Psychosis spectrum illnesses as disorders of prefrontal critical period plasticity

Sophia Vinogradov, Matthew V. Chafee, Erik Lee, Hirofumi Morishita

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


Emerging research on neuroplasticity processes in psychosis spectrum illnesses—from the synaptic to the macrocircuit levels—fill key gaps in our models of pathophysiology and open up important treatment considerations. In this selective narrative review, we focus on three themes, emphasizing alterations in spike-timing dependent and Hebbian plasticity that occur during adolescence, the critical period for prefrontal system development: (1) Experience-dependent dysplasticity in psychosis emerges from activity decorrelation within neuronal ensembles. (2) Plasticity processes operate bidirectionally: deleterious environmental and experiential inputs shape microcircuits. (3) Dysregulated plasticity processes interact across levels of scale and time and include compensatory mechanisms that have pathogenic importance. We present evidence that—given the centrality of progressive dysplastic changes, especially in prefrontal cortex—pharmacologic or neuromodulatory interventions will need to be supplemented by corrective learning experiences for the brain if we are to help people living with these illnesses to fully thrive.

Original languageEnglish (US)
Pages (from-to)168-185
Number of pages18
Issue number1
StatePublished - Jan 2023

Bibliographical note

Funding Information:
This work was supported by National Institute of Mental Health grants 5P50MH119569 to SV; NIMH 1R01MH12059 and the Redleaf Foundation to SV; 5P50MH119569 to MVC; and grants NIMH R01 MH119523, NIMH R01 MH118297, and NEI R01 EY031009 to HM.

Publisher Copyright:
© 2022, The Author(s).

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, N.I.H., Extramural


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