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.

Using motivational techniques to reduce cardiometabolic risk factors in long term psychiatric inpatients: a naturalistic interventional study.

BACKGROUND: People with severe mental illness have markedly reduced life expectancy; cardiometabolic disease is a major cause. Psychiatric hospital inpatients have elevated levels of cardiometabolic risk factors and are to a high degree dependent of the routines and facilities of the institutions. Studies of lifestyle interventions to reduce cardiometabolic risk in psychiatric inpatients are few. The current study aimed at assessing the feasibility and effects of a lifestyle intervention including Motivational Interviewing (MI) on physical activity levels, cardiometabolic risk status and mental health status in psychotic disorder inpatients. METHODS: Prospective naturalistic intervention study of 83 patients at long term inpatient psychosis treatment wards in South-Eastern Norway. Patients were assessed 3-6 months prior to, at start and 6 months after a life-style intervention program including training of staff in MI, simple changes in routines and improvements of facilities for physical exercise. Assessments were done by clinical staff and included level of physical activity, motivation, life satisfaction, symptom levels (MADRS, AES-C, PANSS, and GAF) as well as anthropometric and biochemical markers of cardiometabolic risk. A mixed model was applied to analyze change over time. RESULTS: A total of 88% of patients received MI interventions, with a mean of 2.5 MI interventions per week per patient. The physical activity level was not increased, but activity level was positively associated with motivation and negatively associated with positive symptoms. Triglyceride levels and number of smokers were significantly reduced and a significant decrease in symptom levels was observed. CONCLUSIONS: The current results suggest that a simple, low cost life-style intervention program focusing on motivational change is feasible and may reduce symptoms and improve lifestyle habits in psychosis patients in long term treatment facilities. Similar programs may easily be implemented in other psychiatric hospitals. TRIAL REGISTRATION: ClinicalTrials.gov . NCT03528278 , date of registration: 05/16/2018 (retrospectively registered).

Cardiometabolic risk factors, physical activity and psychiatric status in patients in long-term psychiatric inpatient departments.

PURPOSE: Cardiovascular diseases are a major cause for the markedly reduced life expectancy in people with severe mental illness (SMI). Hospital departments should provide adequate prevention of cardiometabolic risk by optimizing prevention and treatment. Characteristics of cardiometabolic risk factors in inpatients are still not well known. We aimed to describe the status of cardiometabolic risk factors in inpatients with SMI and identify associations with psychiatric status and treatment. METHODS: A cross sectional descriptive study of inpatients with SMI from long term psychosis treatment wards in South Eastern Norway was performed. Comprehensive assessments of cardiometabolic risk factors, physical activity, lifestyle habits, symptoms, life satisfaction and treatment were made. Associations and potential prognostic factors were analyzed using linear and logistic regressions. RESULTS: A total of 83 patients were included in the study, but many individual datasets were incomplete. Over half of the subjects had unhealthy eating habits. Obesity (class 1-3) was found in 44%, 23% had elevated fasting triglycerides, 26% had elevated blood pressure and 78% smoked daily. Low levels of physical activity were significantly associated with higher levels of depression (p = .007). A nominal increase in cardiometabolic risk factors was found for olanzapine and clozapine users. CONCLUSION: Inpatients in long term psychosis treatment wards have alarmingly high cardiometabolic risk. Level of physical activity was associated with both psychiatric and somatic health. Focus on lifestyle and somatic health should be an integral part of the treatment for hospitalized SMI patients.

Lipid profiles in schizophrenia associated with clinical traits: a five year follow-up study.

BACKGROUND: Alterations in serum and membrane lipids may be involved in schizophrenia pathophysiology. It is not known whether lipid profiles are associated with disease severity or current symptom level. METHODS: Clinical and lipid data were gathered from 55 patients with schizophrenia admitted to psychiatric emergency wards in an acute stage of the disease (T1). The patients were re-examined after 5 years at a stable phase (T2). The clinical assessments included Positive and Negative Syndrome Scale (PANSS total, positive, negative) and Global Assessment of Functioning (GAF S, symptom and F, function). Serum lipids (cholesterol and triglyceride) and membrane polyunsaturated fatty acids (PUFA, LCPUFA) were measured. Healthy controls were recruited among hospital workers. RESULTS: Serum triglyceride was significantly higher in patients with schizophrenia compared to healthy controls both at T1 and T2 (p < 0.001), while serum cholesterol did not differ significantly. The levels of serum lipids in patients remained stable over time. At T1, serum lipids and symptoms were not significantly correlated. At T2, higher serum lipids were associated with more severe symptoms and poorer functioning. Higher serum lipid levels at T1 were associated with more severe symptoms and poorer functioning at T2; cholesterol with GAF-S (p < 0.05), triglyceride with PANSS total (p < 0.05), GAF-S (p < 0.01) and GAF-F (p < 0.01). Membrane lipids were significantly lower in the patient group compared to healthy controls at T1 (PUFA p < 0.001, LCPUFA p < 0.001), but not at T2. Membrane lipids were not significantly correlated with symptoms at T1, but significantly associated with negative symptoms and functioning at T2 as previously reported. CONCLUSIONS: The present findings suggest different roles of membrane and serum lipids in schizophrenia pathophysiology. To further elucidate the relation of lipid biology to disease traits, replication in independent studies of longitudinal samples are warranted.

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.