Swallownest Court Hospital, Aughton Road, Sheffield S26 4TH, UK.
Correspondence: Tel: +44 (0)114 2872570; fax: +44 (0)114 2879147; e-mail: malcolmpeet{at}yahoo.com
Declaration of interest M.P. has received research funding from Laxdale Ltd, a company which is developing ethyleicosapentaenoic acid as a treatment for psychiatric and neurological disorders.
See editorial, pp.
381382, this
issue.
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ABSTRACT |
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Aims To explore dietary predictors of the outcome of schizophrenia and the prevalence of depression.
Method Ecological analysis of national dietary patterns in relation to international variations in outcome of schizophrenia and prevalence of depression.
Results A higher national dietary intake of refined sugar and dairy products predicted a worse 2-year outcome of schizophrenia. A high national prevalence of depression was predicted by a low dietary intake of fish and seafood.
Conclusions The dietary predictors of outcome of schizophrenia and prevalence of depression are similar to those that predict illnesses such as coronary heart disease and diabetes, which are more common in people with mental health problems and in which nutritional approaches are widely recommended. Dietary intervention studies are indicated in schizophrenia and depression.
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INTRODUCTION |
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METHOD |
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The countries included in the analysis were: Denmark, India, Colombia, Nigeria, UK, USSR, USA and Czechoslovakia for the IPSS study; Denmark, India, Colombia, Ireland, USA, Nigeria, USSR, Japan, UK and Czechoslovakia for the DOSMED study; and New Zealand, Canada, Germany, France, USA, USSR, Taiwan and Japan for the depression study. No data on social outcome were available for Japan. Data on food usage were taken from the FAOSTAT database (Food and Agriculture Organization, 2002), which records the apparent national food consumption. This is estimated from the total domestic production of food (including non-commercial production and production from kitchen gardens) plus imports, minus exports, taking into account changes in stocks such as stored grain and minus the food lost to waste during commercial processing. The following foodstuffs were included in the analysis: meat (including beef, mutton, goat, pig and poultry); fish and seafood; eggs; dairy products (milk, cheese, butter and ghee); vegetable oil, vegetables; cereals (excluding beer); fruits (excluding wine); starchy roots; refined sugar; pulses; nuts; coffee; and alcoholic beverages. All were expressed as supply in kilograms per capita per year. Food consumption data were taken for the year that approximated to the time when the clinical studies were conducted (1970 for the IPSS study, 1980 for the DOSMED study and 1990 for the depression prevalence study). It was not considered necessary to analyse more than one year because national food consumption patterns change slowly over decades and there is little variation from year to year.
Each foodstuff group was correlated with each of the clinical databases. Stepwise multiple regression was then carried out using the Statistical Package for the Social Sciences for Windows, Version 11.5, with the clinical measures as dependent variables and dietary measures as independent variables.
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RESULTS |
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The results of the multiple regression analysis are shown in Table 2. The most striking relationship in the schizophrenia databases is between sugar consumption and outcome. This was an independent predictor of poor outcome of schizophrenia as judged by both social and hospital admission criteria, as well as the total outcome score. An exception to this was the hospital admission data from the IPSS study, in which increased intake of dairy products predicted fewer days spent out of hospital. Also, alcohol consumption was found to be an additional weak but significant positive predictor of overall total best outcome in the DOSMED study, although this accounted for only a very small part of the variance relative to sugar. All of these associations predicted the majority of variance in the outcome of schizophrenia.
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The sole independent predictor of depression prevalence emerging from the multiple regression analysis was the consumption of fish and seafood, which predicted the prevalence of depression with an adjusted R2 of 0.74.
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DISCUSSION |
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Diet and outcome of schizophrenia
The finding that the outcome of schizophrenia is better in developing than
in developed countries has never been satisfactorily explained and does not
appear related simply to confounding factors such as diagnostic differences
and selective outcome measures (Hopper
& Wanderling, 2000). Christensen & Christensen
(1988) reported a correlation
between international variations in outcome of schizophrenia according to the
IPSS study and the ratio in the diet of animal (mainly saturated) fat to fish
and vegetables (mainly polyunsaturated) fats. This was reflected in the
present study, where correlations were shown between a higher consumption of
meat and dairy products and a worse outcome of schizophrenia. However, strong
intercorrelations are found between various dietary constituents, and on
multiple regression analysis it was sugar consumption that was the predominant
predictor of poor outcome in schizophrenia. Exceptions to this were that the
consumption of dairy products predicted hospital admission in the IPSS study,
and alcohol was a weak predictor of global good outcome in the DOSMED study.
Therefore, the dominant and robust finding of this analysis is the predictive
value of sugar consumption.
Diet and prevalence of depression
There has been recent interest in the relationship between fish consumption
and depression. Hibbeln & Salem
(1995) noted that the increased
prevalence of depression in the 20th century parallels the increased rates of
coronary heart disease that are thought to be associated with altered dietary
patterns, including reduced dietary intake of omega-3 polyunsaturated fatty
acids. Hibbeln (1998) has
subsequently demonstrated striking correlations between dietary fish intake
and international variations in major depression. Using the same depression
database as Hibbeln (1998), we
have confirmed the relationship between fish consumption and international
variations in rates of depression, and also found that sugar consumption
relates to the prevalence of depression. This had been noted previously by
Westover & Marangell
(2002). However, multiple
regression analysis shows that fish and seafood consumption provides the
strongest and most robust independent predictor of depression prevalence.
Limitations
Association does not prove causation. Diet is partly determined by
sociocultural factors, so diet could be a proxy for other social variables.
Correlation studies of this type, particularly when taken in conjunction with
other sources of information, have their greatest value in generating
hypotheses. Issues of cause and effect can be clarified only by intervention
studies in which diet is manipulated, by either supplementation or
restriction, and mental health outcome is assessed.
Correlations are only as good as the data-sets utilised. The national apparent food consumption data are the best available but they are inexact and do not necessarily reflect the dietary practices of individuals or of population subgroups. This can be done only by casecontrol or cohort studies in which individual dietary practices are recorded. There are several large prospective studies relating diet to subsequent heart disease, diabetes and cancer, but there are no large prospective studies relating diet to subsequent mental health problems.
The databases used for schizophrenia outcome are well accepted and often cited. The data on major depression prevalence reported by Weissman et al (1996) are derived from rigorous methodologies and are among the most reliable cross-national data available.
It is well recognised that the use of multiple correlations can give rise to spurious associations by chance. Also, multiple regression analysis can be sensitive to the exact regressors entered. However, the breadth of data used in this study has enabled patterns to be identified and this was strengthened by the robust findings from the use of multiple regression analysis.
Implications
Diabetes, coronary heart disease and other related conditions that cluster
together have been conceptualised as manifestations of the metabolic
syndrome (De Fronzo &
Ferrannini, 1991; Hansen,
1999). Because these diseases also cluster with schizophrenia and
depression, it has been proposed that these mental disorders may share some
aetiological factors with physical diseases that constitute the metabolic
syndrome (Peet & Edwards,
1997; Ryan & Thakore,
2002). A fundamental abnormality in the metabolic syndrome is
insulin resistance (Hansen,
1999). Abnormal glucose utilisation reflecting insulin resistance
has been demonstrated in patients with depression
(Peet & Edwards, 1997). In
schizophrenia, abnormalities of glucose utilisation were demonstrated before
the introduction of modern antipsychotic drugs
(Ryan & Thakore, 2002).
Insulin resistance is altered by diet. Regular consumption of significant
quantities of foodstuffs with a high glycaemic load, such as
sugar and white bread, which rapidly release glucose into the blood-stream,
gives rise to insulin resistance and subsequent susceptibility to diabetes and
cardiovascular disease (Ludwig,
2002). A high dietary intake of saturated fat leads to increased
insulin resistance, whereas substitution of saturated fat with polyunsaturated
fat can reverse this effect and may be protective against future development
of insulin resistance (Summers et
al, 2002). The risk of mortality from coronary heart disease
is decreased by regular consumption of fish and pulses
(Mann, 2002). Thus, dietary
patterns that influence insulin resistance and lead to diseases of the
metabolic syndrome are reflected by the dietary predictors of outcome of
schizophrenia and prevalence of depression in the present study. It can
therefore be hypothesised that insulin resistance and associated metabolic
disturbances resulting from dietary factors may account for the clinical
association between depression, schizophrenia and the physical diseases of the
metabolic syndrome.
An obvious practical consequence of this hypothesis is the possibility that mental health could be improved by dietary manipulation. There have been few controlled trials of nutrition in the treatment of psychiatric disorders. If food with a high glycaemic load is of importance in determining the outcome of schizophrenia, then modification of glycaemic load or its metabolic consequences should be beneficial in the management of schizophrenia. Diets with a low glycaemic load were promoted decades ago as being potentially useful in the treatment of schizophrenia but have been supported only by anecdotal evidence (Meiers, 1973).
With regard to depression, the overriding association was between fish and seafood consumption and prevalence of depression, which supports previous epidemiological data (Hibbeln, 1998). This leads directly to the proposition that depression should be treatable with omega-3 fatty acids. This proposition has been tested recently, with strong positive antidepressant benefits reported and confirmed (Nemets et al, 2002; Peet & Horrobin, 2002). This is now a matter of intense further research.
It is premature to speculate on molecular mechanisms, save to note that a number of potential mechanisms do exist. Insulin receptors are widely distributed in the brain where they are involved in cell signalling and modulate the actions of other neurotransmitters (Kyriaki, 2003). Also, a high-fat, refined sugar diet has been shown to reduce levels of brain-derived neurotrophic factor in rat hippocampus (Molteni et al, 2002): brain-derived neurotrophic factor promotes a variety of neuromodulatory processes during early development and adulthood and has been implicated in schizophrenia (Durany et al, 2001).
In conclusion, this study has shown that national dietary factors predict international variations in the outcome of schizophrenia and prevalence of depression. The nutritional predictors are similar to those reported for other Western diseases such as diabetes and coronary heart disease, which are more common in people with mental health problems. Whether the relationship between nutritional factors and mental health is causal can be determined only by intervention studies. Initial treatment studies with omega-3 fatty acids in depression are encouraging but other nutritional strategies should be explored.
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Clinical Implications and Limitations |
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LIMITATIONS
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Received for publication January 24, 2003. Revision received May 30, 2003. Accepted for publication September 3, 2003.
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