Evidence of phenotypes indexing cognitive resilience and vulnerability in the early course of mood and psychosis spectrum illness; mapping the latent structure, characteristics, and longitudinal stability of cognitive heterogeneity.

Van Rheenen TE., Ringin E., Meyer D., Allott K., Wenzel J., Upthegrove R., Stainton A., Salokangas RKR., Ruhrmann S., Rosen M., Meisenzahl E., Maggioni E., Lichtenstein T., Lencer R., Kambeitz J., Dannlowski U., Dwyer DB., Chisholm K., Borgwardt S., Bonivento C., Bertolino A., Antonucci L., Koutsouleris N., Brambilla P., Pantelis C., Kambeitz-Ilankovic L., Wood SJ., PRONIA Consortium .

The latent structure and longitudinal stability of cognitive heterogeneity during the early course of mood and psychosis spectrum illness has not been well-studied. We determined the presence, stability and characteristics of latent cognitive profiles underlying a transdiagnostic sample of individuals at high risk for psychosis (CHR) or with a recent onset of psychosis (ROP) or depression (ROD). The sample comprised 666 CHR, ROP or ROD individuals. Latent Profile Analysis identified transdiagnostic cognitive profiles in baseline and 11-month follow up data. Latent Transition Analysis established the stability of these profiles and their transition probabilities. Profiles were characterised across several clinical factors and those indexing functioning, neurodevelopment, stress exposure, and physical/brain health. A 3-profile model was most optimal at both timepoints, with profile equivalence metrics indicating a low likelihood of transition between them, and thus, temporal stability. The profiles were labelled 'Average Cognition', Moderately Impaired', 'Severely Impaired', with all diagnoses represented in each. No changes in cognition were observed for any profile over the follow-up despite clinical symptom improvement. The Severely Impaired profile had the lowest premorbid adjustment, brain and cognitive reserve, and the highest levels of functional impairment. A higher number and burden of recent stressful life events were reported in the Average Cognition profile. The findings suggest that stable transdiagnostic latent cognitive profiles are observable even at very early stages of manifest mood and psychotic illness. The Severely Impaired profile appears to map to indices of abnormal neurodevelopment, while the Average Cognition profile appears to represent a more stress-resilient phenotype.

DOI

10.1016/j.euroneuro.2026.112800

Type

Journal article

Publication Date

2026-03-09T00:00:00+00:00

Volume

107

Keywords

Brain reserve, Cognition, Cognitive heterogeneity, Cognitive profiles, Cognitive reserve, Cognitive stability, Cognitive subgroups, Cognitive trajectory, Depression, Neurodevelopment, Psychosis

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