Diet, Depression, Inflammation and the Brain

October 4, 2011 · Posted in Current Treatments, Risk Factors 

knife and fork

We’ve been posting recently about diet and about treatments that are weight-neutral.  There is evidence that diet, inflammation and depression are all linked. Epidemiological studies by Joe Hiblen have shown that in countries whose populations eat more fish and thus have high levels of omega-3 fatty acids in their diet, there is lower incidence of depression, suicide, and cardiovascular disease such as heart attacks and strokes. This may be because the major omega-3 fatty acids, EPA and DHA, are anti-inflammatory, and inflammation has been linked to depression. EPA inhibits the enzymes phospholipase A2 and cyclo-oxygenase-2 (COX-2), and their subsequent inflammatory effects on cytokines. DHA inhibits the pro-inflammatory cytokine IL6.

Researcher John Davis recently reviewed relevant literature and found that diets high in anti-inflammatory omega-3 fatty acids are associated with lower incidence of depression, cardiovascular disease, and markers of inflammatory processes. Conversely, diets high in fat and in inflammatory omega-6 fatty acids are associated with obesity, depression, and cardiovascular disease.

Various studies have shown the links between inflammation and depression. For example, when patients are given alpha-interferon to treat viral hepatitis, there is a subsequent increase in inflammatory cytokines IL-1 and IL-6, and depression often follows. Also, depressed patients have an increased ratio of pro-inflammatory to anti-inflammatory cytokines in their blood.

Another sign of a link between bipolar illness and inflammation can be seen in biochemical analysis of brain specimens obtained at autopsy. Researcher Rapaka Rao in the laboratory of Stanley Rapoport at the National Institute on Aging at the National Institutes of Health in Bethesda, Maryland, has reported that increased markers of neuronal inflammation and excitotoxicity were found in the brains of people who had had bipolar disorder. Phospholipase A2 and COX-2 were significantly elevated in the brains of those with bipolar illness and those with schizophrenia compared with controls. Pro-inflammatory interleukin I was also significantly increased in the brains of those who had had either illness.

Another finding from the autopsy studies was that excitatory amino acid transporter type 2 was reduced in the frontal cortex of bipolar patients, but not in schizophrenic patients. The reduction in this glial transporter that removes glutamate from the synapse suggests that bipolar illness is associated with a hyper-glutamatergic state. This would increase enzymes in the arachidonic acid cascade, leading to increases in neuronal inflammation in brain.

On the positive side, when patients with rheumatoid arthritis are treated with anti-inflammatory drugs called TNF-alpha inhibitors, the patients experience not only improvement in their arthritis, but lower levels of depression as well, again linking anti-inflammatory effects to antidepressant effects.

Rapoport and colleagues also reported that the mood stabilizers lithium, valproate, carbamazepine and lamotrigine all down-regulate parts of the brain’s inflammatory arachidonic acid cascade, suggesting that this could be part of their mechanism of therapeutic action in bipolar illness.

As we have reported in previous BNNs, other substances with more direct anti-inflammatory properties, such as the antibiotic minocycline, have been reported to have positive effects on mental health in schizophrenia.

See the findings of Bilbo et al. on page 2 for more about the link between diet, inflammation, and depression. The offspring of mother rats fed high fat diets during pregnancy were more obese as adults than offspring of mothers with normal diets. The offspring of mothers with high-fat diets also had more brain inflammation and behavior abnormalities linked to depression and anxiety.

All of these links between diet, obesity, inflammation, and depression suggest the importance of personal, clinical, and public health measures to curb the current trends of increasing obesity and depression in the US. The data suggest the possibility that both dietary and anti-inflammatory interventions may be useful for both depression and obesity.


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