Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression

Treatment-resistant depression (TRD) is a serious problem in adolescents. Development and optimization of novel interventions for these youth will require a deeper knowledge of the neurobiology of depression. A well-established phenomenon of depression is an attention bias toward negativity and away...

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Main Authors: Michelle Thai, Zeynep Başgöze, Bonnie Klimes-Dougan, Bryon A. Mueller, Mark Fiecas, Kelvin O. Lim, C. Sophia Albott, Kathryn R. Cullen
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-08-01
Series:Frontiers in Psychiatry
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fpsyt.2020.00820/full
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author Michelle Thai
Zeynep Başgöze
Bonnie Klimes-Dougan
Bryon A. Mueller
Mark Fiecas
Kelvin O. Lim
C. Sophia Albott
Kathryn R. Cullen
author_facet Michelle Thai
Zeynep Başgöze
Bonnie Klimes-Dougan
Bryon A. Mueller
Mark Fiecas
Kelvin O. Lim
C. Sophia Albott
Kathryn R. Cullen
author_sort Michelle Thai
collection DOAJ
description Treatment-resistant depression (TRD) is a serious problem in adolescents. Development and optimization of novel interventions for these youth will require a deeper knowledge of the neurobiology of depression. A well-established phenomenon of depression is an attention bias toward negativity and away from positivity that is evidenced behaviorally and neurally, but it is unclear how symptom reduction is related to changes to this bias. Neurobiological research using a treatment probe has promise to help discover the neural changes that accompany symptom improvement. Ketamine has utility for such research because of its known rapid and strong antidepressant effects in the context of TRD. Our previous study of six open-label ketamine infusions in 11 adolescents with TRD showed variable response, ranging from full remission, partial response, non-response, or clinical worsening. In this study, we examined the performance of these participants on Word Face Stroop (WFS) fMRI task where they indicated the valence of affective words superimposed onto either congruent or incongruent emotional faces before and after the ketamine infusions. Participants also completed a clinical assessment (including measurement of depression symptomology and anhedonia/pleasure) before and after the ketamine infusions. Following ketamine treatment, better WFS performance correlated with self-reported decreased depressive symptoms and increased pleasure. Analyses of corticolimbic, corticostriatal and default mode (DMN) networks showed that across networks, decreased activation during all conditions (congruent negative, congruent positive, incongruent negative, and incongruent positive) correlated with decreases in depressive symptoms and with increases in pleasure. These findings suggest that in adolescents with TRD, clinical improvement may require an attenuation of the negativity bias and re-tuning of these three critical neural networks to attenuate DMN and limbic regions activation and allow more efficient recruitment of the reward network. Lower activation across conditions may facilitate shifting across different salient emotional stimuli rather than getting trapped in downward negative spirals.
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spelling doaj.art-870b101576424105b3eac20bd74edf0b2022-12-22T00:50:31ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402020-08-011110.3389/fpsyt.2020.00820539003Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant DepressionMichelle Thai0Zeynep Başgöze1Bonnie Klimes-Dougan2Bryon A. Mueller3Mark Fiecas4Kelvin O. Lim5C. Sophia Albott6Kathryn R. Cullen7Psychology Department, College of Liberal Arts, University of Minnesota, Twin Cities, MN, United StatesDepartment of Psychiatry and Behavioral Sciences, School of Medicine, University of Minnesota, Twin Cities, MN, United StatesPsychology Department, College of Liberal Arts, University of Minnesota, Twin Cities, MN, United StatesDepartment of Psychiatry and Behavioral Sciences, School of Medicine, University of Minnesota, Twin Cities, MN, United StatesBiostatistics Department, School of Public Health, University of Minnesota, Twin Cities, MN, United StatesDepartment of Psychiatry and Behavioral Sciences, School of Medicine, University of Minnesota, Twin Cities, MN, United StatesDepartment of Psychiatry and Behavioral Sciences, School of Medicine, University of Minnesota, Twin Cities, MN, United StatesDepartment of Psychiatry and Behavioral Sciences, School of Medicine, University of Minnesota, Twin Cities, MN, United StatesTreatment-resistant depression (TRD) is a serious problem in adolescents. Development and optimization of novel interventions for these youth will require a deeper knowledge of the neurobiology of depression. A well-established phenomenon of depression is an attention bias toward negativity and away from positivity that is evidenced behaviorally and neurally, but it is unclear how symptom reduction is related to changes to this bias. Neurobiological research using a treatment probe has promise to help discover the neural changes that accompany symptom improvement. Ketamine has utility for such research because of its known rapid and strong antidepressant effects in the context of TRD. Our previous study of six open-label ketamine infusions in 11 adolescents with TRD showed variable response, ranging from full remission, partial response, non-response, or clinical worsening. In this study, we examined the performance of these participants on Word Face Stroop (WFS) fMRI task where they indicated the valence of affective words superimposed onto either congruent or incongruent emotional faces before and after the ketamine infusions. Participants also completed a clinical assessment (including measurement of depression symptomology and anhedonia/pleasure) before and after the ketamine infusions. Following ketamine treatment, better WFS performance correlated with self-reported decreased depressive symptoms and increased pleasure. Analyses of corticolimbic, corticostriatal and default mode (DMN) networks showed that across networks, decreased activation during all conditions (congruent negative, congruent positive, incongruent negative, and incongruent positive) correlated with decreases in depressive symptoms and with increases in pleasure. These findings suggest that in adolescents with TRD, clinical improvement may require an attenuation of the negativity bias and re-tuning of these three critical neural networks to attenuate DMN and limbic regions activation and allow more efficient recruitment of the reward network. Lower activation across conditions may facilitate shifting across different salient emotional stimuli rather than getting trapped in downward negative spirals.https://www.frontiersin.org/article/10.3389/fpsyt.2020.00820/fulldepressionadolescenceketaminefMRIaffective conflicttreatment resistance
spellingShingle Michelle Thai
Zeynep Başgöze
Bonnie Klimes-Dougan
Bryon A. Mueller
Mark Fiecas
Kelvin O. Lim
C. Sophia Albott
Kathryn R. Cullen
Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression
Frontiers in Psychiatry
depression
adolescence
ketamine
fMRI
affective conflict
treatment resistance
title Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression
title_full Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression
title_fullStr Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression
title_full_unstemmed Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression
title_short Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression
title_sort neural and behavioral correlates of clinical improvement to ketamine in adolescents with treatment resistant depression
topic depression
adolescence
ketamine
fMRI
affective conflict
treatment resistance
url https://www.frontiersin.org/article/10.3389/fpsyt.2020.00820/full
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