Can 'differential display' methodologies make an impact on biological psychiatry?

The past decade has been marked by a dramatic increase in the availability of techniques to identify and clone genes that are differentially expressed in disease states and by drug treatments. The applications of such techniques to problems in biological psychiatry are manifold and the implications of discovering novel and/or known genes that are perturbed in neuropsychiatric disorders profound. While there are success stories, it is becoming ever more apparent that each of these techniques has its limitations, particularly when applied to the central nervous system. Given that these methods (e.g. differential display, RNA fingerprinting, suppression-subtractive hybridization, microarrays) are labour-intensive and potentially time-consuming, it is important to understand these limitations. For example, differential display is capable of detecting very small changes in the expression of mRNA species. Methods like suppression-subtractive hybridization are better suited to examine potential differences in rare transcripts, but only when their expression is changed substantially (currently ? 5-fold). Moreover, both the functional and morphological organization of the central nervous system present challenges that may not be encountered in other systems. In this overview, we will discuss the advantages and disadvantages of some of these approaches and their application to research in biological psychiatry.