BIOmarkers in DEPression (BIODEP)
Research type
Research Study
Full title
Peripheral immunomarker validation in treatment-resistant depression
IRAS ID
169230
Contact name
Edward T. Bullmore
Contact email
Sponsor organisation
CPFT and University of Cambridge (joint sponsorship)
Duration of Study in the UK
2 years, 7 months, 31 days
Research summary
This is a study to characterise the role of inflammatory processes in depression. There is compelling evidence that inflammation is often associated with, and can cause, depression. It is currently less clear that anti-inflammatory drugs have meaningful anti-depressant effect. One of our goals is to identify the subset of depressed patients that is most likely to respond better to an anti-inflammatory drug than to a conventional anti-depressant. We will therefore undertake a study of patients with a diagnosis of major depressive disorder including four groups: i) incompletely responsive patients who have demonstrated failure to respond consistently or completely to standard treatment, ii) those who have responded well to treatment and are not currently depressed, iii) untreated patients who are currently depressed, iv) healthy volunteers with no history of depression. Participants will undergo a clinical assessment, an interview with a trained member of the research team and will complete self-rated questionnaires. We will collect blood and saliva samples to measure certain immune markers. We will also perform magnetic resonance imaging (MRI) scans to look for MRI markers in the brain and investigate brain inflammation in a sub-sample of these patients using positron emission topography (PET) and cerebrospinal fluid (CSF) sampling (also called lumbar puncture).
Summary of results:
The BIODEP study aimed to characterise the role of inflammatory processes in depression. There is compelling evidence that inflammation is often associated with, and can cause, depression. It is currently less clear that anti-inflammatory drugs have meaningful antidepressant effect. Our main goal was to identify the subset of people with depression that is most likely to respond better to an anti-inflammatory drug than to a conventional antidepressant.The study team has successfully completed collection of a rich set of measures of the immune system from blood samples from people with major depressive disorder (MDD) and people without depression (healthy controls). We have identified several indicators in the blood samples, as well as changes in brain function that can be seen using MRI scans, which are associated with both depression and inflammation in the body.
The Primary Cohort recruited healthy controls and people with MDD, subdivided into those who were responding to treatment with antidepressants, those who were not responding and those who were not on any treatment. All participants completed demographic and clinical questionnaires and provided a venous blood sample to look at changes in the immune system (immunophenotyping).
The Secondary Cohort comprised healthy controls and people with MDD. A measure of inflammation in the blood, C-reactive protein (CRP), was taken at the screening visit and people with MDD were subdivided into “hiCRP” (CRP greater than 3mg/L) and “loCRP” (CRP less than 3 mg/L). All participants completed demographic and clinical questionnaires, venous blood sampling for immunophenotyping, and brain MRI studies. A subset of secondary cohort participants additionally consented for PET scans; and a small number also consented to sampling of the fluid surrounding the brain and spinal column by lumbar puncture.
Using the whole blood samples from the Primary Cohort we looked at difference in genes and the processes they cause (gene-expression). We found strong evidence of increased expression of genes that cause inflammation in people with MDD compared to healthy controls. The main two examples of these are called P2RX7 and IL1-β. Other genes which work in the opposite direction were reduced in people with MDD. This is a biologically and clinically plausible pattern of results which has partly been shown in previous studies. These results indicate that a simple blood test could maybe be used to predict if someone would respond to a drug that affects these particular genes.
On the basis of these, and other data, a phase 2 clinical trial of a novel anti-inflammatory drug (P2X7 antagonist JNJ-54175446), to be given to people with MDD who are not responding to treatment was designed. This was called the ATP Trial which started recruitment in late 2019. Unfortunately, this trial was closed prematurely in June 2022, because of COVID and other operational reasons.
REC name
East of England - Cambridge Central Research Ethics Committee
REC reference
15/EE/0092
Date of REC Opinion
17 Apr 2015
REC opinion
Further Information Favourable Opinion