White matter microstructure in relatives of people with schizophrenia or bipolar disorder: an ENIGMA meta-analysis
Year: 2026
Type: review
Abstract: Bipolar and psychotic disorders are highly heritable and associated with widespread white matter microstructure abnormalities. In this project, we compare white matter microstructure of unaffected first-degree relatives of individuals with bipolar disorder (FDR-BD) or psychotic disorder (FDR-SZ) to that of control participants. As secondary, exploratory aims, we examined the associations of childhood traumatic experiences and working memory with white matter microstructure across relatives and controls. Finally, we compared participants with BD or SZ to controls. We combined 11 samples from 9 institutions with 408 FDR-BD, 542 FDR-SZ, 841 controls, 255 BD and 464 SZ. Analysis of the diffusion-weighted imaging data followed the ENIGMA pipeline protocols, resulting in mean fractional anisotropy (FA). Sample-level analyses were linear mixed-effects models with group as the main predictor, adjusting for age and sex and correcting for dependence between family members. Samples were combined using random-effects meta-analysis. FDR-BD showed higher FA in the posterior limb of the internal capsule (PLIC) than controls. FDR-SZ did not demonstrate any FA differences from controls. Participants with BD or SZ diagnoses from the same samples did show the expected lower FA than controls in several tracts. Working memory scores were more positively related to FA in the PLIC in FDR-SZ than in controls. The level of childhood traumatic experiences was not related to FA. White matter deficits observed in people with SZ and BD were not detected in FDR-BD and FDR-SZ, suggesting that these findings in patients are not due to familial risk but may pertain to illness itself.
Source: Molecular Psychiatry
Authors: Marjolein E. A. Barendse, Simon R. Poortman, Christopher R. K. Ching, W. Cahn, Dara M. Cannon, Josefina Castro-Fornieles, Farnaz Delavari, Janice M. Fullerton, Manon Hillegers, Colm McDonald, Philip B. Mitchell, Bryon A. Mueller, Marta Pena, Aysegul Ozerdem, Camille Piguet, Gloria Roberts, Luigi F. Saccaro, Aybala Saricicek Aydogan, Elena de la Serna, Scott R. Sponheim, Gisela Sugranyes, Lei Xuan, Nabi Zorlu, Paul M. Thompson, Neeltje E. M. van Haren
Institutions: Erasmus MC, University of Southern California, Utrecht University, University Medical Center Utrecht, Ollscoil na Gaillimhe – University of Galway, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, University of Geneva, École Polytechnique Fédérale de Lausanne, UNSW Sydney, Neuroscience Research Australia, University of Minnesota, Mayo Clinic, University Hospital of Geneva, Izmir Kâtip Çelebi University, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, Minneapolis VA Health Care System
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,490
Funders: Eli Lilly and Company, AstraZeneca, Fundación Alicia Koplowitz, National Alliance for Research on Schizophrenia and Depression, National Institute for Health and Care Research, King's College London, European Commission, ZonMw, Universiteit Maastricht, Generalitat de Catalunya, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, GGZ inGeest, Rivierduinen, GGZ Friesland, GGZ Drenthe, Dokuz Eylül Üniversitesi, H. Lundbeck A/S, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, National Institute of Mental Health, Cilag
Awards: G1271024219, Marcadores de disfunción glutamatérgica en adolescentes con alto riesgo de psicosis: relación con estructura cerebral, sintomatología y metabolismo oxidativo, G1359848195, G1583731048, 5/5 BIPOLAR-SCHIZOPHRENIA NETWORK FOR INTERMEDIATE PHENOTYPES (B-SNIP) - Resubmission - 1, 2/5 Bipolar-Schizophrenia Network for Intermediate Phenotypes 2 (B-SNIP2), 1/5 Bipolar-Schizophrenia Network for Intermediate Phenotypes 2 (B-SNIP 2) - Resu, G2458313802, G246808151, Running in the FAMILY - Understanding and predicting the intergenerational transmission of mental illness, G2702798117, G2729925620, Intervención psicológica telemática para potenciar la reserva cognitiva mediante realidad virtual en hijos de pacientes con esquizofrenia o trastorno bipolar. Valoración de cambios con un abordaje psicológico., G3044022158, G3308515383, G3488404912, G3494930099, G3576591634, G3631308110, G4136061041, Interacción genética y ambiente en hijos de pacientes con esquizofrenia o trastorno bipolar., G4654876786, G4805832265, G4944702325, G5030780214, G5109451877, Improving outcomes for youth at risk of bipolar disorder, The biology of risk for bipolar disorder: genetic effects in a high-risk longitudinal study, Large-scale neuroimaging of brain development: a population neuroscience approach, Construcción de un modelo multimodal con capacidad diagnóstica y pronóstica en adolescentes con alto riesgo de psicosis: integración de factores genéticos, ambientales y de neuroimagen., Improving our Understanding of the Diagnosis, Prevention and Treatment of Bipolar Disorder, G6768028322, Depressive and bipolar disorders: Causes, presentation and treatment innovations, G85990368, G8638566328, G8800743586, G9000054595, G9000135962, G9000147293, G9000236679, Unravelling the genetic causes of bipolar disorder: lessons from rare but highly penetrant variants in very heritable forms of illness
OpenAlex ID: W7161967318