Biomarkers are useful characteristics to evaluate disease progress and targets of therapeutic agents. They are objectively measured and obtained by non-invasive procedures collecting readily accessible matrixes (Blood, CSF). Biomarkers should be easy to detect, specific and reproducible. Most importantly when detected early in the course of a disease they should be effective in predicating long term clinical response.

Only a few innovations have been made in recent decades with regard to psychiatric, and particularly antidepressant, drugs (Insel et al., 2006) (Figure 1). This conundrum reflects, at least partly, the lack of understanding of the disease biology. This poses a challenge not only to inventive drug development, but also to clinical practice, which faces remission rates of 30 per cent and less in patients given state-of-the-art pharmacological treatment for major depressive disorders (Trivedi et al., 2006). The situation is further aggravated by the exclusive current use of clinically based diagnostic criteria for major depression, which some critics view as ‘a pseudo-category, effectively homogenizing multiple expressions of depression’ (Parker, 2004).

The category of type 0 biomarkers refers to pre-existing factors that influence disease susceptibility, outcome or therapeutic response (efficacy or toxicity) (Downing 2000). These markers may be genetic or acquired during life (e.g. viral infection, mutations in cancer) and constitute risk factors for disease.

Biomarker application during drug development is driven by the need to define disease and therapeutic efficacy/safety earlier, better and with reduced cost.

The past decade has witnessed a growing interest in biomarkers, previously referred to as pharmacodynamic markers, PD markers, or pharmacologic read-outs. This increasing interest has been largely driven by evolutionary changes in drug discovery and development and in regulatory science. One key driver has involved the increasing need to reach early go/no-go decisions about an increasing number of compounds entering early clinical development each year.