Research projects

Ongoing projects

A phase I, multi-centre, double-blind, placebo-controlled parallel group study to assess the pharmacoMRI effects of AZD6765 in male and female subjects fulfilling the criteria for Major Depressive Disorder

Abstract

The mechanism by which NMDA receptor antagonists may exert rapid antidepressant effects is not known. However, a recent pharmacoMRI study revealed that an iv bolus of ketamine induced a rapid decrease in blood oxygenation level dependent (BOLD) signal in the subgenual cingulate cortex in normal volunteers (Deakin et al 2008). This is of particular interest because the subgenual cingulate cortex activity increases in response to sad thoughts and decreases in response to a wide variety of antidepressant treatments. Thus it may be that a rapid decrease in subgenual cingulate (BA25) activity predicts a rapid antidepressant response. The purpose of the current proposed study is to determine whether ketamine and AZD6765 exert rapid changes in BOLD responses in BA25 in subjects with depression. If successful, this model could serve as a method for identifying other novel, rapid-acting antidepressants.

Duration of the project

October 2009 - March 2011 (18 months)

Funding body

P1vital

Members of the project

Professor Bill DeakinPrincipal investigator
Professor Steve WilliamsPrincipal investigator
Dr Darragh DowneyResearch associate
Dr Arpan DuttaResearch assistant

Aims

  • To assess the effect of a single dose iv infusion of ketamine (Part 1) and AZD6765 (Part 2) compared to placebo on the Blood Oxygen Level Dependent (BOLD) signal in brain area BA25 using functional Magnetic Resonance Imaging (fMRI) in subjects meeting the criteria for Major Depressive Disorder (MDD)

  • To assess whether a single dose iv infusion of ketamine (Part 1) and AZD6765 (Part 2) alter the effects of emotional processing on the BOLD signal in various brain areas such as BA25, amygdala and other areas of interest