f one accepts that psychiatric disorders are brain disorders, then direct examination of the brain is as integral to their biological study as is the study of bone marrow for a hematologist. Howver, such studies are rare in this journal: in 1998, only approxiately 3% of data articles were based on postmortem brain tissue, nd in 2008, the figure was 2%— compared with more than 20% sing brain imaging of one modality or another. It is not that postortem studies are not of interest; the mean number of times they ave been cited equals or exceeds the journal average for that year. This special issue was stimulated by discussion among the ediors as to why there are so few postmortem brain papers, and what, f anything, should be done about it. One good reason for their arity is, of course, that biological psychiatry is a broad church— ncreasingly so—and a wide range of approaches and methods are sed. There are also insurmountable limits as to what postmortem tudies can achieve, of which two in particular stand out. First, they re subject to many confounders and differential confounders (e.g., hronicity of illness, medication, smoking, perimortem factors), hich make primary changes intrinsic to the illness hard to distinuish from myriad secondary, compensatory, and epiphenomenal ffects. Second, by their nature, results are ultimately descriptive nd correlational; it is not possible to manipulate or perturb the rain and measure a response to test hypotheses or probe mechaisms critically. These two factors make it appropriate that only a mall proportion of articles in a leading biological psychiatry journal re based on the use of postmortem tissue. However, as in any other eld, there are good and bad studies, strengths and weaknesses of he approach, and a mixture of established and controversial findngs. The articles in this issue discuss one or more of these topics. he focus is on postmortem studies of psychosis, although the key onsiderations generalize to other psychiatric disorders. The first prerequisite is to have brain tissue of suitable quality nd quantity. Norms for both parameters have increased substanially over recent years. For example, exclusion of brains with a low H (because this predicts poor mRNA integrity) has become comon and reduces the number of brains available. Over the same eriod, the average sample size has risen dramatically: in 1991, an arly molecular study of schizophrenia in a leading journal had 14 ubjects (1), whereas now 150 or more are becoming commonplace 2,3), and a recent study included 400 (4). The trend toward large amples reflects a) a desire to make results more robust, b) studies n which findings are related to genotype (see Kleinman et al., [5]), nd c) the inclusion of additional diagnostic categories, for examle, addition of a mood disorder group to a “schizophrenia versus ontrol” study, a strategy championed by the Stanley Medical Reearch Institute (6). Fortunately, the ability to rate and control for rain quality in a molecular sense has improved (see Mccullummith and Meador-Woodruff; Tunbridge et al. [7,8]), as have the size