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Review
. 2025 Apr 7;15(4):539.
doi: 10.3390/biom15040539.

Biogenic Amine Metabolism and Its Genetic Variations in Autism Spectrum Disorder: A Comprehensive Overview

Claudio Tabolacci  1 , Angela Caruso  1 , Martina Micai  1 , Giulia Galati  1 , Carla Lintas  2   3 , Maria Elena Pisanu  4 , Maria Luisa Scattoni  1
Affiliations
Review

Biogenic Amine Metabolism and Its Genetic Variations in Autism Spectrum Disorder: A Comprehensive Overview

Claudio Tabolacci et al. Biomolecules. .

Abstract

Autism spectrum disorder (ASD) is a genetically heterogeneous syndrome characterized by repetitive, restricted, and stereotyped behaviors, along with persistent difficulties with social interaction and communication. Despite its increasing prevalence globally, the underlying pathogenic mechanisms of this complex neurodevelopmental disorder remain poorly understood. Therefore, the identification of reliable biomarkers could play a crucial role in enabling early screening and more precise classification of ASD subtypes, offering valuable insights into its physiopathology and aiding the customization of treatment or early interventions. Biogenic amines, including serotonin, histamine, dopamine, epinephrine, norepinephrine, and polyamines, are a class of organic compounds mainly produced by the decarboxylation of amino acids. A substantial portion of the genetic variation observed in ASD has been linked to genes that are either directly or indirectly involved in the metabolism of biogenic amines. Their potential involvement in ASD has become an area of growing interest due to their pleiotropic activities in the central nervous system, where they act as both neurotransmitters and neuromodulators or hormones. This review examines the role of biogenic amines in ASD, with a particular focus on genetic alterations in the enzymes responsible for their synthesis and degradation.

Keywords: autism spectrum disorder; biogenic amines; metabolism; neurodevelopmental disorders.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Chemical structure of principal biogenic amines (BAs) discussed in the present review. Chemical structures are drawn using the Chemical Sketch online tool (https://www.rcsb.org/chemical-sketch; Accessed on 7 February 2025).
Figure 2
Figure 2
The biochemical pathway of serotonin (5-HT) synthesis and metabolism. L-tryptophan, the essential precursor of 5-HT, is the substrate of the enzyme tryptophan hydroxylase (TPH) that represents the rate-limiting step for 5-HT synthesis. BH4—tetrahydrobiopterin; SAM—S-adenosyl-methionine.
Figure 3
Figure 3
Schematic presentation of histamine synthesis and degradation.
Figure 4
Figure 4
The biochemical pathway of catecholamine synthesis and metabolism. FAD—flavin adenine dinucleotide; BH4—tetrahydrobiopterin; SAM—S-adenosyl-methionine.
Figure 5
Figure 5
Schematic representation of diamine and polyamine metabolism. SAM—S-adenosyl-methionine; dcSAM—decarboxylated S-adenosylmethionine.
See this image and copyright information in PMC

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