Cognitive profiles across the psychosis continuum.

Cognitive impairments are core features in individuals across the psychosis continuum and predict functional outcomes. Nevertheless, substantial variability in cognitive functioning within diagnostic groups, along with considerable overlap with healthy controls, hampers the translation of research findings into personalized treatment planning. Aligned with precision medicine, we employed a data driven machine learning method, self-organizing maps, to conduct transdiagnostic clustering based on cognitive functions in a sample comprising 228 healthy controls, 200 individuals at ultra-high risk for psychosis, and 98 antipsychotic-naïve patients with first-episode psychosis. The self-organizing maps revealed six clinically distinct cognitive profiles that significantly predicted baseline functional level and changes in functional level after one year. Cognitive flexibility in particular, as well as specific executive functions emerged as cardinal in differentiating the profiles. The application of self-organizing maps appears to be a promising approach to inform clinical decision-making based on individualized cognitive profiles, including patient allocation to different interventions. Moreover, this method has the potential to enable cross-diagnostic stratification in research trials, utilizing data-driven subgrouping informed by categories from underlying dimensions of cognition rather than from clinical diagnoses. Finally, the method enables cross-diagnostic profiling across other data modalities, such as brain networks or metabolic subtypes.
Competing Interests: Declaration of competing interest Dr. Ebdrup is part of the Advisory Board of Eli Lilly Denmark A/S, Janssen-Cilag, Lundbeck Pharma A/S, and Takeda Pharmaceutical Company Ltd; and has received lecture fees from Bristol-Myers Squibb, Otsuka Pharma Scandinavia AB, Eli Lilly Company, and Lundbeck Pharma A/S. Dr. Bojesen received lecture fees from Lundbeck Pharma A/S. The rest of the authors have no conflicts to disclose.
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