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Report of the National Institute of Mental Health’s Genetics Workgroup
REPORT OF THE NATIONAL INSTITUTE HEALTH’S GENETICS WORKGROUP
OF
MENTAL
Introduction The Genetics Workgroup of the National Institute of Mental Health (NIMH) met repeatedly over a 6-month period in 1997 to review attempts to identify the gene variants (allelles) that influence susceptibility to mental disorders, and to recommended ways to facilitate this research. The Workgroup members were: Aravinda Chakravarti (Case Western Reserve University); MaryClaire King (University of Washington); Eric Lander (Massachusetts Institute of Technology); Robert Nussbaum (National Human Genome Research Institute); Theodore Reich (Washington University School of Medicine); Joseph Takahashi (Northwestern University); Stephen Warren (Emory University) and Samuel Barondes (University of California, San Francisco, Chair of the Workgroup). The Workgroup’s staff was led by Jane Steinberg, Associate Director of NIMH and Steven Moldin of NIMH’s Genetics Research Branch. In formulating our recommendations to the NIMH Council, the Workgroup members recognized both the complexity of the genetics of mental disorders and the changing statistical and molecular approaches that are being applied to find the relevant gene variants—matters that are well addressed throughout this special issue of Biological Psychiatry. Be-
cause of the rapid ongoing evolution of this field, the Workgroup members did not feel qualified to provide an explicit set of guidelines for such research. Instead we emphasized the importance of accumulating the necessary infrastructure, including the development of a repository of clinical materials and DNA samples that would be made available to all qualified investigators. We also recommended close cooperation with other Institutes, the training of more people with an interest in psychiatric genetics, and the establishment by NIMH of a Genetics Advisory Group to monitor progress in this field and to ensure swift reaction to new opportunities. The recommendations of the Workgroup are summarized in a report that was published by the NIMH in 1998, and that is excerpted in the following pages. I am very pleased that a substantial portion of our report is being made available to the readers of this journal. Samuel H. Barondes Center for Neurobiology and Psychiatry Department of Psychiatry University of California, San Francisco San Francisco, California 94143-0984
Genetics and Mental Disorders Introduction Since its inception, the National Institute of Mental Health (NIMH) has recognized the importance of genetics in understanding mental disorders. From the earliest epidemiologic studies to today’s molecular approaches, the Institute has invested broadly in genetics research in hopes of discovering the interplay between genes and the environment in the predisposition to mental disorders. The clearest finding from this research is that there is no simple relationship between genes and mental disorders. Single, causative genes, such as those resulting in sickle-cell anemia or Huntington’s disease, do not explain how mental disorders affect one out of five Americans. Instead, researchers now believe that several susceptibility genes interact with each other and with environmental factors to influence the risk of developing a particular disorder. Finding the susceptibility genes amid multiple environmental factors is a formidable task, but not unique © 1999 Society of Biological Psychiatry
to mental disorders. Many diseases, such as asthma, hypertension, and diabetes, appear to have equally complex patterns of transmission. This labyrinth of genetic susceptibility and environmental factors poses a great challenge to geneticists. These gene hunters have responded to this challenge by developing increasingly powerful molecular and statistical tools. What seemed hopelessly complicated a few years ago is becoming solvable. Recognizing this promise and the intensive work yet to come in molecular genetics, biotechnology, biostatistics, and informatics, Dr. Steven Hyman, NIMH Director, and the National Advisory Mental Health Council formed a Council Workgroup to explore new approaches and opportunities in this area. The membership of the NIMH Genetics Workgroup, which includes basic, clinical, and statistical geneticists, is presented in Dr. Barondes’ Introduction to this report. Dr. Hyman charged the Workgroup with considering how to invest NIMH 0006-3223/99/$19.00 PII S0006-3223(98)00283-2
OF
MENTAL
Introduction The Genetics Workgroup of the National Institute of Mental Health (NIMH) met repeatedly over a 6-month period in 1997 to review attempts to identify the gene variants (allelles) that influence susceptibility to mental disorders, and to recommended ways to facilitate this research. The Workgroup members were: Aravinda Chakravarti (Case Western Reserve University); MaryClaire King (University of Washington); Eric Lander (Massachusetts Institute of Technology); Robert Nussbaum (National Human Genome Research Institute); Theodore Reich (Washington University School of Medicine); Joseph Takahashi (Northwestern University); Stephen Warren (Emory University) and Samuel Barondes (University of California, San Francisco, Chair of the Workgroup). The Workgroup’s staff was led by Jane Steinberg, Associate Director of NIMH and Steven Moldin of NIMH’s Genetics Research Branch. In formulating our recommendations to the NIMH Council, the Workgroup members recognized both the complexity of the genetics of mental disorders and the changing statistical and molecular approaches that are being applied to find the relevant gene variants—matters that are well addressed throughout this special issue of Biological Psychiatry. Be-
cause of the rapid ongoing evolution of this field, the Workgroup members did not feel qualified to provide an explicit set of guidelines for such research. Instead we emphasized the importance of accumulating the necessary infrastructure, including the development of a repository of clinical materials and DNA samples that would be made available to all qualified investigators. We also recommended close cooperation with other Institutes, the training of more people with an interest in psychiatric genetics, and the establishment by NIMH of a Genetics Advisory Group to monitor progress in this field and to ensure swift reaction to new opportunities. The recommendations of the Workgroup are summarized in a report that was published by the NIMH in 1998, and that is excerpted in the following pages. I am very pleased that a substantial portion of our report is being made available to the readers of this journal. Samuel H. Barondes Center for Neurobiology and Psychiatry Department of Psychiatry University of California, San Francisco San Francisco, California 94143-0984
Genetics and Mental Disorders Introduction Since its inception, the National Institute of Mental Health (NIMH) has recognized the importance of genetics in understanding mental disorders. From the earliest epidemiologic studies to today’s molecular approaches, the Institute has invested broadly in genetics research in hopes of discovering the interplay between genes and the environment in the predisposition to mental disorders. The clearest finding from this research is that there is no simple relationship between genes and mental disorders. Single, causative genes, such as those resulting in sickle-cell anemia or Huntington’s disease, do not explain how mental disorders affect one out of five Americans. Instead, researchers now believe that several susceptibility genes interact with each other and with environmental factors to influence the risk of developing a particular disorder. Finding the susceptibility genes amid multiple environmental factors is a formidable task, but not unique © 1999 Society of Biological Psychiatry
to mental disorders. Many diseases, such as asthma, hypertension, and diabetes, appear to have equally complex patterns of transmission. This labyrinth of genetic susceptibility and environmental factors poses a great challenge to geneticists. These gene hunters have responded to this challenge by developing increasingly powerful molecular and statistical tools. What seemed hopelessly complicated a few years ago is becoming solvable. Recognizing this promise and the intensive work yet to come in molecular genetics, biotechnology, biostatistics, and informatics, Dr. Steven Hyman, NIMH Director, and the National Advisory Mental Health Council formed a Council Workgroup to explore new approaches and opportunities in this area. The membership of the NIMH Genetics Workgroup, which includes basic, clinical, and statistical geneticists, is presented in Dr. Barondes’ Introduction to this report. Dr. Hyman charged the Workgroup with considering how to invest NIMH 0006-3223/99/$19.00 PII S0006-3223(98)00283-2