̽��ֱ�� of Cambridge - Avon Longitudinal Study of Parents and Children (ALSPAC)

Many of us could carry up to 17kg of fat due to a change in a single gene

Anonymous — Thu, 27 May 2021 15:00:14 +0000

̽��ֱ��study led by scientists at the MRC Metabolic Diseases Unit which is part of the Wellcome-MRC Institute of Metabolic Science at the ̽��ֱ�� of Cambridge and the MRC Integrative Epidemiology Unit at the ̽��ֱ�� of Bristol is published today in Nature Medicine.

It has been known for a long time that obesity tends to run in families, but it was not until about 20 years ago that scientists started to discover that changes in specific genes can have very large effects on our weight even from early childhood.

One of these genes, the Melanocortin 4 Receptor (MC4R), makes a protein that is produced in the brain where it sends signals to our appetite centres, telling them how much fat we have stored. When the MC4R gene does not work properly, our brains think we have lower fat stores than we do, signalling that we are starving and need to eat.

̽��ֱ��research team found that around one in every 340 people may carry a disruptive mutation at MC4R. People who carry these mutations were more likely to have a greater weight from early childhood and, by 18 years of age, they were on average 17 kg (37 lbs or 2.5 stone) heavier, with the majority of this excess weight likely to be fat.

These results were found by studying the MC4R gene in a random sample of around 6,000 participants born in Bristol in 1990-91, who were recruited to Children of the 90s, a health study based at the ̽��ֱ�� of Bristol. This is a unique UK study that recruited approximately 80 percent of the births occurring in a specific region of the South West and which has continued to follow participants. As the Children of the 90s study managed to recruit such a high percentage of mothers during pregnancy, it is one of the most representative and comprehensive studies of its kind.

̽��ֱ��authors examined the MC4R gene in all 6,000 people and, whenever a mutation was found, went on to study its functional effects in the laboratory. This meticulous approach has provided the best estimates so far of the frequency and impact of MC4R mutations on people’s weight and body fat. Based on the frequency of mutations in this study, it is possible that around 200,000 people in the UK could carry a substantial amount of additional fat because of mutations in MC4R.

Professor Sir Stephen O’Rahilly, from the ̽��ֱ�� of Cambridge and one of the authors of the study, said: “Parents of obese children are often blamed for poor parenting and not all children obtain appropriate professional help. Our findings show that weight gain in childhood due to a single gene disorder is not uncommon. This should encourage a more compassionate and rational approach to overweight children and their families – including genetic analysis in all seriously obese children.”

Dr Kaitlin Wade, from the ̽��ֱ�� of Bristol’s MRC Integrated Epidemiology Unit and an author on the paper, added: “Work like this is really made possible as a result of the amazing properties presented by a study like Children of the 90s. Having biological samples for sequencing and rich life course data within a representative population sample is critical to allow new understanding and deep characterisation of important biological genetic effects like these.”

Professor Nic Timpson, Children of the 90s' Principal Investigator, and also one of the study’s authors, explained: “This work helps to recalibrate our understanding of the frequency and functional impact of rare MC4R mutations and will help to shape the future management of this important health factor – we extend our thanks to the participants of the Children of the 90s.”

Though the MC4R gene is a striking example, this is only one gene of many that affect our weight and there are likely to be further examples that emerge as genetic sequencing becomes more common.

In the longer term, knowledge of the brain pathways controlled by MC4R should help in the design of drugs that bypass the signalling blockade and help restore people to a healthy weight.

Reference
Wade KH et al. Loss-of-function mutations in the melanocortin 4 receptor in a UK birth cohort. Nature Medicine; 27 May 2021

Adapted from a press release by the Wellcome-MRC Institute of Metabolic Science at the ̽��ֱ�� of Cambridge and the ̽��ֱ�� of Bristol

New research has found that one in every 340 people might carry a mutation in a single gene that makes them more likely to have a greater weight from early childhood and, by 18 years of age, they could be up to 30 pounds heavier with the excess weight likely to be mostly fat.

Our findings show that weight gain in childhood due to a single gene disorder is not uncommon. This should encourage a more compassionate and rational approach to overweight children and their families

Stephen O'Rahilly

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Breastfeeding linked to lower risk of postnatal depression

cjb250 — Tue, 19 Aug 2014 23:01:00 +0000

A new study of over 10,000 mothers has shown that women who breastfed their babies were at significantly lower risk of postnatal depression than those who did not.

̽��ֱ��study, by researchers in the UK and Spain, and published today in the journal Maternal and Child Health, shows that mothers who planned to breastfeed and who actually went on to breastfeed were around 50% less likely to become depressed than mothers who had not planned to, and who did not, breastfeed. Mothers who planned to breastfeed, but who did not go on to breastfeed, were over twice as likely to become depressed as mothers who had not planned to, and who did not, breastfeed.

̽��ֱ��relationship between breastfeeding and depression was most pronounced when babies were 8 weeks old, but much smaller when babies were 8 months or older.

̽��ֱ��research, funded by the Economic and Social Research Council, used data drawn from the Avon Longitudinal Survey of Parents and Children (ALSPAC), a study of 13,998 births in the Bristol area in the early 1990s. Maternal depression was measured using the Edinburgh Postnatal Depression Scale when babies were 8 weeks, and 8, 21 and 33 months old. Depression was also assessed at two points during pregnancy, enabling the researchers to take into account mothers’ pre-existing mental health conditions.

This is one of the largest studies of its kind; as well as being one of the few studies taking into account mothers’ previous mental health, it also controls for socioeconomic factors such as income and relationship status, and for other potential confounders such as how babies were delivered, and whether they were premature.

“Breastfeeding has well-established benefits to babies, in terms of their physical health and cognitive development; our study shows that it also benefits the mental health of mothers,” says Dr Maria Iacovou, from the ̽��ֱ�� of Cambridge’s Department of Sociology and a Bye Fellow at Fitzwilliam College.

“In fact, the effects on mothers’ mental health that we report in this study are also likely to have an impact on babies, since maternal depression has previously been shown to have negative effects on many aspects of children’s development.”

Dr Iacovou believes that health authorities should not only be encouraging women to breastfeed, but should also provide a level of support that will help mothers who want to breastfeed succeed.

“Lots of mothers and babies take to breastfeeding pretty easily. But for many others, it doesn’t come naturally at all; for these mothers, having someone with the training, the skills, and perhaps most importantly the time to help them get it right, can make all the difference,” she adds.

“However good the level of support that’s provided, there will be some mothers who wanted to breastfeed and who don’t manage to. It’s clear that these mothers need a great deal of understanding and support; there is currently hardly any skilled specialist help for these mothers, and this is something else that health providers should be thinking about.”

Around one in 12 women in the sample experienced depressive symptoms during pregnancy, while one in eight experienced depression at one or more of the four measurement points after giving birth.

According to figures from the UK’s Department of Health, almost three-quarters of mothers initiated breastfeeding in 2012/13; by the time of the 6-8 week check, only 47% of babies were being breastfed. This is one of the lowest rates of breastfeeding in Europe.

̽��ֱ��study was carried out in collaboration with Dr Almudena Sevilla from Queen Mary ̽��ֱ�� of London and Cristina Borra from Universidad de Sevilla, Spain.

A new study of over 10,000 mothers has shown that women who breastfed their babies were at significantly lower risk of postnatal depression than those who did not.

Breastfeeding has well-established benefits to babies. Our study shows that it also benefits the mental health of mothers

Maria Iacovou

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Mind and body: Scientists identify immune system link to mental illness

cjb250 — Wed, 13 Aug 2014 20:00:00 +0000

̽��ֱ��study, published today in JAMA Psychiatry, indicates that mental illness and chronic physical illness such as coronary heart disease and type 2 diabetes may share common biological mechanisms.

When we are exposed to an infection, for example influenza or a stomach bug, our immune system fights back to control and remove the infection. During this process, immune cells flood the blood stream with proteins such as interleukin-6 (IL-6), a tell-tale marker of infection. However, even when we are healthy, our bodies carry trace levels of these proteins – known as ‘inflammatory markers’ – which rise exponentially in response to infection.

Now, researchers have carried out the first ever longitudinal study – a study that follows the same cohort of people over a long period of time – to examine the link between these markers in childhood and subsequent mental illness.

A team of scientists led by the ̽��ֱ�� of Cambridge studied a sample of 4,500 individuals from the Avon Longitudinal Study of Parents and Children – also known as Children of the 90s – taking blood samples at age 9 and following up at age 18 to see if they had experienced episodes of depression or psychosis. ̽��ֱ��team divided the individuals into three groups, depending on whether their everyday levels of IL-6 were low, medium or high. They found that those children in the ‘high’ group were nearly two times more likely to have experienced depression or psychosis than those in the ‘low’ group.

Dr Golam Khandaker from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, who led the study, says: “Our immune system acts like a thermostat, turned down low most of the time, but cranked up when we have an infection. In some people, the thermostat is always set slightly higher, behaving as if they have a persistent low level infection – these people appear to be at a higher risk of developing depression and psychosis. It’s too early to say whether this association is causal, and we are carrying out additional studies to examine this association further.”

̽��ֱ��research indicates that chronic physical illness such as coronary heart disease and type 2 diabetes may share a common mechanism with mental illness. People with depression and schizophrenia are known to have a much higher risk of developing heart disease and diabetes, and elevated levels of IL-6 have previously been shown to increase the risk of heart disease and type 2 diabetes.

Professor Peter Jones, Head of the Department of Psychiatry and senior author of the study, says: “Inflammation may be a common mechanism that influences both our physical and mental health. It is possible that early life adversity and stress lead to persistent increase in levels of IL-6 and other inflammatory markers in our body, which, in turn, increase the risk of a number of chronic physical and mental illness.”

Indeed, low birth weight, a marker of impaired foetal development, is associated with increased everyday levels of inflammatory markers as well as greater risks of heart disease, diabetes, depression and schizophrenia in adults.

This potential common mechanism could help explain why physical exercise and diet, classic ways of reducing risk of heart disease, for example, are also thought to improve mood and help depression. ̽��ֱ��group is now planning additional studies to confirm whether inflammation is a common link between chronic physical and mental illness.

̽��ֱ��research also hints at interesting ways of potentially treating illnesses such as depression: anti-inflammatory drugs. Treatment with anti-inflammatory agents leads to levels of inflammatory markers falling to normal. Previous research has suggested that anti-inflammatory drugs such as aspirin used in conjunction with antipsychotic treatments may be more effective than just the antipsychotics themselves. A multicentre trial is currently underway, into whether the antibiotic minocycline, used for the treatment of acne, can be used to treat lack of enjoyment, social withdrawal, apathy and other so called negative symptoms in schizophrenia. Minocycline is able to penetrate the ‘blood-brain barrier’, a highly selective permeability barrier which protects the central nervous system from potentially harmful substances circulating in our blood.

̽��ֱ��‘blood-brain barrier’ is also at the centre of a potential puzzle raised by research such as today’s research: how can the immune system have an effect in the brain when many inflammatory markers and antibodies cannot penetrate this barrier? Studies in mice suggest that the answer may lie in the vagus nerve, which connects the brain to the abdomen. When activated by inflammatory markers in the gut, it sends a signal to the brain, where immune cells produce proteins such as IL-6, leading to increased metabolism (and hence decreased levels) of the ‘happiness hormone’ serotonin in the brain. Similarly, the signals trigger an increase in toxic chemicals such as nitric oxide, quinolonic acid, and kynurenic acid, which are bad for the functioning of nerve cells.

̽��ֱ��research was mainly funded by the Wellcome Trust, with further support from the National Institute for Health Research Cambridge Biomedical Research Centre and the Medical Research Council.

Children with high everyday levels of a protein released into the blood in response to infection are at greater risk of developing depression and psychosis in adulthood, according to new research which suggests a role for the immune system in mental illness.

Inflammation may be a common mechanism that influences both our physical and mental health

Peter Jones

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