Gasotransmitters and their influence on autism spectrum disorders - a systematic review

Gasotransmitters, including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H₂S), play an important role in normal physiological processes in the body, such as neurotransmission, synaptic plasticity, and neuroinflammation. Dysregulation of signaling pathways of gasotransmitters contributes to the pathophysiology of autism spectrum disorder (ASD), which is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors. This systematic review aims to identify the potential role of gasotransmitters in ASD pathophysiology and their correlation with ASD severity. Following PRISMA guidelines, we conducted a systematic review by searching PubMed and Google Scholar databases in May 2024. We included studies that investigated the role of NO, H₂S, and CO in ASD between 2000 and 2024. We extracted data on the type of gasotransmitters, the model of the study (human or animal model), in vivo or in vitro, and the main role of these gasotransmitters as a risk factor or protective factor obtained findings. Out of 81 published papers screened from the databases, 39 reports were assessed for eligibility. After excluding studies that mentioned NO and CO as environmental pollutants, short communication, editorial letters, narrative reviews, systematic reviews, and meta-analyses, 28 original articles satisfied the inclusion and exclusion criteria. Results indicate a correlation between gasotransmitters and ASD, which contributed to the severity of ASD and its symptoms. An increase in gasotransmitters causes additional complications for individuals with ASD and can be mentioned as a risk factor or biomarker for ASD, except H₂S. The link between these endogenous gaseous molecules and ASD remains unclear; this systematic review offers strong evidence of the significant correlation between gasotransmitters and autism spectrum disorder.