title: The "polyenviromic risk score": Aggregating environmental risk factors predicts conversion to psychosis in familial high-risk subjects.
abstract: Young relatives of individuals with schizophrenia (i.e. youth at familial high-risk, FHR) are at increased risk of developing psychotic disorders, and show higher rates of psychiatric symptoms, cognitive and neurobiological abnormalities than non-relatives. It is not known whether overall exposure to environmental risk factors increases risk of conversion to psychosis in FHR subjects.
  
  
  
  Subjects consisted of a pilot longitudinal sample of 83 young FHR subjects. As a proof of principle, we examined whether an aggregate score of exposure to environmental risk factors, which we term a 'polyenviromic risk score' (PERS), could predict conversion to psychosis. The PERS combines known environmental risk factors including cannabis use, urbanicity, season of birth, paternal age, obstetric and perinatal complications, and various types of childhood adversity, each weighted by its odds ratio for association with psychosis in the literature.
  
  
  
  A higher PERS was significantly associated with conversion to psychosis in young, familial high-risk subjects (OR=1.97, p=0.009). A model combining the PERS and clinical predictors had a sensitivity of 27% and specificity of 96%.
  
  
  
  An aggregate index of environmental risk may help predict conversion to psychosis in FHR subjects.
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Behavioral Neurology and Neuropsychiatry, McLean Hospital, Belmont, MA, USA.
authors.forename: Jaya L
authors.initials: JL
authors.lastname: Padmanabhan
authors.affiliation: PEPP-Montréal, Douglas Mental Health University Institute, Montreal, Canada; Department of Psychiatry, McGill University, Montreal, Canada.
authors.forename: Jai L
authors.initials: JL
authors.lastname: Shah
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Baylor College of Medicine, Texas Medical Center, Houston, TX, USA.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Tandon
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Electronic address: mkeshava@bidmc.harvard.edu.
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
mesh_terms: D000293:Adolescent; D018450:Disease Progression; D004777:Environment; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016017:Odds Ratio; D010865:Pilot Projects; D011618:Psychotic Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D012680:Sensitivity and Specificity
keywords: Environment; Familial high risk; Prediction; Psychosis; Schizophrenia