title: Prevention of oxidative stress-mediated neuropathology and improved clinical outcome by adjunctive use of a combination of antioxidants and omega-3 fatty acids in schizophrenia.
abstract: Schizophrenia is associated with a broad range of neurodevelopmental, structural and behavioral abnormalities that often progress with or without treatment. Evidence indicates that such neurodevelopmental abnormalities may result from defective genes and/or non-genetic factors such as pre-natal and neonatal infections, birth complications, famines, maternal malnutrition, drug and alcohol abuse, season of birth, sex, birth order and life style. Experimentally, these factors have been found to cause the cellular metabolic stress that often results in oxidative stress, such as increased cellular levels of reactive oxygen species (ROS) over the antioxidant capacity. This can trigger the oxidative cell damage (i.e., DNA breaks, protein inactivation, altered gene expression, loss of membrane lipid-bound essential polyunsaturated fatty acids [EPUFAs] and often apoptosis) contributing to abnormal neural growth and differentiation. The brain is preferentially susceptible to oxidative damage since it is under very high oxygen tension and highly enriched in ROS susceptible proteins, lipids and poor DNA repair. Evidence is increasing for increased oxidative stress and cell damage in schizophrenia. Furthermore, treatments with some anti-psychotics together with the lifestyle and dietary patterns, that are pro-oxidant, can exacerbate the oxidative cell damage and trigger progression of neuropathology. Therefore, adjunctive use of dietary antioxidants and EPUFAs, which are known to regulate the growth factors and neuroplasticity, can effectively improve the clinical outcome. The dietary supplementation of either antioxidants or EPUFAs, particularly omega-3 has already been found to improve some psychopathologies. However, a combination of antioxidants and omega-3 EPUFAs, particularly in the early stages of illness, when brain has high degree of neuroplasticity, potentially may be even more effective for long-term improved clinical outcome of schizophrenia.
authors.affiliation: Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta, 30904, USA. smahadik@mail.mcg.edu
authors.forename: Sahebarao P
authors.initials: SP
authors.lastname: Mahadik
authors.forename: Anilkumar
authors.initials: A
authors.lastname: Pillai
authors.forename: Sadhana
authors.initials: S
authors.lastname: Joshi
authors.forename: Adriana
authors.initials: A
authors.lastname: Foster
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000097:blood / Q000633:toxicity; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D014150:Antipsychotic Agents; D015525:Fatty Acids, Omega-3; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species