The challenges in developing novel therapeutics for psychiatric disorders result from the paucity of novel, valid targets. This results from etiological heterogeneity, the complex and polygenic nature of genetic risk and the definition of psychiatric disorders based on the range and duration of symptoms (that are subjective, self-reported or observational). In addition, the complexity of the human brain means that large gaps exist in our knowledge of how brain expressed biochemical pathways relate to identified brain circuits and neuronal networks. The few examples of aetiology relevant higher order human behavioural functional domains and behavioural quantitative trait dimensions4 limit the potential targets and measurable readouts that can used in animal and human experimental medicine studies. While target identification based on genetics and biology looks increasingly feasible, concerns about the validity of existing model systems, especially rodents, have hampered the assessment of the value of potential new drug targets (target qualification) and have led to calls for proof of concept human studies as the ultimate approach in hypothesis testing for target validation.5 However clinical proof-of concept validation studies are expensive and carry
