Transcranial Magnetic Stimulation Markers of Antidepressant Treatment in Adolescents with Major Depressive Disorder

Deniz Doruk Camsari; Charles P. Lewis; Ayse Irem Sonmez; Aiswarya Laks Nandakumar; Marjorie A. Gresbrink; Zafiris J. Daskalakis; Paul E. Croarkin

doi:10.1093/ijnp/pyz021

Transcranial Magnetic Stimulation Markers of Antidepressant Treatment in Adolescents with Major Depressive Disorder

Deniz Doruk Camsari, Charles P. Lewis, Ayse Irem Sonmez, Aiswarya Laks Nandakumar, Marjorie A. Gresbrink, Zafiris J. Daskalakis, Paul E. Croarkin

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

12 Scopus citations

Abstract

Background: The goal of this study was to examine baseline transcranial magnetic stimulation measures of cortical inhibition and excitability in depressed patients and characterize their longitudinal posttreatment changes. Methods: Fifteen adolescents (age 13-17 years) with moderate to severe major depressive disorder and 22 healthy controls (age 9-17) underwent single- and paired-pulse transcranial magnetic stimulation and clinical assessments. Transcranial magnetic stimulation measures included short-interval intracortical inhibition (2 and 4 milliseconds), long-interval intracortical inhibition (100, 150, and 200 milliseconds), cortical silent period, and intracortical facilitation (10, 15, and 20 milliseconds). Ten participants with major depressive disorder initiated antidepressant treatment or had dose adjustments. These participants were reassessed after treatment. Depression symptom severity was measured with the Children's Depression Rating Scale, Revised. Robust regression modeling compared healthy and depressed adolescents at baseline. Relationships between changes in cortical inhibition and changes in depressive symptom severity were assessed in the depressed adolescents receiving antidepressant treatment. Results: Our results revealed that at baseline, short-interval intracortical inhibition-2 was significantly reduced (P_adj =. 01) in depressed participants, suggesting impaired cortical inhibition compared with healthy controls. At follow-up, improvement in Children's Depression Rating Scale, Revised scores correlated with improvement in short-interval intracortical inhibition-4 amplitude (greater inhibition) after antidepressant treatment (R² = 0.63; P =. 01). Conclusions: These results suggest that cortical inhibition measures may have promise as biomarkers in adolescents treated for depression.

Original language	English (US)
Article number	pyz021
Pages (from-to)	435-444
Number of pages	10
Journal	International Journal of Neuropsychopharmacology
Volume	22
Issue number	7
DOIs	https://doi.org/10.1093/ijnp/pyz021
State	Published - Jul 1 2019
Externally published	Yes

Bibliographical note

Funding Information:
P.E.C. has received research grant support from Pfizer, Inc, NIMH (K23 MH100266 and R01MH113700), 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 the primary investigator for a multicenter study funded by Neuronetics, Inc. He is a site primary investigator for a study funded by NeoSync, Inc. He has consulted for Procter and Gamble. In the last 5 years, Z.J.D. has received research and equipment in-kind support for an investigator-initiated study through Brainsway, Inc. and Magventure, Inc. His work was supported by the Ontario Mental Health Foundation (OMHF), the Canadian Institutes of Health Research (CIHR), the National Institutes of Mental Health (NIMH), and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. A.I.S., A.L.N., and M.A.G. have no financial disclosures.

Funding Information:
This research was supported by grants from the Brain and Behavior Research Foundation (Young Investigator Award 20883), the National Institute of Mental Health (K23 MH100266 and R01MH113700). This publication was also made possible by the Mayo Clinic Clinical Translational Science Award (CTSA) through grant number UL1TR002377 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
D.D.C. receives research support from the Mayo Clinic Foundation Departmental Small Grant Program. C.P.L. receives research support from the Brain and Behavior Research Foundation and the Mayo Clinic Foundation Departmental Small Grant Program and is a site investigator for a multicenter studies funded by Neuronetics, Inc and NeoSync, Inc.

Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of CINP.

Keywords

adolescent
cortical inhibition
mood disorders
paired-pulse transcranial magnetic stimulation
short-interval intracortical inhibition

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10.1093/ijnp/pyz021

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@article{44198405d4274cbaadd2a44bce235f57,

title = "Transcranial Magnetic Stimulation Markers of Antidepressant Treatment in Adolescents with Major Depressive Disorder",

abstract = "Background: The goal of this study was to examine baseline transcranial magnetic stimulation measures of cortical inhibition and excitability in depressed patients and characterize their longitudinal posttreatment changes. Methods: Fifteen adolescents (age 13-17 years) with moderate to severe major depressive disorder and 22 healthy controls (age 9-17) underwent single- and paired-pulse transcranial magnetic stimulation and clinical assessments. Transcranial magnetic stimulation measures included short-interval intracortical inhibition (2 and 4 milliseconds), long-interval intracortical inhibition (100, 150, and 200 milliseconds), cortical silent period, and intracortical facilitation (10, 15, and 20 milliseconds). Ten participants with major depressive disorder initiated antidepressant treatment or had dose adjustments. These participants were reassessed after treatment. Depression symptom severity was measured with the Children's Depression Rating Scale, Revised. Robust regression modeling compared healthy and depressed adolescents at baseline. Relationships between changes in cortical inhibition and changes in depressive symptom severity were assessed in the depressed adolescents receiving antidepressant treatment. Results: Our results revealed that at baseline, short-interval intracortical inhibition-2 was significantly reduced (Padj =. 01) in depressed participants, suggesting impaired cortical inhibition compared with healthy controls. At follow-up, improvement in Children's Depression Rating Scale, Revised scores correlated with improvement in short-interval intracortical inhibition-4 amplitude (greater inhibition) after antidepressant treatment (R2 = 0.63; P =. 01). Conclusions: These results suggest that cortical inhibition measures may have promise as biomarkers in adolescents treated for depression.",

keywords = "adolescent, cortical inhibition, mood disorders, paired-pulse transcranial magnetic stimulation, short-interval intracortical inhibition",

author = "{Doruk Camsari}, Deniz and Lewis, {Charles P.} and Sonmez, {Ayse Irem} and Nandakumar, {Aiswarya Laks} and Gresbrink, {Marjorie A.} and Daskalakis, {Zafiris J.} and Croarkin, {Paul E.}",

note = "Funding Information: P.E.C. has received research grant support from Pfizer, Inc, NIMH (K23 MH100266 and R01MH113700), 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 the primary investigator for a multicenter study funded by Neuronetics, Inc. He is a site primary investigator for a study funded by NeoSync, Inc. He has consulted for Procter and Gamble. In the last 5 years, Z.J.D. has received research and equipment in-kind support for an investigator-initiated study through Brainsway, Inc. and Magventure, Inc. His work was supported by the Ontario Mental Health Foundation (OMHF), the Canadian Institutes of Health Research (CIHR), the National Institutes of Mental Health (NIMH), and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. A.I.S., A.L.N., and M.A.G. have no financial disclosures. Funding Information: This research was supported by grants from the Brain and Behavior Research Foundation (Young Investigator Award 20883), the National Institute of Mental Health (K23 MH100266 and R01MH113700). This publication was also made possible by the Mayo Clinic Clinical Translational Science Award (CTSA) through grant number UL1TR002377 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: D.D.C. receives research support from the Mayo Clinic Foundation Departmental Small Grant Program. C.P.L. receives research support from the Brain and Behavior Research Foundation and the Mayo Clinic Foundation Departmental Small Grant Program and is a site investigator for a multicenter studies funded by Neuronetics, Inc and NeoSync, Inc. Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press on behalf of CINP.",

year = "2019",

month = jul,

day = "1",

doi = "10.1093/ijnp/pyz021",

language = "English (US)",

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T1 - Transcranial Magnetic Stimulation Markers of Antidepressant Treatment in Adolescents with Major Depressive Disorder

AU - Doruk Camsari, Deniz

AU - Lewis, Charles P.

AU - Sonmez, Ayse Irem

AU - Nandakumar, Aiswarya Laks

AU - Gresbrink, Marjorie A.

AU - Daskalakis, Zafiris J.

AU - Croarkin, Paul E.

N1 - Funding Information: P.E.C. has received research grant support from Pfizer, Inc, NIMH (K23 MH100266 and R01MH113700), 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 the primary investigator for a multicenter study funded by Neuronetics, Inc. He is a site primary investigator for a study funded by NeoSync, Inc. He has consulted for Procter and Gamble. In the last 5 years, Z.J.D. has received research and equipment in-kind support for an investigator-initiated study through Brainsway, Inc. and Magventure, Inc. His work was supported by the Ontario Mental Health Foundation (OMHF), the Canadian Institutes of Health Research (CIHR), the National Institutes of Mental Health (NIMH), and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. A.I.S., A.L.N., and M.A.G. have no financial disclosures. Funding Information: This research was supported by grants from the Brain and Behavior Research Foundation (Young Investigator Award 20883), the National Institute of Mental Health (K23 MH100266 and R01MH113700). This publication was also made possible by the Mayo Clinic Clinical Translational Science Award (CTSA) through grant number UL1TR002377 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: D.D.C. receives research support from the Mayo Clinic Foundation Departmental Small Grant Program. C.P.L. receives research support from the Brain and Behavior Research Foundation and the Mayo Clinic Foundation Departmental Small Grant Program and is a site investigator for a multicenter studies funded by Neuronetics, Inc and NeoSync, Inc. Publisher Copyright: © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of CINP.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background: The goal of this study was to examine baseline transcranial magnetic stimulation measures of cortical inhibition and excitability in depressed patients and characterize their longitudinal posttreatment changes. Methods: Fifteen adolescents (age 13-17 years) with moderate to severe major depressive disorder and 22 healthy controls (age 9-17) underwent single- and paired-pulse transcranial magnetic stimulation and clinical assessments. Transcranial magnetic stimulation measures included short-interval intracortical inhibition (2 and 4 milliseconds), long-interval intracortical inhibition (100, 150, and 200 milliseconds), cortical silent period, and intracortical facilitation (10, 15, and 20 milliseconds). Ten participants with major depressive disorder initiated antidepressant treatment or had dose adjustments. These participants were reassessed after treatment. Depression symptom severity was measured with the Children's Depression Rating Scale, Revised. Robust regression modeling compared healthy and depressed adolescents at baseline. Relationships between changes in cortical inhibition and changes in depressive symptom severity were assessed in the depressed adolescents receiving antidepressant treatment. Results: Our results revealed that at baseline, short-interval intracortical inhibition-2 was significantly reduced (Padj =. 01) in depressed participants, suggesting impaired cortical inhibition compared with healthy controls. At follow-up, improvement in Children's Depression Rating Scale, Revised scores correlated with improvement in short-interval intracortical inhibition-4 amplitude (greater inhibition) after antidepressant treatment (R2 = 0.63; P =. 01). Conclusions: These results suggest that cortical inhibition measures may have promise as biomarkers in adolescents treated for depression.

AB - Background: The goal of this study was to examine baseline transcranial magnetic stimulation measures of cortical inhibition and excitability in depressed patients and characterize their longitudinal posttreatment changes. Methods: Fifteen adolescents (age 13-17 years) with moderate to severe major depressive disorder and 22 healthy controls (age 9-17) underwent single- and paired-pulse transcranial magnetic stimulation and clinical assessments. Transcranial magnetic stimulation measures included short-interval intracortical inhibition (2 and 4 milliseconds), long-interval intracortical inhibition (100, 150, and 200 milliseconds), cortical silent period, and intracortical facilitation (10, 15, and 20 milliseconds). Ten participants with major depressive disorder initiated antidepressant treatment or had dose adjustments. These participants were reassessed after treatment. Depression symptom severity was measured with the Children's Depression Rating Scale, Revised. Robust regression modeling compared healthy and depressed adolescents at baseline. Relationships between changes in cortical inhibition and changes in depressive symptom severity were assessed in the depressed adolescents receiving antidepressant treatment. Results: Our results revealed that at baseline, short-interval intracortical inhibition-2 was significantly reduced (Padj =. 01) in depressed participants, suggesting impaired cortical inhibition compared with healthy controls. At follow-up, improvement in Children's Depression Rating Scale, Revised scores correlated with improvement in short-interval intracortical inhibition-4 amplitude (greater inhibition) after antidepressant treatment (R2 = 0.63; P =. 01). Conclusions: These results suggest that cortical inhibition measures may have promise as biomarkers in adolescents treated for depression.

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KW - mood disorders

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Transcranial Magnetic Stimulation Markers of Antidepressant Treatment in Adolescents with Major Depressive Disorder

Abstract

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