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Transdiagnostic Identification of Cognitive Subtypes and White Matter Correlates

Poster Session F - Tuesday, March 10, 2026, 8:00 – 10:00 am PDT, Fairview/Kitsilano Ballroom

Alina Nostadt¹ (), Rieke Roxanne Mülfarth¹, Jannik Lepper¹, Svenja Seuffert¹, Lea Teutenberg¹, Florian Thomas-Odenthal¹, Paula Usemann¹, Susanne Meinert², Tiana Borgers², Kira Flinkenflügel², Janik Goltermann², Dominik Grotegerd², Hamidreza Jamalabadi¹, Igor Nenadic¹, Benjamin Straube¹, Nina Alexander¹, Udo Dannlowski^2,3, Andreas Jansen¹, Tilo Kircher¹, Frederike Stein¹; ¹Philipps-University Marburg, ²University of Münster, ³Bielefeld University

Cognitive impairments are widespread across affective and psychotic disorders, frequently persisting beyond symptom remission and limiting both functional recovery and treatment engagement. Yet substantial heterogeneity remains. Individuals with the same diagnosis can show markedly different cognitive, clinical, and neurobiological profiles, while patients with different diagnoses may share similar characteristics. Transdiagnostic identification of cognitive subtypes, along with investigation of underlying neural mechanisms such as white matter tract integrity, may therefore provide a more powerful framework of variability in illness presentation and support personalized, mechanism-based interventions. Using data from our large-scale transdiagnostic and deeply phenotyped cohort (N = 2472; HC, MDD, BD, SSD), we applied k-Means clustering, based on principal components derived from eight neuropsychological tests comprising more than 40 variables, to derive transdiagnostic cognitive subgroups. Group differences in cognitive and clinical variables were examined using non-parametric tests, with multiple comparison control and rank-based effect sizes. Logistic regression assessed associations between sociodemographic, clinical, and symptom characteristics and cluster membership. To explore neurobiological relevance, diffusion-tensor imaging was used to examine whether cognitive subtypes differ in white matter microstructure. Since white matter pathways support information processing across distributed brain networks, structural alterations may offer mechanistic insight into cognitive variability beyond categorical diagnoses. Two transdiagnostic cognitive subtypes emerged, showing significant differences in neuropsychological performance, white matter integrity, and clinical characteristics. These findings highlight clinically meaningful cognitive heterogeneity in major psychiatric disorders and emphasize the value of cognitive profiling for improving prognostic assessment and guiding personalized treatment approaches.

Topic Area: EXECUTIVE PROCESSES: Other