• Carter, Cameron S (PI)
  • Puig-Antich, Joaquim (PI)
  • Ryan, Neal (PI)
  • Casey, Betty J. (PI)
  • Cameron, Judy (PI)
  • Brent, David A. (PI)
  • Birmaher, Boris (PI)
  • Iyengar, Satish (PI)
  • Dahl, Ronald E. (PI)
  • Axelson, David (PI)

Project: Research project

Project Details


This Project is composed of four interrelated studies on the neurobiology
of prepubertal major depressive illness: 1) Neurobiological Markers and
Mechanisms in Pepubertal Children with Major Depressive Illness Stability
Over Time; 2) Neurobiology of Suicidal Behavior in Affective and
Nonaffective Prepubertal Children; 3) Red Cell Membrane Defects in
Prepubertal Depressive Illness; and 4) High Risk Study: Trait Markers for
Early Onset Affective Illness. These will be supported by seven different
core facilities, with funding requested for only three. The main
objectives are: (1) to determine: a) if markers found in the euthymic
state in prepubertal major depressive children (shortened REM latency,
increased sleep GH secretion, deceased GH response to ITT) and in adult
bipolars (RBC membrane hydrocarbon defects) are stable over long term
recovery; b) if they change with recurrences of dysthymia, major depression
or bipolar disorder. (2) To determine: a) if they are true trait markers
by ascertaining if they are present significantly more ofen in as yet
unaffected, normal pepubertal children from families with very high
morbidity risk for affective illness, compared to normal children from
families with negative familial history for affective illness; and b) if
the presence of such markers predicts the development of affective illness
during follow-up in the high risk children. (3) To test the roles of three
different neurotransmitter systems (cholinergic, noradrenegic and
serotonergic) in the regulation of these markers by carrying out day and
night tests including baseline measures (including urinary 6-OH melatonin)
and provocative challenges including physostigmine, clonidine, orthostatic
challenge, and 5-hydroxytryptophan. Data about the site of neuroregulatory
disturbances will be gathered by synthetic CRF and GRF challenges. (4) To
determine to which exent the neurobiology of suicidal planning and behavior
converges, diverges, or interact with that of affective illness in
prepuberty. (5) In addition, these studies will provide much needed
normative data on the neuroregulation of EEG sleep and neuroendocrine
function before puberty, and also, during follow-up, on the possible
effects of puberty. To accomplish these aims, patient samples and two samples of normal
children, all prebubertal, will be studied at baseline: 1) children with
major depression, 2) children with nonaffective, nonsuicidal psychiatric
disorders, 3) children with suicidal nonaffective psychiatic disorders, 4)
normal children at very high risk for affective illness and 5)\normal
children at very low risk for affective illness. All samples will be
followed for up to 5 years and restudied at pre-specified points in time. The resarch program has the potential to significantly advance our
understanding of familial transmission, risk factors, course and
neurobiology of early onset affective illness and suicidal behavior, and
can form the basis of significant diagnostic, prognostic, and prophylactic
advances in this important area of child psychopathology.
Effective start/end date7/1/866/30/08


  • National Institutes of Health


  • Medicine(all)


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