An intriguing new study, led by scientists from the University of Glasgow, suggests there is a direct causative link between eating a high-fat diet and the development of depression. The new research demonstrates how certain dietary fats can enter the brain, disrupt specific signaling pathways in the hypothalamus, and subsequently induce signs of depression.

Scientists have long observed a strong correlation between obesity and depression and, while it may seem like the two are simply interlinked through obvious psychological associations, some studies are starting to suggest the connection may actually be underpinned by biological mechanisms.

One compelling study from 2018 found that mice given a high-fat diet displayed depressive behaviors until microbiome-altering antibiotics returned their behavior back to normal. This study inferred that high-fat diets may cultivate certain populations of gut bacteria that have the capacity to induce neurochemical changes leading to depression symptoms.

This new study moves away from specifically investigating gut bacteria to examine what neurological mechanisms could be triggered by high-fat diets that lead to the development of depression. After the research initially verified that both dietary and genetically induced obesity led to depression-like behaviors in mouse models, the scientists zoomed in on what was happening in the animal’s brains to induce the changes.

The research revealed that the characteristics of depression were being induced in the animals through disruptions in the cAMP/PKA signaling pathway in the hypothalamus. It was further revealed that these disruptions were caused by the accumulation of different dietary fatty acids directly in the hypothalamus. This striking finding is the first time scientists have seen dietary fatty acids move through the bloodstream, accumulate in a specific region of the brain, and then induce depression-like behavioral changes.

“This is the first time anyone has observed the direct effects a high-fat diet can have on the signaling areas of the brain related to depression,” says lead author on the study, George Baillie. “This research may begin to explain how and why obesity is linked with depression and how we can potentially better treat patients with these conditions.”

For some time scientists have noted obese patients suffering from depression respond poorly to antidepressant treatments compared to lean patients. This study raises an interesting hypothesis, suggesting a potential new generation of antidepressants that can specifically target this neurological mechanism and deliver an effective novel drug to overweight or obese patients suffering major depression.

“We often use fatty food to comfort ourselves as it tastes really good, however in the long term, this is likely to affect one’s mood in a negative way,” says Baillie. “Of course, if you are feeling low, then to make yourself feel better you might treat yourself to more fatty foods, which then would consolidate negative feelings.”

The study also suggests the association between obesity and depression is not entirely bi-directional. A high-fat diet can possibly directly induce the onset of depression symptoms. Observational studies in humans have so far delivered mixed conclusions on whether an unhealthy diet actively causes depression and this new study has only demonstrated this neurological mechanism in animals.

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