This protocol uses functional magnetic resonance imaging (fMRI) to examine neurocognitive 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.

A total of 630 children, adolescents, and adults will be recruited and comprehensively studied. This will include 150 juveniles with only a current anxiety disorder, 60 juveniles with current major depression, 150 juveniles with no psychiatric disorder, 60 adults with major depression, 60 adults with an anxiety disorder, and 150 adults with no psychiatric disorder. 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. Adolescent subjects then will be re-tested after eight-weeks using only the attention, memory, and conditioning paradigms.

Prior studies note that mood and anxiety disorders are associated with deficits in attention and emotional memory. 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.

Prior studies suggest that SSRIs, CBT, and IPT effectively treat symptoms of mood and anxiety disorders. Moreover, prior studies in adults also suggest that fMRI response patterns predict response to these treatments. In the current protocol, juvenile subjects will be treated for eight-weeks using either SSRIs, CBT, or IPT. Subjects also may elect to receive attention-retraining as part of their treatment with one of these agents. A subset of subjects 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.