Neurodevelopmental disorders and obesity: Potential links.

Abstract

Wentz et al. (1) sought to investigate the prevalence of neurodevelopmental disorders, including attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder (DCD), in children recruited from a university outpatient clinic specializing in severe obesity. The authors also compared body mass index (BMI) and metabolic profile among the 76 children recruited. The results indicated that one-third of children (31.6%) recruited had at least one neurodevelopmental disorder. Girls diagnosed with ADHD/ASD had a higher BMI index compared with girls with no neurodevelopmental disorder. Moreover, nearly one-fifth of parents screened positive for ADHD which could complicate adherence to treatment regimens in obesity units. Interestingly, the finding that neurodevelopmental disorders are “highly over-represented” in children with obesity coincides with recent research implicating a role for air pollution in the etiology of these disorders. Fluegge (2) recently published a review outlining the possible role of environmental exposure to the air pollutant nitrous oxide (N2O) in the etiology of a range of neurodevelopmental disorders, including ADHD and ASD. The review of the N2O toxicity literature posits several mechanisms that may be responsible for this effect. First, subanalgesic N2O targets the reversible inhibition of the α7 nicotinic acetylcholine receptor (α7nAChR), a receptor widely found in the CNS and involved in long-term memory as well as food intake behavior. The α7nAChR has been shown to be downregulated in the subcutaneous adipose tissue and isolated mature adipocytes of human subjects with obesity, and a lifestyle intervention not only rescued this downregulation but also facilitated weight loss in these subjects (3). N2O is also an NMDA receptor antagonist, and central activation of the NMDA receptor may exert potent metabolic effects through a brain-liver axis to reduce glucose production (4), suggesting that chronic exposure to environmental N2O may challenge an endogenous protective mechanism against metabolic dysfunction. Furthermore, low-dose N2O exposure is also characterized by the endogenous release of the opioid peptide dynorphin, which acts upon its cognate opioid receptor, the kappa opioid receptor (KOR). Interestingly, Czyzyk et al. (5) reported that central activation of KOR may play an integral role in the metabolic adaptation to a high-energy diet in mice. KOR-knockout mice experienced improved glycemic control and a reduction in triglyceride synthesis in the liver, while wild-type mice experienced increases in body weight. The authors concluded that KOR activation may play a permissive role in the development of an obesogenic phenotype under conditions of a high-energy diet. Importantly, these endogenous pathways may have direct roles in facilitating adverse psychiatric and metabolic outcomes, potentially linking the finding that neurodevelopmental disorders are “highly over-represented” in obesity. Parents who are affected by similar conditions may lack the discipline to enforce strict dietary controls in their children with obesity, and this may further compound obesogenic risk profiles. Therefore, more attention should be paid to environmental air pollutants, like N2O, that may play a role in onset of neurodevelopmental disorders and accompanying metabolic co-morbid conditions, like obesity.