New Genetic Study Highlights Oxytocin's Role in Treating Obesity and Postnatal Depression

Scientists have identified a gene that, when missing or impaired, can cause obesity, behavioral problems and, in mothers, postnatal depression. The discovery, reported in the journal Cell, may have wider implications for the treatment of postnatal depression, with a study in mice suggesting that oxytocin may alleviate symptoms.

Obesity and postnatal depression are significant global health problems. Postnatal depression affects more than one in 10 women within a year of giving birth and is linked to an increased risk of suicide, which accounts for as many as one in five maternal deaths in high-income countries.

Meanwhile, obesity has more than doubled in adults since 1990 and quadrupled in adolescents, according to the World Health Organization.

In the study, scientists from the University of Cambridge, UK, and Baylor College of Medicine, Houston, USA, investigated two boys from different families who exhibited severe obesity, anxiety, autism, and behavioral problems triggered by sounds or smells. They discovered that both boys were missing a single gene known as TRPC5, located on the X chromosome.

TRPC5 is part of a family of genes involved in detecting sensory signals such as heat, taste, and touch. This gene acts on a pathway in the hypothalamus region of the brain, which controls appetite. Detailed examination revealed that TRPC5 acts on oxytocin neurons—nerve cells producing the hormone oxytocin, which is released in response to affection, emotion, and bonding.

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

To determine if the TRPC5 gene was the cause of the issues in the boys and their mothers, researchers turned to animal models. They genetically engineered mice with a defective version of the gene. Male mice with this defective gene exhibited the same problems as the boys, including weight gain, anxiety, social interaction issues, and aggressive behaviour. Female mice displayed similar behaviours and, as mothers, also showed depressive behaviour and impaired maternal care.

The researchers also found that TRPC5 acts on neurons known for regulating weight. Children with non-functional genes often have an insatiable appetite and gain weight early in life. Although TRPC5 gene deletions are rare, an analysis of DNA samples from around 500,000 individuals in the UK Biobank revealed 369 people with variants of the gene and a higher-than-average body mass index.

The findings suggest that restoring oxytocin could help treat individuals with missing or defective TRPC5 genes and potentially mothers experiencing postnatal depression.

Reference: Li, Y, Cacciottolo, TM & Yin, N. Loss of Transient Receptor Potential Channel 5 Causes Obesity and Postpartum Depression. Cell; 2 July 2024; DOI: 10.1016/j.cell.2024.06.001