Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap.

The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism-based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity

Perspectives: Rationale and design of the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) project

During the past 10 years, the health of people in Eastern Europe and the former Soviet Union has undergone changes very different from the health patterns seen in their Western counterparts. Mortality from cardiovascular disease has been decreasing continuously in the USA and many Western European countries, but it has increased or remained unchanged in many of the states of Eastern Europe. Analysis of this phenomenon has been hindered by insufficient information. The International Registry of Acute Coronary Syndromes registry study in Transitional Countries (ISACS-TC) is both a retrospective - over a 1-year period - and prospective study which was designed in order to obtain data of patients with acute coronary syndromes (ACSs) in countries with economy in transition in Central and Eastern Europe, and herewith control and optimize internationally guideline recommended therapies in these countries. Adhesion to the project was given by 112 Collaborating Centres in 17 countries with economy in transition (Albania, Bosnia and Herzegovina, Belarius, Bulgaria, Croatia, Hungary, Kosovo, Latvia, Lithuania, Macedonia, Moldova, Montenegro, Romania, Russian Federation, Serbia, Slovakia, Slovenia, and Ukraine). A total of 47 cluster sites in 11 countries in Central and Eastern Europe are currently collaborating in ISACS-TC. The registry encourages optimal individualization of evidence-based therapies and the international patient body ensures good representation of multiple practice patterns. It may help to make an additional improvement in clinical outcomes of countries with economy in transition