Researchers have identified a gene that, when absent or dysfunctional, can lead to obesity, behavioral issues, and postnatal depression in mothers. This breakthrough finding, highlighted in a recent report in Cell, could potentially revolutionize the treatment of postnatal depression. Studies in mice suggest that oxytocin might have a therapeutic effect in alleviating postnatal depression symptoms.
Obesity and postnatal depression represent significant global health challenges. Postnatal depression affects over 10% of women within a year of childbirth and is associated with a higher risk of suicide, contributing to around 20% of maternal deaths in high-income nations. Concurrently, obesity rates have more than doubled in adults and quadrupled in adolescents since 1990, according to the World Health Organization.
An investigation into two boys from different families who exhibited severe obesity, anxiety, autism, and behavioral sensitivities to stimuli like sounds or smells led a team of scientists from the University of Cambridge and Baylor College of Medicine to discover a crucial missing gene called TRPC5 on the X chromosome.
Further analysis revealed that both boys inherited the gene deletion from their mothers, who not only lacked the gene on one of their X chromosomes but also experienced postnatal depression in addition to obesity.
By creating genetically modified mice with a defective version of the TRPC5 gene (Trpc5 in mice), researchers confirmed that this gene was responsible for the observed issues in both boys and their mothers.
Male mice with this genetic modification displayed symptoms like weight gain, anxiety, social aversion, and aggression similar to the affected boys. Female mice showed corresponding behaviors, with mothers also exhibiting signs of depression and compromised maternal care. Interestingly, male and female mice without offspring did not display depressive behaviors even with the genetic mutation.
The deletion of TRPC5, a gene involved in sensory signal processing, particularly affects the pathway in the hypothalamus region of the brain responsible for regulating appetite.
Upon in-depth exploration of this brain region, researchers found that TRPC5 influences oxytocin neurons, which are nerve cells producing oxytocin, a hormone associated with affection, emotion, and bonding. Deleting the gene from these neurons in otherwise healthy mice led to symptoms like anxiety, overeating, social impairment, and postnatal depression in mothers. Reintroduction of the gene in these neurons alleviated body weight issues and symptoms of anxiety and postnatal depression.
Besides oxytocin neurons, TRPC5 also impacts POMC neurons, known for their role in weight regulation. Individuals with disrupted POMC genes often struggle with insatiable appetite and weight gain from a young age.
The findings from DNA samples of around 500,000 individuals in the UK Biobank revealed 369 individuals, most of whom were women, carrying gene variants linked to higher-than-average body mass index, suggesting a potential connection between TRPC5 variants and obesity.
The researchers propose that restoring oxytocin levels could be beneficial for individuals with TRPC5 gene deficiencies and mothers experiencing postnatal depression.
Professor Sadaf Farooqi from the University of Cambridge emphasized the importance of this research in shedding light on postnatal depression and its potential treatment with oxytocin.
Existing evidence in animals supports the involvement of the oxytocin system in depression and maternal care, with preliminary trials exploring oxytocin as a treatment option. This study provides concrete evidence of oxytocin’s role, paving the way for more extensive clinical trials.
Professor Farooqi underscores the biological underpinnings of behaviors related to eating habits, anxiety, and postnatal depression, urging a more compassionate approach towards individuals grappling with these conditions.
This research received funding from various organizations, including Wellcome, the National Institute for Health and Care Research (NIHR), NIHR Cambridge Biomedical Research Centre, Botnar Foundation, and Bernard Wolfe Health Neuroscience Endowment.
