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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. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) signaling pathway is a central regulator of cell metabolism, growth, and survival in response to hormones, growth factors, nutrients, and stress-induced signals. In this review, we analyzed the studies on the molecular abnormalities of the mTOR-associated signaling cascades in autism spectrum disorders (ASDs) and outlined the prospects for the pathogenicity-targeting pharmacotherapeutic approaches to ASDs, in particular syndromic ASDs. Based on available experimental and clinical data, we suggest that very early detection of molecular abnormalities in the ASD risk groups can be facilitated by using peripheral blood platelets. Also, identification of the time window of critical dysregulations in the described pathways in the ASD risk groups might suggest further research directions leading to more efficacious pharmacotherapeutic interventions in ASDs. [ABSTRACT FROM AUTHOR]