From The Quarterly, Fall 2014

The Brain & Behavior Research Foundation is proactive in its awarding of research grants related to the study of suicide each year. This feature highlights the work of several recent NARSAD Grantees taking diverse approaches to understand what biology and brain activity lead to suicide and to identify specific techniques to avert the tragic loss of life.

One of the most hopeful approaches in reducing the number of suicides involves finding a reliable way to predict who is at what doctors call “imminent risk.” A powerful way to address this begins with better understanding genetic factors, which are estimated to account for up to 50 percent of total risk. Researchers are making steady progress in identifying the complex relationships between variations in a person’s genetic material and illnesses of all kinds. There is an additional complication that applies to suicide—the fact that more than 90 percent of people who die by suicide have a diagnosable mental illness.

2008 NARSAD Young Investigator Grantee Vincenzo De Luca, M.D., of the University of Toronto, in his comprehensive 2012 book chapter on “The Neurobiological Basis of Suicide” that he co-authored with several colleagues, discusses the difficulty of teasing out genetic factors specifically related to suicide risk from those related to any “background” psychiatric conditions an individual may have. Broad scans of the human genome, called genome-wide association studies*, have turned up some possible links between specific gene variations and suicide, but it has been hard to corroborate results from different studies. Potential ways to get more useful results, say Dr. De Luca and colleagues, include efforts to study interactions among multiple genes—since only very rarely do “risk” genes act alone. Dr. De Luca and others are now also engaged in studying the impact of epigenetic* factors in altering gene expression. Epigenetic factors change the “expression,” or activity levels, of genes without changing the order of DNA letters in the genome. Comprehensively understanding epigenetic modifications of gene activity, in addition to identifying those genes linked to suicide risk, could lead to more effective diagnostic tools that could in turn enable more effective interventions for those at highest risk.

A number of studies have identified clinical behavioral warning signs that are associated with an increased likelihood of suicide attempt/ completion including aggression, and impulsivity. 2010 NARSAD Young Investigator Grantee Alison Gilbert, Ph.D., of Zucker Hillside Hospital in New York, and her colleagues have been using NARSAD Grant support to study the role of impulsivity in suicide attempters with bipolar disorder. As a group, patients with bipolar disorder are more impulsive than healthy individuals, even during periods of relative affective remission. This trait-like impulsivity has been linked with changes in brain functioning in specific regions, including the orbitofrontal cortex (an area in the front of the brain responsible for decision making).

Dr. Gilbert is taking brain images of the white matter—tracts that connect various brain regions to one another—with an imaging method called diffusion tensor imaging. She is comparing the images from patients with bipolar disorder who have and who have not made a suicide attempt. Her hypothesis is that there will be reduced integrity in the white matter in the orbitofrontal cortex of the brain in those who have attempted suicide versus those who have not. The goal of her study is to use brain imaging to identify reliable biological markers to predict suicide risk in combination with behavioral measures, including impulsivity. Her hope is that these predictors will enhance the tools available to clinicians to identify individuals at greatest risk of suicide.

Preventative techniques on “the front lines” with primary care doctors and mental health professionals, could have a major impact in preventing suicide. This is the subject of research by 2008 NARSAD Young Investigator Grantee Johanne Renaud, M.D., of McGill University in Canada. She has studied how young people at high risk in Quebec are served by “the system.” Between 1995 and 2005, 422 youths under age 18 died of suicide in the province; only one-third received services from youth centers, and only about one-fourth had any psychiatric help in the year preceding suicide.

Dr. Renaud was recognized in 2012 with the Foundation’s Klerman Prize, Honorable Mention for demonstrating that, although most children and adolescent suicide completers suffer from a diagnosable mental illness, a significant proportion of them are left without appropriate healthcare support (including psychiatric consultation, psychotherapy and pharmacotherapy) in the period preceding their suicide. Results from her NARSAD Grant-supported work published in October in the Canadian Journal of Psychiatry show that the most important gap in having received appropriate health care support still exists among young people suffering from depression and substance use disorders. Her findings can already inform policies in mental health services and suicide prevention, and her ultimate goal is to develop standard, effective clinical interventions as well as suicide prevention guidelines for public health officials to follow.