodulation Plasminogen Activator Inhibitor 1 Schizophrenia Tissue Inhibitor of Metalloproteinase-1 Young Adult Psychiatry and Mental Health Cellular and Molecular Neuroscience Biological Psychiatry 0302 clinical medicine Blood plasma 2.1 Biological and endogenous factors Psychology Aetiology Serious Mental Illness Blood proteins Psychiatry and Mental health Mental Health Public Health and Health Services medicine.medical_specialty Psychosis Biomarkers/blood Blood Proteins/analysis Matrix Metalloproteinase 9/blood Plasminogen Activator Inhibitor 1/blood Schizophrenia/blood Schizophrenia/diagnosis Schizophrenia/immunology Tissue Inhibitor of Metalloproteinase-1/blood Clinical Sciences Article lcsh:RC321-571 03 medical and health sciences Text mining Clinical Research Internal medicine medicine lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry business.industry Neurosciences medicine.disease Brain Disorders 030104 developmental biology Endocrinology Neuroimmunology business 030217 neurology & neurosurgery Homeostasis |
| Zdroj: | Translational Psychiatry, Vol 8, Iss 1, Pp 1-10 (2018) Translational psychiatry, vol. 8, no. 1, pp. 112 Translational psychiatry, vol 8, iss 1 Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | Levels of certain circulating cytokines and related immune system molecules are consistently altered in schizophrenia and related disorders. In addition to absolute analyte levels, we sought analytes in correlation networks that could be prognostic. We analyzed baseline blood plasma samples with a Luminex platform from 72 subjects meeting criteria for a psychosis clinical high-risk syndrome; 32 subjects converted to a diagnosis of psychotic disorder within two years while 40 other subjects did not. Another comparison group included 35 unaffected subjects. Assays of 141 analytes passed early quality control. We then used an unweighted co-expression network analysis to identify highly correlated modules in each group. Overall, there was a striking loss of network complexity going from unaffected subjects to nonconverters and thence to converters (applying standard, graph-theoretic metrics). Graph differences were largely driven by proteins regulating tissue remodeling (e.g. blood-brain barrier). In more detail, certain sets of antithetical proteins were highly correlated in unaffected subjects (e.g. SERPINE1 vs MMP9), as expected in homeostasis. However, for particular protein pairs this trend was reversed in converters (e.g. SERPINE1 vs TIMP1, being synthetical inhibitors of remodeling of extracellular matrix and vasculature). Thus, some correlation signals strongly predict impending conversion to a psychotic disorder and directly suggest pharmaceutical targets. |
| Databáze: | OpenAIRE |
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