Cortical inhibitory and excitatory correlates of depression severity in children and adolescents

Charles P. Lewis; Paul A. Nakonezny; Stephanie H. Ameis; Jennifer L. Vande Voort; Mustafa M. Husain; Graham J. Emslie; Zafiris J. Daskalakis; Paul E. Croarkin

doi:10.1016/j.jad.2015.10.020

Cortical inhibitory and excitatory correlates of depression severity in children and adolescents

Charles P. Lewis, Paul A. Nakonezny, Stephanie H. Ameis, Jennifer L. Vande Voort, Mustafa M. Husain, Graham J. Emslie, Zafiris J. Daskalakis, Paul E. Croarkin

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Objectives Neurophysiologic correlates of depression severity potentially have great utility in diagnosis and treatment planning. Transcranial magnetic stimulation (TMS) measures of cortical inhibition and excitability have shown promise as biomarkers in psychiatry, but no prior work has examined correlates of illness severity in pediatric mood disorders. This study sought to examine the relationship between depression severity and TMS measures of cortical inhibition and excitability in children and adolescents. Methods Twenty-four depressed and 22 healthy control youth underwent TMS testing (cortical silent period [CSP], short-interval intracortical inhibition at 2-ms and 4-ms interstimulus intervals (ISIs) [SICI-2,-4], resting motor threshold [RMT] and intracortical facilitation at 10-, 15-, and 20-ms ISIs [ICF-10,-15,-20]). Symptom severity was assessed with the Quick Inventory of Depressive Symptomatology (QIDS-A₁₇-SR) and the Children's Depression Rating Scale-Revised (CDRS-R). Results In the overall sample, the following significant negative correlations were observed: CDRS-R and CSP (right hemisphere, ρ=-0.35, p=0.021); QIDS-A₁₇-SR and CSP (left, ρ=-0.33, p=0.031; right, ρ=-0.42, p=0.004); and CDRS-R and SICI-4 (right, ρ=-0.30, p=0.042). Among healthy control participants, additional significant negative correlations were observed between QIDS-A₁₇-SR and right ICF-10; QIDS-A₁₇-SR and right ICF-15; and QIDS-A₁₇-SR and left ICF-20. Among depressed participants, significant negative correlations were observed between QIDS-A₁₇-SR and bilateral CSP; CDRS-R and bilateral ICF-10; CDRS-R and bilateral ICF-15; QIDS-A₁₇-SR and left ICF-10; and QIDS-A₁₇-SR and bilateral ICF-15. Limitations Small sample, potential developmental/age- and sex-related effects. Conclusions These preliminary results provide evidence for a relationship between depression severity and dysfunction in GABAergic and glutamatergic cortical processes in a pediatric population.

Original language	English (US)
Pages (from-to)	566-575
Number of pages	10
Journal	Journal of Affective Disorders
Volume	190
DOIs	https://doi.org/10.1016/j.jad.2015.10.020
State	Published - Jan 15 2016
Externally published	Yes

Bibliographical note

Funding Information:
Dr. Lewis receives research support from the Mayo Clinic Foundation's Departmental Small Grant Program. Dr. Ameis receives financial support from the O'Brien Scholar's Program, the Ontario Mental Health Foundation New Investigator Fellowship, and the University of Toronto Dean's Fund New Staff Grant. Dr. Husain has received research support from NIH/NIMH, NIDA, NINDS, NIA, the Brain and Behavior Research Foundation, the Stanley Foundation, Cyberonics, Inc., Neuronetics, Inc. (past), St. Jude Medical, Inc. (ANS), Magstim Co. Ltd. (equipment only), Brainsway Ltd., NeoSync, Inc., Alkermes plc, and Corcept Therapeutics, Inc. Dr. Emslie has received research support from NIMH, NCS Pearson, Inc. (previously BioBehavioral Diagnostics), BioMarin Pharmaceutical, Inc., Duke University, Eli Lilly and Co., Forest Laboratories, Inc., GlaxoSmithKline plc, Mylan N.V., and Somerset Pharmaceuticals, Inc.; has served as a consultant for Alkermes plc, Allergan plc, NCS Pearson, Inc. (previously BioBehavioral Diagnostics), Bristol-Myers Squibb Co., Eli Lilly and Co., Forest Laboratories, Inc., GlaxoSmithKline plc, INC Research, LLC, Lundbeck A/S, Merck & Co., Inc., Neuronetics, Inc., Otsuka Pharmaceutical Co., Ltd., Pfizer, Inc., Seaside Therapeutics, LLC, Shire plc, the Texas Department of State Health Services, the University of Miami, Valeant Pharmaceuticals International, Inc., and Wyeth Pharmaceuticals; and was on the Speakers Bureau for Forest Laboratories, Inc. Dr. Daskalakis has received research and equipment in-kind support for an investigator-initiated study through 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. Dr. Croarkin 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 (disposable Senstar shields) from Neuronetics, Inc.; and receives supplies and genotyping services from AssureRx Health, Inc. for an investigator-initiated study. Drs. Nakonezny and Vande Voort have no financial disclosures.

Funding Information:
Dr. Lewis was supported by the Mayo Clinic Foundation’s Psychiatry and Psychology Small Grant program. Dr. Croarkin was supported by the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) under Award number 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. This research was also supported by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (Dr. Croarkin).

Publisher Copyright:
© 2015 Published by Elsevier B.V.

Keywords

Child and adolescent depression
Cortical inhibition
GABA
Glutamate
Intracortical facilitation
Transcranial magnetic stimulation

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http://europepmc.org/articles/pmc4685002

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@article{116599d1d6794e6f9df95bf0868b3f02,

title = "Cortical inhibitory and excitatory correlates of depression severity in children and adolescents",

abstract = "Objectives Neurophysiologic correlates of depression severity potentially have great utility in diagnosis and treatment planning. Transcranial magnetic stimulation (TMS) measures of cortical inhibition and excitability have shown promise as biomarkers in psychiatry, but no prior work has examined correlates of illness severity in pediatric mood disorders. This study sought to examine the relationship between depression severity and TMS measures of cortical inhibition and excitability in children and adolescents. Methods Twenty-four depressed and 22 healthy control youth underwent TMS testing (cortical silent period [CSP], short-interval intracortical inhibition at 2-ms and 4-ms interstimulus intervals (ISIs) [SICI-2,-4], resting motor threshold [RMT] and intracortical facilitation at 10-, 15-, and 20-ms ISIs [ICF-10,-15,-20]). Symptom severity was assessed with the Quick Inventory of Depressive Symptomatology (QIDS-A17-SR) and the Children's Depression Rating Scale-Revised (CDRS-R). Results In the overall sample, the following significant negative correlations were observed: CDRS-R and CSP (right hemisphere, ρ=-0.35, p=0.021); QIDS-A17-SR and CSP (left, ρ=-0.33, p=0.031; right, ρ=-0.42, p=0.004); and CDRS-R and SICI-4 (right, ρ=-0.30, p=0.042). Among healthy control participants, additional significant negative correlations were observed between QIDS-A17-SR and right ICF-10; QIDS-A17-SR and right ICF-15; and QIDS-A17-SR and left ICF-20. Among depressed participants, significant negative correlations were observed between QIDS-A17-SR and bilateral CSP; CDRS-R and bilateral ICF-10; CDRS-R and bilateral ICF-15; QIDS-A17-SR and left ICF-10; and QIDS-A17-SR and bilateral ICF-15. Limitations Small sample, potential developmental/age- and sex-related effects. Conclusions These preliminary results provide evidence for a relationship between depression severity and dysfunction in GABAergic and glutamatergic cortical processes in a pediatric population.",

keywords = "Child and adolescent depression, Cortical inhibition, GABA, Glutamate, Intracortical facilitation, Transcranial magnetic stimulation",

author = "Lewis, {Charles P.} and Nakonezny, {Paul A.} and Ameis, {Stephanie H.} and {Vande Voort}, {Jennifer L.} and Husain, {Mustafa M.} and Emslie, {Graham J.} and Daskalakis, {Zafiris J.} and Croarkin, {Paul E.}",

note = "Funding Information: Dr. Lewis receives research support from the Mayo Clinic Foundation's Departmental Small Grant Program. Dr. Ameis receives financial support from the O'Brien Scholar's Program, the Ontario Mental Health Foundation New Investigator Fellowship, and the University of Toronto Dean's Fund New Staff Grant. Dr. Husain has received research support from NIH/NIMH, NIDA, NINDS, NIA, the Brain and Behavior Research Foundation, the Stanley Foundation, Cyberonics, Inc., Neuronetics, Inc. (past), St. Jude Medical, Inc. (ANS), Magstim Co. Ltd. (equipment only), Brainsway Ltd., NeoSync, Inc., Alkermes plc, and Corcept Therapeutics, Inc. Dr. Emslie has received research support from NIMH, NCS Pearson, Inc. (previously BioBehavioral Diagnostics), BioMarin Pharmaceutical, Inc., Duke University, Eli Lilly and Co., Forest Laboratories, Inc., GlaxoSmithKline plc, Mylan N.V., and Somerset Pharmaceuticals, Inc.; has served as a consultant for Alkermes plc, Allergan plc, NCS Pearson, Inc. (previously BioBehavioral Diagnostics), Bristol-Myers Squibb Co., Eli Lilly and Co., Forest Laboratories, Inc., GlaxoSmithKline plc, INC Research, LLC, Lundbeck A/S, Merck & Co., Inc., Neuronetics, Inc., Otsuka Pharmaceutical Co., Ltd., Pfizer, Inc., Seaside Therapeutics, LLC, Shire plc, the Texas Department of State Health Services, the University of Miami, Valeant Pharmaceuticals International, Inc., and Wyeth Pharmaceuticals; and was on the Speakers Bureau for Forest Laboratories, Inc. Dr. Daskalakis has received research and equipment in-kind support for an investigator-initiated study through 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. Dr. Croarkin 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 (disposable Senstar shields) from Neuronetics, Inc.; and receives supplies and genotyping services from AssureRx Health, Inc. for an investigator-initiated study. Drs. Nakonezny and Vande Voort have no financial disclosures. Funding Information: Dr. Lewis was supported by the Mayo Clinic Foundation{\textquoteright}s Psychiatry and Psychology Small Grant program. Dr. Croarkin was supported by the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) under Award number 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. This research was also supported by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (Dr. Croarkin). Publisher Copyright: {\textcopyright} 2015 Published by Elsevier B.V.",

year = "2016",

month = jan,

day = "15",

doi = "10.1016/j.jad.2015.10.020",

language = "English (US)",

volume = "190",

pages = "566--575",

journal = "Journal of Affective Disorders",

issn = "0165-0327",

publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - Cortical inhibitory and excitatory correlates of depression severity in children and adolescents

AU - Lewis, Charles P.

AU - Nakonezny, Paul A.

AU - Ameis, Stephanie H.

AU - Vande Voort, Jennifer L.

AU - Husain, Mustafa M.

AU - Emslie, Graham J.

AU - Daskalakis, Zafiris J.

AU - Croarkin, Paul E.

N1 - Funding Information: Dr. Lewis receives research support from the Mayo Clinic Foundation's Departmental Small Grant Program. Dr. Ameis receives financial support from the O'Brien Scholar's Program, the Ontario Mental Health Foundation New Investigator Fellowship, and the University of Toronto Dean's Fund New Staff Grant. Dr. Husain has received research support from NIH/NIMH, NIDA, NINDS, NIA, the Brain and Behavior Research Foundation, the Stanley Foundation, Cyberonics, Inc., Neuronetics, Inc. (past), St. Jude Medical, Inc. (ANS), Magstim Co. Ltd. (equipment only), Brainsway Ltd., NeoSync, Inc., Alkermes plc, and Corcept Therapeutics, Inc. Dr. Emslie has received research support from NIMH, NCS Pearson, Inc. (previously BioBehavioral Diagnostics), BioMarin Pharmaceutical, Inc., Duke University, Eli Lilly and Co., Forest Laboratories, Inc., GlaxoSmithKline plc, Mylan N.V., and Somerset Pharmaceuticals, Inc.; has served as a consultant for Alkermes plc, Allergan plc, NCS Pearson, Inc. (previously BioBehavioral Diagnostics), Bristol-Myers Squibb Co., Eli Lilly and Co., Forest Laboratories, Inc., GlaxoSmithKline plc, INC Research, LLC, Lundbeck A/S, Merck & Co., Inc., Neuronetics, Inc., Otsuka Pharmaceutical Co., Ltd., Pfizer, Inc., Seaside Therapeutics, LLC, Shire plc, the Texas Department of State Health Services, the University of Miami, Valeant Pharmaceuticals International, Inc., and Wyeth Pharmaceuticals; and was on the Speakers Bureau for Forest Laboratories, Inc. Dr. Daskalakis has received research and equipment in-kind support for an investigator-initiated study through 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. Dr. Croarkin 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 (disposable Senstar shields) from Neuronetics, Inc.; and receives supplies and genotyping services from AssureRx Health, Inc. for an investigator-initiated study. Drs. Nakonezny and Vande Voort have no financial disclosures. Funding Information: Dr. Lewis was supported by the Mayo Clinic Foundation’s Psychiatry and Psychology Small Grant program. Dr. Croarkin was supported by the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) under Award number 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. This research was also supported by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (Dr. Croarkin). Publisher Copyright: © 2015 Published by Elsevier B.V.

PY - 2016/1/15

Y1 - 2016/1/15

N2 - Objectives Neurophysiologic correlates of depression severity potentially have great utility in diagnosis and treatment planning. Transcranial magnetic stimulation (TMS) measures of cortical inhibition and excitability have shown promise as biomarkers in psychiatry, but no prior work has examined correlates of illness severity in pediatric mood disorders. This study sought to examine the relationship between depression severity and TMS measures of cortical inhibition and excitability in children and adolescents. Methods Twenty-four depressed and 22 healthy control youth underwent TMS testing (cortical silent period [CSP], short-interval intracortical inhibition at 2-ms and 4-ms interstimulus intervals (ISIs) [SICI-2,-4], resting motor threshold [RMT] and intracortical facilitation at 10-, 15-, and 20-ms ISIs [ICF-10,-15,-20]). Symptom severity was assessed with the Quick Inventory of Depressive Symptomatology (QIDS-A17-SR) and the Children's Depression Rating Scale-Revised (CDRS-R). Results In the overall sample, the following significant negative correlations were observed: CDRS-R and CSP (right hemisphere, ρ=-0.35, p=0.021); QIDS-A17-SR and CSP (left, ρ=-0.33, p=0.031; right, ρ=-0.42, p=0.004); and CDRS-R and SICI-4 (right, ρ=-0.30, p=0.042). Among healthy control participants, additional significant negative correlations were observed between QIDS-A17-SR and right ICF-10; QIDS-A17-SR and right ICF-15; and QIDS-A17-SR and left ICF-20. Among depressed participants, significant negative correlations were observed between QIDS-A17-SR and bilateral CSP; CDRS-R and bilateral ICF-10; CDRS-R and bilateral ICF-15; QIDS-A17-SR and left ICF-10; and QIDS-A17-SR and bilateral ICF-15. Limitations Small sample, potential developmental/age- and sex-related effects. Conclusions These preliminary results provide evidence for a relationship between depression severity and dysfunction in GABAergic and glutamatergic cortical processes in a pediatric population.

AB - Objectives Neurophysiologic correlates of depression severity potentially have great utility in diagnosis and treatment planning. Transcranial magnetic stimulation (TMS) measures of cortical inhibition and excitability have shown promise as biomarkers in psychiatry, but no prior work has examined correlates of illness severity in pediatric mood disorders. This study sought to examine the relationship between depression severity and TMS measures of cortical inhibition and excitability in children and adolescents. Methods Twenty-four depressed and 22 healthy control youth underwent TMS testing (cortical silent period [CSP], short-interval intracortical inhibition at 2-ms and 4-ms interstimulus intervals (ISIs) [SICI-2,-4], resting motor threshold [RMT] and intracortical facilitation at 10-, 15-, and 20-ms ISIs [ICF-10,-15,-20]). Symptom severity was assessed with the Quick Inventory of Depressive Symptomatology (QIDS-A17-SR) and the Children's Depression Rating Scale-Revised (CDRS-R). Results In the overall sample, the following significant negative correlations were observed: CDRS-R and CSP (right hemisphere, ρ=-0.35, p=0.021); QIDS-A17-SR and CSP (left, ρ=-0.33, p=0.031; right, ρ=-0.42, p=0.004); and CDRS-R and SICI-4 (right, ρ=-0.30, p=0.042). Among healthy control participants, additional significant negative correlations were observed between QIDS-A17-SR and right ICF-10; QIDS-A17-SR and right ICF-15; and QIDS-A17-SR and left ICF-20. Among depressed participants, significant negative correlations were observed between QIDS-A17-SR and bilateral CSP; CDRS-R and bilateral ICF-10; CDRS-R and bilateral ICF-15; QIDS-A17-SR and left ICF-10; and QIDS-A17-SR and bilateral ICF-15. Limitations Small sample, potential developmental/age- and sex-related effects. Conclusions These preliminary results provide evidence for a relationship between depression severity and dysfunction in GABAergic and glutamatergic cortical processes in a pediatric population.

KW - Child and adolescent depression

KW - Cortical inhibition

KW - GABA

KW - Glutamate

KW - Intracortical facilitation

KW - Transcranial magnetic stimulation

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JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

ER -

Cortical inhibitory and excitatory correlates of depression severity in children and adolescents

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Bibliographical note

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