Psychiatric Clinics of North America RSS feed: Current Issue. Psychiatric Clinics of North America updates you on the latest trends in patient management; keeps you up to date on the newest advances; and provides a sound basis for choosing treatment options. Each issue focuses on a single topic in psychiatry and is presented under the direction of an experienced guest editor.http://www.psych.theclinics.com/?rss=yesElsevier Inc.en © 2009 Published by Elsevier Inc. All rights reserved. Psychiatric Clinics of North America0193-953X331March 2010 © 2009 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.psych.theclinics.com/article/PIIS0193953X10000067/abstract?rss=yesContributors List10.1016/S0193-953X(10)00006-7Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8iiivhttp://www.psych.theclinics.com/article/PIIS0193953X10000079/abstract?rss=yesContents10.1016/S0193-953X(10)00007-9Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8viixhttp://www.psych.theclinics.com/article/PIIS0193953X10000080/abstract?rss=yesForthcoming Issues10.1016/S0193-953X(10)00008-0Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8xixihttp://www.psych.theclinics.com/article/PIIS0193953X09001105/abstract?rss=yes The end of the last decade marked the beginning of a new phase in psychiatric genetics. It was a time when the previously uncharted territory of the genome came into much sharper focus and our tools for probing this territory became far more sophisticated. In his recent book, The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science, Richard Holmes describes the excitement in the 1780s when William Herschel, using a telescope more powerful than any that had come before, discovered Uranus, the first new planet identified since ancient times. While our field spent 20 years in search of genetic variants contributing to psychiatric illness, only in the past few years have our instruments become powerful enough that we can effectively scan the universe of DNA inside ourselves at a resolution sufficient to unlock its secrets.Preface: Promises Kept: Robust Discovery in Psychiatric GeneticsJames B. Potash10.1016/j.psc.2009.12.008Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8xiiixvihttp://www.psych.theclinics.com/article/PIIS0193953X09001099/abstract?rss=yesA typographical error appeared in the author affiliation information for article, “Management of Schizophrenia with Obsessive-Compulsive Features” by Drs Michael Y. Hwang, MD, Sung-Wan Kim, MD, PhD, Sun Young Yum, MD, and Lewis A. Opler, MD, PhD, published in the December 2009 issue of Psychiatric Clinics of North America (Vol. 32, No. 4, p. 835). Only Dr Hwang is affiliated with Mental Health Service, Franklin Delano Roosevelt Hospital, Veterans Affairs Hudson Valley Healthcare System. The other authors are not affiliated with this institution. All other affiliation information is correct.Erratum10.1016/j.psc.2009.12.007Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8xviixviihttp://www.psych.theclinics.com/article/PIIS0193953X09001087/abstract?rss=yesThe practice of psychiatry has long suffered from the limited information available on the biological basis of mental disorders. This limitation is now coming to an end. Advances in DNA analysis technologies and in our understanding of the human genome, together with our new knowledge of the properties of the genome and significant efforts toward generating large patient and control sample collections, have paved the way for successful genome-wide association studies. As a result, reports now appear in the literature every week identifying new genes for complex disorders. Next-generation sequencing methods, combined with the results of association and perhaps linkage studies, will help us uncover missing heritability factors, achieve a better understanding of the genetic aspects of psychiatric disease, and devise the best strategies for incorporating genetics in the service of patients.Genetics of Psychiatric Disorders Methods: Molecular ApproachesDimitrios Avramopoulos10.1016/j.psc.2009.12.006Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8113http://www.psych.theclinics.com/article/PIIS0193953X09001075/abstract?rss=yesGiven the potential benefits of gene identification in psychiatry, genetic epidemiology has become a mainstream discipline within the field. This article discusses the main tools for gene discovery. The focus is on the designs and analytic approaches for each of these methods. Because most gene discovery has now moved to genetic association studies, and most recently to genome-wide association studies, the focus is on methods for this design. Also highlighted are the current challenges of genetic epidemiology as a prelude to future approaches that may be applied to psychiatric disorders in the coming years.Methods: Genetic EpidemiologyKelly S. Benke, M. Daniele Fallin10.1016/j.psc.2009.12.005Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-81534http://www.psych.theclinics.com/article/PIIS0193953X09001051/abstract?rss=yesSchizophrenia is a complex genetic disorder manifesting combined environmental and genetic causation. Recently, genome-wide association experiments yielded remarkable new experimental evidence that is leading to a better understanding of the genetic models and the biological risk factors involved in schizophrenia. These studies have discovered uncommon copy number variations (mainly deletions) and common single nucleotide polymorphisms with alleles associated with schizophrenia. The aggregate data provide support for polygenic inheritance and for genetic overlap of schizophrenia with autism and with bipolar disorder. It is anticipated that the application of a myriad of tools from systems biology, in combination with biological functional experiments, will lead to a delineation of biological pathways involved in the pathophysiology of schizophrenia, and eventually to new therapies.The Role of Genetics in the Etiology of SchizophreniaPablo V. Gejman, Alan R. Sanders, Jubao Duan10.1016/j.psc.2009.12.003Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-83566http://www.psych.theclinics.com/article/PIIS0193953X09000999/abstract?rss=yesResearch into the genetic basis of bipolar disorder (BD) has reached a turning point. Genome-wide association studies (GWAS), encompassing several thousand samples, have produced replicated evidence for some novel susceptibility genes; however, the genetic variants implicated so far account for only a fraction of disease liability, a phenomenon not limited to psychiatric phenotypes but characteristic of all complex genetic traits studied to date. It appears that pure genomic approaches, such as GWAS alone, will not suffice to unravel the genetic basis of a complex illness like BD. Genomic approaches will need to be complemented by a variety of strategies, including phenomics, epigenomics, pharmacogenomics, and neurobiology, as well as the study of environmental factors. This review highlights the most promising findings from recent GWAS and candidate gene studies in BD. It furthermore sketches out a potential research framework integrating various lines of research into the molecular biological basis of BD.Genetic Research into Bipolar Disorder: The Need for a Research Framework that Integrates Sophisticated Molecular Biology and Clinically Informed Phenotype CharacterizationThomas G. Schulze10.1016/j.psc.2009.10.005Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-86782http://www.psych.theclinics.com/article/PIIS0193953X0900104X/abstract?rss=yesAutism spectrum disorders (ASDs) are highly heritable. Gene discovery promises to help illuminate the pathophysiology of these syndromes, yielding opportunities for the development of novel treatments and understanding of their natural history. Although the underlying genetic architecture of ASDs is not yet known, the literature demonstrates that it is not a monogenic disorder with mendelian inheritance, rather a group of complex genetic syndromes with risk deriving from genetic variations in multiple genes. This article reviews the origins of the common versus rare variant debate, highlights recent findings in the field, and addresses the clinical implications of common and rare variant discoveries.The Genetics of Autism: Key Issues, Recent Findings, and Clinical ImplicationsPaul El-Fishawy, Matthew W. State10.1016/j.psc.2009.12.002Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-883105http://www.psych.theclinics.com/article/PIIS0193953X09000975/abstract?rss=yesAddictions include a group of common, heritable psychiatric illnesses that have multiple psychiatric and medical comorbidities. Robust genetic associations have been found for alcohol dependence, nicotine dependence, and cocaine dependence. Common genetic associations have been found between alcohol dependence and aerodigestive cancers and between nicotine dependence and lung disease. These associations highlight the importance of understanding the genetics of substance dependence in the context of its multiple medical and psychiatric comorbidities.Genetics of AddictionsSarah M. Hartz, Laura J. Bierut10.1016/j.psc.2009.10.003Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8107124http://www.psych.theclinics.com/article/PIIS0193953X09000987/abstract?rss=yesEfforts to unlock the biology of major depressive disorder (MDD) are proceeding on multiple fronts. In this article, the authors review the current understanding of epidemiological evidence for a heritable component to MDD risk, as well as recent advances in linkage, candidate gene, and genome-wide association analyses of MDD and related disease subtypes and endophenotypes. While monoamine signaling has preoccupied the bulk of scientific investigation to date, nontraditional gene candidates such as PCLO and GRM7 are now emerging and beginning to change the landscape for future human and animal research on depression.The Genetics of Major Depression: Moving Beyond the Monoamine HypothesisStanley I. Shyn, Steven P. Hamilton10.1016/j.psc.2009.10.004Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8125140http://www.psych.theclinics.com/article/PIIS0193953X09001002/abstract?rss=yesObsessive-compulsive disorder is a common debilitating condition affecting individuals from childhood through adult life. There is good evidence of genetic contribution to its etiology, but environmental risk factors also are likely to be involved. The condition probably has a complex pattern of inheritance. Molecular studies have identified several potentially relevant genes, but much additional research is needed to establish definitive causes of the condition.Genetics of Obsessive-Compulsive DisorderGerald Nestadt, Marco Grados, Jack F. Samuels10.1016/j.psc.2009.11.001Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8141158http://www.psych.theclinics.com/article/PIIS0193953X09001063/abstract?rss=yesAlthough twin studies demonstrate that ADHD is a highly heritable condition, molecular genetic studies suggest that the genetic architecture of ADHD is complex. The handful of genome-wide linkage and association scans that have been conducted thus far show divergent findings and are, therefore, not conclusive. Similarly, many of the candidate genes reviewed here (ie, DBH, MAOA, SLC6A2, TPH-2, SLC6A4, CHRNA4, GRIN2A) are theoretically compelling from neurobiological systems perspective but available data are sparse and inconsistent. However, candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder, with meta-analyses supportive of a role of the genes coding for DRD4, DRD5, SLC6A3, SNAP-25, and HTR1B in the etiology of ADHD.Molecular Genetics of Attention Deficit Hyperactivity DisorderStephen V. Faraone, Eric Mick10.1016/j.psc.2009.12.004Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8159180http://www.psych.theclinics.com/article/PIIS0193953X09001038/abstract?rss=yesExisting psychotropic medications for the treatment of mental illnesses, including antidepressants, mood stabilizers, and antipsychotics, are clinically suboptimal. They are effective in only a subset of patients or produce partial responses, and they are often associated with debilitating side effects that discourage adherence. There is growing enthusiasm in the promise of pharmacogenetics to personalize the use of these treatments to maximize their efficacy and tolerability; however, there is still a long way to go before this promise becomes a reality. This article reviews the progress that has been made in research toward understanding how genetic factors influence psychotropic drug responses and the challenges that lie ahead in translating the research findings into clinical practices that yield tangible benefits for patients with mental illnesses.The Promise and Reality of Pharmacogenetics in PsychiatryPeter P. Zandi, Jennifer T. Judy10.1016/j.psc.2009.12.001Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8181224http://www.psych.theclinics.com/article/PIIS0193953X09000835/abstract?rss=yesThe recent advent of commercially available genetic tests for the diagnosis of several mental illnesses has led to intense controversy amongst the psychiatric research community. In this article the authors review these developments, and contrast these with the growing evidence from genome-wide association studies that highly heritable psychiatric conditions such as schizophrenia are due to the contributions and interaction of multiple allelic variants, each of small effect size. There is also evidence for the contribution of some highly penetrant rare de novo copy number variants, though the lack of disease specificity for these is of concern. This article outlines the prerequisites for predictive and diagnostic genetic tests, such as clinical validity and utility, and reviews the opportunity that genetic tests for mental illnesses present. As the scientific discourse on genetic tests for complex disorders is not limited to psychiatry, the authors outline current thoughts on the significance of genome-wide association studies across health, and the phenomenon of direct-to-consumer tests in medicine. The attitudes and understanding of patients, families, and clinicians about the future (currently hypothetical) scenario of psychiatric genetic tests are discussed, as is the potential for such testing to increase, rather than diminish stigma. Finally, recommendations on the future development and availability of genetic tests in psychiatry are provided.Predictive and Diagnostic Genetic Testing in PsychiatryPhilip B. Mitchell, Bettina Meiser, Alex Wilde, Janice Fullerton, Jennifer Donald, Kay Wilhelm, Peter R. Schofield10.1016/j.psc.2009.10.001Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8225243http://www.psych.theclinics.com/article/PIIS0193953X10000092/abstract?rss=yesIndex10.1016/S0193-953X(10)00009-2Psychiatric Clinics of North America 33, 1 (2010)2010-03-01Psychiatric Clinics of North America2010-03-01331S0193-953X(10)X0002-8245255