First-episode psychosis patients who deteriorated in the premorbid period do not have higher polygenic risk scores than others: A cluster analysis of EU-GEI data

Ferraro, Laura, Quattrone, Diego, La Barbera, Daniele, La Cascia, Caterina, Morgan, Craig, Kirkbride, James B., Cardno, Alastair G., Sham, Pak, Tripoli, Giada, Sideli, Lucia, Seminerio, Fabio, Sartorio, Crocettarachele, Szoke, Andrei, Tarricone, Ilaria, Bernardo, Miquel, Rodriguez, Victoria, Stilo, Simona A., Gayer-Anderson, Charlotte, de Haan, Lieuwe, Velthorst, Eva, Jongsma, Hannah, Bart, Rutten B. P., Richards, Alexander, Arango, Celso, Menezez, Paulo Rossi, Lasalvia, Antonio, Tosato, Sarah, Tortelli, Andrea, Del Ben, Cristina Marta, Selten, Jean-Paul, Jones, Peter B., van Os, Jim, Di Forti, Marta, Vassos, Evangelos and Murray, Robin M. 2023. First-episode psychosis patients who deteriorated in the premorbid period do not have higher polygenic risk scores than others: A cluster analysis of EU-GEI data. Schizophrenia Bulletin: The Journal of Psychoses and Related Disorders 49 (1) , pp. 218-227. 10.1093/schbul/sbac100

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Abstract

Cluster studies identified a subgroup of patients with psychosis whose premorbid adjustment deteriorates before the onset, which may reflect variation in genetic influence. However, other studies reported a complex relationship between distinctive patterns of cannabis use and cognitive and premorbid impairment that is worthy of consideration. We examined whether: (1) premorbid social functioning (PSF) and premorbid academic functioning (PAF) in childhood and adolescence and current intellectual quotient (IQ) define different clusters in 802 first-episode of psychosis (FEP) patients; resulting clusters vary in (2) polygenic risk scores (PRSs) for schizophrenia (SCZ_PRS), bipolar disorder (BD_PRS), major depression (MD_PRS), and IQ (IQ_PRS), and (3) patterns of cannabis use, compared to 1,263 population-based controls. Four transdiagnostic clusters emerged (BIC = 2268.5): (1) high-cognitive-functioning (n = 205), with the highest IQ (Mean = 106.1, 95% CI: 104.3, 107.9) and PAF, but low PSF. (2) Low-cognitive-functioning (n = 223), with the lowest IQ (Mean = 73.9, 95% CI: 72.2, 75.7) and PAF, but normal PSF. (3) Intermediate (n = 224) (Mean_IQ = 80.8, 95% CI: 79.1, 82.5) with low-improving PAF and PSF. 4) Deteriorating (n = 150) (Mean_IQ = 80.6, 95% CI: 78.5, 82.7), with normal-deteriorating PAF and PSF. The PRSs explained 7.9% of between-group membership. FEP had higher SCZ_PRS than controls [F(4,1319) = 20.4, P < .001]. Among the clusters, the deteriorating group had lower SCZ_PRS and was likelier to have used high-potency cannabis daily. Patients with FEP clustered according to their premorbid and cognitive abilities. Pronounced premorbid deterioration was not typical of most FEP, including those more strongly predisposed to schizophrenia, but appeared in a cluster with a history of high-potency cannabis use.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Oxford University Press
ISSN:	0586-7614
Funders:	no funder mentioned in text
Date of First Compliant Deposit:	11 October 2022
Date of Acceptance:	19 July 2022
Last Modified:	09 May 2023 19:50
URI:	https://orca.cardiff.ac.uk/id/eprint/153288

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