Understanding the role of the reward system in the pathophysiology and treatment of mood disorders

Reward sensitivity (the value attributed to rewarding outcomes by an individual) is attenuated in people with mood disorders and is known to be mediated by dopaminergic signalling. Reward sensitivity can be estimated using computer-based learning tasks and analysed using computational modelling (Huys and Browning). We hypothesise that reduced reward sensitivity is causally related to the lack of motivation (i.e. anhedonia) experienced in depressive episodes, that it may be improved by enhancing dopaminergic function and that it is therefore a potentially useful treatment target.

Aripiprazole acts as an augmenting agent in the treatment of difficult to treat major depressive disorder. It enhances dopamine function and facilitates reward activation. Quetiapine has demonstrated efficacy in the treatment bipolar depression but does not have a pro-dopamine effect.

ASCEnD is an NIHR-HTA funded RCT of aripiprazole vs quetiapine (n=270) in bipolar depression (led by Watson). It focuses on clinical effectiveness, but not on mechanisms. This studentship would provide a unique opportunity to utilise this substantial clinical-research framework to apply computational psychiatry approaches to study reward and anhedonia. The studentship will begin with a systematic literature review to inform an amendment to the ASCEnD study protocol, specifically the inclusion of a probabilistic decision-making task to determine whether reward sensitivity is differentially impacted by aripiprazole vs quetiapine, whether reward sensitivity predicts response to pharmacological intervention in bipolar depression, whether this effect is specific to pro-dopamine drug treatment and whether changes in reward sensitivity mediate the change in depressive symptoms.

How to Apply:

FURTHER DETAILS AND A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.ncl.ac.uk/research/transformative-neuroscience/studentship/ . Please read the information there before submitting your application. Applications not meeting these criteria may be rejected.

Applications should be made by emailing [Email Address Removed] with:

• a completed copy of the Application Form. A blank copy of the form can be found at: https://www.ncl.ac.uk/research/transformative-neuroscience/studentship/
• a CV (including contact details of two academic referees).
• a covering letter. This should explain your particular interest in the projects selected, and include any additional information you feel is pertinent to your application
• copies of your degree transcripts and certificates
• a copy of your passport (photo page).
• your English language certificate (IELTS or TOEFL certificate, where applicable)

Informal enquiries may be made to the supervisors.