Abstract

Adults with autism spectrum disorder (ASD) are frequently prescribed selective serotonin reuptake inhibitors (SSRIs). However, there is limited evidence to support this practice. Therefore, it is crucial to understand the impact of SSRIs on brain function abnormalities in ASD. It has been suggested that some core symptoms in ASD are underpinned by deficits in executive functioning (EF). Hence, we investigated the role of the SSRI citalopram on EF networks in 19 right-handed adult males with ASD and 19 controls who did not differ in gender, age, IQ or handedness. We performed pharmacological functional magnetic resonance imaging to compare brain activity during two EF tasks (of response inhibition and sustained attention) after an acute dose of 20 mg citalopram or placebo using a randomised, double-blind, crossover design. Under placebo condition, individuals with ASD had abnormal brain activation in response inhibition regions, including inferior frontal, precentral and postcentral cortices and cerebellum. During sustained attention, individuals with ASD had abnormal brain activation in middle temporal cortex and (pre)cuneus. After citalopram administration, abnormal brain activation in inferior frontal cortex was ‘normalised’ and most of the other brain functional differences were ‘abolished’. Also, within ASD, the degree of responsivity in inferior frontal and postcentral cortices to SSRI challenge was related to plasma serotonin levels. These findings suggest that citalopram can ‘normalise’ atypical brain activation during EF in ASD. Future trials should investigate whether this shift in the biology of ASD is maintained after prolonged citalopram treatment, and if peripheral measures of serotonin predict treatment response.

Details

Title
Modulation of brain activation during executive functioning in autism with citalopram
Author
Wichers, Robert H 1   VIAFID ORCID Logo  ; Findon, James L 2 ; Jelsma, Auke 3 ; Giampietro, Vincent 4   VIAFID ORCID Logo  ; Stoencheva, Vladimira 5 ; Robertson, Dene M 1 ; Murphy, Clodagh M 1   VIAFID ORCID Logo  ; McAlonan, Grainne 1 ; Ecker, Christine 6 ; Rubia, Katya 7 ; Murphy, Declan G M 1   VIAFID ORCID Logo  ; Daly, Eileen M 2 

1  Department of Forensic and Neurodevelopmental Sciences, The Sackler Centre for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; Behavioural and Developmental Psychiatry Clinical Academic Group, South London and Maudsley NHS Trust, London, UK 
2  Department of Forensic and Neurodevelopmental Sciences, The Sackler Centre for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK 
3  Department of Forensic and Neurodevelopmental Sciences, The Sackler Centre for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; VU University Medical Center, Amsterdam, The Netherlands 
4  Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK 
5  Behavioural and Developmental Psychiatry Clinical Academic Group, South London and Maudsley NHS Trust, London, UK 
6  Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt am Main, Goethe-University Frankfurt am Main, Frankfurt, Germany 
7  Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK 
Pages
1-11
Publication year
2019
Publication date
Nov 2019
Publisher
Nature Publishing Group
e-ISSN
21583188
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41398-019-0641-0
ProQuest document ID
2313761172
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.