Elevated plasma lipid peroxides at the onset of nonaffective psychosis.

BACKGROUND: Impaired antioxidant defense and increased lipid peroxidation has been reported in chronic schizophrenic patients. Recently, we have reported an impaired antioxidant defense in never medicated first-episode schizophrenic and schizophreniform patients. We report now a concomitant increase in plasma lipid peroxides. METHODS: The plasma lipid peroxides [thiobarbituric acid reactive substances (TBARS)] were analyzed by chemical and high performance liquid chromatography procedures in 26 patients admitted for a first episode of schizophrenic (N = 17) or schizophreniform psychosis (N = 9) and 16 normal control subjects. The patients had a duration of 4.5 days (SD 2.8) of psychosis at the time of the study. RESULTS: Plasma TBARS levels were significantly higher in the patients than in normal controls (P < .002). TBARS levels were above the normal range in 16 of the 26 patients. Higher TBARS levels were associated with a greater severity of negative symptoms and lower red blood cell activity of the glutathione peroxidase. CONCLUSIONS: The findings indicate ongoing oxidative injury at the very onset of psychosis. If valid, this would indicate the need for adjunctive antioxidant treatment from the beginning of the course of nonaffective psychoses. This might prevent a deteriorating course and development of the deficit syndrome.

Utilization of precursor essential fatty acids in culture by skin fibroblasts from schizophrenic patients and normal controls.

Based on the lower levels of long-chain polyunsaturated analogs of essential fatty acids (EPUFAs) in plasma membrane phospholipids of red blood cells, brain and cultured skin fibroblasts from schizophrenic patients, a defective utilization (uptake, conversion to EPUFAs and incorporation into membrane phospholipids) of precursor EFAs has been suggested. Utilization of radiolabeled linoleic (LA, 18:2(n-6)) and alpha-linolenic (ALA, 18:3(n-3)) acids was studied in cultured skin fibroblasts from patients with established schizophrenia and at the first episode of psychosis, and normal controls. Uptake and incorporation of both the EFAs were similar in fibroblasts from both groups of patients studied compared with normal controls. However, although the utilization of LA into arachidonic acid (AA, 20:4n-6) was similar in patients and controls, the utilization of eicosapentaenoic acid (EPA, 20:5(n-3)) into docosahexaenoic acid (DHA, 22:6(n-3)) was significantly lower in first-episode psychotic patients (patients, 96.33 +/- 27.16 versus normals, 161.66 +/- 26.33 nmoles per mg total protein; P = < 0.001). This data indicates that the level of delta 6- as well as delta 5-desaturase may be normal. However, the levels of delta 4-desaturase may be lower in fibroblasts from schizophrenic patients even at the first episode of psychosis.

Plasma membrane phospholipid fatty acid composition of cultured skin fibroblasts from schizophrenic patients: comparison with bipolar patients and normal subjects.

Recent studies have found lower red cell plasma membrane contents and composition of the long chain polyunsaturated essential fatty acid derivatives, particularly arachidonic acid and docosahexaenoic acid, in a subgroup of chronic schizophrenic patients. These fatty acids are particularly enriched in the brain. Red blood cell levels of fatty acids are influenced by diet, medications, and other factors. Cell plasma membrane compositions of arachidonic and docosahexaenoic acids were therefore examined in cultured skin fibroblasts from 12 schizophrenic patients, 8 of whom were drug-naive and in a first episode of psychosis, 6 bipolar patients, and 8 normal control subjects. Docosahexaenoic acid as well as total n-3 essential fatty acid contents were significantly lower in cell lines from schizophrenic patients than in cell lines from bipolar patients and normal subjects, with no difference between the latter two groups. Arachidonic acid levels did not differ across the groups. The essential fatty acid profile observed is consistent with deficient delta-4 desaturase activity in schizophrenic patients.

Impaired antioxidant defense at the onset of psychosis.

Previous studies found peripheral activities of antioxidant enzymes to be abnormal in schizophrenic patients. It is not understood whether this is integral to the disease process or a result of long-term treatment with neuroleptics. Red blood cell activities of three antioxidant enzymes--superoxide dismutase, glutathione peroxidase, and catalase--were therefore examined in 14 drug-naive, first episode patients with a diagnosis of schizophrenia or schizophreniform disorder and 10 normal subjects. The patients had an average duration of psychosis of 4.46 days (SD 2.5). Superoxide dismutase activity was significantly lower in patients than in normal controls, with no difference between the groups in activities of the other two enzymes. Lower superoxide dismutase activity was associated with deterioration of school functioning from childhood to early adolescence and a history of poorer school functioning during early adolescence. These findings indicate a compromised antioxidant defense at the onset of psychosis, and suggest that oxidative injury might contribute to adverse developmental events in the pathogenic cascade of schizophrenia.

Plasma membrane phospholipid and cholesterol distribution of skin fibroblasts from drug-naive patients at the onset of psychosis.

Contents of plasma membrane major phospholipids, cholesterol, and cholesteryl esters of fibroblasts from drug-naive psychotic patients were compared with those from normal controls. Total membrane lipids were extracted and individual lipids were separated on high-performance thin-layer chromatography. The contents of lipid bands were quantitated by densitometric scanning and comparing with standards. Contents of total phospholipids as well as phosphatidylserine, phosphatidylinositol and phosphatidylethanolamine were significantly lower in fibroblasts from patients than in those from normal controls (P < 0.001, < 0.005, < 0.05 respectively). Total cholesterol fraction and cholesteryl esters were also significantly lower in fibroblasts from patient (P < 0.005, < 0.001 respectively). These changes were not related to differences in age or sex. These data support the hypothesis that schizophrenia is associated with disordered membrane lipid metabolism, and that this predates the onset of psychosis.

Support of the pregnant soldier in the workplace: a comparison of her assessment with that of her supervisor.

Comparison of pregnant soldiers' responses to statements concerning job performance, job satisfaction, and support in the workplace with those of their supervisors reveal no significant difference in how the two groups view the work situation prior to pregnancy. Although the pregnant soldiers do not feel less supported during the pregnancy than before, they do not appreciate the significant increase in support during the pregnancy that is reported by the supervisors. Interviews of pregnant soldiers suggest that they and their supervisors define support differently, and this difference in perception may have negative implications for the optimal utilization of servicewomen during pregnancy.