Oxytocin Linked to Treatment for Obesity & Postnatal Depression

Scientists have identified a gene, TRPC5, whose impairment or absence can lead to obesity, behavioral problems, and postnatal depression in mothers. The groundbreaking discovery, detailed in the journal Cell, suggests potential new treatments for postnatal depression, particularly through the hormone oxytocin.

Global Health Impact of Obesity and Postnatal Depression

Obesity and postnatal depression are significant global health issues. According to the World Health Organization, adult obesity rates have more than doubled since 1990, and adolescent rates have quadrupled. Postnatal depression affects over one in ten women within a year of giving birth and is a leading cause of maternal deaths due to suicide in high-income countries.

Discovery and Initial Findings

The discovery began with the study of two boys from different families who exhibited severe obesity, anxiety, autism, and behavioral problems triggered by sounds or smells. Researchers from the University of Cambridge and Baylor College of Medicine found that both boys were missing the TRPC5 gene, located on the X chromosome. The mothers, who also lacked this gene on one of their X chromosomes, had similar issues with obesity and postnatal depression.

To determine if TRPC5 was the cause, researchers genetically engineered mice to lack the gene. Male mice exhibited the same symptoms as the boys, including weight gain, anxiety, social avoidance, and aggression. Female mice showed these behaviors and, when they became mothers, also displayed signs of depression and impaired maternal care. Non-mother female mice did not exhibit depression-like behaviors, highlighting a specific link to postnatal depression.

Role of TRPC5 in the Brain

TRPC5 is part of a gene family involved in sensing sensory signals like heat, taste, and touch. This gene influences the hypothalamus, a brain region that controls appetite. The researchers found that TRPC5 affects oxytocin neurons in the hypothalamus. Oxytocin, known as the “love hormone,” is released in response to affection and bonding. Removing TRPC5 from these neurons led to anxiety, overeating, impaired sociability, and, in mothers, postnatal depression. Restoring the gene reduced weight and alleviated anxiety and depression symptoms.

TRPC5 and POMC Neurons

TRPC5 also impacts POMC neurons, crucial in weight regulation. Children with non-functional POMC genes often have an insatiable appetite and early weight gain. Professor Sadaf Farooqi from the University of Cambridge explained that the hypothalamus regulates instinctive behaviors essential for survival, such as seeking food, social interactions, and maternal care. TRPC5’s role in these processes underscores its importance.

Broader Implications and Potential Treatments

Although TRPC5 gene deletions are rare, an analysis of 500,000 DNA samples from UK Biobank identified 369 individuals, primarily women, with gene variants associated with higher body mass index. This suggests broader implications for understanding obesity and related conditions.

Restoring oxytocin could be a potential treatment for those with TRPC5 deficiencies and mothers with postnatal depression. Evidence from animal studies supports oxytocin’s involvement in depression and maternal care. The researchers advocate for larger trials to explore oxytocin as a treatment.

Conclusion

This discovery provides critical insights into postnatal depression and obesity, revealing the significant biological underpinnings of behaviors previously thought to be entirely controllable. It emphasizes the need for empathy and understanding for those affected by these conditions and opens new avenues for treatment, particularly through oxytocin. The research was supported by various institutions, including Wellcome, NIHR, and the Botnar Foundation.