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The Division of Developmental Translational Research

Description:

The Division of Developmental Translational Research directs, plans, and supports programs of research and research training leading to the prevention and cure of childhood psychopathology. This long-term goal will be accomplished through an integrated program of research across behavioral/psychological processes, brain development, environment and genetics. The topics listed below reflect the NIMH interest in technologies related to this research area, but should not be considered a complete list. Prospective applicants are strongly encouraged to contact Dr. Margaret Grabb (listed below) with questions about the relevance of their interests to the mission of this division.

A. Technologies for Clinical Pediatric Research. It is important to develop reliable methods that can correctly identify the normal and abnormal components of cognitive, emotional, and psychosocial behavior, as well as normal and abnormal physiological and biochemical functions, in human development. Computer-based methods of accomplishing this are also needed to increase the accessibility and reliability of information made available to the research community. Examples include:

1. Measurements of Alterations in Pediatric Development in Patients with Mental Health Disorders Using Physiological and Behavioral Measures. Research studies indicate that some mental health disorders, such as autism, may begin to develop as early as infancy. Therefore non-invasive modern equipment that use the most recent technological advances are needed to isolate specific physiological and behavioral changes during development, to identify potential diagnostic markers of mental health disorders. A priority for this program is to support research and development of hardware and software tools to measure pediatric development. Examples of technologies needed include:

a. Psychophysiological measures to evaluate infants, children or adolescents.

b. Miniaturized non-invasive instruments to record psychophysiological data (e.g., heart and respiration rate, galvanic skin response, and defensive motor behavior).

c. Telemetry capability for non-invasive devices so that children can be monitored for prolonged periods without interfering with their behavior.

d. Computer programs and inexpensive computers that will collect, analyze and identify recurring patterns in the psychophysiological measure(s) of interest.

2. Pediatric Assessment Tool. Diagnosis of mental health disorders in children and adolescents is vital to providing early interventions to treat the disorder. In addition, a better understanding of the concept of functioning in psychopathology, and its appropriate measurement, is needed in pediatric populations. In the future, diagnostic tools may even help detect the initial onset of illness in children at risk, before symptoms occur. A priority for this program is to develop novel diagnostic tools to detect mental health disorders in children and adolescents. Of particular interest to this division are methods that can be used with children and adolescents with limited verbal communication (i.e., very young or developmentally disabled). Biochemical, genetic, physiological and psychological tool development is welcomed.

a. Technologies to assess CNS effects of psychosocial or pharmacological interventions.

b. Development of reliable and stable biomarkers/biosignatures that can identify at-risk individuals prior to disease onset, biological and behavioral indicators or predictors of treatment response, measures of disease progression, measures to identify dose ranges prior to clinical studies, preclinical or clinical efficacy testing, toxicity measures for drug development, defining patients to enroll in the clinical study, identifying CNS abnormalities, etc.

c. Assessment tools for pediatric mental health disorders that are sensitive to developmental change, gender and cultural diversity, variation in cognitive and behavioral functioning, hearing and/or speech impairment, and co-morbid disorders.

d. Innovative approaches to assessing mental disorders using new statistical and psychometric techniques such as Item Response Theory.

e. Computerized methodologies for assessing various mental disorders suitable for use in primary care settings, e.g. they would need to function rapidly and reliably.

f. Biological and behavioral measures to define and assess specific impairment-related components of psychiatric disorders, e.g., cognitive dysfunctions in schizophrenia.

g. Development of valid and reliable measures that operationalize functioning within and across developmental periods, and that can be used in a variety of service settings. Such measures can lead to more accurate diagnoses, a better understanding of the impact of psychiatric disorders, and better tracking of treatment effectiveness.

3. Behavior Monitoring and Analysis of Pediatric Mental Health Disorders.

a. Improve or create new video devices to monitor human behavior and ease analysis of behavior.

b. Computer software to ease analysis of behavior monitored by video or telemetry systems.

c. Automated methods to detect specific emotional states using behavioral and autonomic indicators: This Division is specifically interested in technologies that can identify children with heightened or dampened emotional states that could be associated with particular mental health disorders, including children with limited verbal skills (i.e., very young or developmentally disabled). If the technology will primarily be used to investigate basic mechanisms of behavior, the Division of Neuroscience and Basic Behavioral Science at NIMH would be the most appropriate division to contact.

4. Intervention Development for Childhood-Onset Mental Disorders.

a. Strategies (e.g., animal behavioral testing, computer simulation) for evaluating, in early developmental periods, the effects of pharmacological agents on specific functional domains and brain circuits associated with mental disorders.

b. Strategies (e.g., animal behavioral testing, computer simulation) for evaluating, in early developmental periods, the effects of cognitive or behavioral interventions (e.g., cognitive rehabilitation, attention training) or device-based protocols (e.g., transcranial magnetic stimulation or direct current stimulation) on specific functional domains and brain circuits associated with mental disorders.

c. Methods for evaluation of long-term effects of psychotherapeutic drug administration or brain stimulation protocols in developmental animal models.

5. Methodological Research and Development. There is a need to devise new ways of data collection, analysis, management and dissemination. Examples include:

a. Technologies that use the most recent technological advances to identify aberrations in the CNS during development, associated with mental disorders. Once these aberrations are identified and localized, rational therapies can be developed and evaluated.

b. Innovative, computer-based methods to monitor preventive and treatment intervention efforts and correlate them with outcome measures are needed. Results should be accessible to other interested parties without compromising the privacy of the individual.

c. Development of innovative software for addressing the integration of distributed cross-disciplinary data sources into coherent knowledge bases. The data should focus on pediatric mental health disorders.

d. Computer-based intervention development for parents or for school settings.

e. Development of databases containing detailed genetic and behavioral information on pediatric populations and their families, as resources for the field in investigations of gene x environment interactions.

f. Mathematical, statistical and computer algorithms that could be used to analyze large and/or complex data sets. Examples of these data sets include those derived from functional imaging studies. Among other applications, these could be used to segment images such as those obtained from magnetic resonance imagers, filter noise, visualize data or search vast data sets for specified patterns or data (e.g., use of pattern recognition algorithms to search time series data sets obtained from electrophysiological recording of neural activity, or video data obtained from behavioral analysis of genetically altered animals). Improved techniques for path analysis when examining functional imaging datasets would also be of interest.

B. Child and Adolescent Treatment and Preventive Intervention Research. An estimated one in ten children and adolescents in the United States suffers from mental illness severe enough to cause some level of impairment. Yet, it remains unclear what treatments are the best and safest for these developing age groups. A priority for this program is to support research and development of novel psychopharmacological or psychosocial approaches for the treatment and prevention of mental illness in childhood and adolescence, in subjects aged 18 and below.

The goal of this research is broad and inclusive with respect to the heterogeneity of patients, the severity and chronicity of disorders, and the range of outcomes measured. Disorders studied include all mental and behavioral disorders. Interventions studied include pharmacologic approaches (individual and combination medications), somatic approaches, behavioral and psychotherapeutic approaches. Research is supported on individual and combined approaches. Research that translates findings on basic physiological or behavioral processes into novel preventive or treatment interventions is especially encouraged. Effectiveness studies that focus on interventions of known efficacy are assigned to the Division of Services and Intervention Research.

Human subjects include child and adolescent age groups covering the full range of mental disorders individually and in complex patterns of comorbidity with other mental disorders and behavioral problems (e.g., anxiety and depression) and substance abuse (e.g., depression and alcohol abuse).

1. Pharmacologic Treatment Intervention. Clinical testing of novel mechanism therapeutics is the principle aim of this technology development section. This includes Phase IIa and proof of concept studies in pediatric subjects. It is expected the pharmacologic agents selected for these studies be IND-ready and based on novel molecular targets identified through basic and clinical research, preclinical research and animal model research relevant to understanding developmental aspects of mental illness.

2. Combined Intervention. Areas include all research that combines different treatment modalities in a single combined or comparative protocol (e.g., pharmacologic plus psychosocial intervention).

3. Psychosocial Intervention. Areas include development and application of new psychotherapeutic, behavioral, and psychosocial treatments, based on the latest advances in development neuroscience.

4. Preventive Intervention Program. Areas include preventive intervention studies in which efficacy has not been demonstrated, including those designed to reduce the risk of onset or delay onset of mental disorders, dysfunctions and related problems within asymptomatic and subclinical populations and those related to treatment (e.g., prevention of relapse, recurrence) or side effects (prevention/ minimization of tardive dyskinesia, etc.). Prevention studies that focus on behavioral problems, without a focus on a specific mental health disorder or a specific domain of function that significantly impacts a mental health disorder (e.g. cognitive function) should contact NICHD.

5. Development and Maintenance of Clinical Trial Networks. Areas include the development of hardware/software to facilitate research collaborations in conducting clinical trials, technologies to facilitate data sharing, merging of multiple data sets, and the development and maintenance of common protocols across research sites working on a common pediatric preventive or treatment intervention.

C. Science Education in Mental Disorders. There is a critical need for improvement in science education, particularly in areas specifically related to brain, behavior and mental illness. Examples include:

1. Research on the best ways to present neuroscience and behavioral science information, in the context of mental health disorders, to particular groups of students (e.g., kindergarten through sixth grade).

2. Computer-based systems to teach students how to observe scientific phenomena related to the brain, behavior and mental illness, and to report them clearly in writing.

3. Research on better ways to communicate new knowledge and directions of scientific growth in the area of neuroscience and mental illness to teachers and curriculum developers.

For further information on Developmental Translational Research-related topics, contact:

Margaret Grabb, Ph.D.

National Institute of Mental Health

6001 Executive Blvd. Room 7201

Mail Stop Code 9645

Bethesda, MD 20892

301-443-3563, Fax: 301-443-1731

Email: mgrabb@mail.nih.gov

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