Brain imaging predictors of rapid treatment response to low-dose ketamine in patients with severe depression

This joint PhD project will be based at The University of Melbourne with a minimum 12 month stay at the Shanghai Jiao Tong University.

Project description
Low-dose ketamine has emerged as an exciting treatment option for patients with severe depression. Unlike other treatments for depression it has a rapid onset of action, with benefits emerging within hours. While producing profound antidepressant responses in many patients, its effects, as for other antidepressant treatments, are variable. Brain imaging parameters show considerable promise in helping to identify the patients who are likely to benefit. The PhD project will utilise imaging data from two ketamine trials being conducted by The University of Melbourne team, and will develop predictive models to identify the patients who are likely to benefit from treatment.

Depression is a devastating condition for the 1 in 10 Australians who are affected each year. Monoaminergic antidepressants are first-line treatments, but response to them is variable. Only about a third of patients will remit to the first antidepressant. After trialling a second, about half of patients won’t have remitted, which forms the usual definition of treatment-resistant depression (TRD). New treatment approaches for TRD are urgently needed. Emerging evidence indicates that low-dose ketamine holds considerable promise in this regard.

Alleviation of core symptoms of depression is frequently seen within a few hours of a single dose. However, there is considerable variability in duration of response, which last days to weeks after a single treatment, and there are few controlled data on repeat treatment regimens. Brain imaging parameters show promise in helping us to understand the mechanisms of action of ketamine, and   in predicting who is likely to respond. We are collecting treatment and brain imaging data from two ketamine trials.

Study design

  • Study 1 is a multisite NHMRC-funded randomised control trial that is comparing low-dose subcutaneous ketamine compared to an active control in youth with severe depression, scanning participants before and after 4 weeks of treatment.
  • Study 2 is an open-label trial of repeated intravenous infusions of ketamine in adults with TRD, who are scanned before and after their first treatment, with the aim of predicting response after 4 weeks of treatment.

Analyses
In both studies, analyses will aim to use the imaging data to develop prediction models for treatment response to ketamine. Study 1 will take advantage of a larger sample size, and comparison of treatment groups, to derive the prediction model. Participants are also scanned at end of treatment, allowing an additional focus on mechanisms of action. Study 2 is smaller and open-label, but is using a more powerful MRI machine: one of only two 7T scanners in Australia. It will also examine short-term response to ketamine as an additional input to the prediction models. Imaging analyses will be supervised by researchers at the Melbourne Neuropsychiatry Centre, Australia’s premier psychiatric neuroimaging research group, where Prof. Ben Harrison is Deputy Scientific Director. The PhD candidate will develop the requisite skills to perform sophisticated brain imaging analyses using world-leading methodologies.

The research team at SJTU, led by Prof. Fang, have internationally recognised expertise in the development of prediction models using machine learning methods. The Melbourne-based PhD candidate will travel to Shanghai after the data has been collected, and once the brain imaging data have been analysed, to learn how to develop prediction models under the supervision of the SJTU team.

The project will be complemented by the project on A cohort study of neuromodulation interventions for major depressive disorder and the collaboration will ensure a successful completion of the project.

Supervision team:

Professor Christopher Davey (The University of Melbourne)

Professor Yiru Fang (Shanghai Jiao Tong University)

How to apply