An exploratory model for G × E interaction on hippocampal volume in schizophrenia; obstetric complications and hypoxia-related genes |
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Authors: | Unn Kristin Haukvik Peter Saetre Thomas McNeil Petr S Bjerkan Ole A Andreassen Thomas Werge Erik G Jönsson Ingrid Agartz |
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Institution: | 1. Department of Clinical Medicine, section Vinderen, University of Oslo, Norway;2. Department of Clinical Neuroscience, HUBIN project, Karolinska Institute and Hospital, Stockholm, Sweden;3. Department of Psychiatric Epidemiology, Lund University Hospital USiL, Lund, Sweden;4. Department of Psychiatric Research Oslo University Hospital, Norway;5. Department of Clinical Medicine, Ullevål, University of Oslo, Norway;6. Research Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark;g Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway |
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Abstract: | BackgroundSmaller hippocampal volume has repeatedly been reported in schizophrenia patients. Obstetric complications (OCs) and single nucleotide polymorphism (SNP) variation in schizophrenia susceptibility genes have independently been related to hippocampal volume. We investigated putative independent and interaction effects of severe hypoxia-related OCs and variation in four hypoxia-regulated schizophrenia susceptibility genes (BDNF, DTNBP1, GRM3 and NRG1) on hippocampal volume in schizophrenia patients and healthy controls.MethodsClinical assessment, structural MRI scans, and blood samples for genotyping of 32 SNPs were obtained from 54 schizophrenia patients and 53 control subjects. Information on obstetric complications was collected from original birth records.ResultsSevere OCs were related to hippocampal volume in both patients with schizophrenia and healthy control subjects. Of the 32 SNPs studied, effects of severe OCs on hippocampal volume were associated with allele variation in GRM3 rs13242038, but the interaction effect was not specific for schizophrenia. SNP variation in any of the four investigated genes alone did not significantly affect hippocampal volume.ConclusionsThe findings suggest a gene–environment (G × E) interaction between GRM3 gene variants and severe obstetric complications on hippocampus volume, independent of a diagnosis of schizophrenia. Due to the modest sample size, the results must be considered preliminary and require replication in independent samples. |
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Keywords: | BDNF brain-derived neurotrophic factor DTNBP1 dysbindin GRM3 metabotropic glutamate receptor 3 ICV intracranial volume MRI magnetic resonance imaging NRG1 neuregulin1 OCs obstetric complications HCV hippocampal volume LD linkage disequilibrium ICC interclass correlation |
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