Faculty, Staff and Student Publications

Language

English

Publication Date

5-1-2026

Journal

Molecular Psychiatry

DOI

10.1038/s41380-025-03432-z

PMID

41540091

PMCID

PMC13099646

PubMedCentral® Posted Date

1-15-2026

PubMedCentral® Full Text Version

Post-print

Abstract

MRI studies in bipolar disorder (BD) have yielded inconsistent findings, partly due to the varied use of psychotropic medications. This study utilised a mega-analysis approach, accounting for concurrent medication status (syndrome-based and Neuroscience-based Nomenclature (NbN) classifications), in order to assess the association of medication status with subcortical brain volumes in BD. Data from 2,664 BD patients and 4,065 controls (CN) were pooled from 34 research groups as part of the ENIGMA Bipolar Disorder Working Group. Standardized ENIGMA protocols were used to measure subcortical brain volumes. Linear-mixed-effects regression evaluated the association between psychotropic medications and subcortical volumes, and moderation analyses explored interactions. Medication-free patients (n = 410) showed mild ventricular enlargement (d = 0.07) and increased putamen volume (d = 0.06) compared to CN. Patients taking psychotropic medications exhibited smaller subcortical volumes (d = -0.06 to -0.11) and larger ventricles (d = 0.11 to 0.19). Use of antiepileptic and antipsychotic medications was associated with smaller hippocampal and thalamic volumes (d = -0.07 to -0.14), while NbN classification indicated that the categories of 'valproate' and 'dopamine and other monoamine receptor antagonists' are key variables when considering volume differences between BD and CN. Concurrent lithium use weakened the negative association between antiepileptic use and hippocampal volume (β = 0.19, q = 0.038) in patients. Medication status is associated with altered subcortical brain volumes in BD. The NbN classification provides a useful framework for future studies, emphasizing the need for comprehensive longitudinal research to further unravel complex clinical-pharmacological-neurobiological interactions in BD.

Keywords

Humans, Bipolar Disorder, Magnetic Resonance Imaging, Brain, Psychotropic Drugs, Female, Male, Adult, Middle Aged, Organ Size, Antipsychotic Agents, Hippocampus, Anticonvulsants, Thalamus, Neuroscience

Published Open-Access

yes

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