background Major Depressive Disorder (mdd) is a highly heritable disorder with high lifetime prevalence. At present, laboratory blood tests for mdd are not available.
aim To classify mdd patients based on whole blood gene expression profiles. methods A classifier approach on gene expression profiles in (stimulated) blood of unmedicated patients and controls selected from the Netherlands Study of Depression and Anxiety was performed to select genes of which the expression is predictive for the disease status. In total, 35 mdd patients and 36 healthy controls, aged 20 to 63 years. Gene expression was measured using whole genome microarrays, co-hybridizing basal and ex vivo lipopolysaccharide (lps; 10 ng/ml blood)- stimulated blood from each subject, or using quantitative polymerase chain reaction (qpcr).
results We identified a molecular marker set (23 genes) of mdd in 42 subjects based on the combination of basal and stimulated blood gene expression that was superior to that from genes from basal blood only. The mdd-marker was confirmed in an independent validation set of 25 subjects. In addition, a subset of the marker genes (11 genes) classified a partially overlapping set of subjects according to disease state using an independent quantitative pcr method. The mdd-marker correlated with mdd severity, suggesting predictive validity.
conclusion We provide first evidence to classify mdd patients based on whole blood gene expression profiles. The identification of an mdd-marker from challenged blood samples has the prospect for development of prognostic tools and markers for treatment efficacy.