Mood Disorders Research Group

Mood disorders, such as major depressive disorder (MDD) and bipolar disorder, account for a great proportion of the global burden of disease. In 2019, both MDD and bipolar were among the top ten leading causes of disability in Australia in 2019 for people aged 15-49, with depression being the second leading cause of disability worldwide. This highlights the urgent need for valid predictors of effective treatment response. Currently however, there are no accurate predictors of response to antidepressants in MDD, and successful treatment relies greatly on ‘trial and error’.

Bipolar disorder has severe symptoms and is the sixth leading cause of disability in Australia, affecting approximately 1.8 per cent of Australians at some point in their lives and costing $1.6 billion a year. The major challenge for doctors is to differentiate bipolar disorder from other recurrent unipolar or major depressive disorders, meaning most people do not receive the correct diagnosis and treatment for almost five to 10 years from onset of this disorder.

We are using new, cutting-edge imaging techniques to find a way of diagnosing depressive and bipolar disorders using a simple brain scan. Our aim is to reduce the burden of this illness on individuals and the community by ensuring patients receive appropriate and timely treatment.

We hope to develop an objective test for MDD and bipolar disorder using ‘connectomics’, a new technique that maps the structural and functional connections in the brain. Identifying the network changes in the brain early in the course of the disease will enable clinicians to make a clear diagnosis and start appropriate treatment earlier, thus averting the chance of suicide and the other costs associated with bipolar disorder.

We also aim to identify genetic, brain, and cognitive markers that predict specific responses to a range of antidepressants in patients with MDD. Finding the right medication and the right dose can be challenging, often requiring several trial-and-error attempts. Through the utilisation of genetic testing, clinicians will be better informed on how patients may respond to certain medications, hence increasing the efficacy of antidepressant treatment.

Projects

Biomarkers to differentiate bipolar from unipolar depression
Bipolar disorder is the sixth leading cause of disability in Australia and is ranked in the top ten most debilitating of all illnesses worldwide. Differentiating bipolar disorder from unipolar depressive disorders is a major clinical challenge, and optimal clinical care is often hindered by misdiagnosis of this illness. This highlights the need for objective markers that can distinguish both these disorders.

The aim of this study is to identify brain, genetic and cognitive markers (or combinations of markers) for both these disorders. This project aims to study individuals using simultaneous EEG and MRI techniques to 1) identify biomarkers to differentiate bipolar depression, unipolar depression, and healthy controls, and 2) map the biomarkers identified through MRI onto EEG.

We are seeking people (aged between 18-65 years) that 1) have been clinically diagnosed with major depressive disorder, either current or in the past, and 2) have not been clinically
diagnosed with any mental health condition. The focus of this study is to improve our knowledge of depression and will not involve any medication or therapy. Participation involves visiting The Westmead Institute for Medical Research for an interview, and a combined EEG and MRI brain scan. Participants will be reimbursed for their time.
Exclusion Criteria: Pregnant or breastfeeding individuals, personal history of physical brain injury resulting in loss of consciousness (>10mins), substance dependence in the past 6 months, recent history of TMS or ECT, insufficient English comprehension, or severe impairments to vision, hearing, or hand movement.

If you are interested in participating or would like further information, please contact Emily Chan on (02) 8627 3306 or emily.chan@wimr.org.au.

Australian trial of genotype-guided pharmacotherapy for depression (ALIGNED)

Antidepressant medications are the first line of treatment for major depressive disorder. However, successful treatment relies greatly on ‘trial and error’ – over 60% of individuals fail to recover with the first medication they try, and over 30% of people fail to recover even after trying 4 different medications. This highlights the urgent need for a reliable way to determine the most effective medication for each individual.

Pharmacogenomics is a new, simple genetic test which can determine how a person may respond to medication. This study aims to investigate how pharmacogenomics can help to find the right antidepressant medication based on a person’s genetics. Selecting medications in this manner can help to reduce adverse effects and increase medication tolerability, and thereby improve the likelihood of recovery from depression.

We are seeking people (aged between 18-80 years) that are currently experiencing a clinical major depressive episode, and who are thinking about either initiating or changing antidepressant medications. Participants will be randomly allocated to 1 of 2 groups – both groups will receive antidepressant treatment, but the difference is that one group receives standard treatment, while the other receives genetically-tailored treatment. Participants will be required to take this antidepressant for 12 weeks, and all study visits will be conducted remotely. The pharmacogenomic test consists of a cheek swab, which will be sent directly to your home and back to us. Unfortunately, there is no reimbursement for this study.

Exclusion Criteria: Pregnant or breastfeeding individuals, insufficient English comprehension, cognitive or intellectual impairments, liver or kidney failure resulting in difficulty in processing drugs, or any allergies to antidepressants.

If you are interested in participating or would like further information, please visit this website https://www.alignedstudy.org.au/ or contact Min Lou at min.lou@wimr.org.au.

Previous Projects

Treatment-resistant depression study
More than 50% of people with depression are resistant to antidepressant treatment. The aim of this project was to study individuals with treatment resistant depression using a novel MRI based technique called “connectomics”. This technique was used to: 1) map detailed neural circuitry architecture to understand the neural mechanisms behind why some people remain resistant to antidepressants, and 2) identify connectomic based biomarkers that could potentially be clinically useful to identify treatment resistant depressed patients prior to commencement of antidepressants.

Agomelatine in depression
Agomelatine is an atypical antidepressant that has been shown to modulate mood and circadian rhythm. Like all antidepressants, agomelatine works for some individuals better than others; establishing biological predictors may allow for a better understanding of which patients may best respond to treatment with agomelatine. The aim of this study was to understand the brain patterns, cognition, and behaviour in patients with major depressive disorder – specifically those who showed clinical improvement when treated with agomelatine.

The study collected data from electroencephalography (EEG), cognitive testing, genetic sampling, and wearable devices. We examined the electrical activity of the brain to identify specific brain activation patterns and their responses to treatment with commercially available agomelatine.

iSPOT-D study
iSPOT-D was the largest biomarker study ever undertaken in major depressive disorder. The aim of this study was to identify genetic, brain and cognitive markers (or combinations of markers) that predict specific response to a range of antidepressants (sertraline, escitalopram, venlafaxine) in patients diagnosed with major depressive disorder (MDD). This ground breaking study, funded by Brain Resource, may change the way in which personalised medicine is implemented in depression.

Family of Depression Study
The aim of this project was to understand vulnerability for depression in individuals. By understanding how depression develops, we can develop prevention and early intervention strategies. We investigated a range of contributing factors including genetics, brain, behaviour, personality and experienced symptoms, as well as the impact of life events. We will follow participants up one year after the initial visit to see how the initial measures
relate to wellbeing and symptom development overtime. Integration across these measures will contribute to a deeper understanding of the development of depression.