Genetic contribution to disease-course severity and progression in the SUPER-Finland study, a cohort of 10,403 individuals with psychotic disorders.

Journal: Molecular psychiatry

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Affiliated Institutions:  Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. anders.kampe@helsinki.fi. National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA, USA. Department of Psychiatry, University of Turku, Turku, Finland. Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Department of Psychiatry, Oulu University Hospital, Oulu, Finland. Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. Hospital District of Helsinki and Uusimaa, Helsinki, Finland. University of Helsinki, Helsinki, Finland. Tampere University, Tampere, Finland. Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Harvard Medical School, Department of Medicine, Boston, USA. Virginia Institute of Psychiatric and Behavioral Genetics, Richmond, VA, USA.

Abstract summary 

Genetic factors contribute to the susceptibility of psychotic disorders, but less is known how they affect psychotic disease-course development. Utilizing polygenic scores (PGSs) in combination with longitudinal healthcare data with decades of follow-up we investigated the contributing genetics to psychotic disease-course severity and diagnostic shifts in the SUPER-Finland study, encompassing 10 403 genotyped individuals with a psychotic disorder. To longitudinally track the study participants' past disease-course severity, we created a psychiatric hospitalization burden metric using the full-coverage and nation-wide Finnish in-hospital registry (data from 1969 and onwards). Using a hierarchical model, ranking the psychotic diagnoses according to clinical severity, we show that high schizophrenia PGS (SZ-PGS) was associated with progression from lower ranked psychotic disorders to schizophrenia (OR = 1.32 [1.23-1.43], p = 1.26e-12). This development manifested already at psychotic illness onset as a higher psychiatric hospitalization burden, the proxy for disease-course severity. In schizophrenia (n = 5 479), both a high SZ-PGS and a low educational attainment PGS (EA-PGS) were associated with increased psychiatric hospitalization burden (p = 1.00e-04 and p = 4.53e-10). The SZ-PGS and the EA-PGS associated with distinct patterns of hospital usage. In individuals with high SZ-PGS, the increased hospitalization burden was composed of longer individual hospital stays, while low EA-PGS associated with shorter but more frequent hospital visits. The negative effect of a low EA-PGS was found to be partly mediated via substance use disorder, a major risk factor for hospitalizations. In conclusion, we show that high SZ-PGS and low EA-PGS both impacted psychotic disease-course development negatively but resulted in different disease-course trajectories.

Authors & Co-authors:  Kämpe Suvisaari Lähteenvuo Singh Ahola-Olli Urpa Haaki Hietala Isometsä Jukuri Kampman Kieseppä Lahdensuo Lönnqvist Männynsalo Paunio Niemi-Pynttäri Suokas Tuulio-Henriksson Veijola Wegelius Daly Taylor Kendler Palotie Pietiläinen

Study Outcome 

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Citations :  Barkhuizen W, Pain O, Dudbridge F, Ronald A. Genetic overlap between psychotic experiences in the community across age and with psychiatric disorders. Transl Psychiatry. 2020;10:86.
Authors :  27
Identifiers
Doi : 10.1038/s41380-024-02516-6
SSN : 1476-5578
Study Population
Male,Female
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Publication Country
England