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Neural Circuitry Predictors of Suicide Risk in Adolescents and Young Adults with Bipolar Disorder

2014 Standard Research Grant
Amount Awarded: $90,000
Focus Area: Neurobiological Studies

Hilary Blumberg, M.D.
Yale School of Medicine

Inside the Research

Bio: Dr. Blumberg received her medical degree from the Cornell University Medical College in 1990. She is currently Professor of Psychiatry and Diagnostic Radiology at Yale School of Medicine as well as Professor in Yale’s Child Study Center.

Grant Categories: Neurobiological studies, brain functioning studies, child and adolescent studies

Abstract: Bipolar Disorder (BD) is associated with increased risk for suicide, with estimates that up to 50% of individuals with BD attempt suicide in their lifetime. In addition, suicide is a leading cause of death in adolescents and young adults. Research on the development of suicidal behavior in youth with BD is needed. Dr. Blumberg examines the relationship between brain development and the development of suicidal behavior in adolescents and young adults with BD. She uses brain imaging techniques such as fMRI, sMRI and DTI, and psychosocial assessments to re-examine 100 13-22 year olds who had previously participated in brain imaging and psychosocial research at Yale University. Her study includes an examination of the impact of childhood maltreatment, substance abuse, and gender related factors. Of the 100 participants who all have been diagnosed with BD, without initial suicide attempt it is estimated that over the course of the study approximately 20 participants will attempt suicide, and 80 participants will either be completely healthy (n=20) or suffer from BD and no suicide attempt (n=60). Using measures at baseline and 3 years later, Dr. Blumberg’s study will test for neural circuitry abnormalities, long-term neural pathways, and associations among brain function, suicide attempts, substance abuse and child maltreatment.

Impact: Improved understanding of brain development among adolescents with bipolar disorder to inform early identification of suicide risk.

Research Connection

Background

Individuals with bipolar disorder are at increased risk for suicide. It is estimated that around 50 percent of individuals with bipolar disorder attempt suicide in their lifetime and 15-20 percent die by suicide. Despite the prevalence of these issues, few studies examine the brain function and neural circuitry (how different parts of the brain connect with each other) of individuals living with bipolar disorder and suicide attempts, especially among youth.

Previous studies conducted by Dr. Hilary Blumberg with adults indicated that the neural circuits in the brains of people with bipolar disorder and suicidal behavior are different from those with no mental health disorder, and that these differences may be present early in life. This study is one of the first of its kind to use multiple neuroimaging methods to examine the neural circuitry of adolescents and young adults with bipolar disorder who made suicide attempts.

The Question

Among youth with bipolar disorder, are there differences in brain structure and function when the person has a history of a suicide attempt?

The Study

Sample: three groups of individuals with ages ranging from 14 to 25; 42 people with bipolar disorder without a history of suicide attempts; 26 people with bipolar disorder with a history of at least one suicide attempt; and a psychiatrically healthy control group of 45 people participated.

Structured interviews were administered to assess for current and past mental health disorders; past and current suicidal ideation and behavior; and the lethality and intent of previous suicide attempts. Participants completed self-report measures of hopelessness and impulsivity.

Three types of brain scans were administered to all participants: 1) structural magnetic resonance imaging (sMRI) to assess gray matter volume; 2) diffusion tensor imaging (DTI) to assess white matter density; and 3) functional magnetic resonance imaging (fMRI) to assess brain function when presented with happy, neutral, and fearful faces.

The Results

The study found that suicide attempters and nonattempters with bipolar disorder differed significantly from the control group in terms of suicidal ideation severity, but not in impulsivity, hopelessness, medication status, lifetime comorbid substance use or dependence, mood state, psychosis, or rapid cycling. (Rapid cycling refers to rapid shifts in mood during brief periods of time.)

From the brain scans, researchers found significant differences in gray matter volume between the attempter and non-attempter groups. The attempter group had less gray matter in regions related to emotional regulation, emotional responses, and memory. They also had decreased white matter that connects brain areas involved in these functions when compared to the non-attempter group and the healthy control group.

In addition, the attempter group showed significant decreases in the processing of happy and neutral faces, and minimal decrease in the processing of fearful faces. This indicates a decrease in emotional regulation and density of white matter connections when compared to non-attempters and healthy controls. Previously, emotional dysregulation had been linked to increased likelihood of suicide attempts due to intolerable mood states. In this study, white matter was related to lethality of past suicide attempts and current suicidal ideation, suggesting a unique association with suicide risk.

The Takeaway

There are differences in brain structure and functioning in youth with bipolar disorder who have made suicide attempts that relate to the ability to regulate emotion. These findings suggest that someday it may be possible to use brain scans to assess for suicide risk among people with bipolar disorder, which will allow for earlier and targeted intervention.
Cox Lippard, E.T., Johnston, J.A.Y., Blumberg, H.P. (2014)  Neurobiological Risk Factors for Suicide Insights from Brain Imaging. Am J Prev Med. 2014 September ; 47(3 0 2): S152–S162. doi:10.1016/j.amepre.2014.06.009.

Johnston, J.A.Y., Wang, F., Liu, J., Blond, B., Wallace, A., Liu, J., Spencer, L., Lippard, E.T.C., Purves, K.L., Landeros-Weisenberger, A., Hermes, E., Pittman, B., Martin, A., Oquendo, M., & Blumberg, H.P. (2017). Multimodal Neuroimaging of Frontolimbic Structure and Function Associated With Suicide Attempts in Adolescents and Young Adults With Bipolar Disorder. American Journal of Psychiatry.  Jan 31:appiajp201615050652. doi: 10.1176/appi.ajp.2016.15050652. [Epub ahead of print]

Najt, P., Wang, F., Spencer, L., Johnston, J.A.Y., Cox Lippard, E.T., Pittman, B.P., Lacadie, C., Staib, L.H., Papademetris, X., Blumberg H.P. (2016) Anterior Cortical Development During Adolescence in Bipolar Disorder. Biological Psychiatry; 79:303–310 http://www.biologicalpsychiatryjournal.com/.