Genetic study points to oxytocin as a potential treatment for obesity and postpartum depression

Scientists have identified a gene which, when missing or damaged, can cause obesity, behavioral problems and, in mothers, postpartum depression. The discovery, reported in Cellmay have wider implications for the treatment of postpartum depression, with a study in rats suggesting that oxytocin may alleviate symptoms.

Obesity and postpartum depression are important global health problems. Postpartum depression affects more than one in 10 women within a year of giving birth and is associated with an increased risk of suicide, accounting for up to one in five maternal deaths in high-income countries. Meanwhile, obesity has doubled among adults since 1990 and quadrupled among teenagers, according to the World Health Organization.

While investigating two boys from different families with severe obesity, anxiety, autism and behavioral problems triggered by sounds or smells, a team led by scientists at the University of Cambridge, UK and Baylor College of Medicine, Houston, USA, discovered that. boys were missing a single gene, known as TRPC5, which is located on the X chromosome.

Further investigation revealed that both boys inherited the gene deletion from their mothers, who were missing the gene on one of their X chromosomes. The mothers also had obesity but had also experienced postpartum depression.

To test whether it was the TRPC5 gene that was causing the problems in the sons and their mothers, the researchers turned to animal models, genetically engineered mice with a defective version of the gene (Trpc5 in mice).

Male mice with this defective gene showed the same problems as boys, including weight gain, anxiety, dislike of social interactions and aggressive behavior. The female mice exhibited the same behaviors, but when they became mothers, they also exhibited depressed behavior and impaired maternal care. Interestingly, male mice and female mice that were not maternal but carried the mutation did not show depression-like behavior.

Dr. Yong Xu, Associate Director for Basic Sciences at the USDA/ARS Child Nutrition Research Center at Baylor College of Medicine, said, “What we saw in those mice was quite remarkable. They exhibited behaviors very similar to those seen in people missing the TRPC5 gene, which in mothers included signs of depression and difficulty caring for their babies, this tells us that this gene is causing these behaviors.

TRPC5 is one of a family of genes that are involved in detecting sensory signals, such as heat, taste and touch. This particular gene acts on a pathway in the hypothalamus region of the brain, where it is known to control appetite.

When the researchers looked more closely at this region of the brain, they discovered that TRPC5 acts on oxytocin neurons—nerve cells that produce the hormone oxytocin, often nicknamed the “love hormone” because of its release in response to displays of love, emotion and connections. .

Deleting the gene from these oxytocin neurons led to otherwise healthy mice showing similar signs of anxiety, overeating and impaired sociability, and, in the case of the mothers, postpartum depression. Restoring the gene to these neurons reduced body weight and symptoms of postpartum anxiety and depression.

In addition to acting on oxytocin neurons, the team showed that TRPC5 also acts on so-called POMC neurons, which have long been known to play an important role in weight regulation. Children in whom the POMC gene is not functioning properly often have an insatiable appetite and gain weight from an early age.

Professor Sadaf Farooqi from the Institute of Metabolic Sciences at the University of Cambridge said: “There’s a reason why people with TRPC5 deficiency develop all these conditions. We’ve known for a long time that the hypothalamus plays a key role in regulating ‘instinctive behaviours’ that enable humans and animals to survive, such as foraging, social interaction, the flight-or-fight response, and caring for their infants Our work shows that TRPC5 acts on oxytocin neurons in the hypothalamus to play a critical role in regulating .our instincts”.

While TRPC5 gene deletions are rare, an analysis of DNA samples from around 500,000 individuals at UK Biobank found 369 people – around three-quarters of whom were women – who carried variants of the gene and had a higher body mass above average. index.

The researchers say their findings suggest that restoring oxytocin could help treat people with missing or defective TRPC5 genes, and potentially mothers who experience postpartum depression.

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

There is already evidence in animals that the oxytocin system is involved in both depression and maternal care, and there has been little evidence of the use of oxytocin as a treatment. The team says their work provides direct evidence of the role of oxytocin, which will be crucial in supporting larger, multicenter trials.

Professor Farooqi added, “This research reminds us that many behaviors that we assume are completely under our control have a strong basis in biology, whether it’s our eating behaviour, anxiety or postpartum depression. We need to be more understanding and kind to people who suffer with these conditions”.