8. The Relationship Between Treatment, Symptom Severity, and Brain Connectivity in Bipolar Disorder: An International Study Across 16 Enigma-Bipolar Sites

International audience BackgroundThe treatment of bipolar disorder (BD) often involves administering multiple psychotropic medications, yet little research has examined how these medications, especially when used together, affect the brain's white matter in BD. We investigate how polypharmacy and the severity of symptoms are associated with white matter connectivity in BD, in the largest neuroimaging study of its kind.MethodsENIGMA-standardized parcellation and non-tensor-based tractography was used to derive structural connectivity matrices for 449 individuals diagnosed with BD (mean⨦SD age 33⨦13 years, 55% female) and 510 healthy individuals (36⨦13 years, 62% female) across 16 international sites. Linear mixed models were employed, adjusting for age, sex and scanning site (FDR, q < .05).ResultsCompared to controls, the BD group showed lower connectivity density, efficiency, longer pathways, and heightened centrality (d=.16-.2). In BD, longer duration of illness, earlier onset (18-25 yo), and a history of psychosis were associated with more severe connectivity deficits (d=.5-.6). Number of manic and depressive episodes was not associated with any network metrics. Antidepressant use in BD, especially of SSRIs (d=.5-.6), accentuated differences in brain network organization compared to those not taking antidepressants at the time of scanning, particularly across path length and centrality network measures. Lithium, anticonvulsants, and antipsychotics were not associated with any network alterations.ConclusionsHere we present the largest multisite brain connectivity analysis of BD, showing how illness duration and severity impacts the brain in BD and highlighting the importance of modeling polypharmaceutical effects to better understand BD brain signatures.Funding SourceIrish Research Council Postgraduate Scholarship, Health Research Board Grant No. HRA-POR-324; NIH grant R01MH129742 (Bipolar R01). The CIAM group (PI:FMH) was supported by the University Research Committee, University of Cape Town and South African funding bodies National Research Foundation (SANRF) and Medical Research Council (SAMRC); DJS from CIAM was supported by the SAMRC.