Exploring the moderating effects of dopaminergic polymorphisms and childhood adversity on brain morphology in schizophrenia-spectrum disorders.
Journal: Psychiatry research. Neuroimaging
Volume: 281
Issue:
Year of Publication: 2019
Affiliated Institutions:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Australia.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Australia; Centre for Mental Health, Faculty of Health, Arts and Design, School of Health Sciences, Swinburne University, Melbourne, Australia.
School of Psychiatry, University of New South Wales, Australia; Neuroscience Research Australia, New South Wales, Australia; Schizophrenia Research Institute, Sydney, New South Wales, Australia.
School of Psychiatry, University of New South Wales, Australia; Neuroscience Research Australia, New South Wales, Australia; Schizophrenia Research Institute, Sydney, New South Wales, Australia; Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, USA.
Florey Institute of Neuroscience and Mental Health, Australia; Department of Psychiatry, School of Clinical Sciences, Monash University, Clayton, Australia; Mental Health Program, Monash Health, Clayton, Victoria, Australia.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Australia; School of Psychiatry, University of New South Wales, Australia; Neuroscience Research Australia, New South Wales, Australia; Schizophrenia Research Institute, Sydney, New South Wales, Australia; Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, New York, USA.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Australia; School of Psychiatry, University of New South Wales, Australia; Neuroscience Research Australia, New South Wales, Australia; Schizophrenia Research Institute, Sydney, New South Wales, Australia.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Australia; Florey Institute of Neuroscience and Mental Health, Australia; Department of Electrical and Electronic Engineering, University of Melbourne, Victoria, Australia.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Australia; Departments of Medical Genetics, Psychiatry, and Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada. Electronic address: chad.bousman@ucalgary.ca.
Abstract summary
Genetic and environmental etiologies may contribute to schizophrenia and its associated neurobiological profile. We examined the interaction between dopaminergic polymorphisms, childhood adversity and diagnosis (schizophrenia/schizoaffective disorder) on dopamine-related brain structures. Childhood adversity histories and structural MRI data were obtained from 249 (153 schizophrenia/schizoaffective, 96 controls) participants registered in the Australian Schizophrenia Research Bank. Polymorphisms in DRD2 and COMT were genotyped and a dopaminergic risk allelic load (RAL) was calculated. Regression analysis was used to test the main and interaction effects of RAL, childhood adversity and diagnosis on volumes of dopamine-related brain structures (caudate, putamen, nucleus accumbens, dorsolateral prefrontal cortex and hippocampus). A schizophrenia/schizoaffective diagnosis showed significant main effects on bilateral hippocampus, left dorsolateral prefrontal cortex and bilateral putamen volumes. RAL showed a significant main effect on left putamen volumes. Furthermore, across the whole sample, a significant two-way interaction between dopaminergic RAL and childhood adversity was found for left putamen volumes. No brain structure volumes were predicted by a three-way interaction that included diagnosis. Our finding suggests the left putamen may be particularly sensitive to dopaminergic gene-environment interactions regardless of diagnosis. However, larger studies are needed to assess whether these interactions are more or less pronounced in those with schizophrenia/schizoaffective disorders.
Authors & Co-authors:
Hoffmann Cassandra C
Van Rheenen Tamsyn E TE
Mancuso Serafino G SG
Zalesky Andrew A
Bruggemann Jason J
Lenroot Rhoshel K RK
Sundram Suresh S
Weickert Cynthia Shannon CS
Weickert Thomas W TW
Pantelis Christos C
Cropley Vanessa V
Bousman Chad A CA
Study Outcome
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