The concept of endophenotypes in psychiatric diseases meeting the expectations?
ABSTRACT Although the prominent role of genetics in psychiatric diseases has been established in various family, twin and adoption studies over the last decades, the identification of concrete contributing genes has been demanding. The reasons for this are manifold, including inconsistencies in psychiatric classification systems, complexity and heterogeneity of psychiatric disorders, epistatic effects and intervening environmental factors. In recent years interest has focused increasingly on the concept of endophenotypes. Genetic analyses have concentrated on discrete phenotypes supposedly linked to a particular psychiatric disorder by common neurobiological pathways, instead of studying the complex disease itself. Several endophenotypes have been established for psychiatric diseases including electrophysiological abnormalities and alterations in structural and functional brain imaging. Although results seem to be getting more consistent and reliable, several concerns have also emerged with the experience gained on the topic. This review will give an overview of the prospects and limitations related to endophenotypes in psychiatric diseases. We will also summarize essential prerequisites for successful endophenotypes in the future as well as applications for psychiatric diseases which have been envisioned.
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ABSTRACT: Background/Aims: Alcohol dependence is a common severe psychiatric disorder with a multifactorial etiology. Since the completion of the human genome project and with the increased availability of high-throughput genotyping, multiple genetic risk factors for substance-related disorders, including alcohol dependence, have been identified, but not all results could be replicated. Methods: We systematically review the clinical literature on genetic risk factors for alcohol dependence and alcohol-related phenotypes, including candidate gene-based studies, linkage studies and genome-wide association studies (GWAS). Results: Irrespectively of the methodology employed, the most robust findings regarding genetic risk factors for alcohol dependence concern genetic variations that affect alcohol metabolism. GWAS confirm the importance of the alcohol dehydrogenase gene cluster on chromosome 4 in the genetic risk for alcohol dependence with multiple variants that exert a small, but cumulative influence. A single variant with strong influence on individual risk is the aldehyde dehydrogenase 2 ALDHD2*2 variant common in Asian populations. Other robust associations have been found with previously uncharacterized genes like KIAA0040, and such observations can lead to the identification of thus far unknown signaling pathways. Converging evidence also points to a role of glutamatergic, dopaminergic and serotonergic neurotransmitter signaling in the risk for alcohol dependence, but effects are small, and gene-environment interactions further increase the complexity. Conclusion: With few exceptions like ALDH2*2, the contribution of individual genetic variants to the risk for alcohol-related disorders is small. However, the concentration of risk variants within neurotransmitter signaling pathways may help to deepen our understanding of the underlying pathophysiology and thereby contribute to develop novel therapeutic strategies. (C) 2014 S. Karger AG, BaselNeuropsychobiology 01/2014; 70(2):77-94. DOI:10.1159/000364826 · 2.30 Impact Factor
101 edited by Paul C Guest and Sabine Bahn, 11/2011; Academic Press., ISBN: 0123877180
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ABSTRACT: The article deals with recent research in the field of fundamental knowledge about the mechanisms of information processing in the human brain for the diagnosis of mental disorders performed in the laboratory of neurobiology for action programming of the Bechtereva Institute of the Human Brain of the Russian Academy of Sciences. These studies were connected with the analysis of functional components for cognitive event-related potentials (ERPs) obtained under various behavioral conditions. The main goal of this fundamental approach is the decomposition of multi-channel ERPs into functionally different components. These components are generated in various cortical areas, have different temporal dynamics, and reflect a variety of mental operations. The main methodology we used is the independent component analysis, applied to a large set of ERPs (from hundreds of people) obtained by varying functional conditions in the psychological test. In particular, components related to psychological processes, such as the comparison of sensory signals with a trace in working memory, inhibition of current activity, and monitoring of conflict, were identified in the GO/NOGO test. In the European project, a normative database was constructed for the components described above, and this allowed us to compare the data obtained from large groups of patients (including patients with attention deficit disorder, schizophrenia, obsessive disorders, depression, autism, dyslexia, brain trauma, and dementia) with the healthy subjects. This article presents data from patients with a diagnosis of attention deficit disorder and schizophrenia.Human Physiology 01/2013; 39(1). DOI:10.1134/S0362119713010088