This application is for a five-year competitive renewal to study the role of the serotonin (5-hydroxytryptamine [5-HT]) system in suicidal behavior in adolescents. Serotonin system dysfunction is related to suicidal behavior in adults at risk for suicide attempts or suicide. Low levels of the serotonin metabolite 5-HIAA in cerebrospinal fluid (CSF) is a biological marker identifying at-risk adults. Therefore, it may also identify suicidal adolescents at risk for future attempts. One hundred additional adolescents, 33 per group, will be recruited to the supplement the 3 groups previously studied. The resulting sample will include 2 groups of inpatient adolescents with major depressive disorder (MDD), matched for age (12-18 years), who will participate in a prospective 24 month follow-up program using standardized ratings to assess depression and suicidal behavior. The study will recruit MDD attempters (N-53) who are consecutively referred for hospitalization because of a suicide attempt during the previous 12 months and age-matched (N-53) MDD non-attempters. These groups will be studied during a 4-8 week psychiatric inpatient hospitalization with a lumbar puncture, platelet 5-HT2 receptor binding, and a fenfluramine challenge test. Age-matched normal adolescents (N-54), with no history (in self or in 1st- and 2nd-degree relatives) of depression and suicidal behavior, will be recruited as controls for fenfluramine challenge and platelet 5-HT2 binding, but not for CSF 5-HIAA.
Specific Aim 1 is to determine by prospective follow-up if baseline levels of CSF 5-HIAA, platelet 5-HT2 receptor binding, PRL responses to fenfluramine will predict higher rates of more medically damaging re- attempts at the 3-, 12- and 24-month double blind follow-up assessments.
Specific Aim 2 is determine if the enlarged sample of attempters (N-53) will continue to have significantly different prolactin responses to FEN and more 5-HT2 binding sites (BMAX) than depressed non-attempters (N-53) and normal adolescents (N-54); in addition, for the inpatient adolescents only, to determine if the attempter group will have significantly lower baseline levels of CSF 5-HIAA than a group of depressed non-attempters. The attempters with high medical damage will have lower CSF 5-HIAA than those with less medical damage or those in Group 2.
Specific Aim 3 is to determine, for the enlarged attempter and non- attempter groups, if the measures of serotonergic function (CSF 5-HIAA concentrations, delta-Peak PRL, 5-HT2 BMAX) will correlate with severity of suicidal behavior, as shown by extent of medical damage among the attempters, and measures of aggression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH047113-06
Application #
2674991
Study Section
Child Psychopathology and Treatment Review Committee (CPT)
Project Start
1993-04-01
Project End
2001-03-31
Budget Start
1998-06-01
Budget End
1999-03-31
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Greenhill, L L; Waslick, B (1997) Management of suicidal behavior in children and adolescents. Psychiatr Clin North Am 20:641-66