Pulse Brain · Growing Health Evidence Index
Tier 1 — Meta-analysis / systematic reviewPeer-reviewed

Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review

Andrea de Bartolomeis, Annarita Barone, Licia Vellucci, Benedetta Mazza, Mark C. Austin, Felice Iasevoli, Mariateresa Ciccarelli

Molecular Neurobiology · 2022

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Summary

This systematic review synthesises evidence linking neuroinflammation to two core pathophysiological features of schizophrenia: aberrant glutamate-dopamine interaction and post-synaptic structural changes. The authors present a bidirectional relationship wherein inflammatory processes influence dopamine release whilst dopamine regulates discrete inflammatory pathways (interleukin and kynurenine), and demonstrate that inflammation impairs glutamate regulation and NMDAR signalling through effects on microglia activation and post-synaptic density proteins. Elevated plasma inflammatory markers in schizophrenia patients correlate with reduced cortical integrity and functional connectivity relevant to cognitive deficits, suggesting potential targets for novel therapeutic strategies in treatment-resistant schizophrenia.

Regional applicability

The study is a translational review synthesising global clinical and preclinical evidence; geographic specificity is not reported in the abstract. The findings are likely applicable to United Kingdom clinical practice and neuroscience research, particularly regarding inflammatory biomarker assessment and antipsychotic treatment optimisation in schizophrenia, though implementation would depend on NHS clinical trial infrastructure and healthcare commissioning.

Key measures

Plasma inflammatory markers, dopamine release, interleukin and kynurenine pathway dysregulation, NMDAR function, dendritic spine architecture, post-synaptic density scaffold proteins, cortical integrity and functional connectivity

Outcomes reported

The study reviewed evidence linking inflammatory/immune processes to aberrant glutamate-dopamine interaction and post-synaptic architectural changes in schizophrenia pathophysiology. It examined bidirectional inflammatory effects on dopaminergic function, microglia activation, NMDAR dysfunction, and associations between plasma inflammatory markers and reduced cortical integrity in schizophrenia patients.

Theme
Nutrition & health
Subject
Other / interdisciplinary
Study type
Systematic Review
Study design
Systematic review
Source type
Peer-reviewed study
Status
Published
System type
Human clinical
DOI
10.1007/s12035-022-02976-3
Catalogue ID
SNmp7um90r-j5qv6b

Topic tags

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