A SYSTEMATIC REVIEW OF THE PSYCHOLOGICAL AND BIOLOGICAL MEDIATORS BETWEEN ADVERSITY AND PSYCHOSIS: POTENTIAL TARGETS FOR TREATMENT

Various psychological and biological pathways have been proposed as mediators between childhood adverse events (CA) and psychosis. A systematic review of the evidence in this domain is needed. The aim of this work is to systematically review the evidence on psychological and biological mediators between CA and psychosis across the psychosis spectrum. This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (registration number: CRD42018100846). Articles published between 1979 and July 2019 were identified through a literature search in OVID (PsychINFO; Medline and Embase). The evidence by each analysis and each study results are presented by group of mediator categories found in the review. The percentage of total effect mediated was calculated. 47 studies were included, with a total of 79,668 from general population (GP) and 3,189 from clinical samples. The quality of studies was judged as “fair”. Our results showed (i) solid evidence of mediation between CA and psychosis by negative cognitive schemas about the self, the world, and others (NS); by dissociation and other PTSD symptoms; (ii) evidence of al mediation through an affective pathway (affective dysregulation, anxiety, and depression) in GP; (iii) lack of studies exploring biological mediators. To conclude, we found evidence suggesting that various overlapping and not competing pathways contribute partially to the link between adversity and psychosis. Experiences of adversity, along with relevant mediators such as PTSD and mood related symptoms and NS, should be routinely assessed in patients with psychosis. Targeting such mediators through cognitive behavioural aproaches using trauma-focused therapy and/or pharmacological means could be a useful addition to the traditional treatment of positive symptoms. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Swiss National Science Foundation (Grant P2LAP3_171804 to L.A.). This paper represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. South-Eastern Norway Health Authority (#2017060) and the NARSAD Young Investigator Award to Monica Aas (#22388). This paper represents independent research part supported by the ESRC Centre for Society and Mental Health at King’s College London (ESRC Reference: ES/S012567/1). The views expressed are those of the author(s) and not necessarily those of the ESRC or King’s College London ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes This study is a systematic review and is based on data already published.