Identifying the gene-brain mechanisms that contribute to depression


Depression is more than just tearfulness or feelings of sadness. It refers to a range of mood and other symptoms that are intense, long-lasting and distressing to the person. These symptoms will likely interfere with a person’s day-to-day life and relationships.

Symptoms include:

  • not wanting to go out or take part in activities that were previously enjoyable
  • withdrawing from social contact with friends and/or family
  • difficulties in concentrating or sleeping
  • feeling overwhelmed, guilty or frustrated
  • experiencing negative thoughts
  • feeling sick, tired or run down all of the time.

The causes of depression can vary from person to person. For some, stressful life events such as the loss of a relationship or job, long-term unemployment, physical health issues, family problems, or the death of a loved one might trigger depression. For others, there is no obvious cause.


The No Worries Trial

Researchers: Associate Professor Sylvia Gustin, Nell-Norman-Nott, Dr Negin Hesam- Shariati, Dr. Chelsey Wilks (University of Washington).

Emerging evidence has shown that negative emotional states play a key role in the development and maintenance of chronic pain. The No Worries Trial will evaluate the effectiveness of a four-week internet-delivered Dialectical Behaviour Therapy (DBT) skills training to help chronic pain sufferers cope with painful, fearful, worrisome, anxious, and negative thoughts and emotions. Moreover, by having the DBT skills training online it is more accessible to those in remote communities, to those with restricted mobility, and more broadly it adds to the knowledge of internet-delivered therapies at a time when online is increasingly necessary to deliver treatment due to COVID-19.

Unravelling the link between chronic pain and mental health disorders

Chronic pain is a significant problem worldwide that results in enormous suffering and costs to affected individuals, their loved ones, and society. The experience of chronic pain is so much more than a sensation. Chronic pain impacts our emotions, cognition and social life.

Genetic and epigenetic contributors to bipolar disorder in a high risk cohort

The offspring of individuals with bipolar disorder are at increased risk of mental illness, but our tools to predict which of these genetically at-risk young people will eventually develop disorder are very imprecise. Longitudinal studies that ascertain at-risk participants and monitor them prospectively are an effective approach for identifying early clinical and biological markers of future illness. In collaboration with the Black Dog Institute plus groups from four independent US-based sites, including: Johns Hopkins University; University of Michigan; Washington University in St. Louis; Indiana University; we are following a cohort of young kids and siblings of bipolar disorder patients with annual clinical, neurocognitive and lifestyle assessments; plus bi-annual brain imaging of the Australian participants. We are assessing the genetic load of multiple risk variants across the genome in these at-risk individuals to determine if we can use genetic information to help predict which individuals will ultimately transition to illness, and whether genetic load will influence early structural brain changes which are seen prior to onset of symptoms which lead to a clinical diagnosis.

We are also examining whether epigenetic changes – which occur on-top-of the DNA sequence in response to environmental influences – are involved in transition from health to illness. Early identification of those most likely to develop illness will provide a firm basis on which to develop preventive and early intervention strategies to reduce the impact of this devastating disorder.

Genes, environment and depression

In a collaborative study with Professors Kay Wilhelm and Phil Mitchell from the UNSW School of Psychiatry, Professor Peter Schofield and his team examined the genetic variation in the transporter protein that is involved in the reuptake of the neurotransmitter serotonin. There is an association between low serotonin transporter levels, stress and depression. The group has further shown that there is an association between the serotonin transporter genotypes and the way an individual copes with stress. This has led to further clinical studies correlating how individuals can use different methods to handle stress. Their research has significant implications for reducing the likelihood of developing depression and a planned future study will be to evaluate whether specific training in stress management, matched to an individual’s genotype, may lead to a reduction in the incidence of depression.

Falls, ageing and dementia in Indigenous Australians

We aim to identify determinants for the high prevalence of dementia in Indigenous Australians, and will now extend these findings by exploring determinants for the high prevalence of falls.

Koori Growing Old Well Study

The primary aim of a proposed longitudinal study is to find the reasons for the high dementia rates (three times non-Indigenous rates) in urban/regional Aboriginal people.

NeuroSleep: A NHMRC Centre for Research Excellence

This project aims to understand the bidirectional relationship between sleep and the brain to test and develop new approaches to treatment for sleep disruption across a range of medical disorders.  

Role of genetics and stressful trauma in anxiety and depression in various participant groups from the BRID (Brain Resource International Database) (2006-)

Using various cognitive, psychological and neuroimaging measures, they have investigated the role of several genes known to be involved in brain disorders.

Heritability of brain functioning across resting, emotional and cognitive tasks in the TWIN-E Study (2009-)

The TWIN-E Emotional Wellbeing study is a large prospective study of over 1,600 monozygotic (MZ) and dizygotic (DZ) adult twins from Twins Research Australia (Gatt et al., 2012, Twin Res Hum Gen).

What else is happening in Depression research at NeuRA?