The purpose of this study is to use brain imaging technology to examine the brain activity
of adolescents with post-traumatic stress disorder (PTSD) and/or major depressive disorder
(MDD) before and after treatment.
Adults with PTSD or MDD exhibit abnormalities in the structure and function of certain parts
of the brain. Although PTSD and MDD are psychiatric disorders that often emerge in
childhood, the relationship between these disorders and brain structures has not been
thoroughly studied in adolescents with the disorders. This study will use functional
magnetic resonance imaging (fMRI) to study the parts of the brain that are involved in PTSD
and MDD in adolescents.
Adolescents with PTSD and/or MDD will be enrolled along with healthy adolescents with or
without a history of abuse. Healthy adults will also be enrolled. Participants will be
screened with a physical examination; blood tests; and interviews about mood, general degree
of nervousness, and behavior. Adolescents and their parents will be interviewed separately
and together. Following the interviews, participants will undergo psychological tests.
Participants with PTSD and/or MDD will have two weekly sessions of talk therapy.
Participants who continue to experience PTSD or MDD symptoms after the talk therapy may
continue the talk therapy alone, begin treatment with fluoxetine (Prozac ) alone, or begin
fluoxetine in addition to the talk therapy. Participants who take fluoxetine will have blood
collected before treatment and 8 weeks after treatment has begun. If participants do not
respond to the treatment, the treatment will be stopped and the participants will be offered
another treatment. Participants who respond to treatment will continue treatment at NIH
until a referral to an outside physician is made. Depending on the experiment in which they
are enrolled, participants will undergo one or four MRI scans. Participants who will have
four MRI scans will undergo the scans on separate days. During the MRI, participants will
complete tasks on a computer. Saliva samples will be collected before and after the scans.
Participants with PTSD and/or MDD will collect their saliva one or two days before the MRI
Adults with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD) exhibit
abnormalities in the structure and function of the amygdala and hippocampus (temporal lobe),
as well as in the prefrontal cortex (PFC) and striatum (four brain structures underlying the
emotional processing and reward systems). However, while these psychiatric disorders often
emerge in childhood, the integrity of these neural structures has been minimally studied in
psychiatrically impaired children and adolescents. In the current proposal, functional MRI
(fMRI) will be used to evaluate the amygdala, hippocampus, PFC and striatum in (1)
psychiatrically healthy adolescents; (2) adolescents with trauma history and PTSD or anxiety
symptoms; (3) adolescents with trauma history, symptoms of depression and either PTSD or
anxiety symptoms; and (4) adolescents with only major depressive or PTSD/anxiety symptoms;
(5) adolescents with trauma and no trauma related symptoms. The proposed study is conducted
in three separate experiments.
At this stage of the protocol, we completed experiment 1, and a pilot study to help guide
experiments 2 and 3. In Experiment 1, we determined whether a fear conditioning paradigm
elicited amygdala activity in healthy adolescents. The pilot study examined test-retest
reliability of the fMRI signal in healthy adolescents and adults.
In Experiment 2, we will examine the functioning of the amygdala, hippocampus, PFC and
striatum in healthy adolescents and those with the psychiatric conditions described above.
During image acquisition, four cognitive tasks, targeting these regions, will be used: 1) a
social interaction task, 2) an inhibition task (the Stop task or the antisaccade task), 3)
an emotional rating/explicit memory task and 4) a probe detection task. One hundred twenty
five participants (25 in five groups) will be recruited in experiment 2.
Experiment 3 will address the same question as in experiment 2 in relation to treatment
response. In other words, in contrast to experiment 2, patients will be studied prior and
after treatment of the psychopathology associated with their traumatic experience. The
sample will include 125 patients (25 in each of the 4 groups) and 25 controls.
- INCLUSION CRITERIA:
All subjects 7-18 (adolescents).
Consent: can give consent/assent.
IQ: all subjects will have IQ greater than 70.
Subjects currently on antidepressants or benzodiazepines medication.
Subjects suffering from ADHD and currently on stimulants.
SUBJECTS WITH MAJOR DEPRESSION:
Diagnosis: Current diagnosis of MDD.
Clinical Impairment: CGAS less than 60.
SUBJECTS WITH PTSD:
Diagnosis: current diagnosis of PTSD.
Clinical Impairment: CGAS of less than 60.
SUBJECTS WITH HISTORY OF TRAUMA:
Trauma (i.e., sexual or physical abuse, exposure to an accident, etc.) will be defined
according to the KSADS, the Child Trauma Questionnaire, the Life Events Survey and the
history of adoption.
Any medical condition that increases risk for MRI (e.g. pacemaker, metallic foreign
material in eye).
Any medical condition that increases risk for fluoxetine treatment for patients with
Participants suffering from acute psychosis or suicidal ideation; current abuse/dependency
to alcohol or drugs.
Currently in an abusive situation at home.
Weight that is 15% more or less than ideal body weight for sex and height.
Current tobacco use.