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

Abstract

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.

Figure 1. Microglial-mediated inflammation triggered by myelin deficits causes catatonic behavior.

(A) In this issue, Janova et al. show that a minor myelin abnormality in mice lacking CNP causes microglial-mediated neuroinflammation and leads to catatonic symptoms. (B) Microglia ablation by the CSF1R inhibitor PLX5622 can both prevent and treat neuroinflammation and catatonia.