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. 2025 Sep 26:43:100391.
doi: 10.1016/j.scog.2025.100391. eCollection 2026 Mar.

Premorbid functioning trajectories and the one-year course of cognitive performance in first-episode psychosis: a cluster analysis in PSYSCAN

Margot I E Slot  1 , Hendrika H van Hell  1 , Inge Winter-van Rossum  1   2   3 , George Gifford  3   4 , Paola Dazzan  5 , Arija Maat  1 , Lieuwe De Haan  6 , Benedicto Crespo-Facorro  7 , Birte Y Glenthøj  8   9 , Colm McDonald  10 , Thérèse van Amelsvoort  11 , Celso Arango  12 , Irina Falkenberg  13 , Barnaby Nelson  14   15 , Silvana Galderisi  16 , Mark Weiser  17   18 , Gabriele Sachs  19 , Anke Maatz  20 , Jun Soo Kwon  21   22   23 ; PSYSCAN Consortium; Philip McGuire  3   4 , René S Kahn  1   2
Affiliations

Premorbid functioning trajectories and the one-year course of cognitive performance in first-episode psychosis: a cluster analysis in PSYSCAN

Margot I E Slot et al. Schizophr Res Cogn. .

Abstract

Background: We examined the course of cognitive performance in first-episode psychosis (FEP) compared to healthy controls (HC), and whether this varied across subgroups of patients defined by premorbid functioning (PMF) trajectories, using a clustering approach.

Methods: Data were collected in 302 FEP and 136 HC subjects participating in PSYSCAN (HEALTH.2013.2.2.1-2-FEP). K-means clustering (Euclidean distance) was used to cluster longitudinal trajectories of different PMF domains simultaneously. Since PMF was assessed retrospectively using the Premorbid Adjustment Scale (PAS), findings should be interpreted with caution, although PAS ratings have shown reasonable validity against prospective data.

Results: As expected, FEP showed impaired performance across all cognitive domains compared to HC. We identified four trajectories of PMF: a normal premorbid developmental trajectory (globally-normal, 21 %), stable intermediate PMF across domains (stable-intermediate, 29 %), stable poor or deteriorating PMF in the academic domain (normal-social/poor-academic, 29 %), and a globally impaired group with poor/deteriorating PMF across domains (globally-poor, 21 %). These clusters showed distinct levels of post-onset impairments in sustained visual attention, visual working memory and emotion recognition.

Conclusions: This study confirms a positive association between PMF and cognitive performance in the early years following psychosis onset. It aligns with findings that individuals later diagnosed with schizophrenia already show developmental deficits/lags from childhood to early adolescence compared to normally developing children. As PMF can be considered a proxy for cognitive reserve, our results suggest that higher reserve acts as a buffer against cognitive decline and supports better performance on sustained visual attention, complex visual working memory, and aspects of emotion recognition.

Keywords: Clustering; Cognition; FEP; Premorbid functioning; Psychosis; Schizophrenia.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B.Y.G. has been the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) (January 2009–December 2021), which was partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose. S.G. has been a consultant and/or advisor to or has received honoraria from Angelini, Boehringer-Ingelheim, Gedeon Richter-Recordati, Janssen, Lundbeck, Otsuka, ROVI and Bristol Myers Squibb. The other authors declare none. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Flowchart of participants in the cognitive assessments.
Fig. 2
Fig. 2
Grouped error plots showing the distribution of scores on the different domains of premorbid functioning (median and interquartile range) across the groups, separated per premorbid developmental period. Higher scores indicate worse premorbid functioning.
Fig. 3
Fig. 3
Cognitive performance over a one-year period in FEP participants clustered on premorbid functioning in childhood and early adolescence, compared to healthy controls (HC). Results of repeated measures mixed model analyses, corrected for sex.
See this image and copyright information in PMC

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