Differentiated approach to the pharmacotherapy of autism spectrum disorders: biochemical aspects

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 very early developmental stages. Currently, there are no accepted pharmacological treatments for so-called core symptoms of ASD, such as social communication disorders and restricted and repetitive behavior patterns. The lack of knowledge about biological basis of ASD, the absence of clinically significant biochemical parameters reflecting abnormalities in signaling molecular cascades controlling the nervous system development and functioning, and the lack of methods for selection of clinically and biologically homogeneous subgroups are considered among the causes for the failure of clinical trials of ASD pharmacotherapy. This review considers the possibilities of applying a differentiated clinical and biological approach to the targeted search for ASD pharmacotherapy with an emphasis on biochemical markers associated with ASD and attempts to stratify patients by biochemical parameters. The use of approach such as “target-oriented therapy and assessment of the status of the target 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 the identification of biochemical parameters for the identification of distinct subgroups among ASD patients requires research on large samples reflecting the clinical and biological diversity of patients with ASD, and the use of unified approaches for such studies. An integrated approach, including clinical observation, clinical-psychological assessment of patient behavior, study of anamnesis and description of individual molecular profiles should become a new strategy for stratifying and subgrouping patients with ASD for clinical pharmacotherapeutic trials, as well as for evaluating its efficiency.