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Differentiated Approach to Pharmacotherapy of Autism Spectrum Disorders: Biochemical Aspects

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Abstract

Autism Spectrum Disorders (ASD) are highly heterogeneous neurodevelopmental disorders caused by a complex interaction of numerous genetic and environmental factors and leading to deviations in the nervous system formation at the very early developmental stages. Currently, there are no accepted pharmacological treatments for the so-called core symptoms of ASD, such as social communication disorders and restricted and repetitive behavior patterns. Lack of knowledge about biological basis of ASD, absence of the clinically significant biochemical parameters reflecting abnormalities in the signaling cascades controlling the nervous system development and functioning, and lack of methods for selection of clinically and biologically homogeneous subgroups are considered as causes for the failure of clinical trials of ASD pharmacotherapy. This review considers the possibilities of applying differentiated clinical and biological approaches to the targeted search for ASD pharmacotherapy with emphasis on biochemical markers associated with ASD and attempts to stratify patients by biochemical parameters. The use of such approach as “the target-oriented therapy and assessment of the target status before and during the treatment to identify patients with a positive response to treatment” is discussed using the published results of clinical trials as examples. It is concluded that identification of biochemical parameters for selection of the distinct subgroups among the ASD patients requires research on large samples reflecting clinical and biological diversity of the patients with ASD, and use of unified approaches for such studies. An integrated approach, including clinical observation, clinical-psychological assessment of the patient behavior, study of medical history and description of individual molecular profiles should become a new strategy for stratifying patients with ASD for clinical pharmacotherapeutic trials, as well as for evaluating their efficiency.

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Abbreviations

5-HT:

serotonin

5-HTT:

serotonin transporter

Akt:

RAC-alpha serine/threonine protein kinase

ASD:

autistic spectrum disorders

AVP:

arginine–vasopressin

CARS:

childhood autism rating scale

CSF:

cerebrospinal fluid

E/I:

excitation/inhibition balance

FMRP:

fragile X mental retardation protein

FR:

folate receptor

FRab:

folate receptor autoantibodies

FXS:

fragile X syndrome

GABA:

gamma-aminobutyric acid

Glx:

total glutamine + glutamate concentration

MRS:

magnetic resonance spectroscopy

MTHF:

5-methyltetrahydrofolate

mTOR:

mammalian target of rapamycin protein kinase

OT:

oxytocin

OTR:

oxytocin receptor

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    Irina S. Boksha, Tatyana A. Prokhorova, Elena B. Tereshkina, Olga K. Savushkina & Gulnur Sh. Burbaeva

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  2. Tatyana A. Prokhorova
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  3. Elena B. Tereshkina
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  4. Olga K. Savushkina
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  5. Gulnur Sh. Burbaeva
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Contributions

I. S. Boksha, development of the concept and writing the article; T. A. Prokhorova, analysis of the literature and writing the article text; O. K. Savushkina, selection and analysis of the literature; E. B. Tereshkina, selection of the literature and editing the article text; G. Sh. Burbaeva, revision of the critically important intellectual content and final approval of the article.

Corresponding author

Correspondence to Irina S. Boksha.

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The authors declare no conflict of interest in financial or any other sphere. This article does not contain any studies with human participants or animals performed by any of the authors.

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Boksha, I.S., Prokhorova, T.A., Tereshkina, E.B. et al. Differentiated Approach to Pharmacotherapy of Autism Spectrum Disorders: Biochemical Aspects. Biochemistry Moscow 88, 303–318 (2023). https://doi.org/10.1134/S0006297923030021

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  • DOI: https://doi.org/10.1134/S0006297923030021

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