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Longitudinal clinical and functional outcome in distinct cognitive subgroups of first-episode psychosis: a cluster analysis
- Priscilla P. Oomen, Marieke J. H. Begemann, Bodyl A. Brand, Lieuwe de Haan, Wim Veling, Sanne Koops, Jim van Os, Filip Smit, P. Roberto Bakker, Nico van Beveren, Nynke Boonstra, Sinan Gülöksüz, Martijn Kikkert, Joran Lokkerbol, Machteld Marcelis, Bram-Sieben Rosema, Franciska de Beer, Shiral S. Gangadin, Chris N. W. Geraets, Erna van ‘t Hag, Yudith Haveman, Inge van der Heijden, Alban E. Voppel, Elske Willemse, Therese van Amelsvoort, Maarten Bak, Albert Batalla, Agaath Been, Marinte van den Bosch, Truus van den Brink, Gunnar Faber, Koen P. Grootens, Martin de Jonge, Rikus Knegtering, Jörg Kurkamp, Amrita Mahabir, Gerdina H. M. Pijnenborg, Tonnie Staring, Natalie Veen, Selene Veerman, Sybren Wiersma, Ellen Graveland, Joelle Hoornaar, Iris E. C. Sommer
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- Journal:
- Psychological Medicine / Volume 53 / Issue 6 / April 2023
- Published online by Cambridge University Press:
- 19 October 2021, pp. 2317-2327
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- Article
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Background
Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes.
Methods204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up.
ResultsThree distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present.
ConclusionsCurrent results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.
White matter abnormalities in 22q11.2 deletion syndrome patients showing cognitive decline
- Jasper Olivier Nuninga, Marc Marijn Bohlken, Sanne Koops, Ania M. Fiksinski, René C. W. Mandl, Elemi J. Breetvelt, Sasja N. Duijff, René S. Kahn, Iris E. C. Sommer, Jacob A. S. Vorstman
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- Journal:
- Psychological Medicine / Volume 48 / Issue 10 / July 2018
- Published online by Cambridge University Press:
- 16 November 2017, pp. 1655-1663
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Background
Decline in cognitive functioning precedes the first psychotic episode in the course of schizophrenia and is considered a hallmark symptom of the disorder. Given the low incidence of schizophrenia, it remains a challenge to investigate whether cognitive decline coincides with disease-related changes in brain structure, such as white matter abnormalities. The 22q11.2 deletion syndrome (22q11DS) is an appealing model in this context, as 25% of patients develop psychosis. Furthermore, we recently showed that cognitive decline also precedes the onset of psychosis in individuals with 22q11DS. Here, we investigate whether the early cognitive decline in patients with 22q11DS is associated with alterations in white matter microstructure.
MethodsWe compared the fractional anisotropy (FA) of white matter in 22q11DS patients with cognitive decline [n = 16; −18.34 (15.8) VIQ percentile points over 6.80 (2.39) years] to 22q11DS patients without cognitive decline [n = 18; 17.71 (20.17) VIQ percentile points over 5.27 (2.03) years] by applying an atlas-based approach to diffusion-weighted imaging data.
ResultsFA was significantly increased (p < 0.05, FDR) in 22q11DS patients with a cognitive decline in the bilateral superior longitudinal fasciculus, the bilateral cingulum bundle, all subcomponents of the left internal capsule and the left superior frontal-occipital fasciculus as compared with 22q11DS patients without cognitive decline.
ConclusionsWithin 22q11DS, the early cognitive decline is associated with microstructural differences in white matter. At the mean age of 17.8 years, these changes are reflected in increased FA in several tracts. We hypothesize that similar brain alterations associated with cognitive decline take place early in the trajectory of schizophrenia.