Gene discovery suggests oxytocin plays a role in depression

Scientists have identified genes that, when missing or dysfunctional, can lead to obesity, behavioral disorders and, in mothers, postpartum depression. cellThis could have broad implications for treating postnatal depression, with studies in mice suggesting that oxytocin may ease symptoms.

Obesity and postpartum depression are major health issues worldwide. Postpartum depression affects more than one in ten women within the first year after giving birth and is associated with an increased risk of suicide. In high-income countries, postpartum depression accounts for one in five maternal deaths. Meanwhile, according to the World Health Organization, obesity has more than doubled in adults and quadrupled in adolescents since 1990.

While studying two boys from different families with severe obesity, anxiety, autism and behavioural disorders triggered by sounds and smells, a research team led by scientists from the University of Cambridge in the UK and Baylor College of Medicine in Houston, US, discovered that the boys ” TRPC5It is located on the X chromosome.

Further investigation revealed that the boys had inherited a genetic deletion from their mother, who was missing a gene on one of her X chromosomes and who had also been obese but had also suffered from postpartum depression.

To test whether it was the TRPC5 gene that was causing the problems for the boys and their mother, the researchers turned to animal models, genetically engineering mice to carry a defective version of the gene.Trap 5 for mouse).

Male mice with the defective gene showed the same problems as boys, including weight gain, anxiety, aversion to social interactions, and aggressive behavior. Female mice showed the same behaviors, but when they became mothers, they also showed depressive behavior and impaired maternal care. Interestingly, male and female mice carrying the mutation who were not mothers did not show depressive behaviors.

“The behavior we saw in the mice was very surprising. They exhibited behaviors that were very similar to those seen in malnourished people,” said Dr. Yong Xu, associate director of basic science at the USDA/ARS Pediatric Nutrition Research Center at Baylor College of Medicine. TRPC5 “The gene includes signs of depression in the mother and difficulties caring for the baby, indicating that this gene is causing these behaviors.”

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

When the researchers looked more closely at this brain region, TRPC5 It acts on oxytocin neurons, which are nerve cells that produce the hormone oxytocin, also known as the “love hormone” because it is released in response to expressions of affection, emotion, and bonding.

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

In addition to acting on oxytocin neurons, the team TRPC5 It also acts on what are called POMC neurons, which have long been known to play an important role in regulating body weight: Children whose POMC gene is not functioning properly often have a strong appetite and put on weight at an early age.

There's a reason why people are missing TRPC5 It has long been known that the hypothalamus plays a key role in controlling the “instinctual behaviors” humans and animals need to survive, such as food hunting, social interactions, the flight or fight response, and caring for young. TRPC5 It acts on oxytocin neurons in the hypothalamus and plays an important role in regulating instincts.”

Sadaf Farooqui, Professor at the Institute of Metabolic Science, University of Cambridge

To delete TRPC5 The gene is rare, but analysis of DNA samples from around 500,000 people from UK Biobank found that 369 people – around three-quarters of them women – carried the gene mutation and had an above-average BMI.

The researchers say their findings suggest that restoring oxytocin may be useful in treating people with missing or defective TRPC5 genes, as well as mothers experiencing postpartum depression.

Professor Farooqi said: TRPC5 “Oxytocin deficiency is very rare, but it offers important lessons about how the body works. This case marks a breakthrough in our understanding of postpartum depression, a serious health issue about which we know very little despite decades of research. And importantly, it suggests that oxytocin may be a potential treatment for some mothers with this condition.”

The oxytocin system has already been implicated in both depression and maternal care in animal studies, and there have been small trials of oxytocin as a therapeutic agent, but the authors say their study provides direct evidence for a role for oxytocin and supports larger, multi-centre trials.

Prof Farooqui added: “This study reminds us that many behaviours we assume are entirely under our control – such as eating habits, anxiety and post-natal depression – have a strong biological basis and we need to have more understanding and compassion for those who suffer from these conditions.”

This research was supported by Wellcome, the National Institute for Health and Care Research (NIHR), the NIHR Cambridge Biomedical Research Centre, the Botner Foundation and the Bernard Woolf Health and Neuroscience Fund.