Glutamatergic Neurometabolite Levels in Bipolar Disorder: A Systematic Review and Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies.
Level 3 - non-randomized controlled study
systematic review of observational case-control imaging studies
PubMed 36754485 · doi:10.1016/j.bpsc.2022.09.017
What was done
A systematic review and meta-analysis of proton magnetic resonance spectroscopy studies evaluating glutamatergic neurometabolite levels in bipolar disorder versus healthy controls. The review included 40 studies comprising 1135 patients with bipolar disorder and 964 healthy control subjects, with subgroup analyses evaluating age groups (adult vs. pediatric) and mood states.
What was found
Glutamate plus glutamine and glutamine levels in the anterior cingulate cortex were significantly elevated in bipolar disorder compared with healthy controls (standardized mean difference = 0.42 and 0.48, respectively). In subgroup analyses, adult patients with bipolar disorder had significantly higher anterior cingulate cortex glutamate plus glutamine levels than adult controls, whereas pediatric cohorts showed no significant difference. Patients with bipolar depression had higher anterior cingulate cortex glutamate plus glutamine levels than healthy controls.
Why it matters
This review provides quantitative evidence that glutamatergic dysfunction in the anterior cingulate cortex is present in bipolar disorder, with abnormalities most pronounced in adult patients and during depressive episodes.
Limits
The underlying studies are observational case-control designs. The abstract does not report confidence intervals, p-values, between-study heterogeneity metrics, psychotropic medication effects, or metabolite findings for brain regions outside the anterior cingulate cortex and mood states other than depression.
Cited by
- supports Systematic reviews establish that elevated glutamate is a major feature of bipolar disorder and epilepsy, and glutamate reduction is a marker of treatment response.