Biomarker discovery in CSF of depressed patients

Depressive disorders are severe diseases of the central nervous system that impair the afflicted persons in important life areas. Due to their high prevalence, their worldwide distribution and growing importance in developing countries they have a significant impact on public health systems. Aside from the fact that the disease is still underrecognized and undertreated in primary care, the therapeutic possibilities that are currently available do not improve symptoms or prevent chronification in all patients. This is in part due to our limited understanding of the pathophysiology of depression. The identification of specific disease markers for depression would therefore enhance our knowledge about possible pathogenic mechanisms and have the potential to greatly improve diagnosis and therapeutic intervention. Due to its close proximity to the brain CSF reflects the metabolic state and biochemical alterations of this tissue. We have compared the CSF proteome of 12 individuals suffering from severe unipolar depression and healthy controls with the help of twodimensional polyacrylamide gel electrophoresis (2D-PAGE). CSF was first immunodepleted of the six most abundant proteins and the remaining CSF proteins were subjected to 2D-PAGE and image analysis followed by the identification of differentially expressed proteins. Quantitative and qualitative (phosphorylation modification) protein differences between the two replicate groups were found. We were able to identify 11 proteins that are differentially regulated between depressed individuals and controls. Some of the identified proteins have neurotrophic functions, regulate important enzyme activities or are involved in major CNS functions such as sedation or sleep. One of the identified proteins, the Dkk3 protein (Dickkopf protein 3) has recently attracted attention in psychiatric research as its expression was found to be decreased in the brain of schizophrenic subjects. Another protein difference is the pigment epithelium derived factor (PEDF), a serine protease inhibitor that has been implicated as a possible biomarker for Alzheimer's disease. The identified disease markers will allow a more precise definition and categorization of affective disorders than is currently possible and in turn facilitate investigations of the pathogenesis and enhance our ability for treatment.