Comparative psychology and the grand challenge of drug discovery in psychiatry and neurodegeneration

► The failure in translating the apparent successes of preclinical neuroscience constitutes a serious problem for drug discovery on multiple fronts. ► Factors that contribute to this limitation can be categorized under three headings: (1) sociological factors: conflict of interest, social pressures; (2) statistical factors: lack of experimental and statistical design prior to experimentation and replication, susceptibility to false positives; (3) translational factors: weak construct and etiological validity, superficial study of behavior. ► These issues are identified and evaluated within the context of drug discovery. Possible solutions are offered.