Brain Function in Mentally Ill Adolescents
Condition: Healthy; Posttraumatic Stress Disorder; Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Observational

Summary: 
      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
      scan.
    

Detailed description: 
      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.
    

Keywords: fMRI; Depression; PTSD; Emotion; Magnetic Resonance Imaging; Anxiety; Normal Volunteers; Adolescence; Memory; Physical/Sexual Abuse History; Post-Traumatic Stress Disorder; Adolescent; Healthy Volunteer; HV; Normal Control