CLINICAL, CELLULAR AND GENETIC DISSECTION OF SEVERE MENTAL ILLNESSES: A CENTRE FOR BRAIN AND MIND STUDY

Severe mental illnesses (SMIs) pose a heavy burden on global health, affecting ~14% of the world population, or 1.1 billion people (GBD 2021). Despite this, accurate clinical diagnoses and investigations into genetic and environmental contributors to disease etiology has been challenging. The Centre for Brain and Mind (CBM), a multi-institutional platform employs a multi-tier investigation of brain alteration in SMIs to improve disease identification and management.
Most SMIs are neurodevelopmental, with genetic and environmental contributions to their etiology. However, traditional clinical diagnoses fail to identify disease-specific clinical features, the problem compounded by the polygenic basis of SMIs. This 20-yr study uses a multi-dimensional approach to map the evolution of SMIs in a prospective cohort of patients and healthy individuals using (a) clinical and endophenotype evaluations, (b) whole exome sequencing and (c) generation of stem cells for detailed analyses. This generates a rich longitudinal dataset of brain phenotypes and a bio-repository to aid the discovery of genetic, cellular and electrophysiological contributions to altered biology in SMIs.
2138 subjects recruited (Phase I), include patients of selected SMIs (schizophrenia, bipolar, obsessive-compulsive or substance-use disorders, dementia), their first-degree unaffected relatives, plus a set of population controls (N=327) for clinical, endophenotype assessments and sample collection. Repeated evaluations are conducted every 2 years. Stem cell lines (N=130) for each SMI include 2 patients and 1 family control lines. Exome sequencing dataset includes 489 individuals from the cohort. Lastly, the CALM-Brain, a comprehensive data resource houses all datasets, enabling accessibility and further analyses with advanced computational methods.