Name: Dr Adam Bayes
Position/s: Clinical Senior Lecturer, School of Psychiatry, UNSW; Psychiatrist, Sydney Neurostimulation Centre, Black Dog Institute.
How has the Neuroscience, Mental Health and Addiction Theme and CAG enabled you to develop your research interests?
The Neuroscience, Mental Health and Addiction Theme and CAG has facilitated my research interests through funding an arm of this project, which brings together a collaborative network of clinicians and researchers working to better understand the pathophysiology of depressive disorders, with the long-term goals of improving selection of antidepressant therapies and aid development of new treatments. The project takes advantage of basic science, clinical and translational expertise across a number of institutions including the School of Psychiatry (UNSW), Black Dog Institute (BDI), the South Eastern Sydney Local Health District (SESLHD) and Neuroscience Research Australia (NeuRA).
Your project, Blood biomarkers in melancholic and non-melancholic subtypes of depression was successful in the 2019 round of Theme and CAG collaborative research seed funding. Can you please tell us about the project?
Individuals with major depression experience episodes of low mood, loss of interest in everyday activities with associated changes in sleep, appetite and thinking. In Australia, these conditions are common and impact on functioning – with major depressive disorder ranked by the World Health Organization as the second most disabling condition worldwide.
There is increasing evidence that the immune system, including elevated levels of inflammation, may be implicated in depression. This could have relevance for our understanding of the mechanisms behind depression and have important treatment implications, e.g. a recent study found addition of anti-inflammatory drugs to standard antidepressants improved treatment outcomes in depressed individuals.
However major depression has differing subtypes, including melancholic (with distinct cognitive and motor slowing) and non-melancholic subtypes. Previous literature has shown differing patterns of inflammation across subtypes - those with non-melancholic depression displaying elevated levels of inflammation compared to those with melancholic depression. However, these findings have not been replicated and classification of subtypes in these studies was not reliable.
Researchers at the University of New South Wales (UNSW) have devised a clinical method of more accurately diagnosing depressive subtypes with development and validation of the Sydney Melancholia Prototypic Index (SMPI). Using this subtyping model we plan to identify inflammatory markers in individuals’ blood that may distinguish those with melancholic versus non-melancholic depression. We also plan to explore any differences in blood levels of inflammation in healthy individuals, and those with chronic schizophrenia and acute psychosis.
What impact do you imagine the project will have?
The potential impact of this research includes:
Improved diagnostic specificity: Discovery of differential immune mechanisms across differing depressed patient groups could have important implications in the diagnostic evaluation of patients, moving beyond wholly symptom-based approaches and incorporating biological markers of illness.
A personalised medicine approach to depression treatment: The emergence of precision medicine would have distinct advantages over current strategies in selecting treatments. For example, emerging novel therapies for treatment-resistant depression, such as ketamine, have been found to implicate immune mechanisms and potentially to have a preferential effect on the melancholic depression subtype. Additionally, if there are distinct ‘inflammatory’ subtypes of depression, anti-inflammatory treatments may be a new therapeutic paradigm. Therefore, identification of differential peripheral inflammatory marker profiles may predict response to antidepressant therapies and thus aid treatment selection leading to a more precision medicine approach.
Translational impact: Overall, this project would potentially contribute to reducing the burden of treatment-resistant depression by improving understanding of the pathophysiology of depression, assist in treatment selection earlier on in the illness trajectory and aid in discovery of potential new treatments targets.
How will the project support new collaborations?
This project is interdisciplinary, linking clinical psychiatry with the molecular biology. From the clinical side, we will be utilising the vast clinical expertise in subtyping depressive disorders, by involvement of Prof. Gordon Parker at the UNSW School of Psychiatry. Additionally recruitment draws from the Black Dog Institute (the Depression Clinic and Prof. Colleen Loo’s Sydney Neurostimulation Centre) and importantly the local health district. In tandem, the study utilizes Prof. Shannon Weickert and A/Prof. Tom Weickert’s molecular biology laboratory at NeuRA where they are leading experts in the neuroscience of schizophrenia and in particular inflammatory mechanisms that may underpin it. In an expansion of their laboratory’s work, this collaboration will move beyond schizophrenia to examine mood disorders - bringing together this team of basic scientists and clinical experts in mood disorders together for the first time.