B3467 - SoCial Reserve as buffer against psychosis development a psychological and molecular investigation SCORE - 03/03/2020

B number: 
Principal applicant name: 
Eva Velthorst | Icahn School of Medicine at Mount Sinai (United States)
Stanley Zammit, PhD, Hannah Jones, PhD, Avi Reichenberg, PhD, Sven Sandin, PhD, Niamh Mullins, PhD, Paul O'Reilly, PhD, Raquel Gur, PhD, Ruben Gur
Title of project: 
SoCial Reserve as buffer against psychosis development: a psychological and molecular investigation (SCORE)
Proposal summary: 

Social withdrawal (SocW) – defined as reduced social interaction – is a key feature of psychotic disorders and multiple other psychiatric outcomes. Despite growing recognition of its negative consequences, SocW remains one of the least studied human traits, and its underlying mechanisms remain subject of wide speculation. The overall goal of this project is to examine elucidate the role of SocW in the development of psychosis.

By combining clinical data with increasingly powerful ‘genetic risk scores’ (i.e. the sum of risk genes that have shown to be associated with a behavioral trait), we are now able to test whether SocW is a cause or merely a consequence of symptoms in psychosis development. Using the UK Biobank we will create a powerful genetic risk score for SocW, and use this score to examine the role of SocW in psychosis in two large developmental cohorts: The Avon Longitudinal Study of Parents and Children (ALSPAC) and Philadelphia Neurodevelopmental Cohort (PNC). Jointly, these studies followed nearly 16,000 young individuals from childhood to young adulthood, through ages encompassing typical onset of and peak onset age of psychosis. In ALSPAC, we will also test the association between changes in psychotic symptoms and changes in SocW behaviorally, and explore the effects of SocW and established environmental risk in the path to psychosis.

Overall, we aspire to better understand the well-established association between SocW and psychosis, determine critical windows during which individuals may be more or less prone to the influence of SocW, and facilitate much-needed preventive targeted therapies.

Impact of research: 
This project will fill important gaps in our knowledge about genetic underpinnings of social withdrawal, and the (causal) role of social withdrawal in pathways to psychosis, and other severe psychiatric disorders.
Date proposal received: 
Wednesday, 12 February, 2020
Date proposal approved: 
Monday, 17 February, 2020
Genetics, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., GWAS, Genetic epidemiology