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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.

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.

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.

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.

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