This protocol uses functional magnetic resonance imaging (fMRI) to examine neurocognitive correlates of pediatric mood and anxiety disorders. The primary goal of the project is to document deficits in brain systems mediating attention biases, emotional memory perturbations, and hypersensitivity to social stressors in pediatric mood and anxiety disorders. As a secondary goal, the project also will measure the degree of change in these factors during treatment with fluoxetine, a specific serotonin reuptake inhibitor (SSRI), or during treatment with either cognitive behavioral therapy (CBT) or interpersonal psychotherapy (IPT).

A total of 445 children, adolescents, and adults will be recruited and comprehensively studied. This will include 125 juveniles with a current anxiety disorder, 60 juveniles with current major depression, 100 juveniles with no psychiatric disorder, 60 adults with major depression, and 100 adults with no psychiatric disorder. Subjects will be tested using fMRI paradigms designed to examine brain regions engaged by attending to and encoding emotionally salient stimuli. Subjects also will be studied with two social interaction paradigms, a series of reward paradigms, and a fear-conditioning paradigm. After these initial fMRI tests, subjects with depression or an anxiety disorder receive treatment. All subjects will be re-tested after eight-weeks using the same attention and memory paradigms.

Prior studies note that mood and anxiety disorders are associated with deficits in attention modulation and emotional memory. Prior imaging studies in healthy adults note that tasks requiring attention modulation, emotional memory, and social interchange engage cortico-limbic 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 fMRI attention, memory, social interaction, reward, and fear conditioning paradigms will engage these brain regions in both psychiatrically healthy and impaired subjects. However, these 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 patters predict response to these treatments. In the current protocol, subjects will be treated for eight-weeks using either SSRIs, CBT, or IPT. Moreover, 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.

• INCLUSION CRITERIA:

ALL JUVENILE SUBJECTS:

Age: 8 - 17

Consent: can give consent/assent (Parents will provide consent; minors will provide assent)

IQ: all subjects will have IQ greater than 70 (Assessment relies on WASI)

SUBJECTS WITH AN ANXIETY DISORDER:

Diagnosis: Current Diagnosis of Social Phobia, Separation Anxiety, or Generalized Anxiety Disorder (Based on K-SADS)

Symptom Severity: Score greater than 9 on PARS (This score was used to enroll subjects in previous trial demonstrating efficacy of an SSRI in pediatric anxiety)

Clinical Impairment: CGAS less than 60

SUBJECTS WITH A MOOD DISORDER:

Diagnosis: Current Diagnosis of Major Depression (Based on K-SADS (juveniles) or SCID (adults))

Clinical Impairment: CGAS less than 60 (juveniles) GAS less than 70 (adults)

Symptom Severity: CDRS Score greater than 39 (juveniles) (This score was used to enroll subjects in previous trials demonstrating efficacy of an SSRI in pediatric depression)

ALL ADULT SUBJECTS:

Age: 20-40

Consent: can give consent/assent

IQ: all subjects will have IQ greater than 70. Assessment relies on WASI.

EXCLUSION CRITERIA:

ALL SUBJECTS:

Any serious medical condition or condition that interferes with fMRI scanning, and for patients electing medication, any condition that increases risk of SSRI treatment. All patients will have complete physical examination. Healthy volunteer participants will be medication-free and have no current serious medical conditions, based on a review of their medical history.

Pregnancy

Current use of any psychoactive substance; current suicidal ideation; current diagnosis of attention deficit hyperactivity disorder (ADHD) of sufficient severity to require pharmacotherapy. These factors could complicate treatment with an SSRI. No subject on medication will be accepted into the trial. Subjects will not be taken off of medications to enter the trial.

Current diagnoses Tourette's Disorder, OCD, post-traumatic distress disorder, conduct disorder. These factors may be effected by SSRI treatment, influencing ability to detect effects on anxiety/depression

Past or current history of mania, psychosis, or pervasive developmental disorder. These factors may be effected by SSRI treatment, influencing ability to detect effects on anxiety/depression

Recent use of an SSRI; all subjects must have been free of any SSRI-use for at least one month (fluoxetine six months) and must not have been treated with an SSRI for their current depressive episode. This is designed to exclude subjects who have failed a trial of an SSRI for their current episode of major depression.

ALL ADULT SUBJECTS:

Any current psychiatric diagnosis. Assessment relies on SCID.

SUBJECTS WITH AN ANXIETY DISORDER:

Current Major Depressive Disorder