Principal Investigator: Dr Michael Gandal
University of California, Los Angeles, USATags: 48096, genetics/genotyping, Imaging, immune, Polygenic, psychiatric, stress
Collaborator: Mr Richard Bethlehem, University of Cambridge, UK; Dr Aaron Alexander-Bloch, Yale University, USA
Immune system dysregulation has been observed across several neuropsychiatric disorders including depression, bipolar disorder, and autism; however, whether or how immune alterations relate to brain-based changes associated with mental illness is unknown. One mechanism by which immune function may affect brain structure is through elimination of connections between neurons, called synapses. Indeed, altered brain volume and connectivity have been observed using magnetic resonance imaging (MRI) in many psychiatric disorders. Using data collected by the UK Biobank, this study seeks to investigate the relationship between neuroimaging measures of brain structure and connectivity, genetic predisposition to immune dysfunction, and mental health.
Our study has two aims. First, we will assess the additive impact of genetic risk for immune dysfunction across all genes – referred to as a polygenic risk score (PRS) – on MRI measures of brain volume, connectivity, and mental health. Furthermore, we will examine how exposure to stress may enhance the effects of immune-related PRS on the brain, leading to enhanced brain alterations in a subgroup of people with high PRS. Second, we will assess how changes in mental health across time might be predicted by measures of brain structure, PRS, and stress at baseline.
The results of this project may help to identify if certain individuals may be at higher risk for developing psychiatric illness, and eventually contribute to methods for the prediction of people in need of early mental health intervention.
We expect the duration of this project to be 36 months.