Exploring pathological targets and advancing pharmacotherapy in autism spectrum disorder: Contributions of glial cells and heavy metals

Abstract

Autism spectrum disorder (ASD) is a globally recognized neurodevelopmental condition characterized by repetitive and restrictive behavior, persistent deficits in social interaction and communication, mental disturbances, etc., affecting approximately 1 in 100 children worldwide. A combination of genetic and environmental factors is involved in the etiopathogenesis of the disease, but specific biomarkers have not yet been identified. Due to the lack of clinical evidence, fluctuations in symptoms, and difficulties in in-vitro and in-vivo modeling, developing medications for ASD is quite difficult. Although several drugs are used to treat autism, only risperidone and aripiprazole have received FDA approval in the United States. Epidemiological studies have suggested that maternal exposure to valproic acid (VPA), acetaminophen, propionic acid, and metals, such as cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg), may contribute to the development of various neurodevelopmental disorders. Pathological targets directly implicated in the disease include excitatory-inhibitory (E/A) imbalance, hyperserotonemia, GSK-3 inhibition, and Akt pathway activation. However, while a combination of pharmacotherapy, behavioral, and nutritional/dietary interventions has been found to be the most effective conventional therapy to date, many patients have chosen to implement particular dietary supplements for reducing ASD symptoms. In this review, we briefly describe various pathological targets and their roles in the pathophysiology of ASD and treatment strategies, including some future research directions.