Inhibitory Mechanisms of Negative Urgency in Adolescent Suicidal Behavior

Overview

The goal of this study is to understand why some people act more impulsively when feeling negative emotions, which is called negative urgency. The researchers hope to understand how negative urgency relates to the way networks of brain cells communicate with one another. The researchers will measure negative urgency and brain signals in adolescents aged 13-21 years with depression and suicidal thoughts and behaviors. The main questions it aims to answer are: * Whether a type of brain signaling called cortical inhibition is related to negative urgency * Whether depressed adolescents with suicidal behavior have more problems with cortical inhibition than depressed adolescents with suicidal thoughts only * Whether the relationship between negative urgency and cortical inhibition changes over time Adolescents who participate in the study will complete the following activities at the time they join the study, as well as 6 months and 12 months later: * Interviews with researchers and questionnaires to learn about their thoughts, emotions, and symptoms * A questionnaire about impulsive behaviors and negative urgency * Computerized games that measure brain functions * An MRI scan of the brain * Transcranial magnetic stimulation with electroencephalography (TMS-EEG), a way to measure how brain cells communicate (cortical inhibition) using a magnet placed outside of the head and recording brain signals

This project will study the neural underpinnings of impulsivity in adolescent suicidal behavior (SB). Suicide is the second leading cause of death in adolescence, and rates of adolescent SB are increasing. However, its neurobiology remains poorly understood, and treatments specifically targeting SB are lacking. SB in adolescents is a critical public health problem that demands urgent attention, particularly with research that will rapidly translate knowledge to clinical applications. Negative urgency, a component of impulsivity, is the tendency to act rashly in the context of negative emotion. It has been found to be increased among youth with SB and suicide attempts, and has been linked to impaired inhibition of limbic circuitry by the dorsolateral prefrontal cortex (DLPFC), yet precise mechanisms are unclear. Transcranial magnetic stimulation (TMS) permits noninvasive quantification of DLPFC functions such as cortical inhibition (CI), the process by which cortical interneurons regulate the activity of other circuits. Previous research indicates that adolescents with lifetime SB have reduced CI in the motor cortex that distinguishes them from non-suicidal youth. However, DLPFC CI has not been measured in adolescents with SB, nor is it clear how CI relates to cognitive and emotional systems implicated in SB, such as negative urgency. In order to study CI-related mechanisms of negative urgency in the DLPFC, simultaneous TMS and electroencephalography (TMS-EEG) is required. This is a longitudinal study of inhibitory physiology and negative urgency in 40 depressed adolescents with suicidal ideation (but no prior SB) and 40 depressed adolescents with SB. The study will utilize TMS-EEG and self-report measures of negative urgency to test hypotheses that dysregulated CI is associated with negative urgency, that DLPFC CI is deficient in adolescents with SB, and that CI deficits correlate longitudinally with changes in negative urgency and newly emergent SB. The long-term goal of this research is to utilize data gathered in this project to design a large-scale longitudinal study assessing neural and behavioral risk factors for developing SB, as well as trials of neuromodulatory treatments that will reduce the transition from suicidal thoughts to behaviors by targeting alterations in CI and negative urgency.