Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 22 (1), 4-12

Myelination of Parvalbumin Interneurons: A Parsimonious Locus of Pathophysiological Convergence in Schizophrenia

Affiliations
Review

Myelination of Parvalbumin Interneurons: A Parsimonious Locus of Pathophysiological Convergence in Schizophrenia

J Stedehouder et al. Mol Psychiatry.

Abstract

Schizophrenia is a debilitating psychiatric disorder characterized by positive, negative and cognitive symptoms. Despite more than a century of research, the neurobiological mechanism underlying schizophrenia remains elusive. White matter abnormalities and interneuron dysfunction are the most widely replicated cellular neuropathological alterations in patients with schizophrenia. However, a unifying model incorporating these findings has not yet been established. Here, we propose that myelination of fast-spiking parvalbumin (PV) interneurons could be an important locus of pathophysiological convergence in schizophrenia. Myelination of interneurons has been demonstrated across a wide diversity of brain regions and appears highly specific for the PV interneuron subclass. Given the critical influence of fast-spiking PV interneurons for mediating oscillations in the gamma frequency range (~30-120 Hz), PV myelination is well positioned to optimize action potential fidelity and metabolic homeostasis. We discuss this hypothesis with consideration of data from human postmortem studies, in vivo brain imaging and electrophysiology, and molecular genetics, as well as fundamental and translational studies in rodent models. Together, the parvalbumin interneuron myelination hypothesis provides a falsifiable model for guiding future studies of schizophrenia pathophysiology.

Conflict of interest statement

The authors declare no conflict of interest.

Similar articles

See all similar articles

Cited by 19 articles

See all "Cited by" articles

References

    1. Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet 2016; 388: 86–97. - PMC - PubMed
    1. Insel TR. Rethinking schizophrenia. Nature 2010; 468: 187–193. - PubMed
    1. Carlsson A. The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1988; 1: 179–186. - PubMed
    1. Moghaddam B, Javitt D. From revolution to evolution: the glutamate hypothesis of schizophrenia and its implication for treatment. Neuropsychopharmacology 2012; 37: 4–15. - PMC - PubMed
    1. Gonzalez-Burgos G, Cho RY, Lewis DA. Alterations in cortical network oscillations and parvalbumin neurons in schizophrenia. Biol Psychiatry 2015; 77: 1031–1040. - PMC - PubMed

Publication types

Feedback