Jessica R Gilbert1, Elizabeth D Ballard2, Christina S Galiano2, Allison C Nugent2, Carlos A Zarate2. 1. Section on the Neurobiology and Treatment of Mood Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland. Electronic address: jessica.gilbert@nih.gov. 2. Section on the Neurobiology and Treatment of Mood Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
Abstract
BACKGROUND: Defining the neurobiological underpinnings of suicidal ideation (SI) is crucial to improving our understanding of suicide. This study used magnetoencephalographic gamma power as a surrogate marker for population-level excitation-inhibition balance to explore the underlying neurobiology of SI and depression. In addition, effects of pharmacological intervention with ketamine, which has been shown to rapidly reduce SI and depression, were assessed. METHODS: Data were obtained from 29 drug-free patients with major depressive disorder who participated in an experiment comparing subanesthetic ketamine (0.5 mg/kg) with a placebo saline infusion. Magnetoencephalographic recordings were collected at baseline and after ketamine and placebo infusions. During scanning, patients rested with their eyes closed. SI and depression were assessed, and a linear mixed-effects model was used to identify brain regions where gamma power and both SI and depression were associated. Two regions of the salience network (anterior insula, anterior cingulate) were then probed using dynamic causal modeling to test for ketamine effects. RESULTS: Clinically, patients showed significantly reduced SI and depression after ketamine administration. In addition, distinct regions in the anterior insula were found to be associated with SI compared with depression. In modeling of insula-anterior cingulate connectivity, ketamine lowered the membrane capacitance for superficial pyramidal cells. Finally, connectivity between the insula and anterior cingulate was associated with improvements in depression symptoms. CONCLUSIONS: These findings suggest that the anterior insula plays a key role in SI, perhaps via its role in salience detection. In addition, transient changes in superficial pyramidal cell membrane capacitance and subsequent increases in cortical excitability might be a mechanism through which ketamine improves SI.
BACKGROUND: Defining the neurobiological underpinnings of suicidal ideation (SI) is crucial to improving our understanding of suicide. This study used magnetoencephalographic gamma power as a surrogate marker for population-level excitation-inhibition balance to explore the underlying neurobiology of SI and depression. In addition, effects of pharmacological intervention with ketamine, which has been shown to rapidly reduce SI and depression, were assessed. METHODS: Data were obtained from 29 drug-free patients with major depressive disorder who participated in an experiment comparing subanesthetic ketamine (0.5 mg/kg) with a placebo saline infusion. Magnetoencephalographic recordings were collected at baseline and after ketamine and placebo infusions. During scanning, patients rested with their eyes closed. SI and depression were assessed, and a linear mixed-effects model was used to identify brain regions where gamma power and both SI and depression were associated. Two regions of the salience network (anterior insula, anterior cingulate) were then probed using dynamic causal modeling to test for ketamine effects. RESULTS: Clinically, patients showed significantly reduced SI and depression after ketamine administration. In addition, distinct regions in the anterior insula were found to be associated with SI compared with depression. In modeling of insula-anterior cingulate connectivity, ketamine lowered the membrane capacitance for superficial pyramidal cells. Finally, connectivity between the insula and anterior cingulate was associated with improvements in depression symptoms. CONCLUSIONS: These findings suggest that the anterior insula plays a key role in SI, perhaps via its role in salience detection. In addition, transient changes in superficial pyramidal cell membrane capacitance and subsequent increases in cortical excitability might be a mechanism through which ketamine improves SI.
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