The magnitude and variability of brain structural alterations in bipolar disorder: A double meta-analysis of 5534 patients and 6651 healthy controls

TY - JOUR

T1 - The magnitude and variability of brain structural alterations in bipolar disorder

T2 - A double meta-analysis of 5534 patients and 6651 healthy controls

AU - Angelescu, Ilinca

AU - Brugger, Stefan P.

AU - Borgan, Faith

AU - Kaar, Stephen J.

AU - Howes, Oliver D.

N1 - Funding Information: Dr Howes has received investigator-initiated research funding from and/or participated in advisory/ speaker meetings organised by Angellini, Astra-Zeneca, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Mylan, Neurocrine, Otsuka, Sunovion, Rand, Recordati, and Roche. The other authors have no conflicts of interest to declare. Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/8/1

Y1 - 2021/8/1

N2 - Background: Bipolar disorder is thought to be associated with structural brain alterations, but findings have been inconsistent. Our double meta-analysis investigated the variability and magnitude of differences in regional brain volumes in patients with bipolar disorder relative to healthy volunteers. Methods: Databases were systematically searched for MRI studies reporting regional brain volumetric measures in patients with bipolar disorder and controls. The primary outcome measures were variability ratio (VR), coefficient of variability ratio (CVR) and Hedge's g. Results: 118 studies comprising 5534 patients and 6651 controls were included. The variability meta-analysis showed higher variability in amygdala (VR, 1.14; P =.02; CVR, 1.25; P =.005) and hippocampal (VR, 1.16; P =.001; CVR, 1.22; P = <.001) volumes in patients relative to controls. The meta-analysis of volume differences showed higher lateral (g, -0.43; P = <.0001) and third ventricle (g, -0.22; P =.01) volumes in patients; and lower hippocampus (g, 0.41; P =.001), grey matter (g, 0.25; P =.001), white matter (g, 0.23; P =.0002) and total brain volumes (g, 0.20; P =.003) in patients relative to controls. A higher proportion of male subjects was associated with decreased mean volumes of the amygdala, hippocampus and thalamus and increased lateral ventricle volumes. Limitations: There was significant publication bias and between-study inconsistency for several brain regions. Conclusions: Bipolar disorder is associated with generalised alterations in white and grey matter brain volumes, particularly marked in the hippocampus volumes, which were smaller but showed greater variability in volumes relative to controls. This suggests that heterogeneity in neurobiological processes involving the hippocampus contribute to clinical heterogeneity in the disorder, and this may be more marked in males than females.

AB - Background: Bipolar disorder is thought to be associated with structural brain alterations, but findings have been inconsistent. Our double meta-analysis investigated the variability and magnitude of differences in regional brain volumes in patients with bipolar disorder relative to healthy volunteers. Methods: Databases were systematically searched for MRI studies reporting regional brain volumetric measures in patients with bipolar disorder and controls. The primary outcome measures were variability ratio (VR), coefficient of variability ratio (CVR) and Hedge's g. Results: 118 studies comprising 5534 patients and 6651 controls were included. The variability meta-analysis showed higher variability in amygdala (VR, 1.14; P =.02; CVR, 1.25; P =.005) and hippocampal (VR, 1.16; P =.001; CVR, 1.22; P = <.001) volumes in patients relative to controls. The meta-analysis of volume differences showed higher lateral (g, -0.43; P = <.0001) and third ventricle (g, -0.22; P =.01) volumes in patients; and lower hippocampus (g, 0.41; P =.001), grey matter (g, 0.25; P =.001), white matter (g, 0.23; P =.0002) and total brain volumes (g, 0.20; P =.003) in patients relative to controls. A higher proportion of male subjects was associated with decreased mean volumes of the amygdala, hippocampus and thalamus and increased lateral ventricle volumes. Limitations: There was significant publication bias and between-study inconsistency for several brain regions. Conclusions: Bipolar disorder is associated with generalised alterations in white and grey matter brain volumes, particularly marked in the hippocampus volumes, which were smaller but showed greater variability in volumes relative to controls. This suggests that heterogeneity in neurobiological processes involving the hippocampus contribute to clinical heterogeneity in the disorder, and this may be more marked in males than females.

KW - Bipolar disorder

KW - Heterogeneity

KW - Meta-analysis

KW - Subcortical

KW - Variability

KW - Volume

UR - http://www.scopus.com/inward/record.url?scp=85106926179&partnerID=8YFLogxK

U2 - 10.1016/j.jad.2021.04.090

DO - 10.1016/j.jad.2021.04.090

M3 - Review article

C2 - 34038834

AN - SCOPUS:85106926179

SN - 0165-0327

VL - 291

SP - 171

EP - 176

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

ER -