Serotonin dysfunction in ADHD

Abstract

It is well accepted that attention deficit hyperactivity disorder (ADHD) is in part driven by dysfunction in the monoaminergic neurotransmitter system, but both the extent of dysfunction and possible therapeutic avenues presented by serotonergic neurotransmission is frequently overlooked. As such, we present key evidence for dysfunction in serotonergic transmission, as seen from biochemical, genetic and pharmacological perspectives. An overall deficit in serotonin availability is a common theme throughout the literature, thus this review aims to explore possible dysfunctions in the serotonin synthesis pathway which result in this reduced bioavailability, and investigate whether such dysfunctions could be loci of change in ADHD. We have identified several steps in transmission, namely the conversion of tryptophan to 5-hydroxytryptophan and its use of cofactor tetrahydrobiopterin, which could present promising avenues for development of novel clinical interventions for ADHD.

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Item Type:	Article
Authors/Creators:	Jackson, E.F. Riley, T.B. Overton, P.G. https://orcid.org/0000-0003-4334-261X
Copyright, Publisher and Additional Information:	© 2025 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Keywords:	Attention deficit hyperactivity disorder; serotonin; tryptophan; kynurenine; 5-hydroxytryptophan
Dates:	Submitted: 21 December 2024 Accepted: 4 April 2025 Published (online): 22 April 2025 Published: 22 April 2025
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Science (Sheffield) > Department of Psychology (Sheffield)
Depositing User:	Symplectic Sheffield
Date Deposited:	14 Apr 2025 14:31
Last Modified:	29 Apr 2025 08:17
Status:	Published
Publisher:	BioMed Central
Refereed:	Yes
Identification Number:	10.1186/s11689-025-09610-y
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:225261

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Serotonin dysfunction in ADHD

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