Title: Developing Brain Imaging Analysis Expertise for Predicting Treatment Response to Brain Stimulation in Geriatric Depression
Funder: The Academy of Medical Sciences

Abstract: Depressive disorders are among the leading causes of incapacity and disability worldwide. The burden of geriatric depression is expected to increase due to population ageing and its negative impact on clinical conditions and physical and cognitive abilities. Given the limited efficacy of antidepressant drugs, novel treatments such as theta-burst brain stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), are being developed. However, to further advance the field towards treatment personalisation, increasing understanding of TBS antidepressant mechanisms and identifying treatment responders are important issues. Although neuroimaging assessments have been used to address these questions in TMS trials in adult depression, no studies have used neuroimaging in TBS trials in geriatric depression yet. Our group in Brazil is a leading brain stimulation centre, although neuroimaging expertise is lacking. Recently, we have successfully applied for a NARSAD grant to perform a randomized sham-controlled, clinical trial evaluating the safety and efficacy of TBS in 108 patients with geriatric depression. Therefore, the aim of this project is to leverage this ongoing trial to build capacity in neuroimaging analyses by performing magnetic resonance imaging (MRI) assessments at baseline and after 7-10 days of treatment onset in 80 patients. The scientific goal is to test a hypothesis about treatment action: that TBS will reduce negative bias (which causally maintains negative mood) after 1 week of treatment, and patients who show this neurocognitive change will be the ones who go on to respond clinically after 6 weeks. In terms of capacity building, the award of the Newton Fellowship would firmly establish and strengthen our new collaborative partnership with the UK co-applicant and the Wellcome Centre for Integrative Neuroimaging (WIN) at the University of Oxford. The UK co-applicant, Oxford Psychiatry, and the WIN Centre, respectively, are internationally renowned for their work using multimodal neuroimaging to understand mechanisms of action of brain stimulation, of antidepressants, and to predict individual response to these interventions. The budget of this fellowship would allow not only brain imaging data to be acquired, but would also enable two 3-month visits of a Brazilian researcher to WIN, where he/she would be trained in state-of-the-art neuroimaging analyses that can then be applied in present and future brain stimulation trials by our group in Brazil. Scientifically, this proposal and its outcomes will help advance towards next-generation precision brain stimulation, by incorporating cognitive/neuroimaging readouts that inform about mechanism and individual response.

Lay abstract: Depression is a serious disorder in the elderly, affecting almost 1 in 10 adults. Sufferers often have additional health problems (eg: heart disease) and they die earlier. Antidepressant drugs do not work so well in the elderly and often have unwanted side effects. For these reasons, in our research group, we are starting a clinical study to test a promising new treatment, named theta burst brain stimulation (TBS). TBS uses electromagnetic pulses that are delivered painlessly through the scalp. These change brain areas affected by depression. Recent research showed that TBS is safe and very effective in up to 1/3 of depressed adults. However, it is relatively costly and must be done daily, which can be a burden for old people. Our research aims to understand: 1. how brain stimulation improves depression 2. who it works for and why. In future, this would improve how we treat depression by allowing us to offer it to those individuals who are most likely to benefit. To advance these aims, we hvae joined forces with the Wellcome Centre for Integrative Neuroimaging (WIN, University of Oxford). WIN is a world-class research centre with expertise in using brain imaging to understand how brain stimulation works, how antidepressant drugs work, and how individual brains differ. Using this expertise, our ultimate goal is to do a brain exam to “personalise” the treatment right from the beginning, saving time and costs. This would advance the treatment of depression in the elderly, benefiting broader society.

Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: MENTAL HEALTH