Schizophrenia polygenic risk score and 20-year course of illness in psychotic disorders

Abstract

Understanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnosis and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β = 0.21), greater illness severity (β = 0.28), and worse cognition (β = −0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a tool for diagnosis and treatment planning.

Genetic liability in individuals at ultra-high risk of psychosis: A comparison study of 9 psychiatric traits

“…This cohort of UHR is unique in that individuals were antipsychotic naïve and free of illicit substance use [8], which may otherwise mar the association between status and PRS. The investigation of UHR individuals here extends previous knowledge on how schizophrenia PRS indexes the lability for psychosis across the psychosis spectrum, from prodromal phase as evaluated in the current study, to eventual diagnosis of schizophrenia or psychosis investigated previously [46,47,49]. Nevertheless, further research on the generalisability of these findings to other ethnicities is warranted as our cohort is relatively small and composed of Asian individuals.…”

“…Previous studies have reported that the schizophrenia PRS identified and discriminated healthy individuals from individuals with first episode psychosis, schizophrenia and other psychoses [46][47][48][49][50]. More recently, Perkins et al (2020) [51] reported that the schizophrenia PRS discriminated psychosis converters from non-converters in an at-risk sample of European ancestry, while He et al (2019) [52] found no association between schizophrenia PRS and conversion to psychosis.…”

Pleiotropy of polygenic factors associated with focal and generalized epilepsy in the general population

“…The use and generation of PRS is a rapidly developing field, with no established best-practice method. We selected the LD-clumping and P-value thresholding method to generate PRS based on a known excellent performance in neurological and psychiatric disorders [35][36][37]. A commonly used alternative is LDpred, a method that accounts for LD between SNPs and thus allows joint modeling with the potential of improvements in the prediction power [38].…”

Modern Scientific Views on the Clinic, Systematics, Diagnosis and Pathopersonalogy of Endogenous Psychosis With Episodic Course (Literature Riview)

“…I. Spellmann, M. Riedel, J. Städtler та співавторами (2017) отримано дані щодо генетичної природи особливостей патофізіологічних процесів, за рахунок яких відбувається формування нейрокогнітивного дефіциту при ЕПЕП та підтверджено участь глутаматергічних та GABA-ергічних систем [14]. K. G. Jonas, T. Lencz, K. Li зі співавторами (2019) вважають, що за рахунок визначення «показника полігенного ризику шизофренії» можна певною мірою передбачати зміни від афективного психозу в дебюті захворювання (при першій госпіталізації) до шизофренії в майбутньому [15].…”