PMID- 29703993 OWN - NLM STAT- MEDLINE DCOM- 20190311 LR - 20230926 IS - 1740-634X (Electronic) IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 43 IP - 9 DP - 2018 Aug TI - Cortical inhibitory markers of lifetime suicidal behavior in depressed adolescents. PG - 1822-1831 LID - 10.1038/s41386-018-0040-x [doi] AB - 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 gamma-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. FAU - Lewis, Charles P AU - Lewis CP AUID- ORCID: 0000-0001-8791-657X AD - Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. FAU - Nakonezny, Paul A AU - Nakonezny PA AD - Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA. AD - Department of Clinical Sciences, Division of Biostatistics, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Blacker, Caren J AU - Blacker CJ AD - Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. FAU - Vande Voort, Jennifer L AU - Vande Voort JL AD - Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. FAU - Port, John D AU - Port JD AUID- ORCID: 0000-0002-4237-7776 AD - Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. AD - Department of Radiology, Mayo Clinic, Rochester, MN, USA. FAU - Worrell, Gregory A AU - Worrell GA AD - Department of Neurology, Mayo Clinic, Rochester, MN, USA. FAU - Jo, Hang Joon AU - Jo HJ AD - Department of Neurologic Surgery, Neural Engineering Lab, Mayo Clinic, Rochester, MN, USA. FAU - Daskalakis, Zafiris J AU - Daskalakis ZJ AD - Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. AD - Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada. FAU - Croarkin, Paul E AU - Croarkin PE AUID- ORCID: 0000-0001-6843-6503 AD - Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. croarkin.paul@mayo.edu. LA - eng GR - K23 MH100266/MH/NIMH NIH HHS/United States GR - R01 MH113700/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180314 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Receptors, GABA-B) SB - IM MH - Adolescent MH - Cerebral Cortex/*physiopathology MH - Child MH - Depressive Disorder/diagnosis/*physiopathology MH - Evoked Potentials, Motor MH - Female MH - Humans MH - Male MH - Neural Inhibition/*physiology MH - ROC Curve MH - Receptors, GABA-B/metabolism MH - *Suicide MH - Transcranial Magnetic Stimulation MH - Young Adult PMC - PMC6046050 COIS- 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. EDAT- 2018/04/29 06:00 MHDA- 2019/03/12 06:00 PMCR- 2018/03/14 CRDT- 2018/04/29 06:00 PHST- 2017/08/24 00:00 [received] PHST- 2018/02/26 00:00 [accepted] PHST- 2018/01/05 00:00 [revised] PHST- 2018/04/29 06:00 [pubmed] PHST- 2019/03/12 06:00 [medline] PHST- 2018/04/29 06:00 [entrez] PHST- 2018/03/14 00:00 [pmc-release] AID - 10.1038/s41386-018-0040-x [pii] AID - 40 [pii] AID - 10.1038/s41386-018-0040-x [doi] PST - ppublish SO - Neuropsychopharmacology. 2018 Aug;43(9):1822-1831. doi: 10.1038/s41386-018-0040-x. Epub 2018 Mar 14.