Neurobiology of Attention Deficit Disorder

Rapoport, J L.

Abstract

To understand the pathophysiology of Attention Deficit Disorder with Hyperactivity (ADDH), and to develop new treatments, a therapeutic trial of the amino acid, d-phenylalanine, was completed over the past nine months. Eleven ADDH boys participated in a placebo controlled double-blind evaluation of phenylalanine (20/mg/kg/day) and placebo. Phenylalanine had no significant effect upon behavior in spite of elevated blood phenylalanine levels (up to 120 un/l). In an attempt to localize abnormal patterns of cerebral glucose metabolism and cerebral flow in adults with Attention Deficit Disorder (ADD) Residual Type, parents of diagnosed hyperactive children are being studied using the 2-deoxyfluoroglucose method of Positron Emission Tomography (PET). To date, 18 patients have been scanned; preliminary results showed decreased cortisol glucose utilization. Eleven parents were rescanned after receiving dextroamphetamine; results are being analyzed. Because of reports that the spinal fluid (CSF) 5HIAA, a serotonin metabolite; may be low in severely impulsive or aggressive adults, a study has been initiated to compare spinal fluid catecholamine and indoleamine metabolites in severely aggressive, conduct disordered children with and without ADD to children with other neurological problems. Peripheral measures of catecholamines will also be obtained.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Mental Health (NIMH)
• Type: Intramural Research (Z01)
• Project #: 1Z01MH002240-02
• Application #: 3968555
• Support Year: 2
• Fiscal Year: 1986

Institution

• Name: U.S. National Institute of Mental Health
• Country: United States

Publications

Eckstrand, K; Addington, A M; Stromberg, T et al. (2008) Sex chromosome anomalies in childhood onset schizophrenia: an update. Mol Psychiatry 13:910-1

Rapoport, Judith L; Shaw, Philip (2008) Defining the contribution of genetic risk to structural and functional anomalies in ADHD. J Am Acad Child Adolesc Psychiatry 47:2-3

Rapoport, Judith L; Gogtay, Nitin (2008) Brain neuroplasticity in healthy, hyperactive and psychotic children: insights from neuroimaging. Neuropsychopharmacology 33:181-97

Shaw, Philip; Gornick, Michele; Lerch, Jason et al. (2007) Polymorphisms of the dopamine D4 receptor, clinical outcome, and cortical structure in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 64:921-31

Mackie, Susan; Shaw, Philip; Lenroot, Rhoshel et al. (2007) Cerebellar development and clinical outcome in attention deficit hyperactivity disorder. Am J Psychiatry 164:647-55

Shaw, P; Eckstrand, K; Sharp, W et al. (2007) Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci U S A 104:19649-54

Gornick, M C; Addington, Anjene; Shaw, P et al. (2007) Association of the dopamine receptor D4 (DRD4) gene 7-repeat allele with children with attention-deficit/hyperactivity disorder (ADHD): an update. Am J Med Genet B Neuropsychiatr Genet 144B:379-82

Gogtay, Nitin; Nugent 3rd, Tom F; Herman, David H et al. (2006) Dynamic mapping of normal human hippocampal development. Hippocampus 16:664-72

Shaw, Philip; Sporn, Alex; Gogtay, Nitin et al. (2006) Childhood-onset schizophrenia: A double-blind, randomized clozapine-olanzapine comparison. Arch Gen Psychiatry 63:721-30

Shaw, Philip; Lerch, Jason; Greenstein, Deanna et al. (2006) Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 63:540-9