̽��ֱ�� of Cambridge - National Institute for Health Research

Genetic study points to oxytocin as possible treatment for obesity and postnatal depression

cjb250 — Tue, 02 Jul 2024 15:00:18 +0000

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.

While investigating two boys from different families with severe obesity, anxiety, autism, and behavioural problems triggered by sounds or smells, a team led by scientists at the ̽��ֱ�� of Cambridge, UK, and Baylor College of Medicine, Houston, USA, discovered that the boys were missing a single gene, known as TRPC5, which sits 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. ̽��ֱ��mothers also had obesity, but in addition had experienced postnatal depression.

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

Male mice with this defective gene displayed the same problems as the boys, including weight gain, anxiety, a dislike of social interactions, and aggressive behaviour. Female mice displayed the same behaviours, but when they became mothers, they also displayed depressive behaviour and impaired maternal care. Interestingly, male mice and female mice who were not mothers but carried the mutation did not show depression-like behaviour.

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

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 in more detail at this brain region, 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 affection, emotion and bonding.

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 mothers, postnatal depression. Restoring the gene in these neurons reduced body weight and symptoms of anxiety and postnatal depression.

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

Professor Sadaf Farooqi from the Institute of Metabolic Science at the ̽��ֱ�� of Cambridge said: “There's a reason why people lacking TRPC5 develop all of these conditions. We’ve known for a long time that the hypothalamus plays a key role in regulating ‘instinctive behaviours’ – which enable humans and animals to survive – such as looking for food, 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 deletions of the TRPC5 gene are rare, an analysis of DNA samples from around 500,000 individuals in UK Biobank revealed 369 people – around three-quarters of whom were women – that carried variants of the gene and had a higher-than-average body mass index.

̽��ֱ��researchers say their findings suggests that restoring oxytocin could help treat people with missing or defective TRPC5 genes, and potentially mothers experiencing postnatal 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 instance, we have made a breakthrough in understanding postnatal depression, a serious health problem about which very little is known despite many decades of research. And 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 in maternal care and there have been small trials into the use of oxytocin as a treatment. ̽��ֱ��team say their work provides direct proof of oxytocin’s role, which will be crucial in supporting bigger, multi-centre trials.

Professor Farooqi added: “This research reminds us that many behaviours which we assume are entirely under our control have a strong basis in biology, whether that’s our eating behaviour, anxiety or postnatal depression. We need to be more understanding and sympathetic towards people who suffer with these conditions.”

This work was supported by Wellcome, the National Institute for Health and Care Research (NIHR), NIHR Cambridge Biomedical Research Centre, Botnar Fondation and Bernard Wolfe Health Neuroscience Endowment.

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

Scientists have identified a gene which, when missing or impaired, can cause obesity, behavioural problems and, in mothers, postnatal depression. ̽��ֱ��discovery, reported on 2 July in Cell, may have wider implications for the treatment of postnatal depression, with a study in mice suggesting that oxytocin may alleviate symptoms.

This research reminds us that many behaviours which we assume are entirely under our control have a strong basis in biology. We need to be more understanding and sympathetic towards people who suffer with these conditions

Sadaf Farooqi

Olli Turho (Getty Images)

Illustration of a tired African American mother crying

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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One in three young people say they felt happier during lockdown

cjb250 — Tue, 22 Feb 2022 11:25:23 +0000

As the COVID-19 pandemic swept the world, many countries imposed strict lockdown measures, with workplaces and businesses closing and people forced to remain at home. Measures also included school closures, with exceptions for young people whose parents were classified as essential workers and those considered ‘vulnerable’, for example children under the care of social services and those in families or social situations deemed by schools to be of concern.

Several studies have reported that the lockdown had a negative impact on the mental health and wellbeing of young people, but this effect has not been uniformly reported, with a number of studies suggesting that some young people may have benefited from lockdown.

Emma Soneson, a PhD student and Gates Scholar at the Department of Psychiatry, ̽��ֱ�� of Cambridge, said: “ ̽��ֱ��common narrative that the pandemic has had overwhelmingly negative effects on the lives of children and young people might not tell the full story. In fact, it seems as though a sizeable number of children and young people may have experienced what they felt was improved wellbeing during the first national lockdown of 2020.

“After hearing from patients in our clinical practice and informally from several parents and young people that they thought the lockdown was beneficial for their or their child’s mental health, we decided to look at this trend.”

Ms Soneson and colleagues explored this issue using the OxWell Student Survey, a large, school-based survey of students aged eight to 18 years living in England. More than 17,000 students took part in the June/July 2020 survey, during the tail end of the first national lockdown, answering questions about their experiences of the pandemic, school, home life, and relationships, among others. ̽��ֱ��results of their research have been published in European Child and Adolescent Psychiatry.

̽��ֱ��team found that one in three students thought their mental wellbeing had improved during the first lockdown. In fact, an almost identical number of students fell into each of the three categories: their mental wellbeing had improved; there had been no change; or they had experienced a deterioration to their wellbeing.

̽��ֱ��highest proportions of students who reported improved mental wellbeing were among those who were in school every day (39%) and most days (35%), while the highest proportion of students who reported worse wellbeing were those who attended just once or twice (39%).

Students who felt they had had better wellbeing during lockdown were more likely than their peers to report positive lockdown experiences of school, home, relationships, and lifestyle. For example, compared with their peers, a greater percentage of students reporting better wellbeing also reported decreases in bullying, improved relationships with friends and family, less loneliness, better management of schoolwork, more sleep, and more exercise during lockdown compared with before.

Professor Peter Jones, also from Department of Psychiatry at the ̽��ֱ�� of Cambridge, said: “What we’ve seen is a complex mix of factors that affect whether a child’s mental health and wellbeing was affected by the lockdown. These range from their mental health before the pandemic through to their relationships with their families and peers, and their attitudes towards school.”

While previous studies have reported young people worrying about the impact of lockdown on friendships, nearly half of those who reported improved mental wellbeing in this new study reported feeling less left out and lonely and having better relationships with friends and family. In part, this may be because access to digital forms of social interaction can mitigate the negative effects of reduced face-to-face contact. With many parents and carers at home, there was also potential for improved family relationships.

One specific aspect of peer relationships that changed during the pandemic was bullying. ̽��ֱ��researchers found that most young people who had been bullied in the past year reported that the bullying had reduced. ̽��ֱ��proportion that reported that they were bullied less than before lockdown was higher for those who reported improved wellbeing (92%) than for those who reported no change (83%) or deterioration in their wellbeing (81%).

For approximately half of the young people who reported improved mental wellbeing, lockdown was associated with improvements in sleep and exercise – for example, 49% of those who reported improved mental wellbeing reported sleeping more, compared with 30% of those who reported no change and 19% of those who reported deterioration.

Family relationships also clearly played a part: the proportion of students who reported that they were getting along with household members better than before lockdown was higher for the group who reported improved mental wellbeing (53%) than for the groups who reported no change (26%) or deterioration (21%), with a similar pattern for getting along with friends (41%, 26%, and 27% respectively).

Professor Mina Fazel from the Department of Psychiatry at the ̽��ֱ�� of Oxford said: “While the pandemic has undoubtedly had negative consequences for many, it is important to keep in mind that this is not the case for all children and young people. We are interested in how we can learn from this group and determine if some of the changes can be sustained in order to promote better mental health and wellbeing moving forward.”

Some of the school-related factors that may have influenced how a young person responded to the lockdown include: the increased opportunities for flexible and tailored teaching that encouraged different styles of learning; smaller class sizes and more focused attention from teachers for those attending school; and later waking times and more freedom during the school day.

̽��ֱ��research was supported by the Gates Cambridge Trust, the National Institute for Health Research, the Westminster Foundation and UK Research and Innovation.

Emma Soneson is a PhD student at Clare College, Cambridge.

Reference
Soneson, E et al. Happier During Lockdown: A descriptive analysis of self-reported wellbeing in 17,000 UK school students during Covid-19 lockdown. European Child and Adolescent Psychiatry; 17 Feb 2022; DOI: 10.1007/s00787-021-01934-z

One in three young people say their mental health and wellbeing improved during COVID-19 lockdown measures, with potential contributing factors including feeling less lonely, avoiding bullying and getting more sleep and exercise, according to researchers at the universities of Cambridge and Oxford.

̽��ֱ��common narrative that the pandemic has had overwhelmingly negative effects on the lives of children and young people might not tell the full story

Emma Soneson

Lukas Rychvalsky

Boy with football

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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