Tag: anorexia

Categories : Mental HealthTags :

In Anorexia Nervosa, What Triggers Wilful Starvation?

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Photo from Freepik.

A new study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) suggests that female mice that are prone to anxiety may prefer and actively seek out a starvation-like state in response to repeated exposure to stress. The findings, published in the journal Neuron, may provide a useful experimental model for investigating the neural mechanisms underlying anorexia nervosa – particularly its onset.

“While anorexia nervosa has been documented for over 300 years, its underlying causes remain unknown,” said first author Hakan Kucukdereli, PhD, of the division of Endocrinology, Diabetes and Metabolism in the Department of Medicine at BIDMC.

“Current animal models fail to capture a key hallmark of the disorder – wilful starvation. Thus, there has been the pressing need for a pre-clinical mouse model that captures the intentional seeking of a starvation state.”

In healthy individuals, the state of hunger (or caloric deficit) is a mildly uncomfortable state that drives food-seeking behavior. In the lab, Kucukdereli, senior author Mark L. Andermann, and colleagues knew that precise stimulation of a few thousand neurons known as AgRP neurons will cause even a well-fed mouse to seek out another meal.

They also knew that actual food restriction – which activates these AgRP neurons – and the artificial starvation state caused by stimulating these neurons can tamp down anxiety, thereby promoting food-seeking. (Imagine a hungry mouse in your kitchen that needs to be bold enough to hunt for food, even when your cat is around.)

Based on prior associations between stress, anxiety, and anorexia nervosa, Andermann and colleagues hypothesised that exposure to high levels of stress may actually trigger individuals to wilfully seek starvation as a means of reducing anxiety. The scientists trained 15 male and 17 female mice to run through a virtual reality corridor where they could choose to stop in one room associated with stimulation of their AgRP neurons or a second room associated with no stimulation.

In the absences of stress, male mice avoided AgRP stimulation; however, only a minority of female mice exhibited a strong aversion to it. Subsequent to repeated stress, however, many of these same mice behaved very differently. When the researchers exposed the mice to a five-minute period of unpredictable tail shocks, the males became, on average, less averse to AgRP stimulation. Meanwhile, female mice tended to preferAgRP stimulation following stress.

“Strikingly, a subset of females, but not males, began to vigorously seek this starvation-like state following stress,” said Andermann, who is also a professor of Medicine and Neurobiology at Harvard Medical School. “Surprisingly, individuals’ baseline levels of anxiety-like behavior measured weeks before the experiment could predict which females will develop a preference for this starvation-like state.”

Using machine learning to analyse the animals’ facial expressions, the researchers found that, after exposure to stress, female mice with strong preference for AgRP stimulation also showed facial expressions that directly correlated with their behaviour, potentially reflecting relief associated with a reduction in anxiety.

“Future research can link these moment-to-moment changes in facial expressions with ongoing activity of many neurons in brain regions that track physiological states or that process negative emotions,” Kucukdereli said. “Our approach lays the groundwork for future work that will identify the neural circuits that underlie the voluntary maintenance of long-term starvation in individuals with anorexia nervosa.”

Source: Beth Israel Deaconess Medical Center

Categories : Mental Health NeurologyTags :

Scientists may have Found the Specific Neurons Behind Anorexia Nervosa

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Anorexia nervosa, a mental health disorder in which people dangerously restrict their eating or purge their stomachs soon after a meal, is one of the deadliest psychological diseases. Yet, the neural mechanisms behind this have remained unclear, and therapies are limited.

Scientists have been tailing a lead for years, though. They’ve known that the disorder is often associated with anxiety and depression, hinting that the biological basis for anorexia could be regulated by neurons somewhere in the brain region that controls emotion – the amygdala.

That’s exactly where Haijiang Cai, a University of Arizona associate professor in the Department of Neuroscience and BIO5 Institute member, and his team found it: Anorexia is caused by a combination of two subregions in the amygdala, according to new research published in Cell Reports.

One knot of neurons in the central nucleus of the amygdala curbs appetite when a person gets full, feels nauseous or tastes something bitter. The other is in the oval region of the bed nucleus of the stria terminalis, which also halts eating due to inflammation and sickness.

Cai and his research team found that when they destroyed a certain type of brain cell, called PKC-delta neurons, in both of these regions, they could prevent anorexia development.

They also found that PKC-delta neurons become more active in response to eating during the anorexia development. What’s more, when they artificially activated these neurons, they caused a suppression in eating habits and increased exercise.

“This study suggests two important insights to treat anorexia,” Cai said. “One is that we need to target multiple brain regions to develop therapies. We also need to treat multiple conditions. For example, maybe one drug will target nausea and another drug target will target inflammation, and you have to combine them, like a cocktail therapy, to have better therapeutic effects.”

The team relied on mice models for their research.

“There’s no animal model that can mimic human disease completely, but this is as close as we can get,” Cai said. “For example, there are multiple common features, including a warped body image, a very low body weight, limited food intake and excessive exercise. We can’t know if an animal has a warped body image, but we can measure the other three features.”

One future step – since researchers cannot destroy neurons for human treatment – is to develop a method to silence the neurons temporarily, using drugs or some other method to test if that can prevent anorexia development or speed up recovery for people who have already developed the disorder.

Source: University of Arizona

Categories : Mental HealthTags :

In Anorexia, Brain Scans Show that Mindfulness Exercises Reduce Anxiety

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A team of researchers at Kyoto University’s Graduate School of Medicine has now found that mindfulness meditation does reduce anxieties associated with anorexia nervosa. Results from the study, published in BHPsych Open, show changes in the activity of brain regions involved in anxiety.

Anorexia nervosa (AN) is a severe psychiatric illness associated with intense anxieties concerning weight, shape, and self-esteem. AN is characterised by food restriction, voluntary vomiting, and extreme emaciation. Mindfulness meditation has already become a globally recognised method for addressing AN but its effectiveness in clinically treating neurogenic emaciation has not been studied yet.

The team’s mindfulness meditation program has seen a significant decrease in obsessive thoughts about test subject’s self-image and brain activity associated with related emotions.

“Our results suggest that the participants in the study became better at accepting their anxiety as it is,” says lead author Tomomi Noda.

Mindfulness and meditation work hand-in-hand. The former teaches practitioners to hone their awareness of their present experience and their ability to not judge and rather accept their circumstances. The latter is the medium by which mindfulness can be approached.

“We focused on the possibility that patients with AN try to avoid their crippling anxiety about weight gain and self-image by restricting food or vomiting,” adds co-author Masanori Isobe.

A 4-week mindfulness intervention program examined neural changes using tasks designed to induce weight-related anxiety. The researchers then regulated this anxiety by helping patients accept their current situations and experiences at face value, instead of avoiding them.

The researchers used functional magnetic resonance imaging (fMRI) to analyse attention regulation in relation to eating disorders. The study’s results support the subjective experiences of the researchers, although it was unexpected to them that several global events, such as the COVID pandemic and the Russo-Ukrainian war, were significant factors in patients’ anxieties.

“We anticipate practical implications of our results in clinical psychiatry and psychology and broader research into mitigating suffering through mindfulness, using the strategy of self-acceptance to regulate attention,” concludes group leader Toshiya Murai.

Source: Kyoto University

Categories : Diet and Nutrition Mental HealthTags :

Changes in Brain Structures Found in Patients with Anorexia Nervosa

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Anorexia photo created by freepik – www.freepik.com

A major study published in the journal Biological Psychiatry has revealed key differences in brain structure between people with and without anorexia nervosa.

Anorexia nervosa is an eating disorder defined by restriction of energy intake relative to requirements, leading to a significantly low body weight. Patients will have an intense fear of gaining weight and distorted body image and are unable to recognise the seriousness of their significantly low body weight.

Little is known about why some people develop anorexia whilst others do not, although biological factors are widely recognised. The findings from the study, which was coordinated by neuroscientists at the University of Bath with international partners, draws on extensive analyses of brain scans taken from patients around the world and goes some way to answering the question.

They reveal that people with anorexia demonstrate ‘sizeable reductions’ in three critical measures of the brain: cortical thickness, subcortical volumes and cortical surface area. Brain size reductions are significant due the implied loss of brain cells or the connections between them.

The results are some of the clearest yet to show links between structural changes in the brain and eating disorders. The team says that the effect sizes in their study for anorexia are in fact the largest of any psychiatric disorder investigated to date.

This means that people with anorexia showed reductions in brain size and shape two to four times greater than people with conditions such as depression, ADHD, or OCD. The changes observed in brain size for anorexia may be attributable to reductions in body mass index (BMI).

The team emphasised the importance of early treatment to help people with anorexia avoid long-term, structural brain changes. Existing treatment typically involves forms of cognitive behavioural therapy and, critically, weight gain. Many people with anorexia are successfully treated and these results show the positive impact such treatment has on brain structure.

Their study pooled nearly 2000 pre-existing brain scans for people with anorexia, including people in recovery and ‘healthy controls’ (people neither with anorexia nor in recovery). For people in recovery from anorexia, the study found that reductions in brain structure were less severe, suggesting that, with appropriate early treatment and support, brain self-repair is possible.

Lead researcher, Dr Esther Walton of the Department of Psychology at the University of Bath explained: “For this study, we worked intensively over several years with research teams across the world. Being able to combine thousands of brain scans from people with anorexia allowed us to study the brain changes that might characterise this disorder in much greater detail.

“We found that the large reductions in brain structure, which we observed in patients, were less noticeable in patients already on the path to recovery. This is a good sign, because it indicates that these changes might not be permanent. With the right treatment, the brain might be able to bounce back.”

“The international scale of this work is extraordinary,” said Paul Thompson, a professor of neurology and lead scientist for the ENIGMA Consortium, an international effort to understand the link between brain structure, function and mental health. “Scientists from 22 centres worldwide pooled their brain scans to create the most detailed picture to date of how anorexia affects the brain. The brain changes in anorexia were more severe than in other any psychiatric condition we have studied. Effects of treatments and interventions can now be evaluated, using these new brain maps as a reference.”

He added: “This study is novel in term of the thousands of brain scans analysed, revealing that anorexia affects the brain more profoundly than any other psychiatric condition. This really is a wake-up call, showing the need for early interventions for people with eating disorders.”

Source: University of Bath