Evidence for pretreatment LICI deficits among depressed children and adolescents with nonresponse to fluoxetine

Paul E Croarkin, Paul A. Nakonezny, Mustafa M. Husain, John D Port, Tabatha Melton, Betsy D. Kennard, Graham J. Emslie, F. Andrew Kozel, Zafiris J. Daskalakis

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background Research suggests that alterations in gamma-aminobutyric acid receptor functioning have a role in depression. Paired-pulse transcranial magnetic stimulation (TMS) paradigms are noninvasive measures of cortical inhibitory and excitatory circuits. Objective/hypothesis The present study examined pretreatment short-interval intracortical inhibition (SICI), long-interval cortical inhibition (LICI), and intracortical facilitation (ICF) in children and adolescents with major depressive disorder who were initiating fluoxetine treatment. The primary objective was to examine the relationship of these measures with subsequent treatment response. It was hypothesized that alterations in pretreatment GABA and glutamate mediated neurotransmission, would be associated with fluoxetine nonresponse. Methods Sixteen children and adolescents with major depressive disorder underwent paired-pulse TMS testing before beginning fluoxetine treatment. Response was prospectively characterized by scores of 1 or 2 on the Clinical Global Impression Scale and less than 40 on the Children's Depression Rating Scale-Revised after 6 weeks of fluoxetine treatment (20-40 mg/day). Results Eight patients responded to treatment. Least-squares mean LICI values were consistently higher bilaterally for treatment nonresponders. Higher LICI values indicate less inhibition and impaired GABAB functioning. There was no significant effect of treatment response on the measures of SICI and ICF. Conclusions Our findings suggest that deficits in pretreatment GABAB may be related to fluoxetine nonresponse in depressed youth. This is congruent with prior work demonstrating that GABAB interneurons have serotonergic input and antidepressants modulate GABAB receptors. These findings also show that TMS paradigms have utility in studying the neurophysiology and treatment of childhood mood disorders.

Original languageEnglish (US)
Pages (from-to)243-251
Number of pages9
JournalBrain Stimulation
Volume7
Issue number2
DOIs
StatePublished - 2014

Fingerprint

Fluoxetine
Transcranial Magnetic Stimulation
Major Depressive Disorder
Therapeutics
Depression
Neurophysiology
GABA Receptors
Inhibition (Psychology)
Interneurons
Least-Squares Analysis
Mood Disorders
Synaptic Transmission
gamma-Aminobutyric Acid
Antidepressive Agents
Glutamic Acid
Research

Keywords

  • Adolescents
  • Depression
  • Fluoxetine
  • GABA
  • LICI

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Biophysics

Cite this

Evidence for pretreatment LICI deficits among depressed children and adolescents with nonresponse to fluoxetine. / Croarkin, Paul E; Nakonezny, Paul A.; Husain, Mustafa M.; Port, John D; Melton, Tabatha; Kennard, Betsy D.; Emslie, Graham J.; Kozel, F. Andrew; Daskalakis, Zafiris J.

In: Brain Stimulation, Vol. 7, No. 2, 2014, p. 243-251.

Research output: Contribution to journalArticle

Croarkin, PE, Nakonezny, PA, Husain, MM, Port, JD, Melton, T, Kennard, BD, Emslie, GJ, Kozel, FA & Daskalakis, ZJ 2014, 'Evidence for pretreatment LICI deficits among depressed children and adolescents with nonresponse to fluoxetine', Brain Stimulation, vol. 7, no. 2, pp. 243-251. https://doi.org/10.1016/j.brs.2013.11.006
Croarkin, Paul E ; Nakonezny, Paul A. ; Husain, Mustafa M. ; Port, John D ; Melton, Tabatha ; Kennard, Betsy D. ; Emslie, Graham J. ; Kozel, F. Andrew ; Daskalakis, Zafiris J. / Evidence for pretreatment LICI deficits among depressed children and adolescents with nonresponse to fluoxetine. In: Brain Stimulation. 2014 ; Vol. 7, No. 2. pp. 243-251.
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abstract = "Background Research suggests that alterations in gamma-aminobutyric acid receptor functioning have a role in depression. Paired-pulse transcranial magnetic stimulation (TMS) paradigms are noninvasive measures of cortical inhibitory and excitatory circuits. Objective/hypothesis The present study examined pretreatment short-interval intracortical inhibition (SICI), long-interval cortical inhibition (LICI), and intracortical facilitation (ICF) in children and adolescents with major depressive disorder who were initiating fluoxetine treatment. The primary objective was to examine the relationship of these measures with subsequent treatment response. It was hypothesized that alterations in pretreatment GABA and glutamate mediated neurotransmission, would be associated with fluoxetine nonresponse. Methods Sixteen children and adolescents with major depressive disorder underwent paired-pulse TMS testing before beginning fluoxetine treatment. Response was prospectively characterized by scores of 1 or 2 on the Clinical Global Impression Scale and less than 40 on the Children's Depression Rating Scale-Revised after 6 weeks of fluoxetine treatment (20-40 mg/day). Results Eight patients responded to treatment. Least-squares mean LICI values were consistently higher bilaterally for treatment nonresponders. Higher LICI values indicate less inhibition and impaired GABAB functioning. There was no significant effect of treatment response on the measures of SICI and ICF. Conclusions Our findings suggest that deficits in pretreatment GABAB may be related to fluoxetine nonresponse in depressed youth. This is congruent with prior work demonstrating that GABAB interneurons have serotonergic input and antidepressants modulate GABAB receptors. These findings also show that TMS paradigms have utility in studying the neurophysiology and treatment of childhood mood disorders.",
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AU - Port, John D

AU - Melton, Tabatha

AU - Kennard, Betsy D.

AU - Emslie, Graham J.

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AB - Background Research suggests that alterations in gamma-aminobutyric acid receptor functioning have a role in depression. Paired-pulse transcranial magnetic stimulation (TMS) paradigms are noninvasive measures of cortical inhibitory and excitatory circuits. Objective/hypothesis The present study examined pretreatment short-interval intracortical inhibition (SICI), long-interval cortical inhibition (LICI), and intracortical facilitation (ICF) in children and adolescents with major depressive disorder who were initiating fluoxetine treatment. The primary objective was to examine the relationship of these measures with subsequent treatment response. It was hypothesized that alterations in pretreatment GABA and glutamate mediated neurotransmission, would be associated with fluoxetine nonresponse. Methods Sixteen children and adolescents with major depressive disorder underwent paired-pulse TMS testing before beginning fluoxetine treatment. Response was prospectively characterized by scores of 1 or 2 on the Clinical Global Impression Scale and less than 40 on the Children's Depression Rating Scale-Revised after 6 weeks of fluoxetine treatment (20-40 mg/day). Results Eight patients responded to treatment. Least-squares mean LICI values were consistently higher bilaterally for treatment nonresponders. Higher LICI values indicate less inhibition and impaired GABAB functioning. There was no significant effect of treatment response on the measures of SICI and ICF. Conclusions Our findings suggest that deficits in pretreatment GABAB may be related to fluoxetine nonresponse in depressed youth. This is congruent with prior work demonstrating that GABAB interneurons have serotonergic input and antidepressants modulate GABAB receptors. These findings also show that TMS paradigms have utility in studying the neurophysiology and treatment of childhood mood disorders.

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