Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients.

Oxidative stress-mediated cell damage has been considered in the pathophysiology of schizophrenia. Abnormal findings have often been considered related to differences in ethnicity, life style, dietary patterns and medications, all of which influence indices of oxidative stress and oxidative cell damage. To minimize these confounds, schizophrenic patients were compared with age-matched control subjects with the same ethnic background and similar lifestyle, as well as with bipolar mood disorder (BMD) patients. Levels of antioxidant defense enzymes (i.e. superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) were lower in schizophrenic patients than in controls, indicating conditions for increased oxidative stress. The contents of plasma thiobarbituric acid reactive substances (TBARS) were only marginally higher in schizophrenic patients, who had normal levels of arachidonic acid (AA), a major source of TBARS, indicating no significant oxidative membrane lipid peroxidation. Levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), however, were significantly lower in schizophrenic patients. When the same indices in BMD patients were compared with findings in matched controls, levels of only SOD and CAT were lower in the patients, whereas GPx was not. Again, as in schizophrenia, the contents of TBARS were marginally higher in BMD patients with no change in levels of AA. Levels of alpha-linolenic acid and EPA were significantly lower and levels of DHA were slightly lower in BMD patients. These data indicate that certain biochemical characteristics may be common to a spectrum of psychiatric disorders, and suggest supplementation of antioxidants and essential fatty acids might affect clinical outcome.

Essential polyunsaturated fatty acid and lipid peroxide levels in never-medicated and medicated schizophrenia patients.

BACKGROUND: Reduced levels of membrane essential polyunsaturated fatty acids (EPUFAs) and increased levels of lipid peroxidation products (thiobarbituric acid reactive substances; TBARS) have been observed in chronic medicated schizophrenics. The relationship of EPUFA and TBARS to psychopathology is unclear, since their levels may be altered differentially by duration of illness and antipsychotic treatment. To minimize these confounds, their levels were compared among never-medicated patients in early illness, medicated patients and control subjects with similar lifestyle and common ethnic background. METHODS: RBC membrane EPUFAs, plasma TBARS, and various dimensions of psychopathology were measured using established procedures in never-medicated (n = 20) and medicated (n= 32) schizophrenia patients and in control subjects (n= 45). RESULTS: Reduced levels of EPUFAs, particularly arachidonic acid (AA) and docosahexaenoic acid (DHA), were found in never-medicated compared with control subjects; however, the reductions in levels of both AA and DHA were much smaller in medicated versus never-medicated patients; AA levels were similar to levels in control subjects. Only DHA levels were significantly reduced in medicated patients. Lower membrane AA levels were associated with increased levels of plasma TBARS in never-medicated patients. Lower levels of membrane EPUFAs and higher levels of plasma TBARS were associated with the severe symptoms in never-medicated versus medicated patients. CONCLUSIONS: Data indicate that reduced EPUFAs and increased TBARS exist in never-medicated patients, and these measures correlate with the severity of psychopathology indicating that the membrane EPUFA status may reflect the outcome of schizophrenia.