ARRA Investments in Neuroscience of Mental Health
Resource Building and Infrastructure
In contrast to many other chronic medical conditions, the symptoms of mental disorders often begin to appear in childhood and adolescence, and these symptoms may wax and wane throughout a person’s life. NIH supports research to compare trajectories of healthy development to those of mental disorders in order to better understand the initial occurrence when development is altered. By predicting, detecting, and intervening early in the disease process, we can dramatically improve an individual’s likelihood of a life free from the suffering of mental disorders. In pursuit of this goal, ARRA has provided NIMH with the opportunity to build large-scale resources that will serve the research community for years to come. ARRA-funded projects will develop tools to chart the developmental trajectories of neurobiological, genetic, behavioral, and environmental factors that confer a risk for mental disorders. For example:
Three linked ARRA grants support the creation of a web-based atlas of gene expression patterns in the developing human brain, called the Transcriptional Atlas of Human Brain Development, which will facilitate identification of gene variants that may contribute to mental disorders.
Another grant supports the development and validation of an image-based resource describing the developmental trajectory of blood flow patterns in the brains of normally developing children. Blood flow patterns may herald critical changes in neurological and cognitive development.
Researchers will expand brain bank resources for a study investigating brain abnormalities among older adults with late-life depression and who are at increased risk for developing dementia.
Cellular & Molecular Neuroscience
Understanding the cellular and molecular mechanisms in brain function and dysfunction can open the door toward more targeted, personalized treatments and interventions. ARRA-funded research in this area includes the following grants:
One project will examine how selective serotonin reuptake inhibitors (SSRIs), administered during childhood and adolescence, affect regulation of a critical brain growth factor and behavioral responses.
Another ARRA-funded project will develop genetic tools that will enable researchers to manipulate brain cell activity in mouse models of human psychiatric diseases, improving our understanding of brain circuitry function and dysfunction.
Another grant will develop brain imaging agents to detect a molecular transporter for the neurotransmitter, norepinephrine. Alterations in norepinephrine signaling have been implicated in numerous mental disorders.
One ARRA-funded project investigates the role of the hormone leptin in the brain signaling mechanisms underlying co-occurring diabetes and depression.
A particularly promising area of neuroscience research involves induced pluripotent stem cells (iPSCs)—somatic cells, such as skin cells, that are genetically manipulated to become stem cells, which can be induced to generate other cell types, such as brain cells. To study how changes in neuron function contribute to mental disorders, researchers will establish methods for creating a special class of neurons, called interneurons, for in vitro experiments, using iPSCs from adults. Dysfunction of interneurons that communicate via the brain chemical GABA will be studied in this grant. GABA has been implicated in a variety of major mental disorders.
Another ARRA-funded grant aims to develop iPSCs from people with bipolar disorder, to explore underlying molecular mechanisms that cannot be feasibly studied in clinical trials.
Mental illnesses are now studied as brain disorders, specifically as disorders of brain circuits. To further clarify how changes in neural activity contribute to mental disorders, we need to know more about the neuroscience of neural circuit formation and how these circuits interact to contribute to observable behaviors. ARRA funds support these investigations.
An ARRA grant will further our understanding of brain circuits mediating associative learning, with a focus on circuits related to drug addiction and relapse following treatment.
One project will use brain imaging to characterize alterations in neuronal circuits underlying anorexia nervosa to lay the groundwork for devising more effective treatment interventions.
Cognitive & Behavioral Neuroscience
ARRA funds will be used to support the development of integrative approaches to understanding the mechanisms underlying the regulation of emotion, mood, and cognition—domains that can be disrupted in mental disorders. For example:
Investigators will study, at the level of brain cell signaling, how attention affects behavior, an important issue in understanding mental illnesses involving disorders of attention.
An ARRA-funded project will investigate normal and pathological function of spatial working memory in an animal model using pharmacological, brain imaging, and electrophysiological methods, and then use the findings to inform pharmacological and brain imaging studies in humans.
Another project supports research to identify individual differences in risky decision making and to map biologically predictive markers of those differences associated with clinically-defined categories of mental disorders.
, ; 1RC2MH089929-01; 1RC2MH090047-01 -- Transcriptional Atlas of Human Brain Development -- Lein, Ed (WA); Sestan, Nenad (CT); Knowles, James A (CA)
-- Pediatric Template of Brain Perfusion -- Wang, Jiongjiong (PA)
-- Pathways Linking Late-Life Depression to MCI & Dementia -- Butters, Meryl A (PA)
-- Molecular Mechanisms of SSRI Action in Childhood and Adolescence -- Lee, Francis (NY)
-- OptoGenetic Mice for Cell Type-Specific Manipulation of Neuronal Activity -- Feng, Guoping (NC)
-- PET Imaging Tracers to Quantify Norepinephrine Transporter in the Brain -- Gerdes, John M (MT)
-- Hippocampal plasticity in co-morbid diabetes and depression -- Reagan, Lawrence P (SC)
-- Derivation of cerebral cortical GABAergic interneurons from human iPS cells --Anderson, Stewart (NY)
-- Patient-Derived Stem Cells for Phosphoproteomic Profiling Neuropsychopathology -- Snyder, Evan (contact); Wolk, Dieter A (CA)
-- Errors and Expectancies in OFC and VTA and their Roles in Associative Learning -- Schoenbaum, Geoffrey M (MD)
-- Neural Dysfunction of Interoception in Adolescents Diagnosed with Anorexia Nervosa -- Grethe, Amanda B (CA)
-- Optogenetic control of attention through prefrontal synchrony -- Desimone, Robert (MA)
-- Neural mechanisms of spatial working memory -- Snyder, Lawrence H (MO)
-- From Phenotype to Mechanism: Mapping the Pathways underlying Risky Choice -- Huettel, Scott (NC)
Page Last Updated on June 30, 2018
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