Depression is a life-threatening (suicidal), common and costly disease (affecting 300 million people worldwide, costing an unimaginable €380 billion in the EU). Unfortunately, current treatments such as Prozac do not help in many cases. We want to develop new drugs based on neuropeptide antagonists by studying post-mortem brains of people affected by depression. There are >100 neuropeptides with even more receptors (the same type as for many of today's drugs). The focus is on the neuropeptides galanin and substance P, both of which play a role in depression-like behavior in laboratory animals. Our question is: does this also apply to humans? After all, medicines for humans should be developed through human studies. We have shown changes in the 'galanin genes' in patients with depression, and also seen differences in the galanin system in brains of deceased people with depression (suicide). We now want to see if similar changes are present in the substance P system and also in other peptides (84 to be scanned). Preliminary findings show substance P changes, in areas that control emotions. We also want to use microscopic techniques to study in which brain cells these changes occur, and to search for neuropeptide-related biomarkers of depression in the blood. Our results suggest that galanin antagonists are potential antidepressants and that substance P antagonists should be investigated further. Finally, we hope to diagnose certain types of depression using peptide markers in blood samples.