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Review
. 2025 Oct 30;18(11):1644.
doi: 10.3390/ph18111644.

Review of Autism Spectrum Disorder (ASD): Epidemiology, Aetiology, Pathology, and Pharmacological Treatment

Mashal Aljead  1 , Aya Qashta  2 , Zahraa Jalal  1 , Alan M Jones  1
Affiliations
Review

Review of Autism Spectrum Disorder (ASD): Epidemiology, Aetiology, Pathology, and Pharmacological Treatment

Mashal Aljead et al. Pharmaceuticals (Basel). .

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by challenges in social and communication skills and restricted interests. It is associated with behavioural symptoms and/or comorbidities (e.g., attention deficit hyperactivity disorder (ADHD)). Developing effective treatments for ASD remains a challenge because its pathophysiology is not fully understood. Multiple treatment options are used for ASD with varying levels of effectiveness and safety profiles. Atypical antipsychotics (AAPs), particularly risperidone and aripiprazole, provide superiority over other drug classes of pharmacological interventions. However, they are linked to adverse drug reactions (ADRs), specifically metabolic and endocrine ADRs. These ADRs may lead to chronic diseases such as diabetes and cardiovascular conditions, adding strain to healthcare systems beyond the original treatment of ASD. This narrative review enhances our understanding of ASD and highlights a gap in current knowledge about the evaluation of the effectiveness and safety of pharmacological treatments, especially AAPs for ASD in paediatric patients.

Keywords: ADHD medications; aetiology; atypical antipsychotics (AAPs); autism spectrum disorder (ASD); diagnosis; mood stabilizers; pathology; prevalence; selective serotonin reuptake inhibitors (SSRIs).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Timeline of ASD diagnostic tools development. Abbreviations: ASD: (Autism Spectrum Disorder, DSM-III: (Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition), DSM-IV: (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition), DSM-5: (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition), ICD-10: (International Classification of Diseases, 10th Edition), ICD-11: (International Classification of Diseases, 11th Edition) and PDD: (Pervasive Developmental Disorder). Created in BioRender. ALJEAD, M. (2025) https://BioRender.com/mq25uge.
Figure 2
Figure 2
Overview of the aetiology and pathology of ASD. Abbreviations: ARID1B: AT-Rich Interaction Domain 1B, ASD: Autism Spectrum Disorder, GABA: γ-Aminobutyric Acid, IL-6: Interleukin-6, MAPKAPK3: Mitogen-Activated Protein Kinase-Activated Protein Kinase 3, MRPL33: Mitochondrial Ribosomal Protein L33, mTORC1: Mechanistic Target of the Rapamycin Complex 1, PKA: Protein Kinase A, and TNF-α: Tumour Necrosis Factor-alpha. Created in BioRender. ALJEAD, M. (2025) https://BioRender.com/1kt2pyl.
Figure 3
Figure 3
The illustration of the mechanism of action for SSRI. Abbreviations: 5-HT: Serotonin receptors, SSRI: Selective Serotonin Reuptake Inhibitors. Created in BioRender. ALJEAD, M. (2025) https://BioRender.com/fd2gzp8.
Figure 4
Figure 4
Chemical structures of the SSRIs.
Figure 5
Figure 5
Chemical structures of ADHD medications (a) stimulants and (b) non-stimulants (atomoxetine and α2 agonist (guanfacine and clonidine).
Figure 6
Figure 6
Mechanism of action of ADHD medications. Abbreviation: L-DOPA: Levodopa, VMAT-2: Vesicular Monoamine Transporter 2, MAO: Monoamine Oxidase, NE: Norepinephrine, 5-HT: Serotonin (5-Hydroxytryptamine). Created in BioRender. ALJEAD, M. (2025) https://BioRender.com/uzq6p3e.
Figure 7
Figure 7
Mechanism of action of mood stabilizers (antiepileptic drugs). Abbreviation: GABA: Gamma-Aminobutyric Acid, SV2A: Synaptic Vesicle Protein 2A, GAT: GABA Transporter, GABA-T: Gamma-Aminobutyric Acid Transaminase. Created in BioRender. ALJEAD, M. (2025) https://BioRender.com/4olthvw.
Figure 8
Figure 8
Mechanism of action of lithium carbonate. Abbreviation: PI3: phosphatidylinositol-3, Akt: protein kinase B, CREB: response element-binding protein, BDNF: brain-derived neurotrophic factor, GSK3β: Glycogen synthase kinase-3. Created in BioRender. ALJEAD, M. (2025) https://BioRender.com/c19f25e.
Figure 9
Figure 9
Chemical structures of AAPs that are used for treating ASD in children and adolescents.
Figure 10
Figure 10
Proposed mechanisms of atypical antipsychotics (AAPs) in ASD management. Abbreviation: D2: Dopamine, 5-HT2A: Serotonin (2A subtype), 5-HT1A: Serotonin (1A subtype), H1: Histamine, α1: Alpha-1 adrenergic, α2: Alpha-2 adrenergic, M1: Muscarinic acetylcholine (M1 subtype). Created in BioRender. ALJEAD, M. (2025) https://BioRender.com/5id5ng1.
See this image and copyright information in PMC

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