Impaired neural responses to the sight and taste of chocolate: A model of anhedonia in depression.

Lead Research Organisation: University of Oxford
Department Name: Psychiatry

Abstract

Clinical depression is a common illness, often beginning in early adulthood, which can recur throughout a lifetime. The recurrent nature of clinical depression, together with the burden it places on patients and their families, makes this condition one of leading medical causes of suffering and disability. Unfortunately the medical treatment of depression is only modestly helpful and although modern antidepressant drug therapies are relatively safe they are no more effective than original antidepressant drugs discovered by chance over 50 years ago. One of the major stumbling blocks to discovering better treatments for depression is the lack of good human models of the condition. The aim of the present study is to develop a model based on a common symptom of depression, that of anhedonia. Anhedonia means loss of pleasure in things the person usually enjoys and is thought to be caused by impaired functioning of the brain pathways involved in the rewarding effects of pleasant experiences. These pathways have been well studied in healthy people using a form of magnetic brain imaging called ?fMRI? which is non-invasive and quite safe if used carefully. We have found that people at risk of depression, through a personal history of the illness, have lowered responses in these brain pathways when they see or eat or see chocolate which suggests that an impaired response of reward pathways to chocolate might be a good model of depression. The aim of the present study is to build on this idea by studying another group at high risk of depression and also to see whether certain antidepressant drugs increase the rewarding effects of pleasant experiences as would be predicted from the model. If these studies are successful it could mean that our model might be helpful in developing new drugs to treat depression and also perhaps in identifying drugs that might cause depression as side-effect

Technical Summary

The symptom of anhedonia (loss of pleasure) is a key feature of clinical depression and is likely to be caused by abnormalities in brain reward mechanisms. Through collaborations with preclinical neuroscientists we have developed a direct and straightforward way of assessing the function of the neural pathways supporting reward by using functional magnetic resonance imaging (fMRI) to measure the neural response to the sight and taste of chocolate. The present proposal builds on our observation that people at high risk of depression, through virtue of a previous history, have abnormal neural responses in ventral striatum to both the sight and taste of chocolate. This is consistent with proposals than anhedonia may represent an endophenotypic marker of vulnerability to depression. If this is the case, impaired neural responses to chocolate could represent a valuable disease model, able to detect people at risk of depression as well as effects of treatments particularly active against anhedonic symptoms. The aim of the proposed studies is to validate the model further by assessing the neural response to chocolate in another group at high risk of depression, subjects with elevated neuroticism scores. We will also study the effects of two established antidepressants treatments to test the hypothesis that the noradrenaline potentiating agent, reboxetine, facilitates reward processes more than the serotonergic antidepressant, citalopram. Finally we will study whether the cannabinoid type 1 receptor antagonist, rimonabant, decreases the neural response to chocolate as would be predicted from its effects on reward in animals and its liability to cause high rates of depression during clinical therapeutic use.

Publications

10 25 50
 
Description Johnson and Johnson pre-competitive award
Amount $650,000 (USD)
Organisation Johnson & Johnson 
Sector Private
Country United States
Start 09/2013 
End 09/2015
 
Description Researcher initiated grant
Amount £120,000 (GBP)
Organisation GW Pharmaceuticals 
Sector Private
Country United Kingdom
Start 09/2013 
End 08/2015
 
Description Bupropion study 
Organisation Johnson & Johnson
Department Neuroscience Johnson and Johnson
Country United States 
Sector Private 
PI Contribution Models for assessment of dopamine function in emotional processing and reward
Collaborator Contribution Financial contribution for the study
Impact Collaboration on planned study in depressed patients
Start Year 2013
 
Description GMP study 
Organisation Arla Nutrition
Department Nutritional Science
Country Denmark 
Sector Private 
PI Contribution Expertise in assessment of dopamine activity using neural and endocrine measures.
Collaborator Contribution Provision of pure protein preparations for human testing
Impact Studies on effect of tyrosine free protein on dopamine function
Start Year 2013
 
Description GW CB1 antagonist 
Organisation GW Pharmaceuticals
Country United Kingdom 
Sector Private 
PI Contribution Model for measuring the effect of drugs on neural processes of reward using fMRI
Collaborator Contribution Provision of novel endocannibinoid ligand Funding for study
Impact Study investigation novel, plant derived, CB1 antagonist on reward and punishment
Start Year 2012
 
Description Oxford Biomedical Research Centre 
Organisation University of Oxford
Department Nuffield Department of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Study of the effect of interferon alpha on brain neurochemistry using MRS
Collaborator Contribution provision of patients and immunological expertise
Impact papers submitted fro publication
Start Year 2009
 
Description P1vital 
Organisation P1vital Consortium
Country United Kingdom 
Sector Private 
PI Contribution A MICA grant submitted to the MRC. The contribution is from J&J and has been brokered by P1vital
Collaborator Contribution Intellectual and financial contribution to studies of chocolate mediated reward
Impact Application to MRC
Start Year 2010
 
Description BBC TV programme 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Further media enquiries

Dr McCabe consulted and interviewed for a BBC documentary Title "Britain's Favourite Foods" in both Oxford and Glasgow, Aug 2011. Programme will be shown Nov 2011.
Year(s) Of Engagement Activity 2011
 
Description Oxford Neuroscience Festival 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Keynote talk at Oxford Neuroscience Festival attended by several hundred undergraduates and graduates.

Approaches by medical students to carry out electives in our laboratory.
Year(s) Of Engagement Activity 2012