Monash University Makes Strides with Trials Targeting Anorexia Nervosa Biology

Melbourne researchers hope Monash University-led trials using transcranial magnetic stimulation (TMS) or estrogen to treat people living with anorexia nervosa will improve their symptoms.

The TMS trial, the first of its kind, applies electromagnetic stimulation to a brain network that the team identified from brain injury sites to have caused anorexic behaviours.

It is hoped that stimulating this specific brain network (causal target) with non-invasive and safe TMS will improve the difficulties people living with this disorder experience.

The other trial, an Australian first, is a randomised controlled trial investigating the effects of transdermal estrogen patches on symptoms of anorexia compared to placebo.

Estrogen is a hormone with a range of benefits, impacting upon mood, cognition and appetite, areas which are all affected by anorexia nervosa. Hormonal fluctuations have been linked to eating disorders, so there’s optimism that addressing hormonal imbalances could lead to symptom improvement.

Researchers from HER Centre Australia’s Li Transformative Hub for Research Into Eating Disorders (Li-THRED) will oversee the projects through Monash University and Alfred Health. Both trials are seeking participants.

Launched in 2023, with the generous philanthropic support of Mr David Li AM and Mrs Angela Li, Li-THRED is taking a novel approach to eating disorder treatment by targeting brain biology.

Anorexia nervosa is a psychiatric disorder with one of the highest rates of morbidity and mortality, with an estimated risk of death four times higher than that of clinical depression*. More than a third of those with adolescent onset anorexia nervosa never fully recover**.

Transcranial Magnetic Stimulation (TMS)

TMS has been used to treat depression for nearly 30 years. This is the first time it will be used to treat anorexia nervosa by targeting a specific causal brain network for this condition.

The Functional Connectivity-informed Individualised Transcranial Magnetic Stimulation Therapy for Anorexia Nervosa (FUNCTIAN) trial will be a partnership across experts at Monash University,  Alfred Health, Harvard Medical School and the Brigham and Women’s Hospital in Boston.

FUNCTIAN lead investigator, Dr Leo Chen from Monash University and Alfred Health, said their team had mapped out a causal brain network for anorexia nervosa. The network will be identified in each participants’ MRI brain scan, to find a personalised TMS target that is connected to this network.

The 20 participants receive TMS to this target for three weeks, along with scheduled top-up treatments for five months and final follow-up six months later. Participants are eligible if they meet criteria of having anorexia nervosa and a body mass index (BMI) of 15-18.

Dr Chen said TMS was generally well-tolerated. “The person receiving TMS lies on a comfortable recliner and is awake and relaxed during each 10-min session,” he said.

 

“With our colleagues at Brigham and Harvard, we have identified a causal brain network for anorexia behaviours. We can see this network on each individual’s MRI scans and will use it to identify their personalised stimulation target.

“Our hypothesis is that, using TMS, we can facilitate healthy brain cell firing and signal transmission along this network. In turn, we hope to improve the psychological and behavioural challenges experienced by people living with this disorder.”

Estrogen

The estrogen trial is looking to recruit 50 women aged 16 and over, who are living with anorexia nervosa, including in partial remission and atypical anorexia nervosa.

The randomised clinical trial builds on previous work by lead investigator Professor Jayashri Kulkarni AM that used estrogen to treat mental illnesses. In this new trial, Professor Kulkarni and her team will give some participants a 50mcg transdermal patch of the hormone estradiol, while others will receive a placebo patch.

Estradiol is the body’s most potent estrogen and currently used to treat menopause symptoms. It can stimulate the brain’s neural pathways, regulating appetite and improving bone health. Researchers will determine whether estradiol improves hormonal imbalances and symptoms of anorexia nervosa.

While previous research has shown that estrogen can improve bone mineral density and anxiety in those with anorexia, estradiol’s impact has not been tested on mood, cognition and appetite in this group.

Consultant psychiatrist and Li-THRED team researcher Dr Romi Goldschlager hopes the addition of estradiol will improve chemical regulation of the brain’s neural pathways and help to improve these functions.

“It’s more about the fluctuations and changes rather than underlying deficiency – steady and constant rather than peaks and troughs,” Dr Goldschlager said. “My hope is that this hormone therapy will be successful in treating anorexia nervosa, a really severe illness that currently doesn’t have a treatment.

“I would hope that it would improve cognition, mood and the physical complications. We’re hoping for improvements in participants’ bone health, mood and obsessional thoughts.”

Those on the estrogen trial will need to visit its Melbourne base each month, with participants receiving initial psychometric testing, health and nutrition checks, and monitoring throughout the study.

Professor Kulkarni, who is director of both HER Centre Australia and the Multidisciplinary Alfred Psychiatry Research Centre (MAPrc), and leader of Li-THRED research, said the trials aimed to advance better understanding and treatment of anorexia nervosa, one of the most difficult mental illnesses to treat.

“We need new biological treatments for this debilitating, life threatening disease, therefore our new clinical trials are focused on brain biology,” Professor Kulkarni said.

“We now know more about brain function through advances made in neuroscience, and we have the capacity to apply this knowledge in clinical conditions such as Anorexia Nervosa. Five more innovative clinical trials are currently being developed by THRED researchers. With the community’s help, we hope our new treatment trials provide significant results for people with anorexia nervosa.”