Brain clues reshape anorexia treatment hopes for more people

brain clues – New neuroscience research is reframing anorexia nervosa as a disorder with measurable brain changes—altering reward, habit, emotion, and body perception. From reversible effects tied to starvation to emerging brain-stimulation and psychedelic studies, research

Thirteen years ago. Vicki Turner says she was “on the brink of death.” Her nearly year-long battle with anorexia nervosa had reached a tipping point: tests showed her heart could give out at any moment. and she was rushed to the emergency room. Yet she didn’t care. Her mind was fixed on going home and celebrating her 15th birthday with the two chocolate-covered strawberries she had allotted in her self-imposed calorie restrictions.

Turner describes a paradox that makes anorexia so dangerous and so hard to treat. “It wasn’t that I wanted to die,” she writes. “The fear of eating more and gaining weight simply felt more immediate than the reality of my heart failing.”

That contradiction—continuing to starve despite consequences—is at the center of a growing wave of research. Ulrike Schmidt at King’s College London, one of the scientists pushing the field toward the brain for answers, says bluntly: “We could do much, much better. That is clear.”

Her concern is not hypothetical. Roughly a third of people affected by anorexia nervosa don’t recover, even with treatment.

In recent years. studies have suggested that anorexia alters circuits involved in reward. habit. and emotion—changes that may help explain why eating can become aversive even for people who want to recover. While these insights are still early, they’re already reshaping thinking about what comes next. Potential therapies range from brain stimulation to experimental medications. aiming to improve outcomes for those who don’t respond to current care.

Anorexia is traditionally defined by severe calorie restriction and an intense fear of gaining weight. typically leading to dangerously low body weight. Estimates suggest it affects up to 4 per cent of women and 0.3 per cent of men during their lifetime. though some studies indicate incidences are rising. Research suggests shifting beauty standards. social media and the stress of covid-19 lockdowns may be driving that trend—yet anorexia predates those pressures. with the first cases described in the early 1870s.

For decades, much treatment thinking focused on external motivations. Timothy Walsh at Columbia University in New York recalls an older approach: “To be fit. to be thin. to get over some problem. to react to some insult.” Walsh says the premise was that if doctors identified the motive. “they will start eating.” His verdict is unambiguous: “Wrong.”.

Starvation itself can drive and intensify symptoms. That lesson traces back to the University of Minnesota experiment in the 1940s. where researchers halved the calorie intake of 36 young. healthy men to better understand starvation. After six months, the men had lost around 25 per cent of their body weight and experienced profound psychological changes. They became argumentative, obsessed with food and socially withdrawn. The experimenters also documented symptoms of anxiety and depression. Eating habits changed too: the men began toying with food—cutting it into small pieces or diluting it with water—behaviours also seen in anorexia.

Decades later, those findings were connected directly to anorexia. Schmidt says the starvation effect can persist even for people with no prior predisposition: “Even in people who have no genetic. personality or psychological predisposition to an eating disorder. there was this lasting effect from the period of starvation.”.

Doctors increasingly treated starvation as the first crucial step. Joanna Steinglass, also at Columbia University, describes what changes when people are renourished: “After eating and getting renourished, people are less anxious. They are less depressed. They are less obsessional.”

Today. supervised weight restoration—where doctors and dietitians monitor weight and food intake—forms the backbone of anorexia treatment. alongside talk therapies aimed at reshaping thoughts. emotions and behaviours. Steinglass and Schmidt note that roughly two-thirds of people recover, including Turner. But for the rest, the path is unclear.

Schmidt puts the gap plainly: “We have a reasonable set of first-line treatments.” The question is what to do when those approaches fail. “But what do you do if those don’t work? We haven’t really got a clear answer for what should be next.”

That uncertainty is what draws researchers to the brain.

Brain scans and circuitry point toward a disorder that can shift

The field has moved from descriptions to measurements. A 2022 study compared 685 women with anorexia to 963 women without an eating disorder and found that the brain’s outer layer. the cerebral cortex—important for thinking. reasoning and emotion—was significantly thinner in anorexia. The reduction was two to four times greater than changes seen in other mental health conditions. such as depression and obsessive-compulsive disorder (OCD).

Importantly, the thinning looked different in people who had started regaining weight. In 251 participants with anorexia who had begun restoring their weight, thinning was less pronounced. That pattern suggests changes may be reversible and may stem from starvation rather than a pre-existing difference.

Clara Moreau at the University of Montreal says the reason may be biological. “The brain is strongly affected by food restriction because the brain is mainly based on fat.”

To separate starvation effects from anorexia-specific effects. Moreau and colleagues analysed brain scans from 290 children—124 with anorexia and 50 with another eating disorder called avoidant/restrictive food intake disorder (ARFID). ARFID also causes severe food restriction and weight loss. but it is driven differently: sensory sensitivities. disinterest in food. or an intense fear of choking or vomiting.

Compared with children without an eating disorder. those with anorexia showed significant thinning in 32 brain regions. even after accounting for body mass index. A similar pattern appeared when comparing children with anorexia to those with ARFID. indicating that at least some brain differences in anorexia are distinct from changes caused solely by starvation.

The superior parietal lobule and the thalamus—both involved in processing sensory information—were among the most affected. Anael Ayrolles at the Robert Debré Hospital in Paris connects that to a hallmark of anorexia: a disturbed perception of one’s own body. Turner describes the experience personally. “Many, including myself, tend to overestimate their body size,” she writes. “No matter how much weight I lost. my body appeared the same to me.” Only years later. she says. looking at an old photo showed how underweight she had been.

Ayrolles suggests altered brain pathways involved in evaluating the body could contribute to that mismatch.

Moreau also reports that comparisons with imaging studies of other mental health conditions showed anorexia overlapped most with OCD. hinting at a shared mechanism between the two. He emphasizes the link may be more than coincidence: More than a third of people with anorexia also have OCD. and anorexic behaviours such as calorie restriction or excessive exercise may temporarily relieve the anxiety caused by intrusive thoughts—functioning in a way that parallels compulsions.

Still, both Ayrolles and Moreau caution against overreach. “It is difficult to associate one altered [brain] region to a specific function,” Ayrolles says. He and Moreau are part of a consortium aiming to tighten that connection.

Over the next year, they plan to collect functional magnetic resonance imaging (fMRI) scans from nearly 1000 people with anorexia worldwide. Unlike structural brain scans, fMRI measures brain activity over time, offering potential insight into how brain changes influence behaviour.

Other teams are targeting circuits rather than regions. Evidence points to disruptions involving interoception—the ability to detect bodily sensations. Two regions. the thalamus and insula. help process these signals and relay them to other areas. shaping behaviour. emotions and body image. When these circuits are disrupted, many people with anorexia describe feeling disconnected from their body and emotions.

Reward and habit: the brain’s learning loops may trap behaviour

Walsh’s work adds another layer: circuits governing reward and habit have also been implicated. “People aren’t born with anorexia nervosa. It doesn’t just hit them like lightning,” he says.

That idea led him to a habit-formation model proposed in 2013 and investigated since. The model suggests people with anorexia avoid certain foods—especially those high in fat—because the avoidance is initially rewarding. Over time, restrictive eating becomes a habit, and habits are notoriously difficult to break, particularly the longer they are repeated.

The brain reinforces behaviours through dopamine. described as a feel-good chemical that activates pathways in the ventral striatum. the brain’s reward centre. Two kinds of activity engage this system: those tied to positive outcomes such as reward or praise. and those preventing negative outcomes such as threats or harm.

Walsh says both may matter in anorexia. Some people receive compliments as they lose weight. Others avoid high-calorie foods out of genuine fear or disgust. and brain scans in people with anorexia show that such foods can activate the threat-detecting amygdala. “You can make an argument that starvation becomes rewarding,” Walsh says.

As the behaviour is reinforced. the neural pathways can shift from the ventral striatum to a more efficient habit circuit involving the dorsal striatum. nicknamed the habit hub. Steinglass describes how this changes decision-making: “It doesn’t matter any more what the original reward was.” Now. she says. “you are just going to do that thing over and over and over again.” Eating more may not be enough if food avoidance has become automatic.

Turner’s description of her own experience matches that sense of loss of control. At first, hitting her daily calorie count and watching her weight fall gave her an “intense sense of accomplishment.” But the behaviour, she says, spiralled: “I couldn’t hit the brakes.”

Evidence supporting the habit hypothesis includes a seminal 2015 study by Steinglass, Walsh and colleagues. The researchers instructed 42 participants—half hospitalised with anorexia—to choose between various foods. People with anorexia were significantly less likely to choose high-fat foods than those without the condition. Brain scans capturing these decisions showed greater activation in the dorsal striatum compared with controls.

A 2020 study found that people with anorexia have more white matter, which transmits brain signals, in this region than those without an eating disorder—further implicating the habit hub.

Still, the field does not fully understand the starting point. Walsh says one driver for some people is relief: “I think for some folks. one of the drivers is. ‘I feel less anxious. I feel less bad. I feel less depressed. I am more certain of who I am,’ ” But why, then, don’t most people who diet develop anorexia?.

One possibility Walsh points to is reward sensitivity. Studies have found their dopamine-related pathways can be hyperresponsive. Yet it isn’t clear whether that trait comes before anorexia or whether starvation sensitises dopamine receptors.

Genetics may also contribute. Twin studies suggest genetics accounts for up to 60 per cent of risk for developing anorexia nervosa. Walsh says: “There might be a genetic predisposition to altered reward or habit-learning pathways. ” and “There could be some other biological factor that allows them to withstand the pressure to eat. I don’t think we know yet.”.

Several studies also link genes associated with anorexia to a lower body mass index and a reduced risk of obesity and type 2 diabetes. That raises another possibility: anorexia may involve metabolic processes as well, not only mental health. Processes regulating weight and metabolism might differ, making it harder to maintain a healthy weight.

That metabolic idea connects to emerging interest in the ketogenic diet, discussed in a separate thread of research.

New treatments: turning brain learning loops and circuitry into targets

One of the most promising strategies uses electromagnetic pulses to modulate brain activity: repetitive transcranial magnetic stimulation (rTMS). In 2021, Steinglass and colleagues administered rTMS to 10 women hospitalised with anorexia while they made decisions about various foods. They targeted the right dorsolateral prefrontal cortex, which helps inhibit automatic and habitual behaviours. After receiving stimulation. participants were more likely to choose high-fat foods while deciding what they would rather eat. compared with mock stimulation.

Schmidt’s team has tested a related approach in 34 women with anorexia. Half underwent 20 rTMS sessions targeted at the left dorsolateral prefrontal cortex. a region implicated in depression and substance use disorders. alongside usual treatment. Four months later, mood had significantly improved compared with participants who received mock stimulation.

Schmidt says the change mattered in daily life: “They were more relaxed around eating, more able to put people and social connections ahead of their eating disorder.”

Weight effects were slower, but an 18-month follow-up with 24 participants reported promising results. A quarter of those who received targeted rTMS reached a normal body mass index, and another quarter showed partial weight recovery.

The next step is a trial in 66 young women whose anorexia hadn’t responded to standard treatment. This time, researchers are using intermittent theta-burst stimulation, delivering pulses in a different pattern that may produce more durable effects. Schmidt expects the trial to wrap up in the next couple of months. If results are positive. she says it could “really transform the therapy landscape” and “It could be a big step forward.”.

Other research groups are exploring experimental drugs, including psychedelics. A 2023 study found that a single dose of psilocybin improved body image. reduced anxiety and lessened preoccupations about eating and food in 10 women with anorexia nervosa. But without a control group, those effects could reflect placebo. More robust trials are now underway.

For people living with anorexia, the prospect of shifting the brain is more than scientific—it’s personal

Despite the momentum, researchers keep the caution sign up. These approaches are still early, and most studies involve just a handful of participants—mostly young women.

Walsh says he is more hopeful now than at any other point in his nearly 50-year career. “I think we understand the enemy better.”

Turner writes that after her hospitalisation she doubted she would ever beat it. A month after being admitted, she wrote in her journal: “my eating disorder is as strong as ever… will these thoughts ever leave me alone?”

She says the thoughts eventually did leave. “I am grateful to say they have,” she writes. She no longer obsessively thinks about calories or weight loss. Foods that her 15-year-old self could never have imagined eating without fear now only bring her joy.

It’s that lived reality, alongside the new imaging findings and the emerging trials, that gives the research its urgency. While clinicians and scientists admit the field isn’t there yet, Turner says she believes “we are getting closer.”

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