Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety

Conditions

Anxiety

Keywords

Anxiety, Adolescents with Anxiety

Brief summary

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.

Detailed description

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.

Marusak HA, Zundel CG, Shakir T, Ely SL, Carpenter C, Shampine M, Tamimi R, Matsko M, Rogers S, Losiowski J, O'Mara E, Jaster AM, Sharma K, deRoon-Cassini TA, Hillard CJ, Schroeder HK, Mills JA, Strawn JR, Barcelona J.

2025-06-27

10.1038/s41386-025-02155-7

Acute neurofunctional effects of escitalopram during emotional processing in pediatric anxiety: a double-blind, placebo-controlled trial.

Lu L, Li H, Baumel WT, Mills JA, Cecil KM, Schroeder HK, Mossman SA, Huang X, Gong Q, Sweeney JA, Strawn JR.

2021-09-2710 citations

10.1038/s41386-021-01186-0

Acute Neurofunctional Effects of Escitalopram in Pediatric Anxiety: A Double-Blind, Placebo-Controlled Trial.

Lu L, Mills JA, Li H, Schroeder HK, Mossman SA, Varney ST, Cecil KM, Huang X, Gong Q, Ramsey LB, DelBello MP, Sweeney JA, Strawn JR.

2021-02-0417 citations

10.1016/j.jaac.2020.11.023

Short-term Ambient Fine Particulate Matter and Anxiety Symptoms in Adolescents with Generalized Anxiety Disorder

Cole Brokamp, Sarah A. Mossman, Sara T. Varney, Heidi K. Schroeder, Amanda R. Levine et al. (6 authors)

ISEE Conference Abstracts2020-10-26

10.1289/isee.2020.virtual.o-os-564

Escitalopram in Adolescents With Generalized Anxiety Disorder

Jeffrey R. Strawn, Jeffrey A. Mills, Heidi K. Schroeder, Sarah A. Mossman, Sara T. Varney et al. (10 authors)

The Journal of Clinical Psychiatry2020-08-2571 citations

10.4088/jcp.20m13396

Interventions

DRUGEscitalopram

Patients being randomized to receive escitalopram.

OTHERPlacebo

Patients being randomized to receive placebo.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

12 Years to 17 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Early escitalopram-related functional brain activity changes during emotional processing	From baseline to week 2 of treatment	To determine if escitalopram treatment (over a 2 week period) increases functional brain activation during the processing of emotional images while performing a continuous processing task with emotional and neutral distracters (CPT-END) (also over a 2 week period).

Secondary

Measure	Time frame	Description
Change in γ-aminobutyric acid concentrations in the anterior cingulate (from baseline to week 2) predicts improvement in Pediatric Anxiety Rating Scale score from baseline to week 8 (or early termination)	from baseline to week 8 (or early termination)	To determine if the change in γ-aminobutyric acid concentrations in the anterior cingulate (from baseline to week 2) predicts improvement in Pediatric Anxiety Rating Scale score from baseline to week 8 (or early termination)
Change in functional activity in the ventrolateral prefrontal cortex (from baseline to week 2) and improvement in Pediatric Anxiety Rating Scale score (at week 8/early termination)	from baseline to week 8 (or early termination)	To determine if the change in functional activity in the ventrolateral prefrontal cortex (from baseline to week 2) predicts improvement in Pediatric Anxiety Rating Scale score from baseline to week 8/early termination.
Change in functional connectivity between the ventrolateral prefrontal cortex and the amygdala (from baseline to week 2) and improvement in Pediatric Anxiety Rating Scale score (at week 8/early termination)	from baseline to week 8 (or early termination)	To determine if the change in functional connectivity between the ventrolateral prefrontal cortex and the amygdala (from baseline to week 2) predicts improvement in Pediatric Anxiety Rating Scale score from baseline to week 8/early termination.
Change in glutamate concentrations in the anterior cingulate cortex predict improvement in Pediatric Anxiety Rating Scale score from baseline to week 8/early termination.	from baseline to week 8 (or early termination)	To determine if change in glutamate concentrations in the anterior cingulate cortex predict improvement in Pediatric Anxiety Rating Scale score from baseline to week 8/early termination.

Countries

United States

Outcome results

None listed