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Obesity and depression: A new study identifies neural links

Depressed lady
A recent research has discovered connections between depression and obesity in the brain.
  • Obesity and mental health disorders such as depression and anxiety have a two-way relationship.
  • A mice study suggests that a high-fat diet can disrupt a newly discovered neural circuit in the brain that regulates mood and appetite.
  • The animals showed less anxiety and lost weight after taking a combination of two drugs that work on this circuit.
  • After the procedure, the animals lost weight not just because they consumed less, but also because they chose nutritious foods.

Obesity is predicted to impact approximately half of all adults in the United States by 2030, according to researchers.

Obesity has long been related to a host of physical conditions, including type 2 diabetes, hypertension, rheumatoid arthritis, and certain types of cancer.

Obesity and mental disorder, on the other hand, have a complicated two-way relationship.

According to the Centers for Disease Control and Prevention (CDC), 43 percent of people in the United States aged 20 and up who suffer from depression also have obesity. There is also a connection between mental illness and obesity in general.

Many antidepressant drugs cause weight gain as a side effect. Obesity, on the other hand, tends to have a psychological impact on people that predisposes them to depression, according to studies.

However, researchers conclude that the two conditions might have a more direct physiological connection.

Obesity and mental disorder can be related by a variety of factors, including:

  • inflammation
  • hormonal disturbances
  • genetic factors

Brain circuitry

It’s also possible that some neural pathways in the brain predispose people to obesity and mental health problems. However, it is unclear where these circuits are located and how they work.

Researchers from Baylor College of Medicine in Houston, TX, recently led a group of specialists that may have discovered such a circuit in mice.

The researchers discovered that feeding mice a high-fat diet disrupted the circuit, causing weight gain as well as anxiety and depression in standard behavioral experiments.

When the researchers used genetic methods to restore the normal functioning of nerve receptors in the circuit, the animals lost weight and their anxiety and depression symptoms disappeared.

Surprisingly, the mice decreased their food consumption and were no longer interested in high fat food, despite having a healthy appetite.

“We were shocked to see that the animals lost weight not because they lost their appetite, but because genetically assisted mental state readjustment modified their feeding choice from high fat to low fat food,” says Dr. Guobin Xia, a postdoctoral associate at Baylor and the study’s co-first author.

Two drugs that target the same nerve receptors in this brain circuit had similar positive effects on the mice’s eating habits.

The results were published in the journal Molecular Psychiatry.

Emotions and appetite

The newly discovered brain circuit is made up of contacts between neurons in the hypothalamus and those in the bed nucleus of the stria terminalis (BNST).

The hypothalamus is involved in hormonal control of appetite and physiology, whereas the BNST is involved in stress and fear responses, among other things.

The researchers discovered that a high-fat diet impaired the circuit in mice, causing it to lose its ability to control appetite and emotions.

Dr. Xia states, “This newly discovered circuit was malfunctioning in obese and depressed mice.”

The scientists discovered that by altering the function of two nerve receptors in the BNST, either genetically or with drugs that target the receptors, they could restore the circuit.

This reversed the negative effects of a high-fat diet, lowering body weight and removing symptoms of anxiety and depression.

Combination of drugs

The two medications, zonisamide and granisetron, have already been approved by the Food and Drug Administration (FDA) as treatments for epilepsy and nausea prevention, respectively.

Dr. Qi Wu, who is the study’s corresponding author, explains:

“We discovered that the combination of two clinically approved drugs, zonisamide and granisetron, profoundly reduced anxiety and depression in mice and promoted weight loss by synergistically acting upon two different molecular targets within our newly identified brain circuit.”

The results may lead to potential clinical trials of this drug combination to treat the association between obesity and mental health conditions, according to the researchers.

However, before other studies validate the findings and conduct clinical trials, these preliminary findings from an animal study remain tentative and do not apply to humans.

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