Neuroprogression in schizophrenia: Pathways underpinning clinical staging and therapeutic corollaries.

Abstract

OBJECTIVE:

Whilst dopaminergic dysfunction remains a necessary component involved in the pathogenesis of schizophrenia, our current pharmacological armoury of dopamine antagonists does little to control the negative symptoms of schizophrenia. This suggests other pathological processes must be implicated. This paper aims to elaborate on such theories.

METHODS:

Data for this review were sourced from the electronic database PUBMED, and was not limited by language or date of publication.

RESULTS:

It has been suggested that multiple 'hits' may be required to unveil the clinical syndrome in susceptible individuals. Such hits potentially first occur in utero, leading to neuronal disruption, epigenetic changes and the establishment of an abnormal inflammatory response. The development of schizophrenia may therefore potentially be viewed as a neuroprogressive response to these early stressors, driven on by changes in tryptophan catabolite (TRYCAT) metabolism, reactive oxygen species handling and N-methyl d-aspartate (NMDA) circuitry. Given the potential for such progression over time, it is prudent to explore the new treatment strategies which may be implemented before such changes become established.

CONCLUSIONS:

Outside of the dopaminergic model, the potential pathogenesis of schizophrenia has yet to be fully elucidated, but common themes include neuropil shrinkage, the development of abnormal neuronal circuitry, and a chronic inflammatory state which further disrupts neuronal function. Whilst some early non-dopaminergic treatments show promise, none have yet to be fully studied in appropriately structured randomized controlled trials and they remain little more than potential attractive targets.

• Authors: Justin Davis, Steven Moylan, Brian H Harvey, Michael Maes, Michael Berk
• Journal: The Australian and New Zealand journal of psychiatry (Aust N Z J Psychiatry) Vol. 48 Issue 6 Pg. 512-29 (Jun 2014) ISSN: 1440-1614 [Electronic] England
• PMID: 24803587 (Publication Type: Journal Article, Review)
• Copyright: © The Royal Australian and New Zealand College of Psychiatrists 2014.

Chemical References

• Antipsychotic Agents
• Receptors, N-Methyl-D-Aspartate

Topics

• Antipsychotic Agents (therapeutic use)
• Brain (pathology, physiopathology)
• Disease Progression
• Humans
• Receptors, N-Methyl-D-Aspartate (physiology)
• Schizophrenia (diagnosis, drug therapy, etiology, pathology, physiopathology)