Integrating psychological models with biological pathways in psychosis

点击翻译按钮获取中文摘要

Schizophrenia is a complex phenotype characterized by reality distortion, cognitive impairments, and often negative symptoms. Bipolar disorders are characterized by high and low mood with or without psychotic features. Although the prevalence of schizophrenia and bipolar disorders are relatively low, they account for a tremendous personal, economic, and societal burden and people with these disorders have 15 years shorter life expectancy compared to the general population. The recent development of polygenic risk calculations has opened a new avenue for studying the underlying genetic susceptibility while excluding biases related to the selection of specific candidate genes. A polygenic risk score can be computed based on sizeable genome-wide association studies (GWAS) performed for a given phenotype (an individual's observative traits) and summarises genome-wide genotype data into a single variable that measures genetic liability to the disorder, or the trait being studied. Such a polygenic risk score might, in turn, be studied together with environmental risk factors that increase the susceptibility to schizophrenia or bipolar disorders and/or the severity of the clinical expression of these disorders. In other words, that there are individuals who would develop schizophrenia or bipolar disorders only when both genetic liability and environmental exposure (here childhood adverse events) are present but would not develop schizophrenia or bipolar disorders when either genetic liability or environmental exposure is present alone. The proposed study has impact on patient care and a stratified medicine approach: To be able to predict who is more vulnerable of developing a severe mental illness following childhood adverse events can have huge impact on the society as well as for the individual. It has recently been shown that if childhood trauma was prevented, 30% of severe mental illness could be avoided. Moreover, patients with schizophrenia and bipolar disorders who report childhood adverse events respond less well to treatment, have poorer functioning, and shorter telomeres (a marker of accelerated ageing) highlighting the pivotal need to understand if this group has a specific biological pathway that could be pharmacological targeted which we aim to clarify as part of this project. In the long run this knowledge can help improve specialized medicine by focusing on specific biological pathways affected by early life events and prediction models for disease outcomes and ageing.