Neurometabolite Markers of Suicide-Related Cognition in Adolescents

Suicide is the second-leading cause of death in adolescence, and rates of suicides and suicidal behavior among youth are increasing. However, current treatment options for suicidal adolescents are not based on the growing evidence of brain dysfunction in suicidality. Neurobiological treatments that correct disruptions in the brain networks involved in cognitive processes linked to suicidal behavior are desperately needed. Previous research has implicated glutamate, the brain's primary excitatory neurotransmitter, and γ-aminobutyric acid (GABA), the major transmitter responsible for inhibitory functions, in suicidality. The concentrations of glutamate, GABA, and their related metabolites can be measured in brain tissue by proton magnetic resonance spectroscopy (1H-MRS), an imaging technique that has been used extensively to study neurochemical anomalies that occur in a range of psychiatric and neurologic conditions. Our prior work using 1H-MRS found that glutamatergic metabolism was disrupted in the anterior cingulate cortex (ACC), a brain region critical to functions such as emotion regulation, interpreting relevance to the self, and implicit cognitive associations. Other previous research using the suicide and self-injury versions of the implicit association test (SI-IAT) has demonstrated that adolescents with suicidal behavior have stronger implicit cognitive associations with suicide- and death-related stimuli than non-suicidal youth, and that SI-IAT performance may predict future suicidal behavior. The proposed study will obtain 1H-MRS measurements of ACC metabolites and administer the SI-IAT in a sample of 30 depressed adolescent participants (age 13-18) with and without suicidal behavior. This study will expand upon our previous findings by acquiring 1H-MRS data in a 7 Tesla scanner, which is necessary for reliable measurement of both GABA and glutamate, and by linking ACC excitatory-inhibitory neurochemistry with performance on a cognitive task with known relevance to suicidal behavior. We hypothesize that adolescents with recent suicidal behavior will show higher concentrations of ACC glutamate and lower ACC GABA than non-suicidal youth; that ACC glutamate and GABA will correlate with SI-IAT performance; and that ACC glutamate and GABA will correlate with clinical measures of suicidality, including the Beck Scale for Suicide Ideation and the Columbia Suicide Severity Rating Scale. Findings from this study will support future work that will evaluate noninvasive interventions that can modulate ACC function, such as transcranial magnetic stimulation, for treatment of adolescents with suicidal behavior.