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
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
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
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