BY: Andrew Hardaway, PhD

DATE: June 20, 2016

In my previous post, I introduced some emerging research on how diets rich in fat affect brain energy availability. In this post, I hope to layer on some discussion of how excessive consumption of energy-dense foods contributes to anxiety and depressive-like behavior. At the outset, it is important for readers to understand that dietary fat is a critical energy source for the body and necessary for life. The goal of this type of research is to form a new understanding of how excessive consumption of these foods may contribute to the risk for other symptoms commonly observed patients with eating disorders or obesity like anxiety disorders or depression.

In the current article, the authors worked with laboratory rats to investigate the molecular and behavioral impact of chronic high fat diet consumption or a control diet. Similar to previous studies, the authors showed that a chronic high fat diet (16 weeks) produces an obese, diabetic-like state that is characterized by an increase in body weight and impaired blood glucose tolerance. During the middle portion and last three weeks of high fat diet exposure, they measured anxiety and depressive-like behaviors using established, clinically-relevant behavioral paradigms. They observed that rats fed chronic high fat diet were more anxious and displayed one of the clinical hallmarks of depression known as anhedonia (i.e., the inability to experience pleasure). Importantly, the authors noted that it took several months of chronic high fat diet exposure before they could observe these effects, whereas after two months, the high fat diet and control diet mice were indistinguishable.

Previous studies have shown that chronic high fat diet increases inflammation in the brain, so the authors pursued a detailed investigation of the level of inflammatory molecules called cytokines in the brain’s hippocampus (the part of the brain that functions as the center of emotion, memory, and the autonomic nervous system). They show that levels of several key cytokines were elevated. These studies show that chronic high fat diet is increasing inflammation in one of the brain’s key emotional and behavioral centers.

Ketamine is an emerging pharmacological tool for treating depression that is not effectively treated by serotonin selective reuptake inhibitors (like Prozac), the most widely prescribed drugs to treat depression and anxiety. The authors show that ketamine was able to restore anxiety and depressive-like behavior induced by chronic high fat diet to levels seen in rats fed a control diet.. They could also rescue these behavioral abnormalities by treating with a drug that blocks the purinergic receptor P2RX7 which is known to reduce inflammation. These data are intriguing and suggest that both ketamine and P2RXY antagonists might be a novel strategy for treatment-resistant depression in patients with type 2 diabetes and elevated body fat.

The authors show that a chronic high fat diet can produce anxiety and depressive-like behavior in rats, but how does this relate to our own health? Research studies like these are highly controlled and use extreme diets containing up to 60% fat (roughly that of cheesecake). While many people do not have regular access to healthful foods it’s not fully clear how sustained access to research diets actually mirror a typical Western diet. Additionally, for those with a genetic predisposition to obesity or binge-eating disorder, it isn’t clear how diet may contribute to the manifestation of other co-occurring psychiatric disorders like anxiety, depression, or substance use disorders. This latest study contributes to mounting evidence that the brain’s inflammatory response increases the risk of anxiety or depression. However, a key question for the obesity and binge-eating disorder patient community is whether medication treatments that decrease the brain’s inflammatory response may be effective in alleviating the associated anxiety or depression.