Oxidative Stress and Nitric Oxide in Autism Spectrum Disorder and Other Neuropsychiatric Disorders

CNS Neurol Disord Drug Targets. 2016;15(5):587-96. doi: 10.2174/1871527315666160413121751.


The etiology of autism spectrum disorder (ASD) remains unclear; however, the toxic environmental exposure to oxidative stress has been suggested to play an important role in its pathogenesis. A loss of balance between oxidative stress and antioxidant capacity produces an excess of reactive nitrogen species (RNS) such as nitric oxide (NO). Polyunsaturated fatty acids (PUFAs), particularly arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid, are closely related to NO and NO synthase. In the pathophysiology of ASD, NO is related to the activity of primary PUFAs. NO modulates short- and long-term synaptic plasticity and plays essential roles in the regulation of a wide range of physiological processes including neurotransmission. NO affects the function of reactive oxygen species (ROS) in the local cellular milieu, in which biological antioxidants are present. NO plays a double role in the organism showing both neuroprotective and neurotoxic effects. Redox imbalance leads to the activation of the neurotoxic pathway, suggesting crossroads for the neurotoxic or neuroprotective effects of NO. Furthermore, the dual role of NO could depend on the adaptive functions of the antioxidant capacity and oxidative stress-related ROS/RNS as the disease progresses. Increased concentrations of arachidonic acid promote neuronal survival, and the dysregulation of the NO system plays an important role in the pathophysiology of bipolar disorder and recurrent depressive disorders. Therefore, the NO system could provide useful drug targets for these diseases. NO and NO donors also show therapeutic potential for Alzheimer's disease and schizophrenia with refractory symptoms and cognitive dysfunction.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autism Spectrum Disorder / drug therapy
  • Autism Spectrum Disorder / metabolism*
  • Humans
  • Mental Disorders / drug therapy
  • Mental Disorders / metabolism*
  • Neurons / metabolism
  • Nitric Oxide / metabolism*
  • Oxidative Stress / physiology*


  • Nitric Oxide