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The effects of acute fluoxetine administration on temporal discounting in youth with ADHD

Published online by Cambridge University Press:  28 December 2015

C. O. Carlisi ,
K. Chantiluke ,
L. Norman ,
A. Christakou ,
N. Barrett ,
V. Giampietro ,
M. Brammer ,
A. Simmons  and
K. Rubia
C. O. Carlisi
Affiliation:
Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK
K. Chantiluke
Affiliation:
Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK
L. Norman
Affiliation:
Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK
A. Christakou
Affiliation:
Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK
N. Barrett
Affiliation:
South London and Maudsley NHS Trust, London, UK
V. Giampietro
Affiliation:
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK
M. Brammer
Affiliation:
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK
A. Simmons
Affiliation:
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK
K. Rubia*
Affiliation:
Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK
*
*Address for correspondence: Professor K. Rubia, Department of Child Psychiatry/MRC Center for Social, Genetic and Developmental Psychiatry (SGDP), PO46, Institute of Psychiatry, 16 De Crespigny Park, London, SE5 8AF, UK. (Email: [email protected])
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Abstract

Background

Serotonin is under-researched in attention deficit hyperactivity disorder (ADHD), despite accumulating evidence for its involvement in impulsiveness and the disorder. Serotonin further modulates temporal discounting (TD), which is typically abnormal in ADHD relative to healthy subjects, underpinned by reduced fronto-striato-limbic activation. This study tested whether a single acute dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine up-regulates and normalizes reduced fronto-striato-limbic neurofunctional activation in ADHD during TD.

Method

Twelve boys with ADHD were scanned twice in a placebo-controlled randomized design under either fluoxetine (between 8 and 15 mg, titrated to weight) or placebo while performing an individually adjusted functional magnetic resonance imaging TD task. Twenty healthy controls were scanned once. Brain activation was compared in patients under either drug condition and compared to controls to test for normalization effects.

Results

Repeated-measures whole-brain analysis in patients revealed significant up-regulation with fluoxetine in a large cluster comprising right inferior frontal cortex, insula, premotor cortex and basal ganglia, which further correlated trend-wise with TD performance, which was impaired relative to controls under placebo, but normalized under fluoxetine. Fluoxetine further down-regulated default mode areas of posterior cingulate and precuneus. Comparisons between controls and patients under either drug condition revealed normalization with fluoxetine in right premotor-insular-parietal activation, which was reduced in patients under placebo.

Conclusions

The findings show that a serotonin agonist up-regulates activation in typical ADHD dysfunctional areas in right inferior frontal cortex, insula and striatum as well as down-regulating default mode network regions in the context of impulsivity and TD.

Keywords

Attention deficit hyperactivity disorderbasal gangliadelay discountingfunctional magnetic resonance imagingimpulsivenessinsularight inferior frontal cortexselective serotonin reuptake inhibitorserotonintemporal discounting
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 6 , April 2016 , pp. 1197 - 1209
Copyright
Copyright © Cambridge University Press 2015 

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