SA41 - DIFFERENTIAL GENE EXPRESSION IN THE PREFRONTAL CORTEX ASSOCIATED WITH SUICIDE

Abstract

Background Suicide is one of the top five causes of death for individuals between the ages of 10 and 54; however, unlike many other causes of death, it is preventable if recognized and treated. Evidence from family studies suggest that suicide has a genetic basis, though specific associated genes are less well understood. Although suicide is a complicated, multi-factorial behavior, one important associated endophenotype is trait impulsivity. Trait impulsivity and behavioral inhibition is controlled by the prefrontal cortex. While the complexity and circuitry of these regions are still being explored, two regions, the dorsolateral prefrontal cortex (dlPFC) and the Orbitofrontal Cortex (OFC) are consistently associated with impulsive action and loss of impulse control as well as suicidal behavior. Methods The dlPFC and OFC was isolated from 60 demographically similar that had either died from suicide or from natural causes. A psychological autopsy was performed on all individuals, assessing for major depressive disorder and other psychiatric disease. Complete screening was also performed for the Behavioral and Emotional Impulsivity subscales of the SIDP-IV and the MLES. Total RNA was isolated from these regions and next generation sequencing was performed using an Illumina NextSeq. 500 with a 150 bp paired-end protocol. Data was processed using the ‘tuxedo’ pipeline and functional enrichment was performed with Ingenuity Pathway Analysis. Results As with previous studies, an association was observed between behavioral and emotional impulsivity as measured by the SIDP-IV and suicidal behavior. This association held when controlling for gender, alcohol or tobacco use, or major depressive disorder. RNA quality and subsequent next generation sequencing was unaffected by differences in post-mortem death interval, tissue pH, or age at death. Differential gene expression was observed between individuals who died from suicide and those who died from natural causes, regardless of whether the latter were diagnosed with major depressive disorder. These genes partially, though not entirely, overlapped with genes associated with behavioral and emotional impulsivity independent of cause of death. Additional work is ongoing further characterizing the interactions between these factors and their impact on gene expression. Discussion Identifying individuals most at risk for suicide allows for proactive intervention that can directly save lives. By focusing on impulsivity as an endophenotype, it is possible to better identify genetic effects. By using gene expression analyses, it is possible to better place these genetic effects in context. This study allows for a better understanding of the molecular factors underlying executive control in the prefrontal cortex and offers insight into the dysregulation that occurs leading to suicidal behaviors.