Is the cerebellum relevant in the circuitry of neuropsychiatric disorders?

Is the cerebellum relevant in the circuitry of neuropsychiatric disorders?

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J Psychiatry Neurosci 2005;30(3):178-86

Jakub Z. Konarski, MSc; Roger S. McIntyre, MD; Larry A. Grupp, DSc; Sidney H. Kennedy, MD

Konarski — Institute of Medical Science, University of Toronto; McIntyre — Mood Disorders Psychopharmacology Unit, University Health Network, and Department of Psychiatry, University of Toronto; Grupp — Department of Pharmacology, University of Toronto, and Toronto General Hospital, University Health Network; Kennedy — Institute of Medical Science and Department of Psychiatry, University of Toronto, and University Health Network, Toronto, Ont.

Abstract

Contemporary mechanistic models of several psychiatric disorders propose abnormalities in the structure and function of distinct neural networks. The cerebellum has both anatomic and functional connections to the prefrontal cortex, the subcortical limbic structures and monoamine-producing brainstem nuclei. Conspicuously, however, the cerebellum has been underemphasized in neuropsychiatric research. A growing confluence of scientific data indicate that the cerebellum may not be irrelevant, which suggests that an integrated model of neuropsychiatric disorders should include a role for the cerebellum and its relevant neural connections. This review summarizes the published data describing and characterizing the putative role of the cerebellum in normal and abnormal mood regulation, with
specific attention to states of psychosis, depression and mania. The available evidence suggests that a functional role for the cerebellum should be considered in future neuropsychiatric studies.

Résumé

Les modèles mécanistes contemporains de divers troubles psychiatriques mettent en cause des anomalies au niveau de la structure et de la fonction de réseaux neuronaux distincts. Le cervelet contient des connexions anatomiques et fonctionnelles avec le cortex préfrontal, les structures limbiques sous-corticales et les noyaux du tronc cérébral produisant des monoamines. Par ailleurs, il est flagrant que les recherches en neuropsychiatrie ne se sont pas suffisamment attardées au cervelet. La masse de plus en plus importante de données scientifiques convergentes indiquant que le cervelet pourrait avoir de l’importance dans ce contexte signale qu’un modèle intégré des troubles neuropsychiatriques devrait traiter du rôle du cervelet ainsi que de ses connexions neuronales pertinentes. La
présente étude vise à résumer les données publiées décrivant et caractérisant le rôle présumé du cervelet dans la régulation normale et anormale de l’humeur avec accent particulier sur les états de psychose, de dépression et de manie. Les données disponibles semblent indiquer qu’il faudrait envisager le rôle fonctionnel du cervelet dans les études futures en neuropsychiatrie.


Medical subject headings: cerebellum; schizophrenia; depressive disorder, major; bipolar disorder; magnetic resonance imaging; positronemission tomography.

Submitted Nov. 18, 2003; Revised Apr. 15, 2004; Aug. 11, 2004; Accepted Aug. 23, 2004

Competing interests: None declared for Mr. Konarski and Dr. Grupp. Dr. McIntyre is a consultant and speaker for AstraZeneca, Eli-Lilly, Janssen-Ortho, Organon, Wyeth, Lundbeck, GlaxoSmith- Kline and ORYX; he has received research funding from Wyeth. Dr. Kennedy is a consultant or speaker for and has received research funding or honoraria from AstraZeneca, Biovail, Eli Lilly, Glaxo- SmithKline, Janssen-Ortho, Lundbeck, Merck, Organon, Pfizer, Servier and Shire Wyeth.

Contributors: The review was conceived and designed by Mr. Konarski, who was also responsible for data acquisition. Drs. McIntyre, Grupp and Kennedy interpreted the data. All authors participated in drafting the article, and Drs. McIntyre and Kennedy revised the article. All authors gave final approval for the article to be published.

Correspondence to: Dr. Sidney H. Kennedy, Toronto General Hospital, University Health Network, 200 Elizabeth St., Eaton North Wing #8-222, Toronto ON M5G 2C4; fax 416 340-4198; sidney.kennedy@uhn.on.ca