Quantitative Magnetic Resonance Imaging of Human Brain Development: Ages 4-18

Brain magnetic resonance images (MRI) of 104 healthy childrenand adolescents, aged 4–18, showed significant effectsof age and gender on brain morphometry. Males had larger cerebral(9%) and cerebellar (8%) volumes (P < 0.0001 and P = 0.008.respectively), which remained significant even after correctionfor height and weight After adjusting for cerebral size, theputamen and globus pallidus remained larger in males, whilerelative caudate size was larger in females. Neither cerebralnor cerebellar volume changed significantly across this agerange. Lateral ventricular volume increased significantly inmales (trend for females), with males showing an increase inslope after age 11. In males only, caudate and putamen decreasedwith age (P = 0.007 and 0.05, respectively). The left lateralventricles and putamen were significantly greater than the rightP = 0.01 and 0.0001, respectively). In contrast, the cerebralhemispheres and caudate showed a highly consistent right greater-than-leftasymmetry (P < 0.0001 for both). All volumes demonstrateda high degree of variability. These findings highlight gender-specificmaturational changes of the developing brain and the need forlarge gender-matched samples in pediatric neuropsychiatric studies.     

A 2-year prospective follow-up study of children and adolescents with disruptive behavior disorders. Prediction by cerebrospinal fluid 5-hydroxyindoleacetic acid, homovanillic acid, and autonomic measures?

A 2-year prospective follow-up study of 100% (N = 29) of a sample of children and adolescents with disruptive behavior disorders found that the baseline lumbar cerebrospinal fluid monoamine metabolite concentration and autonomic nervous system activity predicted some subsequent outcomes. The 5-hydroxyindoleacetic acid concentration significantly predicted severity of physical aggression during follow-up. The skin conductance level significantly predicted institutionalization. Correlations were in predicted directions with lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and autonomic activity correlated with poor outcome. Moreover, in multivariate analyses, which included nonlaboratory measures as predictors, cerebrospinal fluid and autonomic measures still contributed significantly to the prediction. However, hypothesized predictions of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations for suicide attempts and of low autonomic nervous system activity for arrests were not supported thus far. Patients are still at risk; consequently, these results must be considered preliminary. Nonetheless, the results suggest that further investigation of relationships between biological factors and outcome of children with disruptive behavior disorders is warranted.     

The effect of methylphenidate on urinary catecholamine excretion in hyperactivity: a partial replication

Children with attention deficit disorder with hyperactivity were treated with methylphenidate HCl (0.74 +/- 0.2 mg/kg/day) for 2 weeks in an open trial to assess changes in the urinary excretion of catecholamines and behavior. The purpose of this study was to confirm earlier work that methylphenidate has a distinctly different effect on urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion as compared to earlier studies with dextroamphetamine. Results confirmed the earlier finding that methylphenidate does not significantly change urinary MHPG excretion. No significant relationship was found between behavioral change and any of the urinary catecholamines or metabolites measured.     

Concentration gradient of CSF monoamine metabolites in children and adolescents

Whether the lumbar cerebrospinal fluid (CSF) concentration gradient of monoamine metabolites found in adults is influenced by age or pubertal status was studied in 26 children ranging from 6.5 to 17.3 years of age. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were assayed by high-power liquid chromatography (HPLC) with electrochemical detection. Eight patients were prepubertal (Tanner stage I). The slopes in units of picomoles/milliliter/milliliter for regression lines for CSF monoamine metabolite concentrations versus milliliter of CSF collected were 5.07 +/- 0.65, 10.13 +/- 2.0, and 0.67 +/- 0.22 for 5-HIAA, HVA, and MHPG, respectively, for the group as a whole. Significant correlations with age, height, weight, or Tanner stage were not found for the HVA or MHPG concentration gradients. Tanner stage and 5-HIAA slope were significantly correlated. Three of eight prepubertal patients had nonsignificant 5-HIAA gradients. CSF studies in pediatric populations must control for aliquot collected, as the size of the gradient could produce differences sufficient to mimic a "positive" clinical study if the aliquots collected are not the same.     

Competitive control of the self-renewing T cell repertoire

We develop a mathematical model for the self-renewing part of the T cell repertoire. Assuming that self-renewing T cells have to be stimulated by immunogenic MHC-peptide complexes presented on the surfaces of antigen-presenting cells, we derive a model of T cell growth in which competition for MHC-peptide complexes limits T cell clone sizes and regulates the total number of self-renewing T cells in the animal. We show that for a sufficient diversity and/or degree of cross-reactivity, the total T cell number hardly depends upon the diversity of the T cell repertoire or the diversity of the set of presented peptides. Conversely, for repertoires of lower diversity and/or cross-reactivity, steady-state total T cell numbers may be limited by the diversity of the T cells. This provides a possible explanation for the limited repertoire expansion in some, but not all, mouse T cell re-constitution experiments. We suggest that the competitive interactions described by our model underlie the normal T cells numbers observed in transgenic mice, germ-free mice and various knockout mice.