Grey matter abnormalities in first‐episode mania: A systematic review and meta‐analysis of voxel‐based morphometry studies

Abstract

Objectives: It has been proposed that different stages of bipolar disorder may be underpinned by distinct neurobiological substrates. However, structural neuroimaging studies in early stages of the illness are limited by small sample sizes yielding inconsistent findings. The purpose of this systematic review and meta-analysis, therefore, was to identify regional grey matter volume (GMV) changes that are consistently associated with first episode of mania (FEM).Methods: Following PRISMA guidelines, we conducted a systematic search of the literature to identify Voxel-Based Morphometry (VBM) studies in FEM patients compared with healthy individuals. We then conducted a voxel-wise meta-analysis using Seed-based d-Mapping technique. Finally, we performed univariate meta-regression analyses to explore the potential effects of moderator variables including age, gender, and percentage of lithium users on GMV alterations. Results:We identified 15 VBM studies and included 12 studies in the meta-analysis.Four studies found no regional differences in GM volumes while other 11 studies reported volume changes in frontal and temporal regions as well as anterior cingulate cortex (ACC), cerebellum and basal ganglia. The meta-analysis revealed a single cluster of GMV reduction in bilateral pregenual ACC in patients with FEM compared to healthy individuals (P < .001). The Egger's test showed no evidence of publication bias at peak voxel level (P = .447). Meta-regression analyses revealed no significant effects of moderators evaluated. Conclusions:Structural brain changes are evident in the early stages of bipolar disorder. GMV reduction in bilateral pregenual ACC is the most consistent finding in VBM studies of FEM.

Is first episode mania associated with grey matter abnormalities? We are not sure!

“…1 The new CBMA did not find any consistent GM abnormalities in FEM across studies, which did not replicate the results from previous CBMA. 1 Discrepancies and failure of replication in VBM studies are not uncommon in neuropsychiatric disorders. The present CBMA adds new evidence to the crisis in reliability and reproducibility that has been increasing concern in neuroimaging research.…”

“…3 Keramatian and colleagues stated that they utilized SDM-PSI for the CBMA; however, the detailed processes described in their paper seemed to be the case for the old version of SDM. 1 Specifically, an uncorrected threshold of p < 0.005 was applied for statistical significance in their CBMA, 1 which may be susceptible to false-positive findings. Instead, family wise error (FWE) corrections combined with TFCE were the optimal option in SDM-PSI, which was neither too conservative nor too liberal.…”

“…With great interest, we have read the recent paper by Keramatian and colleagues entitled “Grey Matter Abnormalities in First Episode Mania: A Systematic Review and Meta‐analysis of Voxel‐Based Morphometry Studies” in Bipolar Disorders 1 . The authors systematically reviewed 15 voxel‐based morphometry (VBM) studies and observed heterogeneous findings regarding the brain regions affected and the direction of grey matter (GM) alterations (decreases/increases) as well as statistically non‐significant alterations in patients with first episode mania (FEM) relative to healthy controls.…”

“…The authors systematically reviewed 15 voxel‐based morphometry (VBM) studies and observed heterogeneous findings regarding the brain regions affected and the direction of grey matter (GM) alterations (decreases/increases) as well as statistically non‐significant alterations in patients with first episode mania (FEM) relative to healthy controls. They further performed a quantitative coordinate‐based meta‐analysis (CBMA) of 12 whole‐brain VBM studies and identified consistent GM alterations in the bilateral pregenual anterior cingulate cortex (ACC) in FEM 1 . The paper provided a thorough profile of GM volume alterations in FEM; however, we have some methodological concerns in the CBMA that compromised the validity of the meta‐analytic results.…”

“…These improvements increased reliability of the meta‐analytic results 3 . Keramatian and colleagues stated that they utilized SDM‐PSI for the CBMA; however, the detailed processes described in their paper seemed to be the case for the old version of SDM 1 . Specifically, an uncorrected threshold of p < 0.005 was applied for statistical significance in their CBMA, 1 which may be susceptible to false‐positive findings.…”