National Institute of Mental Health

Bethesda, MD, United States

National Institute of Mental Health

Bethesda, MD, United States

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Insel T.R.,National Institute of Mental Health
Molecular Psychiatry | Year: 2014

Although inherited DNA sequences have a well-demonstrated role in psychiatric disease risk, for even the most heritable mental disorders, monozygotic twins are discordant at a significant rate. The genetic variation associated with mental disorders has heretofore been based on the search for rare or common variation in blood cells. This search is based on the premise that every somatic cell shares an identical DNA sequence, so that variation found in lymphocytes should reflect variation present in brain cells. Evidence from the study of cancer cells, stem cells and now neurons demonstrate that this premise is false. Somatic mutation is common in human cells and has been implicated in a range of diseases beyond cancer. The exuberant proliferation of cortical precursors during fetal development provides a likely environment for somatic mutation in neuronal and glial lineages. Studies of rare neurodevelopmental disorders, such as hemimegencephaly, demonstrate somatic mutations in affected cortical cells that cannot be detected in unaffected parts of the brain or in peripheral cells. This perspective argues for the need to investigate somatic variation in the brain as an explanation of the discordance in monozygotic twins, a proximate cause of mental disorders in individuals with inherited risk, and a potential guide to novel treatment targets. © 2014 Macmillan Publishers Limited All rights reserved.

Giedd J.N.,National Institute of Mental Health
Journal of Adolescent Health | Year: 2012

Remarkable advances in technologies that enable the distribution and use of information encoded as digital sequences of 1s or 0s have dramatically changed our way of life. Adolescents, old enough to master the technologies and young enough to welcome their novelty, are at the forefront of this "digital revolution." Underlying the adolescent's eager embracement of these sweeping changes is a neurobiology forged by the fires of evolution to be extremely adept at adaptation. The consequences of the brain's adaptation to the demands and opportunities of the digital age have enormous implications for adolescent health professionals. © 2012 Society for Adolescent Health and Medicine. All rights reserved.

Cuthbert B.N.,National Institute of Mental Health
Dialogues in Clinical Neuroscience | Year: 2015

The Research Domain Criteria (RDoC) project was initiated by the National Institute of Mental Health (NIMH) in early 2009 as the implementation of Goal 1.4 of its just-issued strategic plan. In keeping with the NIMH mission, to "transform the understanding and treatment of mental illnesses through basic and clinical research," RDoC was explicitly conceived as a research-related initiative. The statement of the relevant goal in the strategic plan reads: "Develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures." Due to the novel approach that RDoC takes to conceptualizing and studying mental disorders, it has received widespread attention, well beyond the borders of the immediate research community. This review discusses the rationale for the experimental framework that RDoC has adopted, and its implications for the nosology of mental disorders in the future. © 2015, AICH - Servier Research Group.

Murray E.A.,National Institute of Mental Health
Current opinion in neurobiology | Year: 2010

Recent research indicates that the orbital prefrontal cortex (PFo) represents stimulus valuations and that the amygdala updates these valuations. An exploration of how PFo and the amygdala interact could improve the understanding of both. PFo and the amygdala function cooperatively when monkeys choose objects associated with recently revalued foods. In other tasks, they function in opposition. PFo uses positive feedback to promote learning in object-reward reversal tasks, and PFo also promotes extinction learning. Amygdala function interferes with both kinds of learning. The amygdala underlies fearful responses to a rubber snake from the first exposure on, but PFo is necessary only after the initial exposure. The amygdala mediates an arousal response in anticipation of rewards, whereas PFo sometimes suppresses such arousal. A role for PFo in advanced cognition, for the amygdala in instinctive behavior, and for cortex-subcortex interactions in prioritizing behaviors provides one account for these findings. (c) 2010 Elsevier Ltd. All rights reserved.

Kozak M.J.,National Institute of Mental Health | Cuthbert B.N.,National Institute of Mental Health
Psychophysiology | Year: 2016

This article describes the National Institute of Mental Health's Research Domain Criteria (RDoC) initiative. The description includes background, rationale, goals, and the way the initiative has been developed and organized. The central RDoC concepts are summarized and the current matrix of constructs that have been vetted by workshops of extramural scientists is depicted. A number of theoretical and methodological issues that can arise in connection with the nature of RDoC constructs are highlighted: subjectivism and heterophenomenology, desynchrony and theoretical neutrality among units of analysis, theoretical reductionism, endophenotypes, biomarkers, neural circuits, construct "grain size," and analytic challenges. The importance of linking RDoC constructs to psychiatric clinical problems is discussed. Some pragmatics of incorporating RDoC concepts into applications for NIMH research funding are considered, including sampling design. © 2016 Society for Psychophysiological Research.

Rapoport J.L.,National Institute of Mental Health
World Psychiatry | Year: 2013

This paper provides a selective overview of the past, present and future of pediatric psychopharmacology. The acceptance of medication use in child psychiatry was based on the results of double-blind, placebo-controlled trials documenting the efficacy of drug treatments for attention-deficit/hyperactivity disorder, enuresis, depression, anxiety disorders, obsessive-compulsive disorder and psychoses. This period of success was followed by a series of challenges, including a growing awareness of the long-term adverse effects of medications and of the inadequacy of long-term drug surveillance. There is great concern today that children are being overtreated with medication, especially in the US. Further advances in pediatric psychopharmacology may come from examination of large medical data sets including both pharmacological and psychiatric information, which could lead to drug repurposing, as well as from preclinical translational studies such as those using human induced pluripotent stem cells. Copyright © 2013 World Psychiatric Association.

Insel T.R.,National Institute of Mental Health
Science Translational Medicine | Year: 2012

There has been a steady retreat by the private sector away from developing medications for mental disorders. This retreat comes just as research is identifying new molecular targets, new clinical targets, and new uses of current treatments that may serve as the basis for the next generation of treatments for mental disorders.

Pajevic S.,U.S. National Institutes of Health | Plenz D.,National Institute of Mental Health
Nature Physics | Year: 2012

Many complex systems reveal a small-world topology, which allows simultaneously local and global efficiency in the interaction between system constituents. Here, we report the results of a comprehensive study that investigates the relation between the clustering properties in such small-world systems and the strength of interactions between its constituents, quantified by the link weight. For brain, gene, social and language networks, we find a local integrative weight organization in which strong links preferentially occur between nodes with overlapping neighbourhoods; we relate this to global robustness of the clustering to removal of the weakest links. Furthermore, we identify local learning rules that establish integrative networks and improve network traffic in response to past traffic failures. Our findings identify a general organization for complex systems that strikes a balance between efficient local and global communication in their strong interactions, while allowing for robust, exploratory development of weak interactions. © 2012 Macmillan Publishers Limited. All rights reserved.

Insel T.R.,National Institute of Mental Health
Nature | Year: 2010

How will we view schizophrenia in 2030? Schizophrenia today is a chronic, frequently disabling mental disorder that affects about one per cent of the world's population. After a century of studying schizophrenia, the cause of the disorder remains unknown. Treatments, especially pharmacological treatments, have been in wide use for nearly half a century, yet there is little evidence that these treatments have substantially improved outcomes for most people with schizophrenia. These current unsatisfactory outcomes may change as we approach schizophrenia as a neurodevelopmental disorder with psychosis as a late, potentially preventable stage of the illness. This ĝ€̃ rethinkingĝ€™ of schizophrenia as a neurodevelopmental disorder, which is profoundly different from the way we have seen this illness for the past century, yields new hope for prevention and cure over the next two decades. © 2010 Macmillan Publishers Limited. All rights reserved.

In 2008, the National Institute of Mental Health (NIMH) included in its new Strategic Plan the following aim: "Develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures". The implementation of this aim was named the Research Domain Criteria project, or RDoC. RDoC is a programmatic initiative that will fund grants, contracts, early-phase trials, and similar activities for the purpose of generating studies to build a research literature that can inform future versions of psychiatric nosologies based upon neuroscience and behavioral science rather than descriptive phenomenology. RDoC departs markedly from the DSM and ICD processes, in which extensive workgroup meetings generate final and finely-honed sets of diagnoses that are modified in field tests only if problems with clinical utility arise. Rather, in keeping with its provenance as an experimental system, the RDoC provides a framework for conducting research in terms of fundamental circuit-based behavioral dimensions that cut across traditional diagnostic categories. While an important aim of the project is to validate particular dimensions as useful for eventual clinical work, an equally important goal is to provide information and experience about how to conceive and implement such an alternative approach to future diagnostic practices that can harness genetics and neuroscience in the service of more effective treatment and prevention. This paper summarizes the rationale for the RDoC project, its essential features, and potential methods of transitioning from DSM/ICD categories to dimensionally-oriented designs in research studies. Copyright © 2014 World Psychiatric Association.

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