Suicide Risk Genes in Schizophrenia Using GWAS and Clozapine Effects on Signaling Mechanisms
2014 Distinguished Investigator Grant
Amount Awarded: $100,001
Focus Area: Genetic Studies
Herbert Meltzer, M.D.
Northwestern University Feinberg School of Medicine
Inside the Research
Research Categories: Genetic studies, neurobiological studies, brain functioning studies
Abstract: About 5% of people with schizophrenia die by suicide. Clozapine, which is an antipsychotic medication, is shown to reduce suicide rates in people with schizophrenia. Twin and family studies suggest that 30 to 50% of the risk for suicidal behavior in this group may be inherited. Identifying genetic markers of the risk for suicide and predicting the ability of clozapine to reduce that risk would provide a way to optimize suicide risk reduction. Neurobiological and genetic studies suggest that complex interactions of gene networks and environmental factors contribute to suicide. There is evidence for the involvement of genes engaged in intracellular signaling (i.e., genes that send messages within a cell), as risk factors for suicide and for a differential effect of clozapine on these crucial complex pathways, in particular, the EGF-MAPK-ERK pathway. In Dr. Meltzer’s study, 140 participants assessed for suicidal ideation and behavior and diagnosed with schizophrenia are evaluated using a case-control design to compare the DNA of those who have made a suicide attempt to those who have not in order to determine if there is a genetic basis to the suicide-preventing properties of clozapine. Dr. Meltzer is attempting to find genes that distinguish the two groups and could be associated with suicidal behavior.
Impact: Identification of genetic markers that may lead to the identification of new and effective medication for suicide prevention.