FRONTOSTRIATAL GLUTAMATE IN ADHD: NEUROPSYCHOLOGICAL AND BEHAVIORAL CORRELATES
Horska Alena
Hugo W. Moser Res Inst Kennedy Kriegercity: Baltimore country: United States (us)
Grant 5R21MH092693-02 from National Institute Of Mental Health
Keywords: 9 year old; Address; Age; Amino Acids; Animal Model; Animals; Anterior; Attention deficit hyperactivity disorder; Basal Ganglia; base; behavior measurement; Behavior Therapy; Behavioral; Biological; boys; Brain; brain behavior; Brain region; Child; Childhood; Choline; Cognitive; Comorbidity; Corpus striatum structure; Data; design; Development; Disease; Dopamine; Excitatory Amino Acids; executive function; Functional disorder; Functional Magnetic Resonance Imaging; gamma-Aminobutyric Acid; gene therapy; Genetic; girls; Glutamates; Glutamine; Goals; Human; Impairment; in vivo; Individual; interest; Investigation; Link; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Mental disorders; Metabolism; Motor; N-acetylaspartate; nervous system disorder; Neurobiology; neurochemistry; neuroimaging; Neurons; neuropsychological; neurotransmission; Neurotransmitters; Parietal; Participant; Pathologic Processes; Performance; Pharmaceutical Preparations; Pharmacological Treatment; Play; Preparation; Protons; public health relevance; Reporting; Research; response; Rest; Risk Factors; Role; Sample Size; Sampling; Serotonin; Severities; sex; Short-Term Memory; skills; Socioeconomic Status; Specificity; success; Symptoms; Time
Relevance: Glutamate is an excitatory amino acid and the most abundant neurotransmitter in the brain. Glutamate levels are linked to a variety of neurological and psychiatric disorders, and have been implicated in the development of core symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Prior neuroimaging studies examining glutamate levels in ADHD had limited success, because at field strengths less than 2.0 Tesla, it is difficult to measure the absolute levels of glutamate in the human brain. The overall goal of the proposed investigation is to investigate the role of frontostriatal glutamatergic metabolism in medication-na¿ve children with ADHD using proton magnetic resonance spectroscopy at 7.0 Tesla, and to determine the specific mechanisms of cognitive and behavioral dysfunction associated with these glutamatergic as well as other neurochemical anomalies. This study will be the first investigation of the neurobiology of ADHD in children using MR spectroscopy at 7.0 Tesla
Project start date: 2011-01-01
Project end date: 2012-12-31
Budget start date: 1-JAN-2012
Budget end date: 31-DEC-2012
5R21MH092693-02 (2012): $182593
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Horska Alena
FRONTOSTRIATAL GLUTAMATE IN ADHD: NEUROPSYCHOLOGICAL AND BEHAVIORAL CORRELATES
Horska Alena, Associate Professor
Hugo W. Moser Res Inst Kennedy Kriegercity: Baltimore country: United States (us)
Grant 1R21MH092693-01 from National Institute Of Mental Health
Abstract: The overall goal of the proposed investigation, "Frontostriatal Glutamate in ADHD Neuropsychological and Behavioral Correlates" is to investigate the role of frontostriatal glutamatergic metabolism in medication-naive children with ADHD using proton magnetic resonance spectroscopy at 7.0 Tesla, and to determine the specific mechanisms of cognitive and behavioral dysfunction associated with these glutamatergic as well as other neurochemical anomalies. This study will be the first investigation of the neurobiology of ADHD in children using MR spectroscopy at 7.0 Tesla. Glutamate is an excitatory neurotransmitter and the most abundant amino acid in the brain. It is the primary excitatory neurotransmitter for the cortico-striato-thalamo-cortical loop (previously shown to abnormal in ADHD via volumetric MRI, fMRI, resting state fMRI, and DTI studies). Glutamate is also the primary excitatory neurotransmitter for the cortico-striatal afferents to the basal ganglia-playing a crucial neuromodulatory role in the striatum, and contributing to efficiency of both cognitive and motor function. Abnormal glutamate concentrations in the brain have been linked to a variety of neurological and psychiatric disorders. In ADHD, glutamate also serves to modulate the release of other neurotransmitters implicated in the disorder, including dopamine and serotonin. Converging findings from animal models, pharmacologic interventions, genetic and neuroimaging studies have identified increased glutamate neurotransmission in the development of core symptoms of ADHD. Using a cross sectional design of single voxel 1H MR spectroscopy obtained with short-echo time at 7.0 Tesla, along with neuropsychological assessment, the current study proposes to 1) measure frontostriatal and (as a control region) parietal glutamate levels in medication-naove children with ADHD, ages 5-9 years (compared to age- sex- and socioeconomic status [SES]-matched typically developing children), emphasizing glutamate in frontal (prefrontal, anterior cingulate), and striatal regions of interest, as well as other metabolites observed in the spectrum (NAA, Cr, Cho, mI, Gln) in all brain regions; and; 2) search for relationships among glutamate levels in regions identified as abnormal in ADHD via Aim 1, and behavioral measures of executive function (EF), non-EF skills, and severity of ADHD symptoms. Glutamate is an excitatory amino acid and the most abundant neurotransmitter in the brain. Glutamate levels are linked to a variety of neurological and psychiatric disorders, and have been implicated in the development of core symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Prior neuroimaging studies examining glutamate levels in ADHD had limited success, because at field strengths less than 2.0 Tesla, it is difficult to measure the absolute levels of glutamate in the human brain. The overall goal of the proposed investigation is to investigate the role of frontostriatal glutamatergic metabolism in medication-naive children with ADHD using proton magnetic resonance spectroscopy at 7.0 Tesla, and to determine the specific mechanisms of cognitive and behavioral dysfunction associated with these glutamatergic as well as other neurochemical anomalies. This study will be the first investigation of the neurobiology of ADHD in children using MR spectroscopy at 7.0 Tesla
Keywords: 0-11 years old; 2-Hydroxy-N, N, N-trimethylethanaminium; 3, 4-Dihydroxyphenethylamine; 3-(2-Aminoethyl)-1H-indol-5-ol; 4-(2-Aminoethyl)-1, 2-benzenediol; 4-Aminobutanoic Acid; 4-Aminobutyric Acid; 5-HT; 5-Hydroxytryptamine; 5HT; 9 year old; AD/HD; Address; ADHD; Age; Aminalon; Aminalone; Amino Acids; aminoacid; Animal Model; Animal Models and Related Studies; Animals; Anterior; attention deficit hyperactive disorder; Attention deficit hyperactivity disorder; Attention-Deficit Disorder, Predominantly Hyperactive-Impulsive Type; Basal Ganglia; Basal Nuclei; base; Behavior Conditioning Therapy; behavior intervention; behavior measurement; Behavior Modification; Behavior or Life Style Modifications; Behavior Therapy; Behavior Treatment; Behavioral; Behavioral Conditioning Therapy; behavioral intervention; behavioral measure; behavioral measurement; Behavioral Modification; Behavioral Therapy; Behavioral Treatment; Biological; boys; Brain; brain behavior; Brain region; Butanoic acid, 4-amino-; Child; Child Youth; Childhood; children; Children (0-21); Choline; Cognitive; Comorbidity; Conditioning Therapy; Corpus Striatum; Corpus striatum structure; Data; design; designing; Development; Disease; disease/disorder; Disorder; Dopamine; drug/agent; Drugs; Dysfunction; Encephalon; Encephalons; Enteramine; Ethanaminium, 2-hydroxy-N, N, N-trimethyl-; Excitatory Amino Acids; excitatory aminoacid; executive control; executive function; fMRI; Functional disorder; Functional Magnetic Resonance Imaging; GABA; gamma-Aminobutyric Acid; gene therapy; Gene Transfer Clinical; Gene Transfer Procedure; Gene-Tx; Genetic; Genetic Intervention; genetic therapy; girls; Gln; Glutamates; Glutamine; Goals; H+ element; Hippophaine; Human; Human, Child; Human, General; Hydrogen Ions; Hydroxytyramine; Hyperactivity Disorder NOS; Hyperactivity Disorder, Predominantly Hyperactive-Impulsive Type; Hyperkinetic Syndrome; Impairment; in vivo; Individual; interest; Intermediary Metabolism; Intervention, Genetic; Investigation; L-Glutamate; L-Glutamine; Life Style Modification; Link; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Magnetic Resonance Imaging, Functional; Magnetic Resonance Spectroscopy; Man (Taxonomy); Man, Modern; Measures; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Medication; Memory, Immediate; Memory, Short-Term; Memory, Shortterm; Mental disorders; Mental health disorders; mental illness; Metabolic Processes; Metabolism; METBL; model organism; Molecular Biology, Gene Therapy; Motor; MR Imaging; MR Spectroscopy; MR Tomography; MRI; MRI, Functional; MRS; MRSI; N-acetyl aspartate; N-acetyl-L-aspartate; N-acetylaspartate; Nerve Cells; Nerve Impulse Transmission; Nerve Transmission; Nerve Transmitter Substances; Nerve Unit; Nervous System Diseases; nervous system disorder; Nervous System, Brain; Neural Cell; neurobiological; Neurobiology; Neurochemistry; neurochemistry; Neurocyte; neuroimaging; Neurologic Disorders; neurological disease; Neurological Disorders; neuronal; Neuronal Transmission; Neurons; neuropsychological; neurotransmission; Neurotransmitters; nine year old; NMR Imaging; NMR Tomography; Nuclear Magnetic Resonance Imaging; Parietal; Participant; Pathologic Processes; Pathological Processes; pathophysiology; pediatric; Performance; Pharmaceutic Preparations; Pharmaceutical Preparations; Pharmacological Treatment; Physiopathology; Play; Preparation; Protons; Psychiatric Disease; Psychiatric Disorder; psychological disorder; public health relevance; Q. Levoglutamide; Reporting; Research; response; Rest; Risk Factors; Role; Sample Size; Sampling; Science of neurochemistry; Serotonin; Severities; sex; Short-Term Memory; skills; social role; Socio-economic status; Socioeconomic Status; Specificity; Status, Socioeconomic; striatal; Striate Body; Striatum; success; Symptoms; Therapy, DNA; Time; Unspecified Mental Disorder; working memory; youngster; Zeugmatography
Relevance: Glutamate is an excitatory amino acid and the most abundant neurotransmitter in the brain. Glutamate levels are linked to a variety of neurological and psychiatric disorders, and have been implicated in the development of core symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Prior neuroimaging studies examining glutamate levels in ADHD had limited success, because at field strengths less than 2.0 Tesla, it is difficult to measure the absolute levels of glutamate in the human brain. The overall goal of the proposed investigation is to investigate the role of frontostriatal glutamatergic metabolism in medication-na¿ve children with ADHD using proton magnetic resonance spectroscopy at 7.0 Tesla, and to determine the specific mechanisms of cognitive and behavioral dysfunction associated with these glutamatergic as well as other neurochemical anomalies. This study will be the first investigation of the neurobiology of ADHD in children using MR spectroscopy at 7.0 Tesla
Project start date: 2011-01-01
Project end date: 2012-12-31
Budget start date: 1-JAN-2011
Budget end date: 31-DEC-2011
PFA/PA: PA-10-069
1R21MH092693-01 (2011): $243077