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

Published online by Cambridge University Press:  24 November 2023

Steven J. Lamontagne ,
Jessica R. Gilbert ,
Paloma K. Zabala ,
Laura R. Waldman ,
Carlos A. Zarate Jr Open the ORCID record for Carlos A. Zarate Jr [Opens in a new window]  and
Elizabeth D. Ballard
Steven J. Lamontagne
Affiliation:
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Jessica R. Gilbert
Affiliation:
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Paloma K. Zabala
Affiliation:
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Laura R. Waldman
Affiliation:
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Carlos A. Zarate Jr
Affiliation:
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Elizabeth D. Ballard*
Affiliation:
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
*
Corresponding author: Elizabeth D. Ballard; Email: Elizabeth.Ballard@nih.gov
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Abstract

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.

Keywords

dynamic causal modelinggamma powerimplicit association taskketaminemagnetoencephalographysuicide
Type
Original Article
Information
Psychological Medicine , Volume 54 , Issue 7 , May 2024 , pp. 1431 - 1440
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Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

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References

Arikan, M. K., Gunver, M. G., Tarhan, N., & Metin, B. (2019). High-Gamma: A biological marker for suicide attempt in patients with depression. Journal of Affective Disorders, 254, 1–6. https://doi.org/10.1016/j.jad.2019.05.007CrossRefGoogle ScholarPubMed
Ballard, E. D., Gilbert, J. R., Fields, J. S., Nugent, A. C., & Zarate, C. A. Jr (2020). Network changes in insula and amygdala connectivity accompany implicit suicidal associations. Frontiers in Psychiatry, 11, 1–8. https://doi.org/10.3389/fpsyt.2020.577628CrossRefGoogle ScholarPubMed
Ballard, E. D., Luckenbaugh, D. A., Richards, E. M., Walls, T. L., Brutsché, N. E., Ameli, R., … Zarate, C. A. Jr (2015). Assessing measures of suicidal ideation in clinical trials with a rapid-acting antidepressant. Journal of Psychiatric Research, 68, 68–73. https://doi.org/10.1016/j.jpsychires.2015.06.003CrossRefGoogle ScholarPubMed
Ballard, E. D., Reed, J. L., Szczepanik, J., Evans, J. W., Yarrington, J. S., Dickstein, D. P., … Zarate, C. A. Jr (2019). Functional imaging of the implicit association of the self with life and death. Suicide and Life-Threatening Behavior, 49(6), 1600–1608. https://doi.org/10.1111/sltb.12543CrossRefGoogle ScholarPubMed
Barnes, S. M., Bahraini, N. H., Forster, J. E., Stearns-Yoder, K. A., Hostetter, T. A., Smith, G., … Nock, M. K. (2017). Moving beyond self-report: Implicit associations about death/life prospectively predict suicidal behavior among veterans. Suicide and Life-Threatening Behavior, 47(1), 67–77. https://doi.org/10.1111/sltb.12265CrossRefGoogle ScholarPubMed
Beck, A. T., Kovacs, M., & Weissman, A. (1979). Assessment of suicidal intention: The scale for suicide ideation. Journal of Consulting and Clinical Psychology, 47(2), 343–352. https://doi.org/10.1037/0022-006X.47.2.343CrossRefGoogle ScholarPubMed
Beck, A. T., Steer, R. A., & Brown, G. (1996). Beck depression inventory–II. San Antonio, TX: The Psychological Corporation. https://doi.org/10.1037/t00742-000Google Scholar
Beck, A. T., Weissman, A., Lester, D., & Trexler, L. (1974). The measurement of pessimism: The hopelessness scale. Journal of Consulting and Clinical Psychology, 42(6), 861–865. https://doi.org/10.1037/h0037562CrossRefGoogle ScholarPubMed
Bostwick, J. M., Pabbati, C., Geske, J. R., & McKean, A. J. (2016). Suicide attempt as a risk factor for completed suicide: Even more lethal than we knew. American Journal of Psychiatry, 173(11), 1094–1100. https://doi.org/10.1176/appi.ajp.2016.15070854CrossRefGoogle ScholarPubMed
Buzsáki, G., & Wang, X. J. (2012). Mechanisms of gamma oscillations. Annual Review of Neuroscience, 35, 203–225. https://doi.org/10.1146/annurev-neuro-062111-150444CrossRefGoogle ScholarPubMed
Cha, C. B., Najmi, S., Park, J. M., Finn, C. T., & Nock, M. K. (2010). Attentional bias toward suicide-related stimuli predicts suicidal behavior. Journal of Abnormal Psychology, 119(3), 616–622. https://doi.org/10.1037/a0019710CrossRefGoogle ScholarPubMed
Dai, Z., Shao, J., Zhou, H., Chen, Z., Zhang, S., Wang, H., … Lu, Q. (2022). Disrupted fronto-parietal network and default-mode network gamma interactions distinguishing suicidal ideation and suicide attempt in depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 113, 1–9. https://doi.org/10.1016/j.pnpbp.2021.110475CrossRefGoogle ScholarPubMed
DeVille, D. C., Kuplicki, R., Stewart, J. L., Paulus, M. P., & Khalsa, S. S. (2020). Diminished responses to bodily threat and blunted interoception in suicide attempters. Elife, 9, e51593. https://doi.org/10.7554/eLife.51593CrossRefGoogle ScholarPubMed
Domínguez-Baleón, C., Gutiérrez-Mondragón, L. F., Campos-González, A. I., & Rentería, M. E. (2018). Neuroimaging studies of suicidal behavior and non-suicidal self-injury in psychiatric patients: A systematic review. Frontiers in Psychiatry, 9, 500. https://doi.org/10.3389/fpsyt.2018.00500CrossRefGoogle ScholarPubMed
Gilbert, J. R., Ballard, E. D., Galiano, C. S., Nugent, A. C., & Zarate, C. A. Jr (2020). Magnetoencephalographic correlates of suicidal ideation in major depression. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 5(3), 354–363. https://doi.org/10.1016/j.bpsc.2019.11.011Google ScholarPubMed
Glenn, C. R., Cha, C. B., Kleiman, E. M., & Nock, M. K. (2017b). Understanding suicide risk within the Research Domain Criteria (RDoC) framework: Insights, challenges, and future research considerations. Clinical Psychological Science, 5(3), 568–592. https://doi.org/10.1177/2167702616686854CrossRefGoogle ScholarPubMed
Glenn, C. R., Kleiman, E. M., Cha, C. B., Deming, C. A., Franklin, J. C., & Nock, M. K. (2018). Understanding suicide risk within the Research Domain Criteria (RDoC) framework: A meta-analytic review. Depression and Anxiety, 35(1), 65–88. https://doi.org/10.1002/da.22686CrossRefGoogle ScholarPubMed
Glenn, C. R., Kleiman, E. M., Coppersmith, D. D., Santee, A. C., Esposito, E. C., Cha, C. B., … Auerbach, R. P. (2017a). Implicit identification with death predicts change in suicide ideation during psychiatric treatment in adolescents. Journal of Child Psychology and Psychiatry, 58(12), 1319–1329. https://doi.org/10.1111/jcpp.12769CrossRefGoogle ScholarPubMed
Hartikainen, K. M., Ogawa, K. H., & Knight, R. T. (2012). Orbitofrontal cortex biases attention to emotional events. Journal of Clinical and Experimental Neuropsychology, 34(6), 588–597. https://doi.org/10.1080/13803395.2012.666231CrossRefGoogle ScholarPubMed
Hermans, E. J., Henckens, M. J., Joëls, M., & Fernández, G. (2014). Dynamic adaptation of large-scale brain networks in response to acute stressors. Trends in Neurosciences, 37(6), 304–314. https://doi.org/10.1016/j.tins.2014.03.006CrossRefGoogle ScholarPubMed
Hermans, E. J., Van Marle, H. J., Ossewaarde, L., Henckens, M. J., Qin, S., Van Kesteren, M. T., … Fernández, G. (2011). Stress-related noradrenergic activity prompts large-scale neural network reconfiguration. Science (New York, N.Y.), 334(6059), 1151–1153. https://doi.org/10.1126/science.1209603CrossRefGoogle ScholarPubMed
Horwitz, A. G., Czyz, E. K., & King, C. A. (2015). Predicting future suicide attempts among adolescent and emerging adult psychiatric emergency patients. Journal of Clinical Child & Adolescent Psychology, 44(5), 751–761. https://doi.org/10.1080/15374416.2014.910789CrossRefGoogle ScholarPubMed
Jensen, O., Kaiser, J., & Lachaux, J. P. (2007). Human gamma-frequency oscillations associated with attention and memory. Trends in Neurosciences, 30(7), 317–324. https://doi.org/10.1016/j.tins.2007.05.001CrossRefGoogle ScholarPubMed
Kim, Y. J., Park, H. J., Jahng, G. H., Lee, S. M., Kang, W. S., Kim, S. K., … Park, J. K. (2017). A pilot study of differential brain activation to suicidal means and DNA methylation of CACNA1C gene in suicidal attempt patients. Psychiatry Research, 255, 42–48. https://doi.org/10.1016/j.psychres.2017.03.058CrossRefGoogle ScholarPubMed
Lengvenyte, A., Conejero, I., Courtet, P., & Olié, E. (2021). Biological bases of suicidal behaviours: A narrative review. European Journal of Neuroscience, 53(1), 330–351. https://doi.org/10.1111/ejn.14635CrossRefGoogle ScholarPubMed
Maier, W., Buller, R., Philipp, M., & Heuser, I. (1988). The Hamilton Anxiety Scale: Reliability, validity and sensitivity to change in anxiety and depressive disorders. Journal of Affective Disorders, 14(1), 61–68. https://doi.org/10.1016/0165-0327(88)90072-9CrossRefGoogle ScholarPubMed
Montgomery, S. A., & Åsberg, M. A. R. I. E. (1979). A new depression scale designed to be sensitive to change. The British Journal of Psychiatry, 134(4), 382–389. https://doi.org/10.1192/bjp.134.4.382CrossRefGoogle ScholarPubMed
Moreno, M., Guitérrez-Rojas, L., & Porras-Segovia, A. (2022). Implicit cognition tests for the assessment of suicide risk: A systematic review. Current Psychiatry Reports, 24, 141–159. https://doi.org/10.1007/s11920-022-01316-5CrossRefGoogle ScholarPubMed
Motoyama, H., & Hishitani, S. (2016). The brain mechanism that reduces the vividness of negative imagery. Consciousness and Cognition, 39, 59–69. https://doi.org/10.1016/j.concog.2015.11.006CrossRefGoogle ScholarPubMed
Nitschke, J. B., Sarinopoulos, I., Mackiewicz, K. L., Schaefer, H. S., & Davidson, R. J. (2006). Functional neuroanatomy of aversion and its anticipation. Neuroimage, 29(1), 106–116. https://doi.org/10.1016/j.neuroimage.2005.06.068CrossRefGoogle ScholarPubMed
Nock, M. K., Millner, A. J., Ross, E. L., Kennedy, C. J., Al-Suwaidi, M., Barak-Corren, Y., … Kessler, R. C. (2022). Prediction of suicide attempts using clinician assessment, patient self-report, and electronic health records. JAMA Network Open, 5(1), e2144373–e2144373. https://doi.org/10.1001/jamanetworkopen.2021.44373CrossRefGoogle ScholarPubMed
Nock, M. K., Park, J. M., Finn, C. T., Deliberto, T. L., Dour, H. J., & Banaji, M. R. (2010). Measuring the suicidal mind: Implicit cognition predicts suicidal behavior. Psychological Science, 21(4), 511–517. https://doi.org/10.1177/0956797610364762CrossRefGoogle ScholarPubMed
Northoff, G., & Bermpohl, F. (2004). Cortical midline structures and the self. Trends in Cognitive Sciences, 8(3), 102–107. https://doi.org/10.1016/j.tics.2004.01.004CrossRefGoogle ScholarPubMed
Nugent, A. C., Ballard, E. D., Gould, T. D., Park, L. T., Moaddel, R., Brutsche, N. E., & Zarate, C. A. Jr (2019). Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects. Molecular Psychiatry, 24(7), 1040–1052. https://doi.org/10.1038/s41380-018-0028-2CrossRefGoogle ScholarPubMed
Orbach, I., Stein, D., Palgi, Y., Asherov, J., Har-Even, D., & Elizur, A. (1996). Perception of physical pain in accident and suicide attempt patients: Self-preservation vs self-destruction. Journal of Psychiatric Research, 30(4), 307–320. https://doi.org/10.1016/0022-3956(96)00008-8CrossRefGoogle ScholarPubMed
Patton, J. H., Stanford, M. S., & Barratt, E. S. (1995). Factor structure of the Barratt impulsiveness scale. Journal of Clinical Psychology, 51(6), 768–774. https://doi.org/10.1002/1097-4679(199511)51:6<768::AID-JCLP2270510607>3.0.CO;2-13.0.CO;2-1>CrossRefGoogle ScholarPubMed
Perlis, R. H., Holt, D. J., Smoller, J. W., Blood, A. J., Lee, S., Kim, B. W., … Breiter, H. C. (2008). Association of a polymorphism near CREB1 with differential aversion processing in the insula of healthy participants. Archives of General Psychiatry, 65(8), 882–892. https://doi.org/10.1001/archgenpsychiatry.2008.3CrossRefGoogle ScholarPubMed
Posner, K., Brown, G. K., Stanley, B., Brent, D. A., Yershova, K. V., Oquendo, M. A., … Mann, J. J. (2011). The Columbia–Suicide Severity Rating Scale: Initial validity and internal consistency findings from three multisite studies with adolescents and adults. American Journal of Psychiatry, 168(12), 1266–1277. https://doi.org/10.1176/appi.ajp.2011.10111704CrossRefGoogle ScholarPubMed
Price, R. B., Iosifescu, D. V., Murrough, J. W., Chang, L. C., Al Jurdi, R. K., Iqbal, S. Z., … Mathew, S. J. (2014). Effects of ketamine on explicit and implicit suicidal cognition: A randomized controlled trial in treatment-resistant depression. Depression and Anxiety, 31(4), 335–343. https://doi.org/10.1002/da.22253CrossRefGoogle ScholarPubMed
Price, R. B., Nock, M. K., Charney, D. S., & Mathew, S. J. (2009). Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biological Psychiatry, 66(5), 522–526. https://doi.org/10.1016/j.biopsych.2009.04.029CrossRefGoogle ScholarPubMed
Qin, S., Hermans, E. J., Van Marle, H. J., Luo, J., & Fernández, G. (2009). Acute psychological stress reduces working memory-related activity in the dorsolateral prefrontal cortex. Biological Psychiatry, 66(1), 25–32. https://doi.org/10.1016/j.biopsych.2009.03.006CrossRefGoogle ScholarPubMed
Quirin, M., Loktyushin, A., Arndt, J., Küstermann, E., Lo, Y. Y., Kuhl, J., & Eggert, L. (2012). Existential neuroscience: A functional magnetic resonance imaging investigation of neural responses to reminders of one's mortality. Social Cognitive and Affective Neuroscience, 7(2), 193–198. https://doi.org/10.1093/scan/nsq106CrossRefGoogle ScholarPubMed
Randall, J. R., Rowe, B. H., Dong, K. A., Nock, M. K., & Colman, I. (2013). Assessment of self-harm risk using implicit thoughts. Psychological Assessment, 25(3), 714–721. https://doi.org/10.1037/a0032391CrossRefGoogle ScholarPubMed
Sarinopoulos, I., Grupe, D. W., Mackiewicz, K. L., Herrington, J. D., Lor, M., Steege, E. E., & Nitschke, J. B. (2010). Uncertainty during anticipation modulates neural responses to aversion in human insula and amygdala. Cerebral Cortex, 20(4), 929–940. https://doi.org/10.1093/cercor/bhp155CrossRefGoogle ScholarPubMed
Schmaal, L., van Harmelen, A. L., Chatzi, V., Lippard, E. T., Toenders, Y. J., Averill, L. A., … Blumberg, H. P. (2020). Imaging suicidal thoughts and behaviors: A comprehensive review of 2 decades of neuroimaging studies. Molecular Psychiatry, 25(2), 408–427. https://doi.org/10.1038/s41380-019-0587-xCrossRefGoogle ScholarPubMed
Shi, Z., & Han, S. (2013). Transient and sustained neural responses to death-related linguistic cues. Social Cognitive and Affective Neuroscience, 8(5), 573–578. https://doi.org/10.1093/scan/nss034CrossRefGoogle ScholarPubMed
Simmons, A., Matthews, S. C., Stein, M. B., & Paulus, M. P. (2004). Anticipation of emotionally aversive visual stimuli activates right insula. Neuroreport, 15(14), 2261–2265. https://doi.org/10.1097/00001756-200410050-00024CrossRefGoogle ScholarPubMed
Simmons, A., Strigo, I., Matthews, S. C., Paulus, M. P., & Stein, M. B. (2006). Anticipation of aversive visual stimuli is associated with increased insula activation in anxiety-prone subjects. Biological Psychiatry, 60(4), 402–409. https://doi.org/10.1016/j.biopsych.2006.04.038CrossRefGoogle ScholarPubMed
Smith, E. G., Kim, H. M., Ganoczy, D., Stano, C., Pfeiffer, P. N., & Valenstein, M. (2013). Suicide risk assessment received prior to suicide death by Veterans Health Administration patients with a history of depression. The Journal of Clinical Psychiatry, 74(3), 226–232. https://doi.org/10.4088/JCP.12m07853CrossRefGoogle ScholarPubMed
Snaith, R. P., Hamilton, M., Morley, S., Humayan, A., Hargreaves, D., & Trigwell, P. (1995). A scale for the assessment of hedonic tone the Snaith–Hamilton Pleasure Scale. The British Journal of Psychiatry, 167(1), 99–103. https://doi.org/10.1192/bjp.167.1.99CrossRefGoogle ScholarPubMed
Sridharan, D., Levitin, D. J., & Menon, V. (2008). A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proceedings of the National Academy of Sciences, 105(34), 12569–12574. https://doi.org/10.1073/pnas.0800005105CrossRefGoogle ScholarPubMed
Stone, D. M., Jones, C. M., & Mack, K. A. (2021). Changes in suicide rates – United States, 2018–2019. Morbidity and Mortality Weekly Report, 70(8), 261–268. https://doi.org/10.15585/mmwr.mm7008a1CrossRefGoogle ScholarPubMed
Tello, N., Harika-Germaneau, G., Serra, W., Jaafari, N., & Chatard, A. (2020). Forecasting a fatal decision: Direct replication of the predictive validity of the suicide–implicit association test. Psychological Science, 31(1), 65–74. https://doi.org/10.1177/0956797619893062CrossRefGoogle ScholarPubMed
Wilkinson, S. T., Ballard, E. D., Bloch, M. H., Mathew, S. J., Murrough, J. W., Feder, A., … Sanacora, G. (2018). The effect of a single dose of intravenous ketamine on suicidal ideation: A systematic review and individual participant data meta-analysis. American Journal of Psychiatry, 175(2), 150–158. https://doi.org/10.1176/appi.ajp.2017.17040472CrossRefGoogle ScholarPubMed
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