Background: Nitro-oxidative stress (NOS) has been implicated in the pathophysiology
of psychiatric disorders. The activity of the polymorphic antioxidant enzyme paraoxonase 1 (PON1)
is altered in diseases where NOS is involved. PON1 activity may be estimated using different substrates
some of which are influenced by PON1 polymorphisms.
Objectives: 1) to review the association between PON1 activities and psychiatric diseases using a
standardized PON1 substrate terminology in order to offer a state-of-the-art review; and 2) to review
the efficacy of different strategies (nutrition, drugs, lifestyle) to enhance PON1 activities.
Methods: The PubMed database was searched using the terms paraoxonase 1 and psychiatric diseases.
Moreover, the database was also searched for clinical trials investigating strategies to enhance
Results: The studies support decreased PON1 activity as determined using phenylacetate (i.e.,
arylesterase or AREase) as a substrate, in depression, bipolar disorder, generalized anxiety disorder
(GAD) and schizophrenia, especially in antipsychotic-free patients. PON1 activity as determined
with paraoxon (i.e., POase activity) yields more controversial results, which can be explained by the
lack of adjustment for the Q192R polymorphism. The few clinical trials investigating the influence
of nutritional, lifestyle and drugs on PON1 activities in the general population suggest that some
polyphenols, oleic acid, Mediterranean diet, no smoking, being physically active and statins may be
effective strategies that increase PON1 activity.
Conclusion: Lowered PON1 activities appear to be a key component in the ongoing NOS processes
that accompany affective disorders, GAD and schizophrenia. Treatments increasing attenuated
PON1 activity could possibly be new drug targets for treating these disorders.