title: Impact of polygenic schizophrenia-related risk and hippocampal volumes on the onset of psychosis.
abstract: Alterations in hippocampal volume are a known marker for first-episode psychosis (FEP) as well as for the clinical high-risk state. The Polygenic Schizophrenia-related Risk Score (PSRS), derived from a large case-control study, indicates the polygenic predisposition for schizophrenia in our clinical sample. A total of 65 at-risk mental state (ARMS) and FEP patients underwent structural magnetic resonance imaging. We used automatic segmentation of hippocampal volumes using the FSL-FIRST software and an odds-ratio-weighted PSRS based on the publicly available top single-nucleotide polymorphisms from the Psychiatric Genomics Consortium genome-wide association study (GWAS). We observed a negative association between the PSRS and hippocampal volumes (β=-0.42, P=0.01, 95% confidence interval (CI)=(-0.72 to -0.12)) across FEP and ARMS patients. Moreover, a higher PSRS was significantly associated with a higher probability of an individual being assigned to the FEP group relative to the ARMS group (β=0.64, P=0.03, 95% CI=(0.08-1.29)). These findings provide evidence that a subset of schizophrenia risk variants is negatively associated with hippocampal volumes, and higher values of this PSRS are significantly associated with FEP compared with the ARMS. This implies that FEP patients have a higher genetic risk for schizophrenia than the total cohort of ARMS patients. The identification of associations between genetic risk variants and structural brain alterations will increase our understanding of the neurobiology underlying the transition to psychosis.
authors: Division of Neuropsychiatry and Brain Imaging, Department of Psychiatry (UPK), Psychiatric University Clinics Basel, University of Basel, Basel, Switzerland.|Psychiatric University Clinics, University of Basel, Basel, Switzerland.
authors: F
authors: F
authors: Harrisberger
authors: Division of Neuropsychiatry and Brain Imaging, Department of Psychiatry (UPK), Psychiatric University Clinics Basel, University of Basel, Basel, Switzerland.|Psychiatric University Clinics, University of Basel, Basel, Switzerland.|Medical Image Analysis Centre, University Hospital Basel, Basel, Switzerland.
authors: R
authors: R
authors: Smieskova
authors: Psychiatric University Clinics, University of Basel, Basel, Switzerland.|Division of Molecular Neuroscience, Department of Psychology, University of Basel, Basel, Switzerland.
authors: C
authors: C
authors: Vogler
authors: Division of Molecular Neuroscience, Department of Psychology, University of Basel, Basel, Switzerland.
authors: T
authors: T
authors: Egli
authors: King's College London, Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, London, UK.
authors: A
authors: A
authors: Schmidt
authors: Division of Neuropsychiatry and Brain Imaging, Department of Psychiatry (UPK), Psychiatric University Clinics Basel, University of Basel, Basel, Switzerland.|Psychiatric University Clinics, University of Basel, Basel, Switzerland.
authors: C
authors: C
authors: Lenz
authors: Specialized Early Psychosis Outpatient Service for Adolescents and Young Adults, Department of Psychiatry, Bruderholz, Switzerland.
authors: A E
authors: AE
authors: Simon
authors: Division of Neuropsychiatry and Brain Imaging, Department of Psychiatry (UPK), Psychiatric University Clinics Basel, University of Basel, Basel, Switzerland.|Psychiatric University Clinics, University of Basel, Basel, Switzerland.
authors: A
authors: A
authors: Riecher-Rössler
authors: Psychiatric University Clinics, University of Basel, Basel, Switzerland.|Division of Molecular Neuroscience, Department of Psychology, University of Basel, Basel, Switzerland.|Transfaculty Research Platform, University of Basel, Basel, Switzerland.|Department Biozentrum, Life Sciences Training Facility, University of Basel, Basel, Switzerland.
authors: A
authors: A
authors: Papassotiropoulos
authors: Division of Neuropsychiatry and Brain Imaging, Department of Psychiatry (UPK), Psychiatric University Clinics Basel, University of Basel, Basel, Switzerland.|Psychiatric University Clinics, University of Basel, Basel, Switzerland.|Medical Image Analysis Centre, University Hospital Basel, Basel, Switzerland.|King's College London, Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, London, UK.
authors: S
authors: S
authors: Borgwardt
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020412:Multifactorial Inheritance; D016017:Odds Ratio; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000235:genetics* / Q000473:pathology; D012306:Risk; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D055815:Young Adult