Roel Ophoff
University of California-Los Angeles, CA·Genetics
Serious psychiatric illnesses such as depression, schizophrenia and bipolar disorder are influenced by genes and biology, but the molecular processes behind them and their treatments are still poorly understood. The lab's work uses molecular measurements in blood, combined with genetic data and statistics, to address two questions: what happens in the body during electroconvulsive therapy for severe depression, and which genes raise risk for schizophrenia and bipolar disorder in Latino populations underrepresented in genetic research.
- Fields
Genetics
Neuroscience
Medicine & Clinical Research
- Topics
electroconvulsive therapy
treatment-resistant depression
cell-free DNA
- Grants
- 2 known grants, through Jun 2028
What they work on
- Measure changes in circulating cell-free DNA (cfDNA) during ECT in patients with treatment-resistant depression, using DNA methylation patterns to identify the tissues and cell types releasing it.
- Relate cfDNA dynamics to blood inflammation markers and MRI measures of brain structural and functional connectivity to test the 'disrupt, potentiate and rewire' hypothesis of ECT.
- Generate transcriptome data from 1,500 Latino individuals with schizophrenia, bipolar disorder or no diagnosis as a public gene expression resource.
- Develop statistical methods that use local and global genetic ancestry to increase the power of TWAS and eQTS analyses in admixed Latino individuals.
- Integrate new expression data with Latino GWAS of schizophrenia and bipolar disorder to identify susceptibility genes, and functionally validate the most promising causal variants.
More about the research
Electroconvulsive therapy (ECT), a brief electrically induced seizure under anesthesia, is the most effective acute treatment for treatment-resistant depression (TRD), but it can cause short-term memory and thinking problems and its mechanisms are unclear. This exploratory project will track circulating cell-free DNA (cfDNA), short DNA fragments released into the blood when cells die or turn over. DNA methylation patterns, chemical tags that differ between cell types, will reveal which tissues the fragments come from, possibly including the brain. Building on an ongoing longitudinal ECT study, the team will relate cfDNA changes over time to blood markers of inflammation and to MRI measures of brain structure and connectivity. This will test the 'disrupt, potentiate and rewire' hypothesis of how ECT works and whether its benefits and cognitive side effects follow different pathways.
Why it matters
Better understanding of ECT could help doctors tailor treatment for treatment-resistant depression to maximize benefit and reduce cognitive side effects. A public gene expression resource and ancestry-aware statistical tools could reveal risk genes for schizophrenia and bipolar disorder in Latino individuals. These could eventually inform diagnosis and treatment for a population long underserved by genomic research.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
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The school
University of California-Los Angeles: 84 labs on PI Pages, $1.9B a year on research, 803 research doctorates a year.
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