Mental health breakthroughs paved by genetics

Improved treatments for debilitating mental health conditions is the challenge being embraced by researchers at QIMR Berghofer, aiming to tap into genetic discoveries from the last decade to deliver a new era of precision psychiatry.

Answers lie within our genetic blueprint

Scientists have discovered hundreds, and in some cases, thousands of genes linked to the full range of mental health conditions, including anxiety, depression, anorexia nervosa, schizophrenia, bipolar disorder, autism spectrum disorder, and ADHD. This has been made possible thanks to new genetic data sets of DNA donated by millions of people, and advancements in supercomputing technology.

The head of QIMR Berghofer’s Translational Neurogenomics Laboratory, Professor Eske Derks, said it is now time to progress this research to the next stage.

She has co-led a new study, published in Nature Genetics, identifying 10 key challenges in overcoming clinical translation of these genetic discoveries.

“We’ve had an era of genetic discovery and now we’re on the threshold of a new era of precision psychiatry which could offer more effective drugs for patients, and could help clinicians to better diagnose and treat these complex conditions.

“The challenges we’ve identified are not simple to solve but with a creative, collaborative, and co-ordinated research approach, and investment that supports scientists to do this work, we could make this new era a reality. We owe it to the people who have generously donated their DNA and to those living with a mental illness,” Professor Derks said.

The research team driving this work (L-R): Jackson Thorp, Dr Zachary Gerring and Professor Eske Derks at QIMR Berghofer
The research team driving this work (L-R): Jackson Thorp, Dr Zachary Gerring and Professor Eske Derks at QIMR Berghofer

The opportunity is great, the necessity for progress is even greater

Two in five Australians have experienced mental illness at some point in their life. Anxiety and depression are the most common, with the COVID-19 pandemic triggering a 25 per cent increase in cases according to the World Health Organisation (WHO). Mental illnesses can significantly impact patients’ quality of life, and cost the Australian economy around $70 billion every year.

Dr Zachary Gerring, who co-led the study, said there is a tremendous opportunity to use genetic data to find more effective treatments.

“For decades, there has been little progress in developing new drugs for mental health conditions. It can be a long process of trial and error for patients to find a treatment.

“We can integrate the genetic data with drug databases to identify potential new drug candidates that can be repurposed, meaning we could get treatments to patients more quickly and cheaply,” Dr Gerring said. 

QIMR Berghofer PhD candidate and co-lead author, Jackson Thorp, said there is huge potential to use genetic discoveries to work out the biological mechanisms of mental illnesses.

“By better understanding the biological processes, we could find the causes of mental health diseases which could lead to identification of high risk groups of people, more tailored interventions, and more accurate tools for diagnosis

“I’m extremely hopeful that we can use this genetic information to improve the lives of people living with mental illness, underpinned by further funding to do this work,” Mr Thorp said.

Looking towards better patient outcomes in schizophrenia

Researchers at the Illawarra Health and Medical Research Institute are looking to improve antipsychotic drug treatments for schizophrenia patients.

Schizophrenia is a developmental brain disorder, which develops in late adolescence, and affects the perception of reality and thoughts. It is a widely stigmatised and misunderstood condition often associated with unpredictable or violent behaviour. The chronic mental health condition affects 1 in 100 Australians and approximately 20 million people worldwide.

IHMRI’s Distinguished Professor Xu-Feng Huang has dedicated the past 20 years to studying schizophrenia, looking at better ways to treat the condition and improve patient outcomes.

Improving current treatments

Antipsychotic drugs are the most widely used method for treating schizophrenia and are used for a range of other conditions, including bipolar, Alzheimer’s Disease, and Parkinson’s Disease. Figures from the Australian Institute of Health and Welfare show prescriptions for antipsychotic drugs under the Pharmaceutical Benefits Scheme (PBS) increased by 359 percent over a 24-year period from 1992 to 2016.

Despite the wide use of antipsychotic drugs, they come with a host of side effects that can create other health issues for patients. In 2019, Professor Huang secured $1.5 million to support his research into the side effects of antipsychotic drugs used in schizophrenia. The funding formed part of the Federal Government’s $440 million investment in world leading health and medical research projects under the National Health and Medical Research Council’s (NHMRC) grant program.

Professor Huang’s research program investigates neuropathology and side effects of antipsychotics in schizophrenia. Current treatment mainly relies on drug therapy, which does not directly address the fundamental neurite and spine deficits. Drug treatment can cause cortical thinning of the brain, which leads to cognitive impairment, as well as severe metabolic side-effects such as obesity.

“I have a huge concern about the widely used antipsychotic drugs without considering the side effects. It has been prescribed to not only the elderly but to teenagers and even young children.”

Professor Huang
Schizophrenia researcher Professor Xu-Feng Huang in the lab at the Illawarra Health and Medical Research Institute
Schizophrenia researcher Professor Xu-Feng Huang in the lab at the Illawarra Health and Medical Research Institute

Addressing the root cause of negative side effects

Metabolic related side effects impact around 45% of users of antipsychotic drugs with the fat primarily stored around the visceral organs like the heart, liver, and gut.

“The problem with this type of fat is that it is bad fat around the inside of the body, and it can happen within two to three months, so it is rapid. On average, in one year, it can cause up to seven kilograms of visceral fat, which is huge,” said Professor Huang.

Professor Huang explained that because of this fat, the number one killer for patients with schizophrenia is not the disease itself, but a heart attack caused by the metabolic related side effects.

The second research program from Professor Huang’s team, aims to prevent and treat antipsychotic drug-induced obesity and cortical thinning by looking at the pharmaceutics. The aim is to keep the therapeutic side of the drug and remove the negative side effects by reviewing its clinical structure. Researchers hope that by addressing the root cause of these side effects, the use of the drug will be safer long-term for schizophrenia patients.”

A disease like schizophrenia – it’s not like a cold where it lasts for a week – it lasts a lifetime. Therefore, you must be on antipsychotic drugs, and if not, it can get much worse. This is why improving antipsychotic therapy and reducing the side effects is important,” Professor Huang added.