| Title: |
Psychotropic medications and their interactions with subcortical brain volume in bipolar disorder: An ENIGMA mega-analysis |
| Authors: |
King, S; O’Connor, J; Corley, E; Tronchin, G; Fontana, E; Nabulsi, L; Kang, MJY; Radua, J; Hallahan, B; Abé, C; Alda, M; Alnæs, D; Alonso-Lana, S; Amoretti, S; Bauer, J; Benedetti, F; Berger, K; Berk, M; Bøen, E; Böhnlein, J; Boye, B; Bravi, B; Canales-Rodríguez, EJ; Dannlowski, U; Demro, C; Di Giorgio, A; Diaz-Zuluaga, AM; Elvsåshagen, T; Favre, P; Erwin-Grabner, T; Forte, MF; Fullerton, JM; Furlong, LS; Rossell, SL; Glahn, DC; Goldstein, BI; Gotlib, IH; Goya-Maldonado, R; Green, MJ; Grotegerd, D; Gruber, O; Haarman, BCM; Hahn, T; Hajek, T; Hater, L; Hermesdorf, M; Houenou, J; Howells, FM; Karantonis, JA; Kennedy, KG; Kircher, T; Klahn, AL; Konowski, M; Krämer, B; Lahud, E; Kuplicki, R; Landén, M; López-Jaramillo, C; MacIntosh, BJ; Meinert, H; Meinert, S; Melloni, EMT; Mitchell, PB; Mwangi, B; Nenadić, I; Overs, BJ; Parker, N; Pearlson, G; Pomarol-Clotet, E; Prisciandaro, JJ; Quidé, Y; Roberts, G; Rodrigue, A; Rodríguez-Cano, E; Rauer, L; Sacchet, MD; Salvador, R; Sambataro, F; Satterthwaite, TD; Savitz, J; Scheffler, F; Schürmeyer, N; Shen, C; Sim, K; Soares, JC; Solanes, A; Soeiro-de-Souza, MG; Sponheim, SR; Stein, DJ; Stein, F; Temmingh, HS; Teutenberg, L; Thomopoulos, SI; Urosevic, S; Van Rheenen, TE; Vieta, E; Westlye, LT; Wolf, DH; Wu, MJ; Yatham, LN; Quide, Yann |
| Source: |
urn:ISSN:1359-4184 ; urn:ISSN:1476-5578 ; Molecular Psychiatry, 1-13 |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2026 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
5202 Biological Psychology; 3214 Pharmacology and Pharmaceutical Sciences; 32 Biomedical and Clinical Sciences; 52 Psychology; Neurosciences; Brain Disorders; Bipolar Disorder; Clinical Research; Mental Health; Mental Illness; Serious Mental Illness; Biomedical Imaging; ENIGMA Bipolar Disorder Working Group; anzsrc-for: 5202 Biological Psychology; anzsrc-for: 3214 Pharmacology and Pharmaceutical Sciences; anzsrc-for: 32 Biomedical and Clinical Sciences; anzsrc-for: 52 Psychology; anzsrc-for: 06 Biological Sciences; anzsrc-for: 11 Medical and Health Sciences; anzsrc-for: 17 Psychology and Cognitive Sciences; anzsrc-for: 3202 Clinical sciences; anzsrc-for: 5203 Clinical and health psychology |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
http://purl.org/au-research/grants/nhmrc/APP1177991; https://hdl.handle.net/1959.4/106830 |
| DOI: |
10.1038/s41380-025-03432-z |
| Availability: |
https://hdl.handle.net/1959.4/106830; https://doi.org/10.1038/s41380-025-03432-z |
| Rights: |
open access ; https://purl.org/coar/access_right/c_abf2 ; CC-BY ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.82661D04 |
| Database: |
BASE |