Diet, diabetes and schizophrenia: review and hypothesis -- Peet 184 (47): s102 -- The British Journal of Psychiatry
Diet, diabetes and schizophrenia: review and hypothesis -- Peet 184 (47): s102 -- The British Journal of Psychiatry
There is substantial evidence that schizophrenia is associated with abnormalities of phospholipid metabolism and cell membrane PUFA levels (Peet, 2002). Two studies have shown that levels of PUFA in the normal daily diet correlate with the severity of schizophrenia symptoms. Mellor et al (1996) showed significant negative correlations between dietary intake of omega-3 fatty acids and symptoms of schizophrenia and of tardive dyskinesia. In a separate study, Stokes (2003) found that total PUFA in the normal daily diet correlated negatively with severity of schizophrenia symptoms and that this was independent of the dietary intake of other nutrients.
In summary, people with schizophrenia consume the type of diet that is known to promote diseases of the metabolic syndrome (i.e. high in saturated fat, low in fibre, with a high glycaemic load). Furthermore, there is emerging evidence of an association between dietary factors and the severity and long-term outcome of schizophrenia.
[...]
Diet, diabetes and schizophrenia: a hypothesis
Insulin resistance results from an interplay of genetic and lifestyle factors (Ukkola & Bouchard, 2001). Insulin resistance is not in itself necessarily harmful and indeed may confer an evolutionary advantage (Colagiuri & Miller, 2002). Australian aboriginals show evidence of increased insulin resistance but this does not manifest itself as pathological until they give up their traditional lifestyle and adopt Western dietary practices (O’Dea, 1991). People with schizophrenia who exhibit insulin resistance at the start of their illness will therefore have an increased susceptibility to the adverse effects of a poor diet.
The most parsimonious explanation for the increased prevalence of diabetes in patients with schizophrenia is that a genetic predisposition to insulin resistance is compounded by an unhealthy lifestyle and the effect of antipsychotic medication on food intake. The genetic influence is suggested by the increased frequency of diabetes in the relatives of patients with schizophrenia (Mukherjee et al, 1989). However, evidence of a significant association between diet and the outcome and severity of schizophrenia raises the possibility that both diabetes and schizophrenia share a common pathology which is influenced by lifestyle factors such as diet and exercise. One physiological factor that could partly explain the link between diabetes, schizophrenia and diet is brain-derived neurotrophic factor (BDNF). This protein is required to maintain dendrites (Gorski et al, 2003), and its expression in the prefrontal cortex shows a significant increase during young adulthood at a time when the frontal cortex matures both structurally and functionally (Webster et al, 2002). The peak requirement for BDNF to preserve dendritic outgrowth thus occurs at the time of life when schizophrenia has its peak age of onset. Apart from influences on neuronal architecture, BDNF is also a neurotransmitter modulator and facilitates long-term potentiation in the hippocampus (Lessman et al, 2003). It has recently been shown that BDNF expression is reduced in the prefrontal cortex of patients with schizophrenia, and it was suggested that this might be a central component of the disease process (Weickert et al, 2003). Polymorphism of the BDNF gene has been associated with the susceptibility to schizophrenia (Szekeres et al, 2003) and with clozapine responders (Hong et al, 2003). It is known that brain expression of BDNF is reduced by a high-fat, high-sugar diet (Molteni et al, 2002) and increased by exercise (Cotman & Berchtold, 2002). In BDNF knockout mice, neuronal soma size and dendrite density in the prefrontal cortex are reduced (Gorski et al, 2003), and the same structural abnormalities have been reported in the brains of people with schizophrenia (Broadbelt et al, 2002). Brain-derived neurotrophic factor is also involved in the control of insulin resistance. Heterozygous BDNF knockout mice show a 50% reduction in brain levels of BDNF, and they also show hyperphagia and features of the metabolic syndrome (Duan et al, 2003). Administration of BDNF into the cerebral ventricles of obese/diabetic rodent models reduces obesity and improves glucose tolerance (Nakagawa et al, 2000), suggesting that the effect of BDNF on the metabolic syndrome is centrally mediated.
On the basis of the findings discussed so far, it is possible to construct a hypothesis whereby the high-fat, high-sugar diet of patients with schizophrenia leads to reduced expression of BDNF in the brain. This would exacerbate any genetically determined abnormalities of BDNF expression. Although very speculative, this provides a possible explanatory model for the observed epidemiological association between a high-fat, high-sugar diet and poor long-term outcome of schizophrenia. Such a diet would also lead to an increased risk of diabetes, through both peripheral and central mechanisms.
There is evidence that typical and atypical antipsychotic medications have differential effects upon BDNF. Haloperidol has been found to reduce hippocampal expression of BDNF, whereas BDNF expression is increased by olanzapine and clozapine (Bai et al, 2003). However, since there is no clear correlation between these effects and the efficacy and side-effect profiles of these drugs, at least in the short term, it is unlikely that these agents are acting through an effect on BDNF.
[...]
DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHOD
RESULTS
DISCUSSION
Clinical Implications and...
REFERENCES
Clinical importance of lifestyle interventions in schizophrenia
In order to reduce the risk of obesity, diabetes and coronary heart disease in people with schizophrenia, the importance of a healthy lifestyle – including good dietary practices and sufficient exercise – cannot be overemphasised. Because insulin resistance is a feature associated with schizophrenia independently of any specific drug treatment, lifestyle advice should be given to all patients with a diagnosis of schizophrenia. This should start immediately as part of the package of care at the first onset of illness.
The evidence presented allows the hypothesis that a diet low in saturated fat, high in polyunsaturated fatty acids and low in glycaemic load might be beneficial also in alleviating the symptoms of schizophrenia. There are five placebo-controlled trials of omega-3 fatty acids in the treatment of schizophrenia, of which three showed significant benefit, one showed benefit of omega-3 fatty acids only in a subgroup of patients already receiving treatment with clozapine, and one showed no advantage of omega-3 fatty acids over placebo (Peet, 2004). The proposition that the symptoms and the outcome of schizophrenia might be improved by a diet low in saturated fat and low in sugar has not been systematically investigated, although there are anecdotal reports of the successful use of this approach (Meiers, 1973).
There is substantial evidence that schizophrenia is associated with abnormalities of phospholipid metabolism and cell membrane PUFA levels (Peet, 2002). Two studies have shown that levels of PUFA in the normal daily diet correlate with the severity of schizophrenia symptoms. Mellor et al (1996) showed significant negative correlations between dietary intake of omega-3 fatty acids and symptoms of schizophrenia and of tardive dyskinesia. In a separate study, Stokes (2003) found that total PUFA in the normal daily diet correlated negatively with severity of schizophrenia symptoms and that this was independent of the dietary intake of other nutrients.
In summary, people with schizophrenia consume the type of diet that is known to promote diseases of the metabolic syndrome (i.e. high in saturated fat, low in fibre, with a high glycaemic load). Furthermore, there is emerging evidence of an association between dietary factors and the severity and long-term outcome of schizophrenia.
[...]
Diet, diabetes and schizophrenia: a hypothesis
Insulin resistance results from an interplay of genetic and lifestyle factors (Ukkola & Bouchard, 2001). Insulin resistance is not in itself necessarily harmful and indeed may confer an evolutionary advantage (Colagiuri & Miller, 2002). Australian aboriginals show evidence of increased insulin resistance but this does not manifest itself as pathological until they give up their traditional lifestyle and adopt Western dietary practices (O’Dea, 1991). People with schizophrenia who exhibit insulin resistance at the start of their illness will therefore have an increased susceptibility to the adverse effects of a poor diet.
The most parsimonious explanation for the increased prevalence of diabetes in patients with schizophrenia is that a genetic predisposition to insulin resistance is compounded by an unhealthy lifestyle and the effect of antipsychotic medication on food intake. The genetic influence is suggested by the increased frequency of diabetes in the relatives of patients with schizophrenia (Mukherjee et al, 1989). However, evidence of a significant association between diet and the outcome and severity of schizophrenia raises the possibility that both diabetes and schizophrenia share a common pathology which is influenced by lifestyle factors such as diet and exercise. One physiological factor that could partly explain the link between diabetes, schizophrenia and diet is brain-derived neurotrophic factor (BDNF). This protein is required to maintain dendrites (Gorski et al, 2003), and its expression in the prefrontal cortex shows a significant increase during young adulthood at a time when the frontal cortex matures both structurally and functionally (Webster et al, 2002). The peak requirement for BDNF to preserve dendritic outgrowth thus occurs at the time of life when schizophrenia has its peak age of onset. Apart from influences on neuronal architecture, BDNF is also a neurotransmitter modulator and facilitates long-term potentiation in the hippocampus (Lessman et al, 2003). It has recently been shown that BDNF expression is reduced in the prefrontal cortex of patients with schizophrenia, and it was suggested that this might be a central component of the disease process (Weickert et al, 2003). Polymorphism of the BDNF gene has been associated with the susceptibility to schizophrenia (Szekeres et al, 2003) and with clozapine responders (Hong et al, 2003). It is known that brain expression of BDNF is reduced by a high-fat, high-sugar diet (Molteni et al, 2002) and increased by exercise (Cotman & Berchtold, 2002). In BDNF knockout mice, neuronal soma size and dendrite density in the prefrontal cortex are reduced (Gorski et al, 2003), and the same structural abnormalities have been reported in the brains of people with schizophrenia (Broadbelt et al, 2002). Brain-derived neurotrophic factor is also involved in the control of insulin resistance. Heterozygous BDNF knockout mice show a 50% reduction in brain levels of BDNF, and they also show hyperphagia and features of the metabolic syndrome (Duan et al, 2003). Administration of BDNF into the cerebral ventricles of obese/diabetic rodent models reduces obesity and improves glucose tolerance (Nakagawa et al, 2000), suggesting that the effect of BDNF on the metabolic syndrome is centrally mediated.
On the basis of the findings discussed so far, it is possible to construct a hypothesis whereby the high-fat, high-sugar diet of patients with schizophrenia leads to reduced expression of BDNF in the brain. This would exacerbate any genetically determined abnormalities of BDNF expression. Although very speculative, this provides a possible explanatory model for the observed epidemiological association between a high-fat, high-sugar diet and poor long-term outcome of schizophrenia. Such a diet would also lead to an increased risk of diabetes, through both peripheral and central mechanisms.
There is evidence that typical and atypical antipsychotic medications have differential effects upon BDNF. Haloperidol has been found to reduce hippocampal expression of BDNF, whereas BDNF expression is increased by olanzapine and clozapine (Bai et al, 2003). However, since there is no clear correlation between these effects and the efficacy and side-effect profiles of these drugs, at least in the short term, it is unlikely that these agents are acting through an effect on BDNF.
[...]
DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHOD
RESULTS
DISCUSSION
Clinical Implications and...
REFERENCES
Clinical importance of lifestyle interventions in schizophrenia
In order to reduce the risk of obesity, diabetes and coronary heart disease in people with schizophrenia, the importance of a healthy lifestyle – including good dietary practices and sufficient exercise – cannot be overemphasised. Because insulin resistance is a feature associated with schizophrenia independently of any specific drug treatment, lifestyle advice should be given to all patients with a diagnosis of schizophrenia. This should start immediately as part of the package of care at the first onset of illness.
The evidence presented allows the hypothesis that a diet low in saturated fat, high in polyunsaturated fatty acids and low in glycaemic load might be beneficial also in alleviating the symptoms of schizophrenia. There are five placebo-controlled trials of omega-3 fatty acids in the treatment of schizophrenia, of which three showed significant benefit, one showed benefit of omega-3 fatty acids only in a subgroup of patients already receiving treatment with clozapine, and one showed no advantage of omega-3 fatty acids over placebo (Peet, 2004). The proposition that the symptoms and the outcome of schizophrenia might be improved by a diet low in saturated fat and low in sugar has not been systematically investigated, although there are anecdotal reports of the successful use of this approach (Meiers, 1973).
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