Brain/Behavior Mechanisms Of Irritability And Suicide In Children And Adolescents

Key Words: Irritability, Suicide, Child, Adolescent, Magnetic Resonance Imaging

Irritability is the most common reason children are brought for psychiatric evaluation, is an explicit diagnostic criterion or associated symptom of multiple Diagnostic and Statistical Manual disorders (including mania, major depression, ADHD, and autism), and childhood irritability is associated with significant impairment in adulthood–including poverty, psychiatric illness, and suicide.

Suicide is the second leading cause of death, starting at age 10 through age 34.

Our long-term goal is to unite these two lines of research, and define brain mechanisms of irritability and suicide that could be translated into better, more accurate ways to diagnose, treat, and prevent psychiatric illness in children and adolescents. The objective of this application is to define brain mechanisms of irritability and suicide in 100 children ages 10-14. Our prior work suggests that brain/behavior changes in cognitive flexibility—defined as adaptation to changing rewards and punishments—may map onto sub-types of irritability. Our central hypothesis is that decreased cognitive flexibility linked to prefrontal cortex (PFC)-striatal-temporal circuit problems are associated specific patterns of irritability, and increased risk for suicide. Our central methodology will use innovative multi-informant assessments, including clinician interviews, daily smart-phone ecological momentary assessment, and magnetic resonance imaging brain scans plus re-assessment at 3- and 6-months to study n=50 children with a prior suicide attempt (SA) vs. n=50 typically-developing controls (TDCs).

We propose 3 specific aims: (1) To use computational psychiatry techniques to identify circuit-based clusters of irritability. (2) To test how changes in cognitive flexibility predict greater risk for suicide. (3) To define the relationship between irritability, suicide, and the circuitry underlying cognitive flexibility.

Our proposal is significant and innovative because it holds the potential to transform mental healthcare for children and adolescents—as mechanisms of irritability and suicide are translated into more effective was to diagnose, treat, and prevent irritability and suicide—akin to the successful example of childhood leukemia.