Researchers have identified a gene that can trigger obesity, behavior problems and postpartum depression when missing or damaged.

The finding could lead to new treatments for postpartum depression and overeating: The study in mice suggests the so-called “love hormone” — oxytocin — may ease symptoms. 

Obesity and postpartum depression are major health problems worldwide.

The new study, published July 2 in the journal Cell, is an outgrowth of research by scientists at Baylor College of Medicine in Houston and the University of Cambridge in the U.K. 

They were studying two boys from different families who were severely obese. The boys had autism, anxiety and behavior problems triggered by smells or sounds. Both were missing a gene called TRP5. 

They inherited the gene deletion from their mothers, who also were missing the gene. Both women were obese and had experienced postpartum depression.

To find out if the missing TRPC5 gene was causing problems in the boys and their moms, researchers put genetic engineering to work. They produced mice with a defective version of the gene — called Trpc5 in mice.

“What we saw in those mice was quite remarkable,” said study co-author Dr. Yong Xu, associate director for basic sciences at the USDA/ARS Children’s Research Center at Baylor College of Medicine in Houston. “They displayed very similar behaviors to those seen in people missing the TRPC5 gene.”

In the mothers, that included signs of depression and difficulty caring for their babies, he said. 

Male mice with the flawed gene had issues similar to those of the boys — weight gain, aggressive behavior, anxiety and a distaste for social interactions. 

This, Xu said, shows that the gene is causing these behaviors.

Researchers described TRPC5 as one of a family of genes involved in detecting sensory signals, such as heat, taste and touch. It acts on a pathway in a brain region known to control appetite. 

Looking more closely at this brain region — the hypothalamus — researchers found that TRPC5 acts on nerve cells that produce the hormone oxytocin. It’s commonly called the “love hormone” because its release accompanies displays of affection, bonding and emotion.

When researchers deleted the gene from these oxytocin neurons, otherwise healthy mice became anxious, overate and were less social. Mouse mothers had signs of postpartum depression.

When the gene was restored, body weight dropped and anxiety and depression eased.

“There’s a reason why people lacking TRPC5 develop all of these conditions,” said co-study author Sadaf Farooqi, of the Institute of Metabolic Science at the University of Cambridge. 

Researchers have known for a long time that the hypothalmus plays a big part in regulating instinctive behaviors essential to survival — looking for food, the flight-or-fight response and caring for babies. 

“Our work shows that TRPC5 acts on oxytocin neurons in the hypothalmus to play a critical role in regulating our instincts,” Farooqi said in a Cambridge news release. 

Deletions of the TRPC5 gene are rare. DNA samples from a half-million people in the U.K. Biobank found 369 who carried variants of the gene and were overweight. Three-quarters were women.

Researchers say the findings suggest that restoring oxytocin might help treat people with missing or flawed TRPC5 genes, including moms experiencing postpartum depression. Research in animals often differs in people, however.

“While some genetic conditions such as TRPC5 deficiency are very rare, they teach us important lessons about how the body works,” Farooqi said. “In this instance, we have made a breakthrough in understanding postnatal depression, a serious health problem about which very little is known despite many decades of research. And importantly, it may point to oxytocin as a possible treatment for some mothers with this condition.”

The research is a reminder that many behaviors that people think they can control are based in biology. 

“We need to be more understanding and sympathetic towards people who suffer with these conditions,” Farooqi noted.

More information

The March of Dimes has more about postpartum depression

SOURCE: University of Cambridge, news release, July 2, 2024