Effects of Methylphenidate During Fear Learning in Antisocial Adolescents: A Randomized Controlled fMRI Trial

Koen van Lith, Dick Johan Veltman, Moran Daniel Cohn, Louise Else Pape, Marieke Eleonora van den Akker-Nijdam, Amanda Wilhelmina Geertruida van Loon, Pierre Bet, Guido Alexander van Wingen, Wim van den Brink, Theo Doreleijers, Arne Popma

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVE: Although the neural underpinnings of antisocial behavior have been studied extensively, research on pharmacologic interventions targeting specific neural mechanisms remains sparse. Hypoactivity of the amygdala and ventromedial prefrontal cortex (vmPFC) has been reported in antisocial adolescents, which could account for deficits in fear learning (amygdala) and impairments in decision making (vmPFC), respectively. Limited clinical research suggests positive effects of methylphenidate, a dopamine agonist, on antisocial behavior in adolescents. Dopamine is a key neurotransmitter involved in amygdala and vmPFC functioning. The objective of this study was to investigate whether methylphenidate targets dysfunctions in these brain areas in adolescents with antisocial behavior.

METHOD: A group of 42 clinical referred male adolescents (14-17 years old) with a disruptive behavior disorder performed a fear learning/reversal paradigm in a randomized double-blinded placebo-controlled pharmacologic functional magnetic resonance imaging study. Participants with disruptive behavior disorder were randomized to receive a single dose of methylphenidate 0.3 to 0.4 mg/kg (n = 22) or placebo (n = 20) and were compared with 21 matched healthy controls not receiving medication.

RESULTS: In a region-of-interest analysis of functional magnetic resonance imaging data during fear learning, the placebo group showed hyporeactivity of the amygdala compared with healthy controls, whereas amygdala reactivity was normalized in the methylphenidate group. There were no group differences in vmPFC reactivity during fear reversal learning. Whole-brain analyses showed no group differences.

CONCLUSION: These findings suggest that methylphenidate is a promising pharmacologic intervention for youth antisocial behavior that could restore amygdala functioning.

CLINICAL TRIAL REGISTRATION INFORMATION: Fear Conditioning During Specific Conditions in Antisocial Adolescents: A Neuroimaging Study. http://www.trialregister.nl/trialreg/index.asp; NTR4088.

Original languageEnglish
Pages (from-to)934-943
Number of pages10
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume57
Issue number12
DOIs
Publication statusPublished - Dec 2018

Cite this

van Lith, Koen ; Veltman, Dick Johan ; Cohn, Moran Daniel ; Pape, Louise Else ; van den Akker-Nijdam, Marieke Eleonora ; van Loon, Amanda Wilhelmina Geertruida ; Bet, Pierre ; van Wingen, Guido Alexander ; van den Brink, Wim ; Doreleijers, Theo ; Popma, Arne. / Effects of Methylphenidate During Fear Learning in Antisocial Adolescents : A Randomized Controlled fMRI Trial. In: Journal of the American Academy of Child and Adolescent Psychiatry. 2018 ; Vol. 57, No. 12. pp. 934-943.
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title = "Effects of Methylphenidate During Fear Learning in Antisocial Adolescents: A Randomized Controlled fMRI Trial",
abstract = "OBJECTIVE: Although the neural underpinnings of antisocial behavior have been studied extensively, research on pharmacologic interventions targeting specific neural mechanisms remains sparse. Hypoactivity of the amygdala and ventromedial prefrontal cortex (vmPFC) has been reported in antisocial adolescents, which could account for deficits in fear learning (amygdala) and impairments in decision making (vmPFC), respectively. Limited clinical research suggests positive effects of methylphenidate, a dopamine agonist, on antisocial behavior in adolescents. Dopamine is a key neurotransmitter involved in amygdala and vmPFC functioning. The objective of this study was to investigate whether methylphenidate targets dysfunctions in these brain areas in adolescents with antisocial behavior.METHOD: A group of 42 clinical referred male adolescents (14-17 years old) with a disruptive behavior disorder performed a fear learning/reversal paradigm in a randomized double-blinded placebo-controlled pharmacologic functional magnetic resonance imaging study. Participants with disruptive behavior disorder were randomized to receive a single dose of methylphenidate 0.3 to 0.4 mg/kg (n = 22) or placebo (n = 20) and were compared with 21 matched healthy controls not receiving medication.RESULTS: In a region-of-interest analysis of functional magnetic resonance imaging data during fear learning, the placebo group showed hyporeactivity of the amygdala compared with healthy controls, whereas amygdala reactivity was normalized in the methylphenidate group. There were no group differences in vmPFC reactivity during fear reversal learning. Whole-brain analyses showed no group differences.CONCLUSION: These findings suggest that methylphenidate is a promising pharmacologic intervention for youth antisocial behavior that could restore amygdala functioning.CLINICAL TRIAL REGISTRATION INFORMATION: Fear Conditioning During Specific Conditions in Antisocial Adolescents: A Neuroimaging Study. http://www.trialregister.nl/trialreg/index.asp; NTR4088.",
author = "{van Lith}, Koen and Veltman, {Dick Johan} and Cohn, {Moran Daniel} and Pape, {Louise Else} and {van den Akker-Nijdam}, {Marieke Eleonora} and {van Loon}, {Amanda Wilhelmina Geertruida} and Pierre Bet and {van Wingen}, {Guido Alexander} and {van den Brink}, Wim and Theo Doreleijers and Arne Popma",
note = "Copyright {\circledC} 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.",
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van Lith, K, Veltman, DJ, Cohn, MD, Pape, LE, van den Akker-Nijdam, ME, van Loon, AWG, Bet, P, van Wingen, GA, van den Brink, W, Doreleijers, T & Popma, A 2018, 'Effects of Methylphenidate During Fear Learning in Antisocial Adolescents: A Randomized Controlled fMRI Trial' Journal of the American Academy of Child and Adolescent Psychiatry, vol. 57, no. 12, pp. 934-943. https://doi.org/10.1016/j.jaac.2018.06.026

Effects of Methylphenidate During Fear Learning in Antisocial Adolescents : A Randomized Controlled fMRI Trial. / van Lith, Koen; Veltman, Dick Johan; Cohn, Moran Daniel; Pape, Louise Else; van den Akker-Nijdam, Marieke Eleonora; van Loon, Amanda Wilhelmina Geertruida; Bet, Pierre; van Wingen, Guido Alexander; van den Brink, Wim; Doreleijers, Theo; Popma, Arne.

In: Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 57, No. 12, 12.2018, p. 934-943.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Effects of Methylphenidate During Fear Learning in Antisocial Adolescents

T2 - A Randomized Controlled fMRI Trial

AU - van Lith, Koen

AU - Veltman, Dick Johan

AU - Cohn, Moran Daniel

AU - Pape, Louise Else

AU - van den Akker-Nijdam, Marieke Eleonora

AU - van Loon, Amanda Wilhelmina Geertruida

AU - Bet, Pierre

AU - van Wingen, Guido Alexander

AU - van den Brink, Wim

AU - Doreleijers, Theo

AU - Popma, Arne

N1 - Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

PY - 2018/12

Y1 - 2018/12

N2 - OBJECTIVE: Although the neural underpinnings of antisocial behavior have been studied extensively, research on pharmacologic interventions targeting specific neural mechanisms remains sparse. Hypoactivity of the amygdala and ventromedial prefrontal cortex (vmPFC) has been reported in antisocial adolescents, which could account for deficits in fear learning (amygdala) and impairments in decision making (vmPFC), respectively. Limited clinical research suggests positive effects of methylphenidate, a dopamine agonist, on antisocial behavior in adolescents. Dopamine is a key neurotransmitter involved in amygdala and vmPFC functioning. The objective of this study was to investigate whether methylphenidate targets dysfunctions in these brain areas in adolescents with antisocial behavior.METHOD: A group of 42 clinical referred male adolescents (14-17 years old) with a disruptive behavior disorder performed a fear learning/reversal paradigm in a randomized double-blinded placebo-controlled pharmacologic functional magnetic resonance imaging study. Participants with disruptive behavior disorder were randomized to receive a single dose of methylphenidate 0.3 to 0.4 mg/kg (n = 22) or placebo (n = 20) and were compared with 21 matched healthy controls not receiving medication.RESULTS: In a region-of-interest analysis of functional magnetic resonance imaging data during fear learning, the placebo group showed hyporeactivity of the amygdala compared with healthy controls, whereas amygdala reactivity was normalized in the methylphenidate group. There were no group differences in vmPFC reactivity during fear reversal learning. Whole-brain analyses showed no group differences.CONCLUSION: These findings suggest that methylphenidate is a promising pharmacologic intervention for youth antisocial behavior that could restore amygdala functioning.CLINICAL TRIAL REGISTRATION INFORMATION: Fear Conditioning During Specific Conditions in Antisocial Adolescents: A Neuroimaging Study. http://www.trialregister.nl/trialreg/index.asp; NTR4088.

AB - OBJECTIVE: Although the neural underpinnings of antisocial behavior have been studied extensively, research on pharmacologic interventions targeting specific neural mechanisms remains sparse. Hypoactivity of the amygdala and ventromedial prefrontal cortex (vmPFC) has been reported in antisocial adolescents, which could account for deficits in fear learning (amygdala) and impairments in decision making (vmPFC), respectively. Limited clinical research suggests positive effects of methylphenidate, a dopamine agonist, on antisocial behavior in adolescents. Dopamine is a key neurotransmitter involved in amygdala and vmPFC functioning. The objective of this study was to investigate whether methylphenidate targets dysfunctions in these brain areas in adolescents with antisocial behavior.METHOD: A group of 42 clinical referred male adolescents (14-17 years old) with a disruptive behavior disorder performed a fear learning/reversal paradigm in a randomized double-blinded placebo-controlled pharmacologic functional magnetic resonance imaging study. Participants with disruptive behavior disorder were randomized to receive a single dose of methylphenidate 0.3 to 0.4 mg/kg (n = 22) or placebo (n = 20) and were compared with 21 matched healthy controls not receiving medication.RESULTS: In a region-of-interest analysis of functional magnetic resonance imaging data during fear learning, the placebo group showed hyporeactivity of the amygdala compared with healthy controls, whereas amygdala reactivity was normalized in the methylphenidate group. There were no group differences in vmPFC reactivity during fear reversal learning. Whole-brain analyses showed no group differences.CONCLUSION: These findings suggest that methylphenidate is a promising pharmacologic intervention for youth antisocial behavior that could restore amygdala functioning.CLINICAL TRIAL REGISTRATION INFORMATION: Fear Conditioning During Specific Conditions in Antisocial Adolescents: A Neuroimaging Study. http://www.trialregister.nl/trialreg/index.asp; NTR4088.

U2 - 10.1016/j.jaac.2018.06.026

DO - 10.1016/j.jaac.2018.06.026

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JO - Journal of the American Academy of Child and Adolescent Psychiatry

JF - Journal of the American Academy of Child and Adolescent Psychiatry

SN - 0890-8567

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ER -