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
Laura Ferraro, Diego Quattrone, Daniele La Barbera, Caterina La Cascia, Craig Morgan, James B. Kirkbride, Alastair G. Cardno, Pak C. Sham, Giada Tripoli, Lucia Sideli, Fabio Seminerio, Crocettarachele Sartorio, Andreı̈ Szöke, Ilaria Tarricone, Miquel Bernardo, Victoria Rodríguez, Simona A. Stilo, Charlotte Gayer‐Anderson, Lieuwe de Haan, Eva Velthorst, Hannah E. Jongsma, Rutten B P Bart, Alexander Richards, Celso Arango, Paulo Rossi Menezez, Antonio Lasalvia, Sarah Tosato, Andrea Tortelli, Cristina Marta Del‐Ben, Jean‐Paul Selten, Peter B. Jones, Jim van Os, The WP2 EU-GEI Group, Marta Di Forti, Evangelos Vassos, Robin Murray
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.