Abstract
BackgroundSubclinical psychotic symptoms, known as schizotypy, predict concurrent and future suicidal ideation and acts. Some suggest this relationship reflects the influence of shared environmental risk factors, or that schizotypy and suicidality are both non-specific indicators of severity of psychopathology. However, this artefactual explanation does not account for the heritability of environmental risk factors, the link between schizotypy and more severe expressions of suicidality, or contemporary theories of suicidality.MethodsWe tested whether schizotypy has a direct (causal) effect on the development of suicidal thoughts using a Mendelian randomisation analysis to avoid problems of reverse causality, confounding, and measurement error associated with traditional observational studies. In Mendelian randomisation analyses, genetic variants are used as a proxy measure for a phenotype in order to make causal inferences about the effect of the phenotype on an outcome. We used a schizophrenia gene risk score (GRS), a measure of schizophrenia liability, as a proxy measure for schizotypy. Participants (n = 4767) were part of the Philadelphia Neurodevelopmental Cohort, a publicly available resource designed to assess behavioural and biological factors contributing to mental illness in young adults (aged 8–21). Regression analyses were used to test relationships.ResultsSchizotypy was found to be a strong predictor of both passive (OR = 1.84, p < .001) and active (OR = 2.69, p < .001) suicidal ideation. No relationship was found between the schizophrenia GRS and schizotypy when analysed in separate ethnic groups to adjust for population stratification (European American; B = .18, p = .708, African American; B = .086, p = .303). No relationship was found between the schizophrenia GRS and passive (OR = .97, p = .721) or active (OR = .99, p = .778) suicidal ideation.DiscussionThe hypothesis that there is a causal relationship between schizotypy and suicidality was not supported, though it is unclear if this is due to the schizophrenia GRS being a poor proxy for schizotypy, or a true absence of a causal relationship. Understanding causal risk factors for suicidality is a key area of research and future research should continue to address this using genetically-sensitive designs.
Highlights
Schizophrenia is a heterogeneous group of disorders
The sporadic schizoaffective bipolar type forms a more homogenous group, with genetic studies hinting at relatively specific genetic risk factors
No relationship was found between the schizophrenia gene risk score (GRS) and schizotypy when analysed in separate ethnic groups to adjust for population stratification (European American; B = .18, p = .708, African American; B = .086, p = .303)
Summary
Many rare genetic syndromes are known to phenotypically manifest with psychiatric symptoms that can be indistinguishable from primary psychiatric disorders. While the majority of ongoing research in psychiatric genetics has been dedicated to the identification and characterization of genes involved in primary psychiatric disorders, there has been a lack of research to determine the extent to which rare genetic variants contribute to the overall psychiatric disease load. We aim to investigate the prevalence of clinically well-characterized pathogenic copy number variant (CNV) syndromes that are associated with neuropsychiatric phenotypes in a large schizophrenia patient cohort. 0. CNVs were called using two algorithms (Canary Software and PennCNV) for deletions >200 kb and duplications >500 kb. CNVs called by both algorithms were included in further analysis. Results: A total of 861 deletions and 171 duplications were called on 348 schizophrenia patients. In-depth analysis revealed a total of 16 schizophrenia patients with significant deletions. Microdeletions associated with known syndromes that were identified include: 16p11.2-p12.2 (n=1), Abstracts for the Sixth Biennial SIRS Conference
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