title: Effects of environmental risks and polygenic loading for schizophrenia on cortical thickness.
abstract: There are established differences in cortical thickness (CT) in schizophrenia (SCZ) and bipolar (BD) patients when compared to healthy controls (HC). However, it is unknown to what extent environmental or genetic risk factors impact on CT in these populations. We have investigated the effect of Environmental Risk Scores (ERS) and Polygenic Risk Scores for SCZ (PGRS-SCZ) on CT. Structural MRI scans were acquired at 3T for patients with SCZ or BD (n=57) and controls (n=41). Cortical reconstructions were generated in FreeSurfer (v5.3). The ERS was created by determining exposure to cannabis use, childhood adverse events, migration, urbanicity and obstetric complications. The PGRS-SCZ were generated, for a subset of the sample (Patients=43, HC=32), based on the latest PGC GWAS findings. ANCOVAs were used to test the hypotheses that ERS and PGRS-SCZ relate to CT globally, and in frontal and temporal lobes. An increase in ERS was negatively associated with CT within temporal lobe for patients. A higher PGRS-SCZ was also related to global cortical thinning for patients. ERS effects remained significant when including PGRS-SCZ as a fixed effect. No relationship which survived FDR correction was found for ERS and PGRS-SCZ in controls. Environmental risk for SCZ was related to localised cortical thinning in patients with SCZ and BD, while increased PGRS-SCZ was associated with global cortical thinning. Genetic and environmental risk factors for SCZ appear therefore to have differential effects. This provides a mechanistic means by which different risk factors may contribute to the development of SCZ and BD.
authors.affiliation: Division of Psychiatry, Centre for Brain Sciences, School of Clinical Sciences, University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, UK. Electronic address: s0830415@sms.ed.ac.uk.
authors.forename: Emma
authors.initials: E
authors.lastname: Neilson
authors.affiliation: Division of Psychiatry, Centre for Brain Sciences, School of Clinical Sciences, University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, UK. Electronic address: C.bois@sms.ed.ac.uk.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bois
authors.affiliation: Division of Psychiatry, Centre for Brain Sciences, School of Clinical Sciences, University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, UK. Electronic address: jude.gibson@ed.ac.uk.
authors.forename: Jude
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Division of Psychiatry, Centre for Brain Sciences, School of Clinical Sciences, University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, UK. Electronic address: barbara.duff@ed.ac.uk.
authors.forename: Barbara
authors.initials: B
authors.lastname: Duff
authors.affiliation: Division of Psychiatry, Centre for Brain Sciences, School of Clinical Sciences, University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, UK; Royal Edinburgh Hospital, Morningside Park, Edinburgh, UK. Electronic address: awatson3@nhs.net.
authors.forename: Andrew
authors.initials: A
authors.lastname: Watson
authors.affiliation: MRC Centre for Inflammation Research Centre for Brain Sciences, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, UK. Electronic address: neil.roberts@ed.ac.uk.
authors.forename: Neil
authors.initials: N
authors.lastname: Roberts
authors.affiliation: AstraZeneca, IMED Neuroscience Unit, Waltham, MA, USA. Electronic address: nick.brandon@azneuro.com.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Brandon
authors.affiliation: AstraZeneca, IMED Neuroscience Unit, Waltham, MA, USA. Electronic address: john.dunlop@azneuro.com.
authors.forename: John
authors.initials: J
authors.lastname: Dunlop
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University School of Medicine, Cardiff, UK. Electronic address: hallj10@cardiff.ac.uk.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hall
authors.affiliation: Division of Psychiatry, Centre for Brain Sciences, School of Clinical Sciences, University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, UK; Royal Edinburgh Hospital, Morningside Park, Edinburgh, UK. Electronic address: andrew.mcintosh@ed.ac.uk.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
authors.affiliation: Division of Psychiatry, Centre for Brain Sciences, School of Clinical Sciences, University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, UK. Electronic address: heather.whalley@ed.ac.uk.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Whalley
authors.affiliation: Division of Psychiatry, Centre for Brain Sciences, School of Clinical Sciences, University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, UK; Royal Edinburgh Hospital, Morningside Park, Edinburgh, UK. Electronic address: s.lawrie@ed.ac.uk.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lawrie
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000209:etiology / Q000235:genetics / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D004777:Environment; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020412:Multifactorial Inheritance; D018570:Risk Assessment; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics / Q000473:pathology
keywords: Bipolar disorder; Environmental risk; Polygenic risk; Schizophrenia; Structural MRI