title: Effects of oxytocin and genetic variants on brain and behaviour: Implications for treatment in schizophrenia.
abstract: Impairments in social cognition and poor social functioning are core features of schizophrenia-spectrum disorders. In recent years, there has been a move towards developing new treatment strategies that specifically target social cognitive and social behavioural deficits. Oxytocin (OXT) is one such strategy that has gained increasing attention. There is a strong rationale for studying OXT in psychosis, from both an evolutionary perspective and neurodevelopmental-cognitive model of schizophrenia. Thus, the aim of this review was to critique and examine the observational and clinical oxytocin trial literature in schizophrenia-spectrum disorders. A handful of clinical trials suggest that OXT treatment may be beneficial for remediating social cognitive impairments, psychiatric symptoms, and improving social outcomes. However, inconsistencies exist in this literature, which may be explained by individual differences in the underlying neural response to OXT treatment and/or variation in the oxytocin and oxytocin receptor genes. Therefore, we additionally reviewed the evidence for structural and functional neural intermediate phenotypes in humans that link genetic variants to social behaviour/thinking, and discuss the implications of such interactions in the context of dysfunctional brain networks in schizophrenia. Factors that pose challenges for future OXT clinical research include the impact of age, sex, and ancestry, task-specific effects, bioavailability and pharmacokinetics, as well as neurotransmitter and drug interactions. While initial findings from OXT single dose/clinical trial studies are promising, more interdisciplinary research in both healthy and psychiatric populations is needed before determining whether OXT is a viable treatment option/adjunct for addressing poor illness outcomes in psychotic disorders.
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health and the Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton South, Victoria, Australia. Electronic address: barc@unimelb.edu.au.
authors.forename: Cali F
authors.initials: CF
authors.lastname: Bartholomeusz
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health and the Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton South, Victoria, Australia.
authors.forename: Eleni P
authors.initials: EP
authors.lastname: Ganella
authors.affiliation: School of Psychology, Australian Catholic University, Fitzroy, Victoria, Australia.
authors.forename: Izelle
authors.initials: I
authors.lastname: Labuschagne
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton South, Victoria, Australia; Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia.
authors.forename: Chad
authors.initials: C
authors.lastname: Bousman
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton South, Victoria, Australia; Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia.
authors.forename: Christos
authors.initials: C
authors.lastname: Pantelis
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001921:Brain / Q000503:physiopathology*; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D010121:Oxytocin / Q000627:therapeutic use*; D011618:Psychotic Disorders / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D018045:Receptors, Oxytocin / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D012565:Schizophrenic Psychology
chemical_list: D014150:Antipsychotic Agents; C569600:OXTR protein, human; D018045:Receptors, Oxytocin; D010121:Oxytocin
keywords: Genetic variants; Neuroimaging; Oxytocin; Schizophrenia; Single nucleotide polymorphisms; Social functioning