New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment

Front Cell Neurosci. 2024 May 10:18:1386583. doi: 10.3389/fncel.2024.1386583. eCollection 2024.

Abstract

Schizophrenia (SZ) is a complex neuropsychiatric disorder associated with severe cognitive dysfunction. Although research has mainly focused on forebrain abnormalities, emerging results support the involvement of the cerebellum in SZ physiopathology, particularly in Cognitive Impairment Associated with SZ (CIAS). Besides its role in motor learning and control, the cerebellum is implicated in cognition and emotion. Recent research suggests that structural and functional changes in the cerebellum are linked to deficits in various cognitive domains including attention, working memory, and decision-making. Moreover, cerebellar dysfunction is related to altered cerebellar circuit activities and connectivity with brain regions associated with cognitive processing. This review delves into the role of the cerebellum in CIAS. We initially consider the major forebrain alterations in CIAS, addressing impairments in neurotransmitter systems, synaptic plasticity, and connectivity. We then focus on recent findings showing that several mechanisms are also altered in the cerebellum and that cerebellar communication with the forebrain is impaired. This evidence implicates the cerebellum as a key component of circuits underpinning CIAS physiopathology. Further studies addressing cerebellar involvement in SZ and CIAS are warranted and might open new perspectives toward understanding the physiopathology and effective treatment of these disorders.

Keywords: cerebellar connectivity; cerebellar neurotransmitters; cerebellum; cognitive impairment; schizophrenia.

Publication types

  • Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR); National Recovery and Resilience Plan (NRRP) project; MNESYS (PE0000006) – A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022); Digital Europe Grant TEF-Health #101100700; HORIZON-HLTH-2023-TOOL-05-03 Integrated, multi-scale computational models of patient patho-physiology (‘virtual twins’) for personalized disease management #101137289 — VIRTUAL BRAIN TWIN — HORIZON-HLTH-2023-TOOL-05.