Vasopressin in the Amelioration of Social Functioning in Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is a developmental disability described by diagnostic criteria that comprise deficits in social communication and the existence of repetitive, restricted patterns of behavior, interests, or activities that can last throughout life. Many preclinical studies show the importance of arginine vasopressin (AVP) physiology in social functioning in several mammalian species. Currently, there is a trend to investigate more specific pharmacological agents to improve social functioning in patients with ASD. Neurobiological systems that are crucial for social functioning are the most encouraging conceivable signaling pathways for ASD therapeutic discovery. The AVP signaling pathway is one of the most promising. The purpose of this commentary is to detail the evidence on the use of AVP as an agent that can improve social functioning. The pharmacologic aspects of the drug as well as its potential to ameliorate social functioning characteristics in human and animal studies are described in this manuscript. AVP, especially in its inhaled form, seems to be safe and beneficial in improving social functioning including in children with autism. Larger randomized studies are required to implement a long awaited safe and feasible treatment in people with a deficiency in social functioning.

Noise during mouthbrooding impairs maternal care behaviors and juvenile development and alters brain transcriptomes in the African cichlid fishAstatotilapia burtoni

“…Nonapeptides (e.g., isotocin, homologous to oxytocin, and vasotocin, homologous to vasopressin) have emerged as candidate therapeutic agents for some childhood psychopathologies because they mediate social recognition and play behaviors 76‐78 . There is robust clinical evidence that treatment with nonapeptides can ameliorate social functioning in neuro‐atypical adults 40,79 . Although not examined in detail here, these changes in gene expression could indicate that exposure to noise during development can change developmental trajectories related to physiology and sociality, possibly influencing future social behaviors as adults.…”

“…[76][77][78] There is robust clinical evidence that treatment with nonapeptides can ameliorate social functioning in neuro-atypical adults. 40,79 Although not examined in detail here, these changes in gene expression could indicate that exposure to noise during development can change developmental trajectories related to physiology and sociality, possibly influencing future social behaviors as adults.…”

Persistent autism-relevant phenotype produced by in utero and lactational exposure of female mice to the commercial PBDE mixture, DE-71

“…Since the promoter regions for genes of both oxytocin 137 and vasopressin systems 138 are susceptible to epigenetic modification 138 , these genes may be altered by global DNA methylation measured after developmental BDE-47 exposure 46, 139 . Our findings may have translational value since altered OXT and AVP mechanisms in humans have been implicated in ASD 140,141,142,143 .…”

“…Our findings may have translational value since altered OXT and AVP mechanisms in humans have been implicated in ASD 140,141,142,143 .…”

Drug REpurposing using AI/ML tools - for Rare Diseases (DREAM-RD): A case study with Fragile X Syndrome (FXS)

“…Therefore there is a high likelihood that one of these drugs could potentially be repurposed to treat ASD symptoms. A mechanistic link to FXS/autism is apparent for some drugs and a few examples are as follows: Chlorpropamide is an oral antihyperglycemic agent which is known to increase the secretion of vasopressin, which may have a positive impact on social functioning (28); Tazarotene is a retinoid compound approved for skin disorders, and through its action on the RAR family, could influence autistic phenotypes (29); Pioglitazone, a PPAR agonist has just recently been shown to improve behavioural deficits in FXS mice by limiting the excessive diacylglycerol signalling in the brain (30) and low dose Trifluoperazine treatment, acting via the PI3K/Akt pathways has been proposed as a potential therapeutic for FXS based on in silico analysis of gene expression data and studies in mice (31). The rationale for drugs belonging to certain drug classes such as immunomodulators and anti-infectives, can be explained on the basis of the link between autism, neuroimmune dysregulation and microbial dysbiosis (32).…”