Neurobiology of Disruptive Behavior Disorders

Rapoport, J L.

Abstract

The relationships between behavioral dimensions of aggression, impulsivity, and concentrations of monoamine metabolites, particularly 5-HIAA, in the spinal fluid of children with disruptive behavior disorders of childhood are being examined. As part of that investigation, methodologic variables in spinal fluid studies of children are being clarified. Measurement of socio- environmental variables is being carried out to assess the relations between family environment and serotonenergic measures. Follow-up study to address the predictive validity of measurement of CSF 5-HIAA in children and adolescents is underway. To investigate the role of serotonin in the pathophysiology of ADD, 20 hyperactive boys received fenfluramine (0.6-2.0 mg/kg), dextroamphetamine or placebo in a double-blind crossover study. Fenfluramine had no behavioral effect whatsoever. However, striking biochemical changes (decreased urinary and plasma MHPG, decreased urinary NE, E and VMA). Central serotonergic effects were inferred from the increased plasma prolactin and decreased platelet serotonin. In spite of its structural similarly to amphetamine, fenfluramine has virtually noen of its therapeutic effects.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Mental Health (NIMH)
• Type: Intramural Research (Z01)
• Project #: 1Z01MH002240-05
• Application #: 3921958
• Support Year: 5
• Fiscal Year: 1988

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