Clinical Trial of Fluoxetine in Anxiety and Depression in Children, and Associated Brain Changes
Status:
Recruiting
Trial end date:
2029-01-01
Target enrollment:
Participant gender:
Summary
Objective: This protocol uses functional magnetic resonance imaging (fMRI) to examine
neuro-cognitive correlates of pediatric and adult mood and anxiety disorders. The primary
goal of the project is to document, in pediatric anxiety disorders and major depression,
perturbations in brain systems mediating attention biases, fear conditioning, emotional
memory, and response to various forms of motivational stimuli. As one secondary goal, the
project measures the relationship between these factors and treatment response to either
fluoxetine, a specific serotonin reuptake inhibitor (SSRI), cognitive behavioral therapy
(CBT), or interpersonal psychotherapy (IPT). Another secondary goal examines similar
associations in adults.
Study Population: A total of 2530 children, adolescents, and adults will be recruited. Most
subjects will not be able to complete all procedures. We seek to comprehensively study 150
juveniles with only a current anxiety disorder, 60 juveniles with current major depression,
150 juveniles with no psychiatric disorder, 100 adults with major depression, 60 adults with
an anxiety disorder, and 150 adults with no psychiatric disorder. To achieve this, we are
recruiting 2530 individuals.
Design: Subjects will be tested using fMRI paradigms designed to examine brain regions
engaged when processing motivationally salient stimuli, as assessed during attention, memory,
social interaction, reward, and fear-conditioning paradigms. After these initial fMRI tests,
subjects with depression or an anxiety disorder receive treatment. Treatment will comprise
open treatment with either fluoxetine or CBT, augmented with computer-based attention
retraining, delivered in a randomized-controlled design, with random assignment to either
active or placebo attentiontraining regimens. Adolescent subjects then will be re-tested
after eight-weeks using only the attention, memory, and conditioning paradigms.
Outcome Measures: Prior imaging studies note that tasks requiring attention modulation,
emotional memory, social interchange, and fear conditioning engage brain regions previously
implicated in adult mood and anxiety disorders. These regions include most consistently the
amygdala and ventral prefrontal cortex. Moreover, imaging studies of reward function
implicate the striatum and prefrontal cortex in adult mood disorders. As a result, we
hypothesize that attention, memory, social interaction, reward, and conditioning paradigms
will engage the amygdala, ventral prefrontal cortex and striatum in both psychiatrically
healthy and impaired subjects. Moreover, we hypothesize that these healthy and
psychiatrically impaired groups will differ in the degree of engagement.
Juvenile subjects also will be treated for eight-weeks, and a subset will be re-tested with
fMRI. We predict that pre-treatment abnormalities in neural circuitry will predict response
to treatment, such that increased amygdala and prefrontal activation will occur in
individuals who show the strongest response to treatment. Moreover, we hypothesize that
effective treatment will normalize abnormalities in attention and emotional memory, as
manifest in fMRI.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Mental Health (NIMH)
Collaborators:
University of Maryland, College Park University of Minnesota University of Oregon