There are three ways to achieve this goal: Knowing the mechanism of action of the drugs. Identifying the genes that are switched on or off, using expression studies. Identifying the susceptibility loci for the psychiatric disorders, using linkage or association studies. Since the genes are expressed by messenger RNA and this is translated into proteins that will determine the functioning

of the brain, the method of proteomics offers another route to new drug targets.16 The essence of proteomics is the identification of proteins that are uniquely expressed in brain tissues. Protein expression profiles in disease are compared with known disease Inhibitors,research,lifescience,medical tissues. This can be done in postmortem brains, CSF, and peripheral blood cells like lymphocytes. This can be a powerful approach to overcome the problem of genome-based technologies that do not consider differences between DNA structure, gene expression, and the functions of the proteins. Preliminary results have already been reported, but so far in an inconsistent manner.17,18 The major difficulty is the collection of representative tissue samples. Most Inhibitors,research,lifescience,medical sample brain tissue comes from Inhibitors,research,lifescience,medical postmortem brains and suicide victims, but it must be representative so as to

avoid pitfalls due to different times after death and different PR 171 unknown treatments. With the help of pharmacogenomics and proteomics, an individualized therapy can be offered to each patient, to overcome the problem of heterogeneity of the disease and heterogeneity of therapeutic response.
Traditional measures of disease burden, such as prevalence and mortality, have vastly underestimated the personal, societal, and economic burdens of mental illnesses, Inhibitors,research,lifescience,medical which are more often disabling than lethal. The highly regarded World Health Organization (WHO)World Bank study Inhibitors,research,lifescience,medical of the Global

Burden of Disease1 defines the “disability-adjusted life year” (DALY) as healthy years of life lost to (i) premature death, or (ii) disability. As a cause of DALYs, depression ranks second only to heart disease in established market economies, and fourth overall.2 Realization of the need for treatments and, ultimately for tested approaches to prevention has grown in response to the recognition of this high degree of burden. Approaches to drug these discovery The textbook approach to drug discovery moves in logical order from the bench to the bedside to the clinic to the community in sequentially ordered steps: molecular targets are defined through basic research; biochemical assays are used to screen for lead compounds; animal studies establish pharmacokinetic and pharmacodynamic parameters; and toxicology studies assess safety and risk. All these lead to human clinical trials in a multiphased developmental process that has been well documented. Though widely held as the ideal for basic, translational, and clinical research, the textbook approach has not characterized drug development in mental health. Rather, there have been three major discovery paradigms.