Eating malfunction

Stephen Klagholz remembers how small his world became—isolated, dark, and singularly focused. What began as a quest for physical fitness morphed into delusion and an obsession with weight loss.

Looking back, the 36-year-old has trouble understanding how it got so bad. "It all seems so twisted now," he recalls. But that's part of the reason that anorexia nervosa is so crippling. When you're at your worst, your brain distorts reality. You can't get better until you get the nutrients you need, but you skip meals and restrict intake because you're obsessed with staying thin. It's an emotional seesaw that leaves patients improving and declining for years. The starved brain plays tricks on victims who look in the mirror and think they're overweight even as bones protrude from their frames.

Klagholz's story started innocently enough when, as a child, he had a severe allergic reaction after eating a carrot. In the sixth grade his parents sent him to a specialist who diagnosed him with a laundry list of allergies to foods that he had been eating without issue his entire life. He's still not sure why he received the diagnosis, and in retrospect a second opinion would have been warranted. But for an already anxious child, the medical opinion changed his perspective on food. He became an expert in reading food labels, at first to know what they contained and then out of fear of fat and calories. By high school, the avid soccer player was becoming more and more infatuated with what he considered a trim and fit physique. In college, Klagholz spent much of his day in the gym, subsisting on a diet of grapes and water. Within the first two years of leaving home the 5-foot-9-inch college sophomore had dropped down to 103 pounds.

Next to opioid use disorder, anorexia is the most deadly mental health illness. In all, 5% of patients will die within the first four years of diagnosis as a result of heart failure, organ shutdown, low blood sugar, or suicide. The Eating Disorders Coalition reports that every 52 minutes, at least one person loses their life as a direct result of an eating disorder. One in five individuals with anorexia who die take their own life, according to findings in Archives of General Psychiatry. Of patients who recover, only half avoid relapsing and losing the weight once again.

Rates of eating disorders have steadily increased in the past two decades, and the pandemic has made matters worse. Stress, trauma, and isolation along with a loss of routine have been the perfect storm, doubling the number of eating disorders among teens and young adults. But researchers at the Johns Hopkins Eating Disorders Program are hoping to turn the tide. A new understanding of what causes the disease—namely the role of genetics as well as brain differences—is opening the door to earlier diagnoses, more effective treatments, and improved patient outcomes.

Although we can't yet predict who will later be diagnosed with anorexia, researchers have shown that genetics plays an outsize role in increasing one's risk of the disease by some 50% to 60%, according to a September 2023 article in the journal Nature. Twin studies on eating disorders have also shown that a considerable portion of observed familial risk is owing to genetic factors. It's not a cause-and-effect type of relationship that you would see with some genes, such as the BRCA mutation that drastically increases one's risk of developing breast cancer, but it definitely has an impact, says Timothy Moran, director of the Behavioral Neuroscience Laboratory at Johns Hopkins. His research is focused on both the genetics of eating disorders and how neural signaling pathways control food intake and body weight. "Like other psychiatric disorders, it's a variety of genes that together add vulnerability," Moran says.

A large genome study published in the 2019 edition of Nature Genetics showed that eight genes significantly impacted risk; some of them were in the brain and have been implicated in other psychiatric disorders—others were metabolic genes. The serotonin 1D receptor (HTR1D), a receptor in the central nervous system that impacts anxiety, and the delta opioid receptor (OPRD1), a protein-coding gene that plays a role in regulating reward pathways in the brain, are both linked to an increased susceptibility to anorexia. Researchers hope that in the future they will be able to use our understanding of genetics to identify a patient's risk factors for disease, improving the likelihood of early diagnosis, which has been shown to improve the likelihood of recovery by more than a third.

Researchers also have a new understanding of differences in the brains of patients with and without the disorder, says Kimberly Smith, a neuroscientist at the Johns Hopkins School of Medicine, whose research is focused on eating disorders. She says that the brains of patients with anorexia are smaller than those of healthy controls, with notable reductions in cortical thickness and cortical surface area likely due to malnurishment. The reward circuitry is also different, meaning that the anorexic brain responds differently to food cues. "Someone with anorexia would see food images as less rewarding than someone who does not have the disorder," Smith says.

There also seems to be less connectivity between the reward centers of the brain and those tasked with decision making, Smith adds. Patients with anorexia also have poorer cognitive flexibility compared to healthy patients, making them less adaptable and more driven by routine. We don't know whether these differences were already there before the brain became starved or whether the disease causes changes, but researchers suspect that it's both. Patients are born with brain differences, and the disease exacerbates what's already there.

During his high school years, Klagholz's parents divorced, and the disease tightened its grip. Without his parents in the same household, he could tell his father he had already eaten at his mother's house and vice versa. "I triangulated the situation masterfully and very much manipulated both of them," he admits. "It was sad and sick, but that's what the disease does; it finds every little way to keep going." And keep going it did. In college, without his parents to watch over him, anorexia took over. He entered what he calls a very dark place, exercising incessantly, eating scant amounts, and avoiding any social situation that would force him to explain his aversion to food.

Anorexia often impacts high achievers who have never been in trouble with their parents—teens and young adults aspiring to high academic standards, driven by good grades, and often displaying type A personalities, says Moran. Certain personality types seem to be more frequent in individuals vulnerable to anorexia such as higher levels of neuroticism, perfectionism, and being routine bound—all traits that led Klagholz to succeed in school. Both his straight A report card and his gender allowed him to fly under the radar.

While it's estimated that around 10% of patients are male, according to the Bulimia Project, they're understudied, underdiagnosed, and undertreated. The same is often true of minority groups, who are also hit hard by eating disorders. Black teenagers are twice as likely to present with bulimia compared to white teens, but they're much less likely to go into any type of treatment. What's more, treatment is largely off limits to the uninsured because it's cost intensive, often requiring frequent prolonged hospitalization for weight restoration as well as medical and psychiatric intervention.

In college, Klagholz isolated himself from all but a few friends. On the rare occasions when he did go to parties, he would open a beer and sneak away to the bathroom to dump it out, refilling the can with water. "I didn't want the calories from alcohol," he admits. When his father came to move him out of his apartment for the summer, Klagholz started having pain in his chest as if he were having a heart attack. After that, at age 20, he was admitted into the Johns Hopkins Eating Disorders Program.

He was lucky to have a treatment facility nearby. While approximately 1% of the population will have anorexia in their lifetime, only about half seek treatment at one of the 75 treatment centers nationwide, according to the Mayo Clinic Proceedings. Still, once in treatment, Klagholz did not initially thrive. Rather, he was able to trick nearly every member of his family as well as his doctors. He figured out a method for playing the system by taping tiny weights under his boxers in time for his weigh-in. Each week as his weight was supposed to increase, so too would the number of weights that he duct-taped beneath his pants.

The disease had taken full control, rewiring his brain in a way that promoted the eating disorder. The brain goes into a starved state because it relies on glucose for fuel. Without it, the brain operates suboptimally, causing the loss of short-term memory, a lack of concentration, and a diminished interest in activities once enjoyed. Now in an almost myopic state, the brain refocuses attention on nutritional labels, calories, exercise, and body shape, which all increase the power of the eating disorder, according to experts.

When Klagholz's father discovered the tiny metal weights hidden among his things, he forced his son to come clean. "I knew I had hit rock bottom. I'd destroyed my family and myself, and everyone knew it," he recalls. That night, after a fight with his father, he turned off his phone and ran out into the night. It was dark and rainy. He recalls his body failing him, his muscles wasting away, and his heart racing. "I didn't want to die, but I also didn't care if I ran into traffic and a car hit me. It seemed easier than what I was going through," he recalls.

With severely ill patients like Klagholz, Johns Hopkins' inpatient treatment includes a team put in place to keep patients alive and start their journey toward recovery. Each week they meet with a psychiatrist, social worker, dietitian, occupational therapist, and nursing staff to discuss progress and a plan for the immediate future, says Angela S. Guarda, director of the Eating Disorders Program at Johns Hopkins Hospital. Her work is focused on designing anorexia treatments that help patients not only get better but stay that way. To reduce rates of relapse, the focus is on normalizing food for patients who feel anxiety around eating.

Peer pressure is another important aspect of treatment. Group therapy is designed on the premise that a good group leader will engage senior patients into helping the newer patients get through meals and eat the foods that are in front of them. Senior patients may also feel like they don't want to be a bad influence on the younger patients. "It's also much easier to see in someone else how this disorder doesn't make sense than it is to see that in yourself," Guarda says. In treatment, Guarda says that including foods that contain fat is also important because this is the macronutrient that presents the most anxiety for patients. Facing fears in treatment is one goal because it helps patients eventually overcome them.

Once patients start completing their meals, they're allowed to select them from a menu. But at the same time, over a period of 10 days, the number of calories a patient eats increases so they can restore weight. Newer patients see the more senior patients gaining autonomy as they gain weight, which motivates them to try to do the same. Once patients get close to a normal weight, they need to be on the unit for only 12 hours a day, for all their meals. As they taper out of the program, which normally takes five to seven weeks, patients are allowed to have some meals at home with family or go out to eat. "In the long run, to recover, patients have to be able to eat independently outside of the hospital," Guarda says.

Unlike other treatment centers, the program at Johns Hopkins does not use feeding tubes or weight gain supplements because though they help patients regain weight, they don't deal with the underlying anxiety around food, Guarda says. Group meals at Johns Hopkins help patients learn to eat socially and choose a balanced diet, so that they have the skills to maintain weight once they're finished with the program. The Johns Hopkins Eating Disorders Program has treated thousands of patients since its inception in 1976. The program is focused on weight gain, the best-known predictor of success, says Guarda, with 71% of patients getting to a normal weight and a body mass index of at least 19 before they leave.

Guarda's work is also focused on promoting outpatient care, especially in adolescents. The newest thinking in care is that outpatient programs are less disruptive to a teen's life, and they allow for early intervention so that the disease isn't allowed to fester. Kids and teens can stay at home with their families and, for the most part, carry on life as normal. Parents can take control and help their teen get back to a normal weight. For patients who seek treatment earlier and younger, getting better can often be much easier. The outpatient program at Johns Hopkins sees patients who are 13 and older. Whether a patient can be outpatient instead of inpatient depends on several factors, says Colleen Schreyer, director of clinical research for the Eating Disorders Program. For example: Are the teen's parents confident they can get them to eat on an outpatient basis? Is the patient medically stable? Other factors may include total weight loss and whether a patient is suicidal.

As part of the outpatient program, patients or their parents log what they eat every day. If there's an indication that a patient is purging, labs are run that look at things like electrolyte imbalances. Parents may also become aware of vomit or laxative abuse in the home. But the scale is the most obvious indicator. "If a patient isn't eating what they're supposed to be eating, they also won't be gaining the weight," Schreyer says.

The good news is that while recovery may be protracted that doesn't mean it's unsuccessful. New research shows that recovery can take multiple admissions into treatment. The more often the brain is allowed to thrive at a normal weight, the less gravitational pull the disease has on patients. And weight management is the most important part of survival. The thoughts become less and less, and the ability to get through them and eat a normal diet becomes more and more. Research from Massachusetts General Hospital found that recovery can and does happen at any age, even for patients who have been fighting this disease all their lives.

There's also hope in the potential of a new generation of treatments. A group of Yale researchers, for example, has started work on a synthetic molecule called Bobcat339 that reduced rates of anorexia in mice. The molecule is a protein inhibitor that regulates a gene as it interacts with neurons in the brain, impacting feeding behavior and energy expenditure as well as compulsive behaviors. Additionally, there's promise in the use of psilocybin therapy for patients with anorexia. While the research is still in its infancy, psilocybin therapy uses a molecule found in psychedelic mushrooms that works on a serotonin receptor in the brain. It's thought that patients with anorexia have altered brain serotonin, which, according to a study published recently in Nature Medicine, supports the idea that the effects of psilocybin might bring about a change in anorexia symptoms.

After his near breakdown, Klagholz would spend an entire year in the Eating Disorders Program at Johns Hopkins Hospital. He got to his stable weight, but this time they kept him there longer to make sure he could maintain it. After Guarda and the rest of the team on the unit found out about the weights, he could no longer hide behind his tricks, and he knew it. This time, he would succeed, and in 16 years he has never relapsed.

When asked how he got better, Klagholz says that the journey was day by day, then week by week, then month by month. It was never a linear recovery; rather it became two steps forward and one step back. But at least he had made progress. Gradually his world became less myopic and more open. Today, Klagholz is a happily married data scientist. He considers himself fully recovered from the disorder and happy to be alive. "I finally started realizing that there is so much worth living for," Klagholz says.