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Meta-Analysis
. 2022 Aug 11;23(16):8974.
doi: 10.3390/ijms23168974.

Glutamatergic and N-Acetylaspartate Metabolites in Bipolar Disorder: A Systematic Review and Meta-Analysis of Proton Magnetic Resonance Spectroscopy Studies

Jonathan Chabert  1 , Etienne Allauze  1 , Bruno Pereira  2 , Carine Chassain  3 , Ingrid De Chazeron  1 , Jean-Yves Rotgé  4 , Philippe Fossati  4 , Pierre-Michel Llorca  1 , Ludovic Samalin  1
Affiliations
Meta-Analysis

Glutamatergic and N-Acetylaspartate Metabolites in Bipolar Disorder: A Systematic Review and Meta-Analysis of Proton Magnetic Resonance Spectroscopy Studies

Jonathan Chabert et al. Int J Mol Sci. .

Abstract

The exact neurobiological mechanisms of bipolar disorder (BD) remain unknown. However, some neurometabolites could be implicated, including Glutamate (Glu), Glutamine (Gln), Glx, and N-acetylaspartate (NAA). Proton Magnetic Resonance Spectroscopy (1H-MRS) allows one to quantify these metabolites in the human brain. Thus, we conducted a systematic review and meta-analysis of the literature to compare their levels between BD patients and healthy controls (HC). The main inclusion criteria for inclusion were 1H-MRS studies comparing levels of Glu, Gln, Glx, and NAA in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and hippocampi between patients with BD in clinical remission or a major depressive episode and HC. Thirty-three studies were included. NAA levels were significantly lower in the left white matter PFC (wmPFC) of depressive and remitted BD patients compared to controls and were also significantly higher in the left dorsolateral PFC (dlPFC) of depressive BD patients compared to HC. Gln levels were significantly higher in the ACC of remitted BD patients compared to in HC. The decreased levels of NAA of BD patients may be related to the alterations in neuroplasticity and synaptic plasticity found in BD patients and may explain the deep white matter hyperintensities frequently observed via magnetic resonance imagery.

Keywords: N-acetylaspartate; NAA; bipolar depression; bipolar disorder; glutamate; magnetic resonance spectroscopy.

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Conflict of interest statement

The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Preferred reporting items for systematic reviews and meta-analyses (PRISMA) diagram for study search. * One study featured two groups (clinical remission and depressive episode) and thus was counted twice, once in each category.
Figure 2
Figure 2
Summary of Standardized Mean Differences (SMDs) and their confidence intervals (95% CI) for each metabolite in each of the different regions by the mood status of bipolar patients.
Figure 3
Figure 3
Studies Standardized Mean Differences (SMDs) of N-acetylaspartate differences between bipolar patients and controls in the left white matter prefrontal cortex [44,46,47,61,62].
See this image and copyright information in PMC

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