title: Catechol-O-methyltransferase (COMT) genotype moderates the effects of childhood trauma on cognition and symptoms in schizophrenia.
abstract: The interaction of genetic and environmental factors may affect the course and development of psychotic disorders. We examined whether the effects of childhood trauma on cognition and symptoms in schizophrenia were moderated by the Catechol-O-methyltransferase (COMT) Val(158)Met polymorphism, a common genetic variant known to affect cognition and prefrontal dopamine levels. Participants were 429 schizophrenia/schizoaffective cases from the Australian Schizophrenia Research Bank (ASRB). Cognitive performance was assessed using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), Controlled Oral Word Association Test (COWAT), Letter Number Sequencing (LNS) test, and the Wechsler Test of Adult Reading (WTAR). Hierarchical regression was used to test the main effects and additive interaction effects of genotype and childhood trauma in the domains of physical abuse, emotional abuse, and emotional neglect, on cognition and symptom profiles of clinical cases. Consistent with previous findings, COMT Val homozygotes performed worse on cognitive measures in the absence of childhood adversity. In addition, a significant interaction between COMT genotype and physical abuse was associated with better executive function in Val homozygotes, relative to those of the same genotype with no history of abuse. Finally, the severity of positive symptoms was greater in Met carriers who had experienced physical abuse, and the severity of negative symptoms in Met carriers was greater in the presence of emotional neglect. These results suggest that the possible epigenetic modulation of the expression of the COMT Val(158)Met polymorphism and consequent effects on cognition and symptoms in schizophrenia, with worse outcomes associated with adverse childhood experiences in Met carriers.
authors.affiliation: School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Schizophrenia Research Institute, Darlinghurst, NSW, Australia. Electronic address: melissa.green@unsw.edu.au.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Green
authors.affiliation: School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Schizophrenia Research Institute, Darlinghurst, NSW, Australia.
authors.forename: T-Yunn
authors.initials: TY
authors.lastname: Chia
authors.affiliation: Schizophrenia Research Institute, Darlinghurst, NSW, Australia; School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia; Centre for Brain and Mental Health and Centre for Information-Based Medicine, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia.
authors.forename: Murray J
authors.initials: MJ
authors.lastname: Cairns
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia; Centre for Brain and Mental Health and Centre for Information-Based Medicine, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia.
authors.forename: Jingqin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Schizophrenia Research Institute, Darlinghurst, NSW, Australia; School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia; Centre for Brain and Mental Health and Centre for Information-Based Medicine, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Tooney
authors.affiliation: Schizophrenia Research Institute, Darlinghurst, NSW, Australia; School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia; Centre for Brain and Mental Health and Centre for Information-Based Medicine, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia; Hunter Area Pathology Service, Newcastle, NSW, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.affiliation: School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Schizophrenia Research Institute, Darlinghurst, NSW, Australia.
authors.forename: Vaughan J
authors.initials: VJ
authors.lastname: Carr
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002649:Child Abuse / Q000523:psychology*; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications*; D012565:Schizophrenic Psychology; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Catechol-O-methyltransferase (COMT); Childhood adversity; Cognition; Epigenetics; Genetics; Psychosis; Symptoms; Trauma