Neurochemical correlates of behavioral treatment of pediatric trichotillomania.


Journal

Journal of affective disorders
ISSN: 1573-2517
Titre abrégé: J Affect Disord
Pays: Netherlands
ID NLM: 7906073

Informations de publication

Date de publication:
01 08 2020
Historique:
received: 20 11 2019
revised: 30 03 2020
accepted: 27 04 2020
entrez: 21 6 2020
pubmed: 21 6 2020
medline: 16 2 2021
Statut: ppublish

Résumé

Trichotillomania (TTM) is a chronic and impairing psychiatric disorder with suspected dysfunctional cortico-striato-thalamo-cortical (CSTC) circuit activity reflecting excitatory/inhibitory signaling imbalance. TTM neurochemistry is understudied, with no prior research using magnetic resonance spectroscopy (MRS). This pilot investigation examined associations between TTM diagnosis, symptom severity, and response to behavioral treatment with MRS neurometabolites glutamate (Glu) and γ-aminobutyric acid (GABA) in CSTC structures. Proton echo-planar spectroscopic imaging (PEPSI) MRS was acquired from bilateral pregenual anterior cingulate cortex (pACC), caudate, putamen, globus pallidus, thalamus, and proximal white matter in 10 unmedicated girls with TTM, ages 9-17 years, before and after treatment, and from 13 age- and sex-matched healthy controls. Nine of 10 TTM patients were treatment responders. Pretreatment mean Glu and GABA did not differ significantly between participants and controls. Pretreatment TTM symptoms were correlated with Glu in (left + right) pACC (r = 0.88, p = 0.02) and thalamus (r = 0.82, p = 0.012), and were negatively correlated with pACC GABA (r = -0.84, p = 0.034). Mean GABA in putamen increased 69% (baseline to post-treatment) (p = 0.027). Higher pretreatment Glu in caudate, putamen, globus pallidus, and thalamus predicted greater symptom decreases with treatment (all r < -0.6, p < 0.05); higher caudate GABA predicted less treatment-related symptom decline (r = 0.86, p = 0.014). Small sample, GABA quantified with spectral fitting rather than editing. Consistent with other neuroimaging, MRS reveals discrete CSTC chemical changes with effective behavior therapy, and possibly with TTM etiology. TTM symptoms relate to excess excitatory versus inhibitory signaling in pACC and thalamus; symptom improvement may reflect reduced excitatory drive of the CSTC direct-pathway activity.

Sections du résumé

BACKGROUND
Trichotillomania (TTM) is a chronic and impairing psychiatric disorder with suspected dysfunctional cortico-striato-thalamo-cortical (CSTC) circuit activity reflecting excitatory/inhibitory signaling imbalance. TTM neurochemistry is understudied, with no prior research using magnetic resonance spectroscopy (MRS). This pilot investigation examined associations between TTM diagnosis, symptom severity, and response to behavioral treatment with MRS neurometabolites glutamate (Glu) and γ-aminobutyric acid (GABA) in CSTC structures.
METHODS
Proton echo-planar spectroscopic imaging (PEPSI) MRS was acquired from bilateral pregenual anterior cingulate cortex (pACC), caudate, putamen, globus pallidus, thalamus, and proximal white matter in 10 unmedicated girls with TTM, ages 9-17 years, before and after treatment, and from 13 age- and sex-matched healthy controls.
RESULTS
Nine of 10 TTM patients were treatment responders. Pretreatment mean Glu and GABA did not differ significantly between participants and controls. Pretreatment TTM symptoms were correlated with Glu in (left + right) pACC (r = 0.88, p = 0.02) and thalamus (r = 0.82, p = 0.012), and were negatively correlated with pACC GABA (r = -0.84, p = 0.034). Mean GABA in putamen increased 69% (baseline to post-treatment) (p = 0.027). Higher pretreatment Glu in caudate, putamen, globus pallidus, and thalamus predicted greater symptom decreases with treatment (all r < -0.6, p < 0.05); higher caudate GABA predicted less treatment-related symptom decline (r = 0.86, p = 0.014).
LIMITATIONS
Small sample, GABA quantified with spectral fitting rather than editing.
CONCLUSION
Consistent with other neuroimaging, MRS reveals discrete CSTC chemical changes with effective behavior therapy, and possibly with TTM etiology. TTM symptoms relate to excess excitatory versus inhibitory signaling in pACC and thalamus; symptom improvement may reflect reduced excitatory drive of the CSTC direct-pathway activity.

Identifiants

pubmed: 32560953
pii: S0165-0327(19)33126-X
doi: 10.1016/j.jad.2020.04.061
pii:
doi:

Substances chimiques

Glutamic Acid 3KX376GY7L

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

552-561

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH081864
Pays : United States

Informations de copyright

Copyright © 2020. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Dr. Peris receives funding from the National Institutes of Mental Health (NIMH) and the TLC Foundation for Body Focused Repetitive Behavior and royalties from Oxford University Press. Dr. McCracken reports receiving consultant income from Roche, Octapharma, and GW Biosciences; research clinical trial contracts from Roche, Think Now, Inc, and NICHD; and payment for expert witness participation for Lannett Pharmaceuticals. Dr. Piacentini has received grant or research support from NIMH, the TLC Foundation for Body-focused Repetitive Behaviors, the Tourette Association of America, and Pfizer Pharmaceuticals through the Duke University Clinical Research Institute Network. He receives publication royalties from Guilford Press and Oxford University Press. He receives speaking honoraria and/or travel support from the Tourette Association of America, the International Obsessive Compulsive Disorder Foundation, and the TLC Foundation for Body-focused Repetitive Behaviors.

Auteurs

Tara S Peris (TS)

Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience at UCLA, Los Angeles, CA 90024, USA.

John Piacentini (J)

Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience at UCLA, Los Angeles, CA 90024, USA.

Allison Vreeland (A)

Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience at UCLA, Los Angeles, CA 90024, USA.

Giulia Salgari (G)

Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience at UCLA, Los Angeles, CA 90024, USA.

Jennifer G Levitt (JG)

Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience at UCLA, Los Angeles, CA 90024, USA.

Jeffrey R Alger (JR)

UCLA Departments of Neurology and Radiological Sciences, Los Angeles, CA 90024, USA.

Stefan Posse (S)

Departments of Electrical and Computer Engineering, Neurology, and Physics and Astronomy, University of New Mexico, Albuquerque, NM 87106, USA.

James T McCracken (JT)

Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience at UCLA, Los Angeles, CA 90024, USA.

Joseph O'Neill (J)

Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience at UCLA, Los Angeles, CA 90024, USA. Electronic address: joneill@mednet.ucla.edu.

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Classifications MeSH