Apr 23, 2018 - Sheri Oduola*, Tom JK Craig, Charlotte Gayer Anderson,. Bhugra Dinesh, Bourque Francois, and Craig Morgan. King's College London.
Plenary S19 and non-psychotic bipolar disorder. Differing patterns of risk by region of origin may indicate that the pre-and post-migration psychosocial stressors, treatment-seeking behavior, or diagnostic patterns may vary between migrant groups, but further research is required to determine the underlying mechanism driving this variation.
30. COMT VAL158MET AND MTHFR C677T MODERATE RISK OF SCHIZOPHRENIA IN RESPONSE TO CHILDHOOD TRAUMA Jean-Christophe Debost*,1, Jakob Grove1, Liselotte Petersen1, Ole Mors2, David Hougaard3, Anders Børglum1, Preben Mortensen1 1 Aarhus University; 2Psychiatric University Hospital Risskov; 3 Danish Centre for Neonatal Screening, Statens Serum Institut, Denmark Background: Childhood trauma is a risk factor in the etiology of schizophrenia. Mesolimbic dopamine sensitization has been hypothesized to be a mediating factor of childhood trauma on the risk of schizophrenia. Activity of catechol-O-methyltransferase (COMT) Val158Met increases mesolimbic dopamine signaling, and COMT activity may be further regulated by methylenetetrahydrofolate reductase (MTHFR) C677T. The objective of the present study was to investigate the hypothesized three-way interaction between childhood trauma, COMT and MTHFR. Methods: We conducted a nested case–control study on individuals born after 1981, linking Danish nationwide population-based registers to obtain information on genetics and exposure to childhood trauma. The study included 1699 schizophrenia cases and 1681 controls. We used an additive genetic model and conditional logistic regression to estimate interactions between allele count and exposure status. Incidence rate ratios (IRRs) were estimated with corresponding 95% confidence intervals (95% CI). Results: Childhood trauma was robustly associated with schizophrenia. No main genetic effects were observed. MTHFR C677T increased schizophrenia risk in a dose-dependent manner per MTHFR T-allele (P = .005) consequent upon trauma exposure. In the 3-way interaction model, the risk was further increased in a dose-dependent manner per high-activity COMT Val-allele. Hence, exposed COMT Val/Met and MTHFR T/T carriers had an IRR of 2.34 (1.51–3.61). Additional adjustments for polygenic risk score, ancestry and parental history of mental illness, attenuated the results with the interaction being only marginally significant. Conclusion: MTHFR C677T and COMT Val158Met interact with childhood trauma to increase risk of schizophrenia.
31. THE ASSOCIATION BETWEEN PSYCHOSIS AND NONNEUROLOGICAL AUTOIMMUNE DISORDERS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE EVIDENCE TO DATE Alexis Cullen*, Scarlett Holmes, Tom Pollak, Graham Blackman, Robin Murray, Philip McGuire, and Valeria Mondelli King’s College London Background: Epidemiological studies conducted over the past 50 years have observed an increased prevalence of psychosis among individuals with nonneurological autoimmune disorders relative to the general population, with the notable exception of rheumatoid arthritis. Whether this association reflects shared risk factors (e.g., infections or genetic liability) or a causal relationship (mediated by inflammation or brain-reactive antibodies) is yet to be determined. Quantifying the extent to which psychosis is associated with individual nonneurological autoimmune disorders may help to address this issue. A systematic review of studies investigating the
comorbidity of psychosis and nonneurological autoimmune disorders was therefore conducted to clarify the nature of this association; meta-analyses were performed for individual autoimmune disorders where possible. Methods: PubMed, PsycINFO, and EMBASE were systematically searched, and supplemented with manual searching, to identify studies examining (1) the prevalence of psychotic disorders among individuals with nonneurological autoimmune disorders, or (ii) the prevalence of nonneurological autoimmune disorders among individuals with psychotic disorders. Studies were assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Raw (unadjusted) data were extracted from studies and used to compute odds ratios (OR). Results: Fourteen studies were suitable for inclusion, the majority of which met STROBE criteria for methodology reporting. These studies provided useable data for 35 non-neurological autoimmune disorders, from which 60 individual effect sizes were computed. Overall, individuals with nonneurological autoimmune disorders were significantly more likely to have a psychotic disorder (OR = 1.51; 95% CI: 1.47–1.56; P < .0001). Metaanalyses for individual disorders were conducted where possible (i.e., when three or more studies were available) and indicated that psychosis was positively associated with autoimmune anaemia (OR = 1.87, P < .0001), type 1 diabetes (OR = 1.40, P < .0001), and coeliac disease (OR = 8.40, P < .0001). In contrast, psychosis was negatively associated with rheumatoid arthritis (OR = 0.75, P = .02) and alopecia areata (OR = .73, P = .04), while associations with ankylosing spondylitis and ulcerative colitis were not statistically significant. Conclusion: This is the first systematic review of the relationship between nonneurological autoimmune disorders and psychosis. Whilst an overall positive association was observed, individual meta-analyses indicated that the strength and direction of this association varied considerably across non-neurological autoimmune disorders types. The implications of these findings for elucidating the mechanisms underlying this association will be discussed.
32. DEMOGRAPHIC AND CLINICAL PREDICTORS OF DURATION OF UNTREATED PSYCHOSIS Sheri Oduola*, Tom JK Craig, Charlotte Gayer Anderson, Bhugra Dinesh, Bourque Francois, and Craig Morgan King’s College London Background: A shorter duration of untreated psychosis (DUP) is associated with better outcomes following first-episode psychosis (FEP; Power et al., 2007; Birchwood et al., 2013; McGorry et al., 2008). However, the evidence on social and clinical factors that may predict to DUP is inconsistent. Aims: To investigate the association between DUP and social and clinical factors. Methods: A retrospective incidence study design was employed, using the Biomedical Research Centre (BRC) clinical record interactive search (CRIS) system. In brief, CRIS is a regional case register based in South London containing a large data set of anonymous clinical data of over 250 000 patient records derived from the South London and Maudsley NHS Foundation Trust (SLaM) electronic health record system. All patients presenting to SLaM adult mental health services for the first time with a psychotic disorder between May 2010 and April 2012 and in the catchment area served by SLaM were screened for inclusion. Data relating to DUP, sociodemographic characteristics, mode of contact, and source of referral were collated from clinical records. Individuals were included as cases if they were: resident in the London boroughs of Lambeth or Southwark (served by SLaM); aged 18–64 years (inclusive), experienced psychotic symptoms of at least one day duration, and were making their first contact for psychosis with mental health services. Results: A total of 558 individuals with first-episode psychosis were identified. Individuals who were unemployed (68.5%) experienced longer
International Congress on Schizophrenia Research Downloaded from https://academic.oup.com/schizophreniabulletin/article-abstract/43/suppl_1/S19/3075391 by guest on 23 April 2018
