title: Polygenic Risk Score associated with specific symptom dimensions in first-episode psychosis.
abstract: Recent Genome-Wide Association Studies (GWAS) have provided evidence for the involvement of a number of genetic variants in schizophrenia (SCZ). The objective of the current study was to examine the association between these variants and symptom dimensions, evaluated prospectively over a period of 24months, in a clinically well-characterized sample of individuals (n=241) with first-episode psychosis (FEP). The genetic variants were analyzed collectively as captured through a Polygenic Risk Score (PRS), calculated for each individual. At each evaluation time point (baseline, 1, 2, 6 and 24months), correlation analysis was conducted with PRS and symptom dimension scores assessed by the Positive and Negative Syndrome Scale (PANSS). We also examined the association of PRS with global symptom rating, depression, anxiety, social and occupational functioning as measured by widely used and well validated scales. At baseline, significant positive correlation was observed between PRS and the general psychopathology dimension of the PANSS but no associations were observed with the positive or negative symptom dimensions. Anxiety, assessed using the Hamilton Anxiety Rating Scale, was also significantly correlated with the PRS. No significant correlation was observed with other symptom dimensions or with the PANSS score at the later evaluations. These results provide novel evidence of an association between general psychopathology and PRS in young people with first episode psychosis. They also demonstrate that it is important to note the dynamic changes of symptoms over time when trying to refine the relationship between genetic factors and phenotypes.
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Ave. West, Montreal, Quebec H3A 1A1, Canada. Electronic address: sarojini.sengupta@douglas.mcgill.ca.
authors.forename: Sarojini M
authors.initials: SM
authors.lastname: Sengupta
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Ave. West, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Kathleen
authors.initials: K
authors.lastname: MacDonald
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Ave. West, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Ferid
authors.initials: F
authors.lastname: Fathalli
authors.affiliation: Department of Medicine, Université de Sherbrooke, Local E5-1283, Sherbrooke, Québec J1K 2R1, Canada.
authors.forename: Anita
authors.initials: A
authors.lastname: Yim
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Ave. West, Montreal, Quebec H3A 1A1, Canada; Integrated Program in Neuroscience, McGill University, Room 141, Montreal Neurological Institute, 3801 University Street, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Lepage
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Ave. West, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Srividya
authors.initials: S
authors.lastname: Iyer
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Ave. West, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Ashok
authors.initials: A
authors.lastname: Malla
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Ave. West, Montreal, Quebec H3A 1A1, Canada; Integrated Program in Neuroscience, McGill University, Room 141, Montreal Neurological Institute, 3801 University Street, Montreal, Quebec H3A 2B4, Canada; Department of Human Genetics, McGill University, Room N5-13, Stewart Biology Building, 1205 Dr. Penfield Ave., Montreal, Quebec H3A 1B1, Canada.
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
mesh_terms: D000328:Adult; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance; D011618:Psychotic Disorders / Q000235:genetics* / Q000503:physiopathology*; D012306:Risk; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D055815:Young Adult
keywords: Anxiety; First-episode psychosis; General psychopathology; PANSS; Polygenic Risk Score; Schizophrenia