TY - JOUR
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.
KW - methylphenidate
KW - disruptive behavior disorders
KW - functional magnetic resonance imaging
KW - amygdala
KW - ventromedial prefrontal cortex
U2 - 10.1016/j.jaac.2018.06.026
DO - 10.1016/j.jaac.2018.06.026
M3 - Article
C2 - 30522739
SN - 0890-8567
VL - 57
SP - 934
EP - 943
JO - Journal of the American Academy of Child and Adolescent Psychiatry
JF - Journal of the American Academy of Child and Adolescent Psychiatry
IS - 12
ER -