A five-year follow-up study of antioxidants, oxidative stress and polyunsaturated fatty acids in schizophrenia.

OBJECTIVE: Oxidative stress and dysregulated antioxidant defence may be involved in the pathophysiology of schizophrenia. In the present study, we investigated changes in antioxidants and oxidative stress from an acute to a later stable phase. We hypothesised that the levels of oxidative markers are increased in schizophrenia compared with healthy controls; change from the acute to the stable phase; and are associated with the levels of membrane polyunsaturated fatty acids (PUFAs) and symptom severity. METHODS: Fifty-five patients with schizophrenia spectrum disorders, assessed during an acute phase and 5 years later during a stable phase, and 51 healthy controls were included. We measured antioxidants (α-tocopherol, uric acid, albumin and bilirubin), markers of oxidative stress (F2-isoprostane and reactive oxygen metabolites) and membrane fatty acids. Antioxidants and oxidative stress markers were compared in schizophrenia versus healthy controls, adjusting for differences in sex, age and smoking, and changes over time. Associations between symptoms and PUFA were also investigated. RESULTS: In the acute phase, α-tocopherol was significantly higher (p < 0.001), while albumin was lower (p < 0.001) compared with the stable phase. Changes in α-tocopherol were associated with PUFA levels in the acute phase. In the stable phase, schizophrenia patients had higher uric acid (p = 0.009) and lower bilirubin (p = 0.046) than healthy controls. CRP was higher in patients in the stable phase (p < 0.001), and there was no significant change from the acute phase. CONCLUSION: The present findings of change in antioxidant levels in the acute versus stable phase of schizophrenia the present findings suggest that redox regulation is dynamic and changes during different phases of the disorder.

Bimodal distribution of polyunsaturated fatty acids in schizophrenia suggests two endophenotypes of the disorder.

BACKGROUND: There is conflicting evidence of whether polyunsaturated fatty acids (PUFA) in red blood cells are bimodally distributed in schizophrenia. The purpose of this study was to examine the distribution of PUFA, as well as its links to plausible causal factors. METHODS: A 16-week cohort study and a case-control study as part of a randomized controlled trial. Ninety-nine patients with DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder, aged 18 to 39, were consecutively included at admission to psychiatric departments of nine Norwegian hospitals. Fatty acids were measured in 97 of these patients and in 20 healthy control subjects. The primary outcome measure was the bimodality test statistic T, assessed by a χ(2) test of the likelihood of one or two normal distributions of PUFA. RESULTS: At baseline, levels of polyunsaturated fatty acids were highly significantly bimodally distributed among patients. One third of patients constituted a group (low PUFA) who had PUFA levels at one fifth (p < .001) of those in high PUFA patients and healthy control subjects, which did not differ. Bimodality was mainly accounted for by docosahexaenoic acid and arachidonic acid. Bimodality was confirmed after 16 weeks. α-tocopherol was a robust predictor of PUFA at both occasions. Desaturase and elongase indexes differed between PUFA groups. Smoking, gender, antipsychotic medication, and dietary factors did not explain the bimodal distribution. CONCLUSIONS: Red blood cell PUFA were bimodally distributed among acutely ill patients with schizophrenia and schizoaffective disorder. Endogenous deficiencies of redox regulation or synthesis of long-chain PUFA in the low PUFA group may explain our findings.