title: Does environmental exposure to the greenhouse gas, N2O, contribute to etiological factors in neurodevelopmental disorders? A mini-review of the evidence.
abstract: BACKGROUND
  Neurodevelopmental disorders are increasing in prevalence worldwide. Previous work suggests that exposure to the environmental air pollutant and greenhouse gas - nitrous oxide (N2O) - may be an etiological factor in neurodevelopmental disorders through the targeting of several neural correlates.
  
  
  METHODS
  While a number of recent systematic reviews have addressed the role of general anesthesia in the surgical setting and neurodevelopmental outcomes, a narrative mini-review was conducted to first define and characterize the relevant variables (i.e., N2O, attention-deficit hyperactivity disorder [ADHD] and autism spectrum disorders [ASD]) and their potential interactions into a coherent, hypothesis-generating work. The narrative mini-review merges basic principles in environmental science, anesthesiology, and psychiatry to more fully develop the novel hypotheses that neurodevelopmental impairment found in conditions like ADHD and ASD may be due to exposure to the increasing air pollutant, N2O.
  
  
  RESULTS
  The results of the present mini-review indicate that exposure to N2O, even at non-toxic doses, may modulate central neurotransmission and target many neural substrates directly implicated in neurodevelopmental disorders, including the glutamatergic, opioidergic, cholinergic, and dopaminergic systems. Epidemiological studies also indicate that early and repeated exposure to general anesthesia, including N2O, may contribute to later adverse neurodevelopmental outcomes in children.
  
  
  CONCLUSIONS
  The current evidence and subsequent hypotheses suggest that a renewed interest be taken in the toxicological assessment of environmental N2O exposure using validated biomarkers and psychiatric endpoints. Given the relevance of N2O as a greenhouse gas, societies may also wish to engage in a more robust monitoring and reporting of N2O levels in the environment for climactic benefit as well.
authors: Institute of Health and Environmental Research, Cleveland, OH 44118, USA. Electronic address: keithfluegge@gmail.com.
authors: Keith
authors: K
authors: Fluegge
mesh_terms: D000397:Air Pollution / Q000009:adverse effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000209:etiology; D000067877:Autism Spectrum Disorder / Q000139:chemically induced / Q000209:etiology; D004298:Dopamine / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D065886:Neurodevelopmental Disorders / Q000139:chemically induced*; D009609:Nitrous Oxide / Q000032:analysis / Q000633:toxicity*; D010121:Oxytocin / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism
chemical_list: D004967:Estrogens; C515653:OPRK1 protein, human; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D010121:Oxytocin; D009609:Nitrous Oxide; D004298:Dopamine
keywords: ADHD; Air pollution; Alpha 7 nicotinic acetylcholine receptor; Autism spectrum disorders; Dopamine; Dynorphin; Estrogen; Gastrointestinal; Glyphosate; Kappa opioid receptor; Maternal immune activation; Methionine synthase; NMDA receptor; Nitric oxide; Nitrogen fertilizers; Nitrous oxide; Ophthalmology; Optimal outcomes; Oxytocin; Thimerosal