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“This inflammatory state can impact the brain…”

Research suggests that there is a bidirectional connection between metabolic health and depression. For instance, metabolic conditions such as obesity and diabetes are associated with chronic low-grade inflammation. This inflammatory state can impact the brain and influence mood regulation. Conversely, mood disturbances may alter metabolic pathways that can impact brain gut communication, including ghrelin and leptin signaling, affecting appetite and satiety.

A 2020 meta-analysis by Mariska Bot, Yuri Milaneschi and coworkers from Vrije Universiteit Amsterdam and published in the journal Biological Psychiatry compared metabolic markers between depressed individuals and nondepressed individuals in order to further investigate the connection between mental health and metabolic health as indexed by lipid metabolites. The study analyzed data from 9 Dutch clinical and population-based studies and assessed the consistency of findings across studies. In total, data from 5,283 individuals with depression and 10,145 control subjects were analyzed.

“The study found that depression was associated with specific metabolic alterations…”

The study found that depression was associated with specific alterations in several components of lipid metabolism including lower levels of high density lipoprotein (HDL) and more very low density lipoprotein (VLDL) and triglycerides in the blood. Other metabolites associated with depression included apolipoprotein B as well as the inflammation marker glycoprotein acetyls and the amino acids tyrosine and isoleucine. Additionally, higher monounsaturated fatty acids, total fatty acids, and estimated fatty acids chain length were associated with an increased odds of depression.

In contrast, higher levels of metabolites that were associated with a lower odds for depression were apolipoprotein A1, cholesterol content for HDL, mean diameter of HDL particles, and ketone body acetate. HDL particles in the blood can vary in size, and larger HDL particles have been shown to be protective against coronary artery disease. HDL particles remove fats and cholesterol from cells, including those within artery wall plaques, and transport it back to the liver for excretion or re-utilization. Thus the cholesterol carried within HDL particles (HDL-C) is sometimes called “good cholesterol” (despite being the same as cholesterol in LDL particles).

“…individuals with depression are more likely to engage in unhealthy behaviors…”

It is possible that altered lipid profiles are a result of depression, as individuals with depression are more likely to engage in unhealthy behaviors such as “sedentariness, excessive alcohol use, and poor nutrition.” These findings of metabolic alterations in depression may explain be one of several reasons why individuals with depression have an increased risk of developing cardiometabolic disease.

The researchers discussed that another explanation could be that “lipid dysregulations may be part of the pathophysiological pathways implicated in depression, such as chronic hypothalamic- pituitary-adrenal (HPA) axis and chronic low grade immune activation, resulting in lipolysis, release of fatty acids, synthesis of VLDL, hypertriglyceridemia, and reduction in HDL cholesterol.” Lipolysis refers to the process through which triglycerides are turned into free fatty acids and glycerol and released into the blood as a means of mobilizing the body’s stored energy. Excess lipolysis can lead to high free fatty acid content in the liver and is associated with diabetes, obesity and fatty liver disease.

An additional explanation is that the metabolic signature of depression may stem from certain genetic factors. It is also possible that all three of these explanations play a role. In line with other studies, the finding of glycoprotein acetyls, a biomarker of chronic and cumulative inflammation, being positively associated with depression links inflammation to depression, suggesting the impact of diet and lifestyle.

“Improving metabolic health through lifestyle changes like a balanced diet and regular exercise might help alleviate symptoms of depression.”

Finding a link between depression and compromised cardiometabolic health provides a potential target for prevention and treatment of depression as well as the onset of other chronic diseases. Improving metabolic health through lifestyle changes like a balanced diet and regular exercise might help alleviate symptoms of depression. Likewise, treating depression effectively through pharmacological and mind targeted therapies might positively impact metabolic health by improving lifestyle habits and reducing stress.