Genetic studies have shown that these diseases are polygenetic with multiple biochemical pathways that

may contribute to the expression of a single disease. Environmental factors may contribute to as much as half the variance in disease expression. Coupled with a system of diagnostic classification that is often ambiguous and incomplete, our challenge is formidable indeed. New opportunities More than ever before we now have the opportunity to revolutionize drug discovery for the mental illnesses. With discoveries in molecular biology, genomics, proteomics, bioinformatics, Inhibitors,research,lifescience,medical and automation, we have the tools we need to move to a whole new approach to drug discovery.4-6 Experiments or procedures that took years now take hours as Inhibitors,research,lifescience,medical information produced through

robot technology and combinatorial chemistry is fed to supercomputers for processing and comparison to established informatics resources.7 Laboratories in the private sector8 and the public sector have revolutionized their methodologies to search for promising compounds. Using genomics and proteomics, it will be possible to produce mechanism-based classifications of clinical patient populations and disease targets for therapeutic or prophylactic Inhibitors,research,lifescience,medical intervention for these new compounds. All this will move us from an approach based on serendipity to one based on rationality.9 The therapeutics of the future will be expected to identify specific molecular targets with minimal side effects in genetically defined clinical populations.10 Our current approaches are largely still broad targets with high side Inhibitors,research,lifescience,medical effect burdens in ill-defined patient populations. An increasingly important piece of this puzzle will be the growing importance of biomarkers and surrogate markers using brain imaging and other technologies for lead compound identification and optimization, Inhibitors,research,lifescience,medical and proof of principle.11 Some

very promising approaches have begun to appear in the literature,12, 13 particularly in the area of Alzheimer disease. After drug discovery Like the drugs we use, the methods we use to study them in human clinical trials were established for the most part in the 1940s and 1950s with the first modern randomized controlled trial, the Medical Research Council (MRC) trial of streptomycin. Yet nearly everything we do in clinical trials in depression old minimizes treatment response, enhances placebo response, and, in the case of AZD0530 in vivo combination treatment approaches, inflates the value of active psychosocial comparators. There are many factors that contribute to this. Patient selection Subject selection often is limited by censoring the severity distribution through entry criteria where exclusions often require elimination of patients who are suicidal or psychotic, or have a variety of common comorbidities, such as physical illness, substance abuse, or personality disorder.