Abstract
Investigating alterations in brain circuitry associated with bipolar disorder (BD) may offer a valuable approach to discover brain biomarkers for genetic and interventional studies of the disorder and related mental illnesses. Some diffusion MRI studies report evidence of microstructural abnormalities in white matter regions of interest, but we lack a fine-scale spatial mapping of brain microstructural differences along tracts in BD. We also lack large-scale studies that integrate tractometry data from multiple sites, as larger datasets can greatly enhance power to detect subtle effects and assess whether effects replicate across larger international datasets. In this multisite diffusion MRI study, we used BUndle ANalytics (BUAN, Chandio 2020), a recently developed analytic approach for tractography, to extract, map, and visualize profiles of microstructural abnormalities on 3D models of fiber tracts in 148 participants with BD and 259 healthy controls from 6 independent scan sites. Modeling site differences as random effects, we investigated along-tract white matter (WM) microstructural differences between diagnostic groups. QQ plots showed that group differences were gradually enhanced as more sites were added. Using the BUAN pipeline, BD was associated with lower mean fractional anisotropy (FA) in fronto-limbic, interhemispheric, and posterior pathways; higher FA was also noted in posterior bundles, relative to controls. By integrating tractography and anatomical information, BUAN effectively captures unique effects along white matter (WM) tracts, providing valuable insights into anatomical variations that may assist in the classification of diseases.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Health Research Board (HRA-POR-324), Irish Research Council (IRC) Postgraduate Scholarship; NIH grants RF1AG057892, R01MH116147, R01MH129742; Australian National Medical and Health Research Council (Program Grant 1037196 and Investigator Grant 1177991); German Research Foundation (DFG, grant FOR2107 DA1151/5-1, DA1151/5-2, DA1151/9-1, DA1151/10-1, DA1151/11-1; SFB-TRR58, Projects C09 and Z02) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/022/22). German Research Foundation (DFG grants FOR2107 KI588/14-1, and KI588/14-2, and KI588/20-1, KI588/22-1,Marburg, Germany).
Revisions in the introduction and discussions. Results have not changed.