Rare copy number variants have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large CNVs at several loci, including microdeletions at 1q21.1, 3q29, 15q13.3 and 22q11.2 and microduplication at 16p11.2. However, these CNVs collectively account for a small fraction of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy (...) number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 patients versus 2 of 7,431 controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs. © 2011 Macmillan Publishers Limited. All rights reserved. (shrink)

Denounced by neighbors and scrutinized by demonologists, the early modern French witch also confessed, self-identified as a witch and as the author of horrific deeds. What led her to this point? Despair, solitude, perhaps even physical pain, but most decisively, demonology's two-pronged prosecutorial and truth-seeking confessional apparatus. This book examines the systematic and well-oiled machinery that served to extract, interpret, and disseminate witches' confessions in early modern France. For the demonologist, confession was the only way to find out the truth (...) about the clandestine activities of witches. For the witch, however, trial confessions opened new horizons of selfhood. In this book, Virginia Krause unravels the threads that wove together the demonologist's will to know and the witch's subjectivity. By examining textual and visual evidence, Krause shows how confession not only generated demonological theory but also brought forth a specific kind of self, which we now recognize as the modern subject. (shrink)