PMID- 27965544 OWN - NLM STAT- MEDLINE DCOM- 20171023 LR - 20181113 IS - 1662-5110 (Electronic) IS - 1662-5110 (Linking) VI - 10 DP - 2016 TI - An Exploratory Study of Spectroscopic Glutamatergic Correlates of Cortical Excitability in Depressed Adolescents. PG - 98 LID - 98 AB - Introduction: Transcranial magnetic stimulation (TMS) research has suggested dysfunction in cortical glutamatergic systems in adolescent depression, while proton magnetic resonance spectroscopy ((1)H-MRS) studies have demonstrated deficits in concentrations of glutamatergic metabolites in depressed individuals in several cortical regions, including the anterior cingulate cortex (ACC). However, few studies have combined TMS and MRS methods to examine relationships between glutamatergic neurochemistry and excitatory and inhibitory neural functions, and none have utilized TMS-MRS methodology in clinical populations or in youth. This exploratory study aimed to examine relationships between TMS measures of cortical excitability and inhibition and concentrations of glutamatergic metabolites as measured by (1)H-MRS in depressed adolescents. Methods: Twenty-four adolescents (aged 11-18 years) with depressive symptoms underwent TMS testing, which included measures of the resting motor threshold (RMT), cortical silent period (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Fourteen participants from the same sample also completed (1)H-MRS in a 3 T MRI scanner after TMS testing. Glutamate + glutamine (Glx) concentrations were measured in medial ACC and left primary motor cortex voxels with a TE-optimized PRESS sequence. Metabolite concentrations were corrected for cerebrospinal fluid (CSF) after tissue segmentation. Pearson product-moment and Spearman rank-order correlations were calculated to assess relationships between TMS measures and [Glx]. Results: In the left primary motor cortex voxel, [Glx] had a significant positive correlation with the RMT. In the medial ACC voxel, [Glx] had significant positive correlations with ICF at the 10-ms and 20-ms interstimulus intervals (ISIs). Conclusion: These preliminary data implicate glutamate in cortical excitatory processes measured by TMS. Limitations included small sample size, lack of healthy control comparators, possible age- and sex-related effects, and observational nature of the study. Further research aimed at examining the relationship between glutamatergic metabolite concentrations measured through MRS and the excitatory and inhibitory physiology measured through TMS is warranted. Combined TMS-MRS methods show promise for future investigations of the pathophysiology of depression in adults as well as in children and adolescents. FAU - Lewis, Charles P AU - Lewis CP AD - Mayo Clinic Depression Center, Department of Psychiatry and Psychology, Mayo Clinic Rochester, MN, USA. FAU - Port, John D AU - Port JD AD - Mayo Clinic Depression Center, Department of Psychiatry and Psychology, Mayo ClinicRochester, MN, USA; Department of Radiology, Mayo ClinicRochester, MN, USA. FAU - Frye, Mark A AU - Frye MA AD - Mayo Clinic Depression Center, Department of Psychiatry and Psychology, Mayo Clinic Rochester, MN, USA. FAU - Vande Voort, Jennifer L AU - Vande Voort JL AD - Mayo Clinic Depression Center, Department of Psychiatry and Psychology, Mayo Clinic Rochester, MN, USA. FAU - Ameis, Stephanie H AU - Ameis SH AD - Faculty of Medicine, Department of Psychiatry, University of TorontoToronto, ON, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of TorontoToronto, ON, Canada; The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Campbell Family Mental Health Research Institute, The Centre for Addiction and Mental Health, University of TorontoToronto, ON, Canada. FAU - Husain, Mustafa M AU - Husain MM AD - Department of Psychiatry, University of Texas Southwestern Medical CenterDallas, TX, USA; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical CenterDallas, TX, USA; Department of Psychiatry and Behavioral Sciences, Duke University School of MedicineDurham, NC, USA. FAU - Daskalakis, Zafiris J AU - Daskalakis ZJ AD - Faculty of Medicine, Department of Psychiatry, University of TorontoToronto, ON, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of TorontoToronto, ON, Canada. FAU - Croarkin, Paul E AU - Croarkin PE AD - Mayo Clinic Depression Center, Department of Psychiatry and Psychology, Mayo Clinic Rochester, MN, USA. LA - eng GR - K23 MH100266/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 - 20161129 PL - Switzerland TA - Front Neural Circuits JT - Frontiers in neural circuits JID - 101477940 RN - 0RH81L854J (Glutamine) RN - 3KX376GY7L (Glutamic Acid) SB - IM MH - Adolescent MH - Child MH - *Depressive Disorder/diagnostic imaging/metabolism/physiopathology MH - Evoked Potentials, Motor/*physiology MH - Female MH - Glutamic Acid/*metabolism MH - Glutamine/*metabolism MH - *Gyrus Cinguli/diagnostic imaging/metabolism/physiopathology MH - Humans MH - Magnetic Resonance Spectroscopy/*methods MH - Male MH - *Motor Cortex/diagnostic imaging/metabolism/physiopathology MH - Neural Inhibition/*physiology MH - Transcranial Magnetic Stimulation/*methods PMC - PMC5127083 OTO - NOTNLM OT - child and adolescent OT - cortical excitability OT - depression OT - glutamate OT - proton magnetic resonance spectroscopy OT - transcranial magnetic stimulation EDAT- 2016/12/15 06:00 MHDA- 2017/10/24 06:00 PMCR- 2016/01/01 CRDT- 2016/12/15 06:00 PHST- 2016/08/26 00:00 [received] PHST- 2016/11/17 00:00 [accepted] PHST- 2016/12/15 06:00 [entrez] PHST- 2016/12/15 06:00 [pubmed] PHST- 2017/10/24 06:00 [medline] PHST- 2016/01/01 00:00 [pmc-release] AID - 10.3389/fncir.2016.00098 [doi] PST - epublish SO - Front Neural Circuits. 2016 Nov 29;10:98. doi: 10.3389/fncir.2016.00098. eCollection 2016.