Magnetoencephalographic correlates of suicidal ideation in major depression
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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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Resting-state studies of SI in adults diagnosed with MDD have found network changes in the hippocampus, thalamus, caudate, and anterior insula associated with SI scores.
“For example, resting-state studies of SI in adults diagnosed with MDD have found network changes in the hippocampus, thalamus, caudate (66), and anterior insula (72) associated with SI scores.”
From New methods for assessing rapid changes in suicide risk (2021) · cites this paper as [72]
These studies have mostly assessed suicide risk in larger clinical samples of participants diagnosed with mood disorders and other psychiatric conditions with which suicide is a comorbid phenotype, but rarely have they investigated suicide transdiagnostically.
“Finally, these studies have mostly assessed suicide risk in larger clinical samples of participants diagnosed with mood disorders (64–75) and other psychiatric conditions (76–79) with which suicide is a comorbid phenotype, but rarely have they investigated suicide transdiagnostically.”
From New methods for assessing rapid changes in suicide risk (2021) · cites this paper as [72]
Ketamine administration lowered the membrane capacitance of superficial pyramidal cells in a study assessing standard dose ketamine and suicidal ideation.
“A second study assessing standard dose ketamine and SI measured salience network connectivity changes between anterior cingulate and insula directly, finding that ketamine administration lowered the membrane capacitance of superficial pyramidal cells (72).”
From New methods for assessing rapid changes in suicide risk (2021) · cites this paper as [72]
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Soltanzadeh, M., Zheng, W., Allohverdi, S. G., Charlton, C. E., Schmidt, A., Vollenweider, F. X., & Diaconescu, A. O. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06952-2 · Cited by 2 · see citing works
A computational model to characterize the time-course of response to rapid antidepressant therapies
Nunes, A., & Singh, S. (2024) · PLoS ONE · doi:10.1371/journal.pone.0297708 · Cited by 1 · see citing works
Ma, L., Katyare, N., Johnston, K., & Everling, S. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1018-23.2024 · Cited by 1 · see citing works
The Role of Rapid-Acting Antidepressants in Suicidal Crisis Management
Lengvenytė, A., Sarchiapone, M., Iosue, M., & Courtet, P. (2024) · Cambridge University Press eBooks · doi:10.1017/9781009067287.016
吕, 志. (2024) · Advances in Clinical Medicine · doi:10.12677/acm.2024.14112885
Hu, H., Chandler, B. H., Sloane, J. L., Verbalis, J. G., Zarate, C. A., Ballard, E. D., & Gilbert, J. R. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1895698
Self-citation
- Authors
- Gilbert, J. R., Ballard, E. D., Galiano, C. S., Nugent, A. C., & Zarate, C. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Gilbert, Jessica R.
- ORCID
- Venue
- Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 5
- Issue
- 3
- Pages
- 354-363
- ISSN
- 2451-9022 (ISSN-L)
- PMC
- PMC7064429
- OpenAlex
- W2992688309
- Cited by
- 28
- References
- 65
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 11 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 2
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry Cognitive Neuroscience and Neuroimaging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- suicidal ideation, major depressive disorder, ketamine, gamma power, excitation-inhibition balance, anterior insula, anterior cingulate cortex, salience network, saliency detection, membrane capacitance, cortical excitability, dynamic causal modeling
- MeSH terms
- Brain, Depression, Major Depressive Disorder, Humans, Ketamine, Psychiatric Status Rating Scales, Magnetoencephalography, Excitatory Amino Acid Antagonists, Suicidal Ideation
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