Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety

Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety

Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents with Anxiety. To determine the effects of escitalopram on functional activation patterns during a Continuous Performance Task with Emotional and Neutral Distracters, the CPT-END. To examine baseline functional activity and functional connectivity profiles in the ventrolateral prefrontal cortex as markers of subsequent treatment response to escitalopram in adolescents with generalized anxiety disorder (GAD). To use proton magnetic resonance spectroscopy (1H MRS) to examine glutamatergic and γ-aminobutyric acid (GABA)-related abnormalities in the anterior cingulate in adolescents with GAD as compared to healthy adolescents.

The long-term goal of this study is to explore the neurobiological basis of generalized anxiety disorder (GAD) using a validated functional MRI (fMRI) paradigm and functional connectivity analyses with a cohort of GAD patients and healthy subjects and generating feasibility and preliminary data regarding treatment-related effects of escitalopram on brain functional activation and Fc patterns in pediatric GAD. An additional goal is to identify biological markers in saliva and urine that will predict treatment response in pediatric subjects with GAD. The central hypothesis of this proposal is that core dysfunction within the prefrontal-amygdala network, which the investigators and others have observed in GAD, will be normalized by successful treatment. The rationale underlying this hypothesis is that, despite the high prevalence of GAD, there is a need to understand its neurobiology and to identify biomarkers of treatment response and the mechanisms by which selective serotonin reuptake inhibitors (SSRIs) putatively effect changes in the neurocircuitry of pediatric GAD.

Inclusion Criteria:

Inclusion - Anxiety Subjects:

• Diagnostic and Statistical Manual-IV (Text Revision) criteria for generalized anxiety disorder diagnosed by the Anxiety Disorders Interview Schedule (ADIS-IV)
• Baseline Pediatric Anxiety Rating Scale (PARS) score ≥15 at baseline
• Ages 12-17 years 11 months old
• Fluent in English
• Provision of written informed consent by a legal guardian and written assent by the subject
• Tanner scale stages II-V, in order to include only post-pubescent subjects and minimize brain changes associated with the onset of puberty
• Does not have a history of intolerance, non-response or hypersensitivity to escitalopram
• No co-occurring Diagnostic and Statistical Manual-IV (Text Revision) diagnosis mood (except dysthymia, depression not otherwise specified), eating, pervasive developmental disorder or psychotic disorders
• Subjects will be excluded if there are any lifetime diagnosis of mental retardation (intelligence quotient < 70)
• Subjects with any history of alcohol or drug dependence or any alcohol abuse within the past 6 months (nicotine dependence is permitted) will be excluded
• No new psychotherapy will be permitted during study participation and if the patient is engaged in psychotherapy, it must have been stable for 1 month prior to baseline
• Females will not be eligible to participate if pregnant, breast feeding or lactating.

Inclusion - Healthy Subjects:

• Ages of 12-17 years and 11 months
• No history of any Diagnostic and Statistical Manual-IV (Text Revision) Axis I disorders (nicotine dependence is permitted)
• No first-degree relatives with an affective or psychotic disorder
• No medications with central nervous system effects within 5 half-lives
• Fluent in English
• Tanner stage II-V
• Provision of informed consent and assent.

Exclusion Criteria:

Exclusion - Generalized Anxiety Disorder Patients & Healthy Subjects:

• Contraindication to an magnetic resonance imaging (MRI) scan (e.g., braces or claustrophobia)
• An unstable medical or neurological illness that could influence fMRI or magnetic resonance spectroscopy results
• Subjects will be excluded if there are any lifetime diagnosis of mental retardation or intelligence quotient < 70)
• A positive pregnancy test
• Adolescents will be excluded for treatment with a medication with central nervous system effects that requires more than 5 days of a screening period in order to minimize the length of time between screening and baseline and maximize patient safety, while recognizing that a longer taper period is required of some medications
• Adolescents with any history of major medical or neurological disorders that may result in neurofunctional or neurochemical abnormalities including loss of consciousness for >10 minutes will be excluded
• No co-occurring Diagnostic and Statistical Manual-IV (Text Revision) diagnosis mood (other than dysthymia or Depression Not Otherwise Specified), eating, pervasive developmental disorder or psychotic disorders
• Subjects will be excluded if there are any lifetime diagnosis of mental retardation or intelligence quotient < 70
• Subjects with any history of alcohol or drug dependence or any alcohol abuse within the past 6 months (nicotine dependence is permitted) will be excluded
• No new psychotherapy will be permitted during study participation and if the patient is engaged in psychotherapy, it must have been stable for 1 month prior to baseline
• Females will not be eligible to participate if pregnant, breast feeding or lactating
• The patient lives >100 miles from the University of Cincinnati or is not able to attend follow-up visits