Sitting within IMPACT, the Centre of Research Excellence for the Development of Innovative Therapies for Psychiatric Disorders (CREDIT) is an innovative centre.
Concerning lack of treatment pathways for common mental health disorders
The landscape for treating mental health challenges is complex. Many people fail to benefit from available care and therefore struggle to find effective treatments for their illness. The costs of these deficits are profound.
There is a particular lack of effective treatments for conditions such as depression and bipolar disorder. Despite the dedication of mental health professionals, some of the routinely available treatments for such conditions have not changed much in decades – not because they are perfect, but because there are no better alternatives.
Currently, the lack of treatment options leaves, for instance, full remission rates for psychosis at just 25 per cent, and for depression, 30 per cent. In other words: if diagnosed with depression, you have only a 30 per cent chance of an individual treatment being effective.
Establishing a centre to facilitate highly innovative research
The Centre of Research Excellence for the Development of Innovative Therapies for Psychiatric Disorders (CREDIT) was established in 2018 after being awarded a grant from the National Health and Medical Research Council worth nearly $2.5 million.
It has a single goal: working collaboratively to discover and create novel treatments to empower those with some of the most prevalent and disabling neuropsychiatric disorders, like depression, bipolar disorder, and schizophrenia.
The Geelong-based team, led by Deakin Distinguished Professor Michael Berk, also works to advance a national strategy and platform supporting the development and translation of such novel therapies.
Discovering new possibilities for potential treatments
The CREDIT research to date has supported key outcomes across Basic Science, Population Health, and Clinical Trials.
Basic Science — Human biomarker samples: Almost two decades ago, the team discovered signs of inflammation and oxidative stress in patients with depression and bipolar disorder, leading them to trial an antioxidant and anti- inflammatory agent, N-acetyl cysteine (NAC) as a treatment.
“We found that NAC improved symptoms in schizophrenia, bipolar disorder, and unipolar depression, which was independently replicated by others,” Prof Berk said. “This work highlights the importance of creative approaches and repurposing existing drugs to find new treatments.”
Basic Science — In-vitro and in-vivo models: Many mental disorders lack clear pathophysiological targets, slowing traditional drug discovery. Professor Ken Walder’s team uses innovative preclinical models to reverse-engineer the effects of known treatments on gene expression in patient-derived stem cells, initially focusing on bipolar disorder and now expanding to other conditions. This approach uses cell and molecular biology to detect new treatments that mimic the effects of known medications so that the drugs can be repurposed for these disorders.
“For example, in the Bipolar Disorders Stem Cell Project, we collect blood samples from patients and healthy controls to identify differences in mitochondrial function, oxidative stress, and inflammation. We then screen drug libraries for potential treatments,” Prof Walder said.
“Also, the Biomarker Program collaborates with clinical researchers across Australia to measure biomarkers in blood samples, aiming to predict treatment responses in clinical trials.”
Population Health and epidemiology: The team uses psychiatric, medical, behavioural, socio-demographic, biomarker, and microbiome data to uncover links between illness and risk factors and potential treatments. By combining machine learning and traditional statistical techniques, they’ve identified biomarkers predicting depression in a large US-based study, leading to clinical trials.
Key datasets include the Geelong Osteoporosis Study, ASPREE Longitudinal Study, and several Scandinavian health surveys.
Clinical Trials: This pillar tests new treatments detected by the stem cell models and validated by epidemiology, and generates leads, leading to trials of novel agents in mental health.
The Trimetazidine in Bipolar Depression (TIDE) trial for example looks at whether trimetazidine can help to reduce depressive symptoms in people with bipolar disorder. It is a double-blinded, randomised, placebo-controlled, phase
2/3 clinical trial which, if successful, may see trimetazidine used as the novel anti-depressant medication for bipolar depression around the world.
“In 2021, we established the Mental Health Australia General Clinical Trial Network (MAGNET), a nationwide collaboration of over 100 partners, to conduct larger, definitive trials to address major unmet needs,” Prof Berk said. “MAGNET includes diverse community partnerships to ensure research outcomes are effective and centred on lived experiences.”
Becoming a world leader in psychiatric treatment discovery
Over the next five years, CREDIT aims to generate evidence that will benefit the community and position Australia as a world leader in psychiatric treatment discovery and will foster and mentor a new generation of mental health researchers.
