Clinical, behavioral, and electrophysiological profiles along a continuum of suicide risk: evidence from an implicit association task.

BACKGROUND: An urgent need exists to identify neural correlates associated with differing levels of suicide risk and develop novel, rapid-acting therapeutics to modulate activity within these neural networks. METHODS: Electrophysiological correlates of suicide were evaluated using magnetoencephalography (MEG) in 75 adults with differing levels of suicide risk. During MEG scanning, participants completed a modified Life-Death Implicit Association Task. MEG data were source-localized in the gamma (30-58 Hz) frequency, a proxy measure of excitation-inhibition balance. Dynamic causal modeling was used to evaluate differences in connectivity estimates between risk groups. A proof-of-concept, open-label, pilot study of five high risk participants examined changes in gamma power after administration of ketamine (0.5 mg/kg), an NMDAR antagonist with rapid anti-suicide ideation effects. RESULTS: Implicit self-associations with death were stronger in the highest suicide risk group relative to all other groups, which did not differ from each other. Higher gamma power for self-death compared to self-life associations was found in the orbitofrontal cortex for the highest risk group and the insula and posterior cingulate cortex for the lowest risk group. Connectivity estimates between these regions differentiated the highest risk group from the full sample. Implicit associations with death were not affected by ketamine, but enhanced gamma power was found for self-death associations in the left insula post-ketamine compared to baseline. CONCLUSIONS: Differential implicit cognitive processing of life and death appears to be linked to suicide risk, highlighting the need for objective measures of suicidal states. Pharmacotherapies that modulate gamma activity, particularly in the insula, may help mitigate risk.Clinicaltrials.gov identifier: NCT02543983, NCT00397111.

Toward objective characterizations of suicide risk: A narrative review of laboratory-based cognitive and behavioral tasks.

Although suicide is a leading cause of preventable death worldwide, current prevention efforts have failed to substantively mitigate suicide risk. Suicide research has traditionally relied on subjective reports that may not accurately differentiate those at high versus minimal risk. This narrative review supports the inclusion of objective task-based measures in suicide research to complement existing subjective batteries. The article: 1) outlines risk factors proposed by contemporary theories of suicide and highlights recent empirical findings supporting these theories; 2) discusses ongoing challenges associated with current risk assessment tools and their ability to accurately evaluate risk factors; and 3) analyzes objective laboratory measures that can be implemented alongside traditional measures to enhance the precision of risk assessment. To illustrate the potential of these methods to improve our understanding of suicide risk, the article reviews how acute stress responses in a laboratory setting can be modeled, given that stress is a major precipitant for suicidal behavior. More precise risk assessment strategies can emerge if objective measures are implemented in conjunction with traditional subjective measures.