Depression

EXTRA INFORMATION

Identifying the gene-brain mechanisms that contribute to depression

WHAT WE KNOW

In addition to Major depression, there are different types of depressive disorders that have different symptoms or varying degrees of the same symptom.

  • Melancholia: a severe form of depression where many of the physical symptoms of depression are present.
  • Post-natal depression: during pregnancy and in the year following childbirth, women may experience feelings of depression that affect not only her emotions, but her relationship with her baby.
  • Psychotic depression: this can involve hallucinations, delusions, or paranoia.
  • Seasonal Affective Disorder: a mood disorder that has a seasonal pattern.

To receive a diagnosis a doctor may conduct a physical examination as well as personal interview that explores how a person feels and how long they’ve experienced their symptoms. They may also follow this up with lab tests to rule out a physical condition that may be causing the symptoms.

There are many effective medical and psychological treatments available for depression. People may use one or a combination to find relief. The primary medical treatment for depression is antidepressant medication. Psychological treatments help people to change negative patterns of thinking and improve their coping skills so they are better equipped to deal with life’s stresses and conflicts.

Our research

Our research focuses on identifying the gene-brain mechanisms that contribute to increased severity of anxiety and depression symptoms. We evaluate various measures of brain function including neurocognitive performance tests, measures of magnetic resonance imaging scan (MRI), autonomic function and electrophysiological (EEG) function at rest and during cognitive tasks.

A lot of our previous work focused on identifying such mechanisms from participants drawn from the normal population. We are also focusing on understanding the same mechanisms but in a large cohort of Australian adult twins – both identical and non-identical twins – who have been tested over time. The added value of a twin design is that we are able to define the percentage contribution of genetics and environment for each measure, which helps pinpoint the measures to focus on when trying to identify specific genes or life experiences that are important in shaping our brain development.

The aim of this work is to understand what predicts anxiety and depression, the optimal ways to prevent it with intervention, as well as potential predictors of treatment response.

What we have discovered

Using the normal population data, the Gatt and Schofield Groups have shown the differential impact of childhood trauma on brain volume and brain function using measures such as EEG, MRI and autonomic activity. We have shown, for instance, that exposure to early life trauma has a detrimental impact on brain volume and/or function that is exacerbated when combined with specific genetic variants such as the BDNF, HTR3A, and 5-HTT-LPR genes. We have also shown the type of trauma exposure (interpersonal versus non-interpersonal trauma, and child versus adult trauma) has a varying impact on depression and anxiety symptoms.

In our twin cohort data, the Gatt Group has also started to show the levels of heritability of anxiety and depression symptoms, and how shared genetic and environmental mechanisms largely contribute to both anxiety and depression symptoms (Burton et al., 2015). In these studies, we are focusing in particular on variation between males and females give known sex differences in prevalence of these disorders. Our findings are starting to show why men and women may differ in prevalence and the potential mechanisms this may impact, including neural responses to specific emotions (e.g., happy versus sad emotions).

Current projects

Our current projects include a focus on the impact of normal variation in anxiety and depression symptoms in the general population, as well as the impact of symptoms and their treatment in clinical groups (e.g., PTSD and Major Depression).

Project 1 – In our large adult cohort of 1,600 twins, we are identifying the factors that contribute to symptoms of anxiety and depression and potentially clinical disorder over time. This includes a focus on mechanisms such as genes, environment (e.g., life experiences, parenting styles), measures of cognitive function, EEG and neuroimaging.

Project 2 – We are also involved in some collaborative work with other groups focusing on identifying neural mechanisms such heart rate variability and EEG brain function in clinical disorders such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD).

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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.
PROJECT