Micro(glial)-managing executive function: white matter inflammation drives catatonia

• Published in: The Journal of clinical investigation Vol. 128; no. 2; pp. 564 - 566
• Main Authors: Pease-Raissi, Sarah E., Chan, Jonah R.
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.02.2018
• Subjects: Age; Aging; Animal models; Attention deficit hyperactivity disorder; Biomedical research; Brain; Catatonia; Cognition & reasoning; Disease; Executive function; Executive function (Psychology); Genes; Human subjects; Immune system; Inflammation; Mental disorders; Metabolism; Metabolites; Microglia; Myelin; Neurodegeneration; Phosphodiesterase; Physiological aspects; Proteins; Psychiatry; Schizophrenia; Studies; Substantia alba; Trends
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI98761

White matter abnormalities are prevalent in neuropsychiatric disorders such as schizophrenia, but it is unclear whether these abnormalities represent a cause or consequence of these disorders. Reduced levels of the myelin protein 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP) are associated with the schizophrenic symptom catatonia in both humans and mouse models. In this issue of the JCI, Janova et al. show that reduced CNP levels correlate with catatonia and white matter inflammation in human subjects. Furthermore, they demonstrate that microglial ablation prevents and alleviates catatonic signs in Cnp-/- mice, indicating that microglial-mediated inflammation causes catatonia. Together, this study identifies a cellular mechanism by which subtle myelin abnormalities cause low-grade neuroinflammation and catatonic behavior.