Unravelling the pathophysiology of psychotic depression: the search for peripheral and endophenotypical biomarkers.

Major depressive disorder (MDD) is a severe psychiatric condition with a major impact on quality of life. Some MDD-patients experience psychotic symptoms (such as hallucinations or delusions) and are therefore classified under psychotic majordepression (PMD). As this condition is associated with a high mortality risk, it should be identified as soon as possible. However, PMD remains underdiagnosed and thus undertreated, even though up to 20% of MDD-patients present with psychotic features. Moreover, little is known about the biological mechanisms underlying these two distinct types of depression.The recommended first line treatment for PMD consists of either combining an antidepressant with an antipsychotic, or electroconvulsive therapy (ECT). However, pharmacotherapy is linked with several disadvantages, such as delayed start of treatment effects and lower responsiveness in PMD-patients, whereas ECT provides faster effects and seems to be more effective in PMD than non-PMD. Although ECT appears to be a valuable therapeutic option, the biological mechanisms underlying its effects remain yet unclear. This project aims to establish biomarkers linked to ECTresponse in psychotic depressed patients.We will explore changes in several peripheral biomarkers related to ECT response in PMD. We will investigate effects on molecules of interest (immune markers, oxidative stress markers, growth factors), but will also explore new potential biomarkers by use of genomics, transcriptomics and proteomics. Moreover, structural and resting-state MRI will provide information on specific brain region and/or network alterations to differentiate psychotic from non-psychotic major depression.In total, 100 subjects will be allocated to age- and gender-matched groups: 1) PMDpatients(n = 40), 2) non-PMD patients (n = 40) and 3) healthy controls (n = 20).PMD- and non-PMD patients will undergo ECT and will therefore be evaluated before and after completion of the ECT treatment schedule.

Keywords:PSYCHOTIC DISORDERS

Disciplines:Psychiatry and psychotherapy, Nursing, Other paramedical sciences, Clinical and counselling psychology, Other psychology and cognitive sciences