Cortical inhibitory markers of lifetime suicidal behavior in depressed adolescents

Charles P. Lewis, Paul A. Nakonezny, Caren J. Blacker, Jennifer L. Vande Voort, John D. Port, Gregory A. Worrell, Hang Joon Jo, Zafiris J. Daskalakis, Paul E. Croarkin

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Although suicide is the second-leading cause of death in adolescents and young adults worldwide, little progress has been made in developing reliable biological markers of suicide risk and suicidal behavior. Converging evidence suggests that excitatory and inhibitory cortical processes mediated by the neurotransmitters glutamate and γ-aminobutyric acid (GABA) are dysregulated in suicidal individuals. This study utilized single-and paired-pulse transcranial magnetic stimulation (TMS) to assess excitatory and inhibitory cortical functioning in healthy control adolescents (n = 20), depressed adolescents without any history of suicidal behavior ("Depressed", n = 37), and depressed adolescents with lifetime history of suicidal behavior ("Depressed+SB", n = 17). In a fixed-effects general linear model analysis, with age, sex, and depression severity as covariates, no significant group main effects emerged for resting motor threshold, intracortical facilitation, short-interval intracortical inhibition, or cortical silent period. However, group main effects were significant for long-interval intracortical inhibition (LICI) at interstimulus intervals (ISIs) of 100 ms and 150 ms, but not 200 ms. Depressed+SB adolescents demonstrated impaired LICI compared to healthy control and Depressed adolescents, while healthy control and Depressed participants did not differ in LICI. Multiple linear robust regression revealed significant positive linear relationships between lifetime suicidal behavior severity and impairment in LICI at 100-ms and 150-ms ISIs. In a post hoc receiver operating characteristic analysis, LICI significantly discriminated Depressed from Depressed+SB youth in 100-ms and 150-ms paradigms. These findings suggest that GABA B receptor-mediated inhibition is distinctly dysregulated in depressed adolescents with histories of suicidal behavior. Further research is warranted to establish the utility of cortical inhibition in the assessment of suicide risk and as a target for treatment interventions.

Original languageEnglish (US)
Pages (from-to)1822-1831
Number of pages10
JournalNeuropsychopharmacology
Volume43
Issue number9
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

Bibliographical note

Funding Information:
Competing interests: CPL receives research support from the Mayo Clinic Foundation Departmental Small Grant Program and is a site investigator for a multicenter study funded by Neuronetics, Inc. CJB receives research support from the Mayo Clinic Foundation Departmental Small Grant Program. JLVV receives equipment in-kind support from Assurex Health, Inc. for an investigator-initiated study and is a site investigator for a multicenter study funded by Neuronetics, Inc. GAW has received research support from Medtronic, Inc., Neuralynx, Inc., and Neuropace, Inc. ZJD has received research and equipment in-kind support for an investigator-initiated study from Brainsway Ltd.; he also has served on the advisory board for F. Hoffmann-La Roche Ltd. and Merck & Co., Inc. and has received speaker support from Eli Lilly and Co. PEC has received research grant support from Pfizer, Inc., NIMH (K23 MH100266), the Brain and Behavior Research Foundation, and the Mayo Clinic Foundation. He has served as a site subprincipal or principal investigator (without additional compensation) for Eli Lilly and Co., Forest Laboratories, Inc., Merck & Co., Inc., and Pfizer, Inc.; has received equipment support from Neuronetics, Inc.; and receives supplies and genotyping services from Assurex Health, Inc. for an investigator-initiated study. He is a site primary investigator for a multicenter study funded by Neuronetics, Inc. The other authors declare no competing interests.

Funding Information:
This research was supported by grants from the Brain and Behavior Research Foundation (Young Investigator Award 20883), the Mayo Clinic Foundation (Departmental Small Grant Award), and the National Institute of Mental Health (K23 MH100266). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2018 The Author(s).

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