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Neuropsychiatry stands to benefit enormously from the new research framework afforded by the sequencing of the human genome and from examining the role of molecular genetics on the clinical presentation of psychiatric patients. A solid foundation is essential if novel genetic breakthroughs are to be translated to successful clinical agents. However, this new research program is magnitudes more complex than any enterprise embarked on hitherto and requires the development, validation and deployment of novel behavioural and neurophysiological phenotypes in order to unravel the pathologies within neural functional systems. This Special Issue provides an introduction to some important findings and implications with a special emphasis on cognition and mental health.