̽��ֱ�� of Cambridge - Bernard Wolfe Health Neuroscience Fund

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

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Brain’s ‘appetite control centre’ different in people who are overweight or living with obesity

cjb250 — Mon, 07 Aug 2023 23:01:09 +0000

̽��ֱ��researchers say their findings add further evidence to the relevance of brain structure to weight and food consumption.

Current estimations suggest that over 1.9 billion people worldwide are either overweight or obese. In the UK, according to the Office for Health Improvement & Disparities, almost two-thirds of adults are overweight or living with obesity. This increases an individual’s risk of developing a number of health problems, including type 2 diabetes, heart disease and stroke, cancer and poorer mental health.

A large number of factors influence how much we eat and the types of food we eat, including our genetics, hormone regulation, and the environment in which we live. What happens in our brains to tell us that we are hungry or full is not entirely clear, though studies have shown that the hypothalamus, a small region of the brain about the size of an almond, plays an important role.

Dr Stephanie Brown from the Department of Psychiatry and Lucy Cavendish College, ̽��ֱ�� of Cambridge, said: “Although we know the hypothalamus is important for determining how much we eat, we actually have very little direct information about this brain region in living humans. That’s because it is very small and hard to make out on traditional MRI brain scans.”

̽��ֱ��majority of evidence for the role of the hypothalamus in appetite regulation comes from animal studies. These show that there are complex interacting pathways within the hypothalamus, with different cell populations acting together to tell us when we are hungry or full.

To get around this, Dr Brown and colleagues used an algorithm developed using machine learning to analyse MRI brain scans taken from 1,351 young adults across a range of BMI scores, looking for differences in the hypothalamus when comparing individuals who are underweight, healthy weight, overweight and living with obesity.

In a study published today in Neuroimage: Clinical, the team found that the overall volume of the hypothalamus was significantly larger in the overweight and obese groups of young adults. In fact, the team found a significant relationship between volume of the hypothalamus and body-mass index (BMI).

These volume differences were most apparent in those sub-regions of the hypothalamus that control appetite through the release of hormones to balance hunger and fullness.

While the precise significance of the finding is unclear – including whether the structural changes are a cause or a consequence of the changes in body weight – one possibility is that the change relates to inflammation. Previous animal studies have shown that a high fat diet can cause inflammation of the hypothalamus, which in turn prompts insulin resistance and obesity. In mice, just three days of a fat-rich diet is enough to cause this inflammation. Other studies have shown that this inflammation can raise the threshold at which animals are full – in other words, they have to eat more food than usual to feel full.

Dr Brown, the study’s first author, added: “If what we see in mice is the case in people, then eating a high-fat diet could trigger inflammation of our appetite control centre. Over time, this would change our ability to tell when we’ve eaten enough and to how our body processes blood sugar, leading us to put on weight.”

Inflammation may explain why the hypothalamus is larger in these individuals, the team say. One suggestion is that the body reacts to inflammation by increasing the size of the brain’s specialist immune cells, known as glia.

Professor Paul Fletcher, the study’s senior author, from the Department of Psychiatry and Clare College, Cambridge, said: “ ̽��ֱ��last two decades have given us important insights about appetite control and how it may be altered in obesity. Metabolic researchers at Cambridge have played a leading role in this.

“Our hope is that by taking this new approach to analysing brain scans in large datasets, we can further extend this work into humans, ultimately relating these subtle structural brain findings to changes in appetite and eating and generating a more comprehensive understanding of obesity.”

̽��ֱ��team say more research is needed to confirm whether increased volume in the hypothalamus is a result of being overweight or whether people with larger hypothalami are predisposed to eat more in the first place. It is also possible that these two factors interact with each other causing a feedback loop.

̽��ֱ��research was supported by the Bernard Wolfe Health Neuroscience Fund, Wellcome and the NIHR Cambridge Biomedical Research Centre, with additional funding from Alzheimer’s Research UK.

Reference
Brown, SSG, et al. Hypothalamic volume is associated with body mass index. Neuroimage: Clinical; 8 Aug 2023; DOI: 10.1016/j.nicl.2023.103478

Cambridge scientists have shown that the hypothalamus, a key region of the brain involved in controlling appetite, is different in the brains of people who are overweight and people with obesity when compared to people who are a healthy weight.

Although we know the hypothalamus is important for determining how much we eat, we actually have very little direct information about this brain region in living humans

Stephanie Brown

World Obesity Federation

Man playing basketball

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Stress does not lead to loss of self-control in eating disorders, study finds

cjb250 — Mon, 12 Apr 2021 17:00:58 +0000

People who experience bulimia nervosa and a subset of those affected by anorexia nervosa share certain key symptoms, namely recurrent binge-eating and compensatory behaviours, such as vomiting. ̽��ֱ��two disorders are largely differentiated by body mass index (BMI): adults affected by anorexia nervosa tend to have BMI of less than 18.5 kg/m2. More than 1.6 million people in the UK are thought to have an eating disorder, three-quarters of whom are women.

One prominent theory of binge-eating is that it is a result of stress, which causes individuals to experience difficulties with self-control. However, until now, this theory has not been directly tested in patients.

To examine this theory, researchers at the ̽��ֱ�� of Cambridge, working with clinicians at Cambridgeshire and Peterborough NHS Foundation Trust, invited 85 women – 22 with anorexia nervosa, 33 with bulimia nervosa and 30 healthy controls – to attend a two-day stay at Wellcome-MRC Institute of Metabolic Science Translational Research Facility (TRF). ̽��ֱ��facility, which includes an Eating Behaviour Unit, is designed so that a volunteer’s diet and environment can be strictly controlled and their metabolic status studied in detail during a residential status. ̽��ֱ��setting is intended to be as naturalistic as possible.

During their stay, each morning the women would receive controlled meals provided by a nutritionist. ̽��ֱ��women then underwent a fasting period during which they were taken to the next door Wolfson Brain Imaging Centre, where they performed tasks while their brain activity was monitored using a functional MRI scanner.

̽��ֱ��first tasks involved stopping the progression of a bar rising up a computer screen by pressing a key. ̽��ֱ��main task involved stopping the moving bar as it reached the middle line. On a minority of trials, stop-signals were presented, where the moving bar stopped automatically before reaching the middle line; participants were instructed to withhold their response in the event of a stop-signal.

̽��ֱ��women then performed a task aimed at raising their stress levels. They were asked to carry out a series of mental arithmetic tests while receiving mild but unpredictable electric shocks, and were told that if they failed to meet the performance criterion, their data would be dismissed from the study. They were given feedback throughout the task, such as ‘Your performance is below average’.

̽��ֱ��women then repeated the stop-signal task again.

Once the tasks had been completed – but while the volunteers might still be expected to be in a heightened state of stress – they returned to the Eating Behaviour Unit, where they were offered an ‘all you can eat’ buffet in its relaxing lounge and were told they could eat as much or as little as they would like.

On the second day of their study, the volunteers carried out the same tasks, but without the added stress of unpleasant electric shocks and pressure to perform. (For some participants, the order of the days was reversed.)

Dr Margaret Westwater, who led the research while a PhD student at Cambridge’s Department of Psychiatry, said: “ ̽��ֱ��idea was to see what happened when these women were stressed. Did it affect key regions of the brain important for self-control, and did that in turn lead to increases in food intake? What we found surprised us and goes counter to the prevailing theory.”

̽��ֱ��team found that even when they were not stressed, those women with bulimia nervosa performed worse on the main task, where they had to stop the rising bar as it reached the middle bar - but this was not the case for those women affected by anorexia nervosa. This impairment occurred alongside increased activity in a region in the prefrontal cortex, which the team say could mean these particular women were unable to recruit some other regions required by the brain to perform the task optimally.

Interestingly – and contrary to the theory – stress did not affect the actual performance in any way for either of the patient groups or the controls. However, the patient groups showed some differences in brain activity when they were stressed – and this activity differed between women with anorexia and those with bulimia.

While the researchers observed that the patients in general ate less in the buffet than the controls, the amount that they ate did not differ between the stress and control days. However, activity levels in two key brain regions were associated with the amount of calories consumed in all three groups, suggesting that these regions are important for dietary control.

Dr Westwater added: “Even though these two eating disorders are similar in many respects, there are clear differences at the level of the brain. In particular, women with bulimia seem to have a problem with pre-emptively slowing down in response to changes in their environment, which we think might lead them to make hasty decisions, leaving them vulnerable to binge-eating in some way.

“ ̽��ֱ��theory suggests that these women should have eaten more when they were stressed, but that's actually not what we found. Clearly, when we're thinking about eating behaviour in these disorders, we need to take a more nuanced approach.”

In findings published last year, the team took blood samples from the women as they performed their tasks, to look at metabolic markers that are important for our sense of feeling hungry or feeling full. They found that levels of these hormones are affected by stress.

Under stress, patients with anorexia nervosa had an increase in ghrelin, a hormone that tells us when we are hungry. But they also had an increase in peptide tyrosine tyrosine (PYY), a satiety hormone. In other words, when they are stressed, people with anorexia nervosa produce more of the hunger hormone, but contradictorily also more of a hormone that should tell them that they are full, so their bodies are sending them confusing signals about what to do around food.

̽��ֱ��situation with bulimia nervosa was again different: while the team saw no differences in levels of ghrelin or PYY, they did see lower levels of cortisol, the ‘stress hormone’, than in healthy volunteers. In times of acute stress, people who are chronically stressed or are experiencing depression are known to show this paradoxical low cortisol phenomenon.

Professor Paul Fletcher, joint senior author at the Department of Psychiatry, said: “It’s clear from our work that the relationship between stress and binge-eating is very complicated. It’s about the environment around us, our psychological state and how our body signals to us that we’re hungry or full.

“If we can get a better understanding of the mechanisms behind how our gut shapes those higher order cognitive processes related to self-control or decision-making, we may be in a better position to help people affected by these extremely debilitating illnesses. To do this, we need to take a much more integrated approach to studying these illnesses. That's where facilities such as Cambridge’s new Translational Research Facility can play a vital role, allowing us to monitor within a relatively naturalistic environment factors such as an individual’s behaviour, hormone levels and, brain activity.”

̽��ֱ��research was funded by the Bernard Wolfe Health Neuroscience Fund, Wellcome, the NIH-Oxford-Cambridge Scholars Program and the Cambridge Trust. Further support was provided by the NIHR Cambridge Biomedical Research Centre.

Reference
Westwater, ML, et al. Prefrontal responses during proactive and reactive inhibition are differentially impacted by stress in anorexia and bulimia nervosa. JNeuro; 12 April 2021; DOI: 10.1523/JNEUROSCI.2853-20.2021

A unique residential study has concluded that, contrary to perceived wisdom, people with eating disorders do not lose self-control – leading to binge-eating – in response to stress. ̽��ֱ��findings of the Cambridge-led research are published today in the Journal of Neuroscience.

It’s clear from our work that the relationship between stress and binge-eating is very complicated. It’s about the environment around us, our psychological state and how our body signals to us that we’re hungry or full

Paul Fletcher

Volkan Olmez

Grey-scale image of a woman

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Chicken korma, Eton mess and a genetic variant provide clues to our food choices

cjb250 — Tue, 04 Oct 2016 14:24:12 +0000

̽��ֱ��research has provided insights into why we make particular food choices, with potential implications for our understanding of obesity. This is one of the first studies to show a direct link between food preference and specific genetic variants in humans.

Most people find high fat, high sugar foods particularly appetising. This can lead to eating more calories than we need and can contribute to weight gain. But what influences food choice? ̽��ֱ��taste, appearance, smell and texture of food are all important, but biology may also play an important role.

Previous studies in mice have shown that disruption of a particular pathway in the brain involving the melanocortin-4 receptor (MC4R) can lead to mice eating a lot more fat. Unusually, these mice eat a lot less sugar. However, the relevance of these findings to eating behaviour in people has been unclear until now.

In a study published today in the journal Nature Communications, researchers at the ̽��ֱ�� of Cambridge gave participants an all-you-can-eat buffet of chicken korma – a popular type of curry – with three options manipulated to look and taste the same, but in which the fat content provided 20% (low), 40% (medium) and 60% (high) of the calories. They tested lean people, obese people, and people who were obese because they have a defect in a gene called MC4R.

After taking a small taster of each meal, people were allowed to eat freely from the three kormas. They could not tell the difference between the foods and were unaware that the fat content varied. ̽��ֱ��researchers found that, although there was no overall difference in the amount of food eaten between the groups, individuals with defective MC4R ate almost double the amount of high fat korma than lean individuals ate (95% more) and 65% more than obese individuals.

In a second arm of the study, people were given Eton mess, a dessert that includes a mixture of strawberries, whipped cream and broken meringue. Again, there were three options from which participants could freely choose, with sugar content providing 8% (low), 26% (medium) and 54% (high) of calorific content, but with the fat content fixed. Participants could choose freely which ones to eat.

Lean and obese individuals said they liked the high sugar Eton mess more than the other two desserts. However, paradoxically, individuals with defective MC4R liked the high sugar dessert less than their lean and obese counterparts and in fact, ate significantly less of all three desserts compared to the other two groups.

One in 100 obese people have a defect in the MC4R gene which makes them more likely to put on weight. ̽��ֱ��researchers think that for these individuals, the fact that the MC4R pathway is not working may lead to them preferring high fat food without realising it and therefore contribute to their weight problem. There are many other genes that increase the risk of gaining weight and the impact of these genes on eating behaviour needs to be studied in the future.

Professor Sadaf Farooqi from the Wellcome Trust–Medical Research Council Institute of Metabolic Science at the ̽��ֱ�� of Cambridge, who led the research team, says: “Our work shows that even if you tightly control the appearance and taste of food, our brains can detect the nutrient content. Most of the time we eat foods that are both high in fat and high in sugar. By carefully testing these nutrients separately in this study, and by testing a relatively rare group of people with the defective MC4R gene, we were able to show that specific brain pathways can modulate food preference.”

Professor Farooqi and colleagues think that humans and animals may have evolved pathways in the brain that modulate the preference for high fat food in order to cope with times of famine.

“When there is not much food around, we need energy that can be stored and accessed when needed: fat delivers twice as many calories per gram as carbohydrates or protein and can be readily stored in our bodies,” she explains. “As such, having a pathway that tells you to eat more fat at the expense of sugar, which we can only store to a limited extent in the body, would be a very useful way of defending against starvation.”

̽��ֱ��research was supported by the Wellcome Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, the Bernard Wolfe Health Neuroscience Fund and the European Research Council, as well the European Union’s Seventh Framework Programme

Reference
van der Klaauw, AA et al. Divergent effects of central melanocortin signalling on fat and sucrose preference in humans. Nature Comms; 4 Oct 2016; DOI: 10.1038/NCOMMS13055

People who carry variants in a particular gene have an increased preference for high fat food, but a decreased preference for sugary foods, according to a new study led by the ̽��ֱ�� of Cambridge.

Our work shows that even if you tightly control the appearance and taste of food, our brains can detect the nutrient content

Sadaf Farooqi

Patrick Talbert

Chicken Korma with Nan Bread

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Brains of overweight people ‘ten years older’ than lean counterparts at middle-age

cjb250 — Thu, 04 Aug 2016 09:10:08 +0000

Our brains naturally shrink with age, but scientists are increasingly recognising that obesity – already linked to conditions such as diabetes, cancer and heart disease – may also affect the onset and progression of brain ageing; however, direct studies to support this link are lacking.

In a cross-sectional study – in other words, a study that looks at data from individuals at one point in time – researchers looked at the impact of obesity on brain structure across the adult lifespan to investigate whether obesity was associated with brain changes characteristic of ageing. ̽��ֱ��team studied data from 473 individuals between the ages of 20 and 87, recruited by the Cambridge Centre for Aging and Neuroscience. ̽��ֱ��results are published in the journal Neurobiology of Aging.

̽��ֱ��researchers divided the data into two categories based on weight: lean and overweight. They found striking differences in the volume of white matter in the brains of overweight individuals compared with those of their leaner counterparts. Overweight individuals had a widespread reduction in white matter compared to lean people.

Comparison of grey matter (brown) and white matter (yellow) in sex-matched subjects A (56 years, BMI 19.5) and B (50 years, BMI 43.4). Credit: Lisa Ronan

̽��ֱ��team then calculated how white matter volume related to age across the two groups. They discovered that an overweight person at, say, 50 years old had a comparable white matter volume to a lean person aged 60 years, implying a difference in brain age of 10 years.

Strikingly, however, the researchers only observed these differences from middle-age onwards, suggesting that our brains may be particularly vulnerable during this period of ageing.

“As our brains age, they naturally shrink in size, but it isn’t clear why people who are overweight have a greater reduction in the amount of white matter,” says first author Dr Lisa Ronan from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, “We can only speculate on whether obesity might in some way cause these changes or whether obesity is a consequence of brain changes.”

Senior author Professor Paul Fletcher, from the Department of Psychiatry, adds: “We’re living in an ageing population, with increasing levels of obesity, so it’s essential that we establish how these two factors might interact, since the consequences for health are potentially serious.

“ ̽��ֱ��fact that we only saw these differences from middle-age onwards raises the possibility that we may be particularly vulnerable at this age. It will also be important to find out whether these changes could be reversible with weight loss, which may well be the case.”

Despite the clear differences in the volume of white matter between lean and overweight individuals, the researchers found no connection between being overweight or obese and an individual’s cognitive abilities, as measured using a standard test similar to an IQ test.

Co-author Professor Sadaf Farooqi, from the Wellcome Trust–Medical Research Council Institute of Metabolic Science at Cambridge, says: “We don’t yet know the implications of these changes in brain structure. Clearly, this must be a starting point for us to explore in more depth the effects of weight, diet and exercise on the brain and memory.”

̽��ֱ��research was supported by the Bernard Wolfe Health Neuroscience Fund, the Wellcome Trust and the Biotechnology and Biological Sciences Research Council.

Reference
Ronan, L et al. Obesity associated with increased brain-age from mid-life. Neurobiology of Aging; e-pub 27 July 2016; DOI: 10.1016/j.neurobiolaging.2016.07.010

From middle-age, the brains of obese individuals display differences in white matter similar to those in lean individuals ten years their senior, according to new research led by the ̽��ֱ�� of Cambridge. White matter is the tissue that connects areas of the brain and allows for information to be communicated between regions.

We’re living in an ageing population, with increasing levels of obesity, so it’s essential that we establish how these two factors might interact, since the consequences for health are potentially serious

Paul Fletcher

Ben Watkin

Measuring tape

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Overweight individuals more likely to make unhealthier choices when faced with real food

cjb250 — Wed, 13 Apr 2016 23:01:47 +0000

̽��ֱ��researchers found that when making hypothetical food choices, lean and overweight people showed highly comparable patterns both in terms of their choices and the accompanying brain activity. ̽��ֱ��activity in the brain was a good predictor of which foods they would choose when later faced with a selection of real food choices. But the presence of real food influenced choices differently across the groups.

In a related study published recently in the International Journal of Obesity, the researchers show that the brain structure in obese people differs from that in lean individuals in key regions of the brain involved in processing value judgements.

More than 1.3 billion people across the world are overweight and an additional 600 million are obese. Being overweight or obese are leading risk factors for deaths globally, being associated with increased incidence of type 2 diabetes, cardiovascular disease and some cancers.

Previous studies have suggested that obesity is associated with a greater consumption of unhealthy foods – those with high sugar and/or fat content – even though lean and overweight people do not appear to differ in their judgements of the relative healthiness of foods. To help explore further this apparent contradiction, researchers from the ̽��ֱ�� of Cambridge and the Medical Research Council Human Nutrition Unit examined the relationship between how people judge the healthiness and tastiness of food and whether this predicts their food choices at a buffet lunch.

̽��ֱ��researchers asked 23 lean and 40 overweight individuals to rate 50 common snack foods, presented on a computer screen, on a five-point scale for their healthiness and tastiness independently. They then examined the degree to which each of these individually-rated attributes appeared to influence a person’s willingness to swap a particular food for one that had previously been rated as “neutral”.

Participants were shown a picture of the “neutral” reference food item at the beginning of the task and told that on each trial they would have to choose between the food item shown on that trial and the reference food item. For example, if they had chosen a granola bar as neutral (and hence their reference food), they might be shown an apple and asked if they would be willing to swap the granola bar for the apple. During this swap-choice task, participants were placed in a functional magnetic resonance imaging (fMRI) scanner, which indirectly measures activity in the brain.

Neither choice behaviour nor accompanying brain activity differed measurably according to participants’ body weight. As one might predict, for both groups, taste was a much better guide to whether a person might choose to swap a food than healthiness. Willingness to swap a given food was associated with greater levels of activity in a key region of the brain: the ventromedial prefrontal cortex, which previous studies have consistently related to the degree to which people value rewards. Activity in this region did not differ across the groups.

Following the scanner experiment, participants were presented with an all-you-can-eat buffet with a selection of sandwiches, desserts, drinks and snacks. For each type of food, there were healthier and less healthy options, such as chicken sandwich and a BLT (bacon, lettuce and tomato) sandwich, or cola and diet cola. Once they had rated the buffet choices for healthiness and tastiness, the participants were allowed to eat freely and as much as they wanted.

Brain activity predicted the proportion of healthy food consumed in both lean and overweight individuals and both groups selected a greater proportion of foods that they had rated as tasty. However, the overweight participants consumed comparably more unhealthy foods than lean participants.

At the start of the experiment, the researchers had also measured each individual’s impulsivity – in other words, their self-control – using a mixture a computer tasks and a questionnaire. While the level of impulsivity made no difference in lean individuals’ selections, the researchers found an association in overweight people between impulsivity and consumption of unhealthy foods – the greater their level of impulsivity, the greater the proportion of unhealthy food they ate. Once again, this effect was apparent only when there was real food available and was not seen during the more hypothetical valuation decisions.

“There’s a clear difference between hypothetical food choices that overweight people make and the food they actually eat,” says Dr Nenad Medic from the Department of Psychiatry. “Even though they know that some foods are less healthy than others and say they wouldn’t necessarily choose them, when they are faced with the foods, it’s a different matter.

“This is an important insight for public health campaigns as it suggests that just trying to educate people about the healthiness of food choices is not enough. ̽��ֱ��presence of unhealthy food options is likely to override people’s decisions. In this respect, food choice does not appear to be a rational decision - it can become divorced from what the person knows and values.”

In a second study, the researchers looked at the brain structure of over 200 healthy individuals using an MRI scanner and found an association between body mass index (BMI) and brain structure. Strikingly, one of the regions showing this relationship overlapped with the region responding to food value in the first study – the ventromedial prefrontal cortex. ̽��ֱ��grey matter layer in this region was thinner in people with greater BMI.

“Perhaps this offers us some clues about the first observation – that rational, hypothetical valuation decisions don’t fully translate into healthy choices in the overweight people when they are offered real food choices,” says Professor Paul Fletcher from the Department of Psychiatry. “While the region is clearly responding in a way that is not distinct from leaner people, perhaps the structural differences suggest a reduced ability to translate what one knows into what one chooses.

“Although we can only speculate at this stage, and we really don’t know, for example, whether this brain change is a cause or a consequence of increased weight, this could help explain why this same group of people found it harder to stick to their original, healthier food choices when presented with a buffet selection.”

Professor Theresa Marteau, Director of the Behaviour and Health Research Unit at the ̽��ֱ�� of Cambridge, a co-author of the study, adds: "These findings attest to the power of environments in overwhelming many people’s desires and intentions to eat more healthily. ̽��ֱ��findings also reinforce the growing evidence that effective obesity policies are those that target food environments rather than education alone.”

̽��ֱ��research was funded by the Bernard Wolfe Health Neuroscience Fund, the Wellcome Trust and the Medical Research Council.

Reference
Medic, N et al. ̽��ֱ��presence of real food usurps hypothetical health value judgment in overweight people. eNeuro; 13 April 2016; DOI 10.1523/ENEURO.0025-16.2016

Medic, N et al. Increased Body Mass Index is Associated with Specific Regional Alterations in Brain Structure. International Journal of Obesity; e-pub 22 March 2016; DOI 10.1038/ijo.2016.42

Overweight people make unhealthier food choices than lean people when presented with real food, even though both make similar selections when presented with hypothetical choices, according to research led by the ̽��ֱ�� of Cambridge and published today in the journal eNeuro.

This is an important insight for public health campaigns as it suggests that just trying to educate people about the healthiness of food choices is not enough. ̽��ֱ��presence of unhealthy food options is likely to override people’s decisions

Nenad Medic

̽��ֱ�� of Exeter

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How hallucinations emerge from trying to make sense of an ambiguous world

cjb250 — Mon, 12 Oct 2015 19:00:41 +0000

Take a look at the black and white image. It probably looks like a meaningless pattern of black and white blotches. But now take a look at the image at the bottom of this article and then return to the black and white picture: it’s likely that you can now make sense of the black and white image. It is this ability that scientists at Cardiff ̽��ֱ�� and the ̽��ֱ�� of Cambridge believe could help explain why some people are prone to hallucinations.

A bewildering and often very frightening experience in some mental illnesses is psychosis – a loss of contact with external reality. This often results in a difficulty in making sense of the world, which can appear threatening, intrusive and confusing. Psychosis is sometimes accompanied by drastic changes in perception, to the extent that people may see, feel, smell and taste things that are not actually there – so-called hallucinations. These hallucinations may be accompanied by beliefs that others find irrational and impossible to comprehend.

In research published today in the journal Proceedings of National Academy of Sciences (PNAS), a team of researchers based at Cardiff ̽��ֱ�� and the ̽��ֱ�� of Cambridge explore the idea that hallucinations arise due to an enhancement of our normal tendency to interpret the world around us by making use of prior knowledge and predictions.

In order to make sense of and interact with our physical and social environment, we need appropriate information about the world around us, for example the size or location of a nearby object. However, we have no direct access to this information and are forced to interpret potentially ambiguous and incomplete information from our senses. This challenge is overcome in the brain – for example in our visual system – by combining ambiguous sensory information with our prior knowledge of the environment to generate a robust and unambiguous representation of the world around us. For example, when we enter our living room, we may have little difficulty discerning a fast-moving black shape as the cat, even though the visual input was little more than a blur that rapidly disappeared behind the sofa: the actual sensory input was minimal and our prior knowledge did all the creative work.

“Vision is a constructive process – in other words, our brain makes up the world that we ‘see’,” explains first author Dr Christoph Teufel from the School of Psychology at Cardiff ̽��ֱ��. “It fills in the blanks, ignoring the things that don’t quite fit, and presents to us an image of the world that has been edited and made to fit with what we expect.”

“Having a predictive brain is very useful – it makes us efficient and adept at creating a coherent picture of an ambiguous and complex world,” adds senior author Professor Paul Fletcher from the Department of Psychiatry at the ̽��ֱ�� of Cambridge. “But it also means that we are not very far away from perceiving things that aren’t actually there, which is the definition of a hallucination.

“In fact, in recent years we’ve come to realise that such altered perceptual experiences are by no means restricted to people with mental illness. They are relatively common, in a milder form, across the entire population. Many of us will have heard or seen things that aren’t there.”

In order to address the question of whether such predictive processes contribute to the emergence of psychosis, the researchers worked with 18 individuals who had been referred to a mental health service run by the NHS Cambridgeshire and Peterborough Foundation Trust, and led by Dr Jesus Perez, one of the co-authors on the study, and who suffered from very early signs of psychosis. They examined how these individuals, as well as a group of 16 healthy volunteers, were able to use predictions in order to make sense of ambiguous, incomplete black and white images, similar to the one shown above.

̽��ֱ��volunteers were asked to look at a series of these black and white images, some of which contained a person, and then to say for a given image whether or not it contained a person. Because of the ambiguous nature of the images, the task was very difficult at first. Participants were then shown a series of full colour original images, including those from which the black and white images had been derived: this information could be used to improve the brain’s ability to make sense of the ambiguous image. ̽��ֱ��researchers reasoned that, since hallucinations may come from a greater tendency to superimpose one’s predictions on the world, people who were prone to hallucinations would be better at using this information because, in this task, such a strategy would be an advantage.

̽��ֱ��researchers found a larger performance improvement in people with very early signs of psychosis in comparison to the healthy control group. This suggested that people from the clinical group were indeed relying more strongly on the information that they had been given to make sense of the ambiguous pictures.

When the researchers presented the same task to a larger group of 40 healthy people, they found a continuum in task performance that correlated with the participants’ scores on tests of psychosis-proneness. In other words, the shift in information processing that favours prior knowledge over sensory input during perception can be detected even before the onset of early psychotic symptoms.

“These findings are important because they tell us that the emergence of key symptoms of mental illness can be understood in terms of an altered balance in normal brain functions,” says Naresh Subramaniam from the Department of Psychiatry at the ̽��ֱ�� of Cambridge. “Importantly, they also suggest that these symptoms and experiences do not reflect a ‘broken’ brain but rather one that is striving – in a very natural way – to make sense of incoming data that are ambiguous.”

̽��ֱ��study was carried out in collaboration with Dr Veronika Dobler and Professor Ian Goodyer from the Department of Child and Adolescent Psychiatry at the ̽��ֱ�� of Cambridge. ̽��ֱ��research was funded by the Wellcome Trust and the Bernard Wolfe Health Neuroscience Fund. It was carried out within the Cambridge and Peterborough NHS Foundation Trust. Additional support for the Behavioural and Clinical Neuroscience Institute at the ̽��ֱ�� of Cambridge came from the Wellcome Trust and the Medical Research Council.

Reference
Teufel, C et al. Shift towards prior knowledge confers a perceptual advantage in early psychosis and psychosis-prone healthy individuals. PNAS; 12 Oct 2015

Why are some people prone to hallucinations? According to new research from the ̽��ֱ�� of Cambridge and Cardiff ̽��ֱ��, hallucinations may come from our attempts to make sense of the ambiguous and complex world around us.

August Natterer

Meine Augen zur Zeit der Erscheinungen

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