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Correspondence: Dr Robin McCreadie, FRCPsych, Department of Clinical Research, Crichton Royal Hospital, Dumfries DGI 4TG. Tel. +44 1387 244000; Fax. +44 1387 257735; e-mail: rgmcreadie_crh{at}compuserve.com
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ABSTRACT |
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Aims To determine plasma lipid peroxide levels and serum vitamin E and A levels in first-episode never-treated people with schizophrenia and in controls.
Method Thirty in-patients with a first episode of schizophrenia or schizophreniform psychosis were recruited, as were controls matched for gender, age, smoking and dietary status. Blood samples were taken, smoking status was recorded and body mass index measured.
Results There were no significant differences between patients and controls in plasma lipid peroxide levels. Seventythree per cent of the patients smoked. Patients who smoked had a higher mean lipid peroxide level than non-smokers. Seventy-seven per cent of patients and 70% of controls had a ratio of vitamin E to cholesterol of less than 5. Body mass index was lower in patients than in controls.
Conclusions As a result of the high prevalence of smoking this group shows increased lipid peroxidation. Low serum ratios of vitamin E to cholesterol in both patients and controls suggest an unsatisfactory diet.
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INTRODUCTION |
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METHOD |
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The study was approved by the local research ethics committee for each hospital. A complete description of the study was given to each patient and control subject and written information was provided. Written informed consent was obtained.
Assessment
A blood sample was taken from patients and control subjects to measure
plasma lipid peroxide and serum cholesterol, vitamin E and vitamin A. Blood
samples were taken by syringe and dispensed into glass tubes containing
tripotassium ethylene diamine tetraacetic acid (EDTA) solution (Becton
Dickinson, Oxford). After centrifugation, carried out within 1 h of blood
collection, 500 µl aliquots of plasma were added to polypropylene
screw-capped tubes containing 50 µl ethanolic butylated hydroxytoluene
(BHT) solution to give a final BHT concentration of 5 mmol/l. These were mixed
thoroughly and stored at -20°C until analysis. The biochemist did not know
whether blood samples were from patients or control subjects.
Plasma lipid peroxide was measured by the high-performance liquid chromatography (HPLC) method of Young & Trimble (1991). Serum concentrations of vitamin E and vitamin A were measured by the method of Catignani & Bieri (1983). Vitamin E status can be expressed either as the serum concentration or as the ratio of vitamin E to cholesterol in the serum. Vitamin E is transported within lipid particles in plasma. Differences in serum vitamin E concentration are influenced by variations in serum cholesterol levels, and therefore it is preferable to use this ratio rather than vitamin E concentration alone.
The patients' mental state was assessed using the Positive and Negative Syndrome Scale (PANSS) for schizophrenia (Kay et al, 1987) and the Clinical Global Impression (CGI) Scale (Guy, 1976). The assessments were carried out by psychiatrists trained in the use of the PANSS. The patients' height and weight were also measured.
Statistical analysis
Differences between patients and control subjects were assessed using
McNemar's test for categorical variables and Student's paired t-test
for continuous variables. Differences between unpaired groups were assessed
using 2 and unpaired t-tests. Correlation between
variables was assessed using the Pearson product moment correlation
coefficient. All P values are two-tailed.
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RESULTS |
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Blood test results
Blood samples were taken from all patients and control subjects. Levels of
plasma lipid peroxide, serum cholesterol, vitamin E and vitamin A are shown in
Table 1. There were no
significant differences between patients and control subjects in plasma lipid
peroxide, serum vitamin A and the ratio of vitamin E to cholesterol, but serum
vitamin E levels were lower in patients with schizophrenia. In 77% of patients
and 70% of control subjects, the ratio of vitamin E to cholesterol was less
than 5, the minimum level said to be necessary to protect against heart
disease (Hense et al,
1993).
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The percentage of smokers in patients with schizophrenia (and therefore in control subjects also) was 73% (76% male, 67% female). The mean number of cigarettes smoked daily was 16 (s.d. 6); in control subjects it was 17 (s.d. 6).
Plasma lipid peroxide levels were higher in smokers than in non-smokers; this difference was statistically significant in patients with schizophrenia (mean 0.54 µmol/l, s.d. 0.15) v. 0.40 (s.d. 0.16); difference in means 0.14; 95% CI 0.01-0.27; unpaired t-test: t=2.27, d.f.=28, P=0.03) but not in control subjects (0.56 (s.d. 0.26) v. 0.47 (s.d. 0.12)).
Body mass index
Height and weight measurements were available for 24 pairs of patients and
control subjects. There were no significant differences between patients and
control subjects in mean height (1.72 m (s.d. 0.08) v. 1.74 (s.d.
0.13)) but patients weighed less (mean 65.7 kg (s.d. 11.1) v. 75.0
(s.d. 149); mean of differences 8.46; 95% CI 0.91-16.00; t=2.32,
d.f.=23, P=0.03). The BMI (weight (kg) ÷height
(m)2) was lower in patients (mean 22.2 (s.d. 3.6) v. 24.7
(s.d. 3.4); mean of differences 2.15; 95% CI 0.06-4.25; paired
t-test: t=2.12, d.f.=23, P=0.04). Nineteen per cent
of the patients were overweight (BMI 25-29.9) or obese (BMI30), compared
with 44% of control subjects (not statistically significant).
Mental state
Mean (s.d.) scores of the patients on the positive, negative, general
psychopathology and total scales of the PANSS were respectively 22 (s.d. 5),
19 (9), 40 (40) and 81 (20). The mean (s.d.) CGI score was 5 (s.d. 1) (5 is
markedly ill).
There were no significant correlations between, on the one hand, scores on any of the PANSS and CGI scales and BMI and, on the other hand, plasma lipid peroxide and serum vitamin E and vitamin A levels, and the ratio of vitamin E to cholesterol.
There was a significant negative correlation between patients' BMI and total score on the negative syndrome sub-scale of the PANSS (Pearson's r=-0.42, P=0.03). Examination of the seven individual items making up the negative sub-scale showed that the only significant correlation with BMI was "passive/apathetic social withdrawal" (r=-0.42, P=0.03).
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DISCUSSION |
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Smoking
Seventy-three per cent of the patients were smokers, a much higher figure
than that found in the general population in southwest Scotland (28%)
(Waldron et al,
1995). The percentage of smokers among our sample of male patients
(mean age 28 years) is also much higher than that found among men aged 25-34
in a national survey (34%) (Bennett et
al, 1996). It has long been known that cigarette smoking is
common in patients with schizophrenia
(Hughes et al, 1986),
and we have also reported in a retrospective study that most such patients
start to smoke before their illness begins
(Kelly & McCreadie, 1999),
a finding confirmed in the present study.
Lipid peroxidation
We found no difference between patients and control subjects in plasma
lipid peroxide levels, and therefore our results do not support the view that
increased lipid peroxidation is associated with the schizophrenic illness
per se. This result is in contrast to that of the only other study
which has examined peroxidation in first-episode patients
(Mahadik et al,
1998). We believe our results are more likely to be valid for two
reasons. First, our patients were more closely matched with control subjects
than those in that earlier study; matching variables included gender, age,
smoking and dietary status; also, the living arrangements were very similar in
both groups. Second, mean plasma levels of lipid peroxide reported in that
study, using the same method as ours
(Young & Trimble, 1991), were, for control subjects and patients respectively, 2.35 µmol/l (s.d.
0.78) and 5.16 µmol/l (s.d. 1.85), five and ten times as high as those in
our study and compared with the mean levels reported in the description of the
original HPLC method (Young & Trimble,
1991). Reference values for most HPLC methods are <1.5
µmol/l (Rumley & Paterson,
1998). It may be that there are methodological differences between
the laboratory of Mahadik and colleagues and our laboratory.
Patients who smoked had higher lipid peroxide levels than those who did not. Smoking is a source of free radicals (Church & Pryor, 1985). As most of our patients were already smoking when first admitted to hospital, and as the prevalence of smoking among them was very much higher than in the general population, it could be argued that there is indeed increased lipid peroxidation in patients with schizophrenia, compared with the general population, but that it is mediated by smoking.
Vitamin E and diet
Serum vitamin E levels were lower in patients than in control subjects and
vitamin E : cholesterol ratios were low in both patients and control subjects;
only 23% of patients had a ratio greater than 5, a level which is said to be
necessary to protect against heart disease
(Hense et al, 1993).
Diet in Scotland is generally poor and contributes to the high death rate from
cardiovascular disease, the highest in the Western world
(Scottish Office, 1993). The
dietary choices of our first-episode patients probably reflect those of the
general population. We have recently reported, however, that a group of
chronic schizophrenic patients in south-west Scotland have an even
worse diet than well-matched controls in terms of fibre, fruit and vegetable
and antioxidant intake (McCreadie et
al, 1998).
Body mass index
Patients had a lower BMI than controls, who were representative of the
general population in south-west Scotland where 41% of males and 52% of
females are either overweight or obese
(Dumfries and Galloway Public Health
Department, 1990). Why patients weigh less is not clear. However,
there was a negative correlation between BMI and negative symptoms of
schizophrenia; perhaps withdrawn, apathetic patients are less motivated to go
out and buy the sorts of food their non-affected peers are purchasing.
Chronically ill patients in south-west Scotland have been found to be
overweight (McCreadie et al,
1998) probably as a result of antipsychotic medication
(Stanton, 1995).
Schizophrenia sufferers die early (Mortensen & Juel, 1990). We have shown in the present study that at the start of the illness there is both a high prevalence of smoking, associated with increased lipid peroxidation, and low serum vitamin E levels. Some of these adverse factors are likely to persist throughout the illness and may contribute to the early death of patients with schizophrenia. We now plan to make a more detailed assessment of the dietary habits of first-episode patients and embark upon dietary intervention studies.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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Received for publication July 19, 1999. Revision received September 17, 1999. Accepted for publication September 21, 1999.