Study of Neuro-Cognitive Correlates of Pediatric Anxiety Disorders

Обзор

Study Description: This study examines relations between neurocognitive and clinical features of pediatric anxiety disorders. The study uses neuro-cognitive tasks, functional magnetic resonance imaging (fMRI), as well as magneto- and electro-encephalography (M/EEG). Patients will be studied over one year, before and after receiving either one of two standard-of-care treatments: cognitive behavioral therapy (CBT) or fluoxetine, a serotonin reuptake inhibitor (SSRI). Healthy comparisons will be studied at comparable time points. Primary Objectives: To compare healthy youth and symptomatic, medication-free pediatric patients studied prior to receipt of treatment. The study seeks to detect relations between clinical features of anxiety disorders at baseline and a wide range of neurocognitive features associated with attention, memory, and response to motivational stimuli. Secondary Objectives: 1. To document relations between baseline neurocognitive features and response to Cognitive Behavioral Therapy (CBT) or fluoxetine, as defined by the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Improvement (CGI) Scale. 2. To document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine. 3. To document relations among broad arrays of clinical, cognitive, and neural measures Primary Endpoints: Indices of percent-signal change in hypothesized brain regions, comprising amygdala, striatum, and prefrontal cortex (PFC) for each fMRI and MEG paradigm. Secondary Endpoints: 1. Treatment-response as defined by a continuous measure, the Pediatric Anxiety Rating Scale score (PARS), and a categorial measure, the Clinical Global Improvement (CGI) score. 2. Levels of symptoms and behaviors evoked by tasks that engage attention, memory, and elicit responses to motivational stimuli. ...

Подробное описание

Study Description:

This study examines relations between neurocognitive and clinical features of pediatric anxiety disorders. The study uses neurocognitive tasks, functional magnetic resonance imaging (fMRI), as well as magneto- and electro-encephalography (M/EEG). Patients will be studied over one year, before and after receiving either one of two standard-of-care treatments: cognitive behavioral therapy (CBT) or fluoxetine, a serotonin reuptake inhibitor (SSRI). Healthy comparisons will be studied at comparable time points.

Primary Objectives:

-To compare healthy youth and symptomatic, medication-free pediatric patients studied prior to receipt of treatment. The study seeks to detect relations between clinical features of anxiety disorders at baseline and a wide range of neurocognitive features associated with attention, memory, and response to motivational stimuli.

Secondary Objectives:

* To document relations between baseline neurocognitive features and response to Cognitive Behavioral Therapy (CBT) or fluoxetine, as defined by the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Improvement (CGI) Scale. * To document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine. * To document relations among broad arrays of clinical, cognitive, and neural measures

Primary Endpoints:

-Indices of percent-signal change in hypothesized brain regions, comprising amygdala, striatum, and prefrontal cortex (PFC) for each fMRI and MEG paradigm.

Secondary Endpoints:

* Treatment-response as defined by a continuous measure, the Pediatric Anxiety Rating Scale score (PARS), and a categorial measure, the Clinical Global Improvement (CGI) score. * Levels of symptoms and behaviors evoked by tasks that engage attention, memory, and elicit responses to motivational stimuli.

Вмешательства

• Поведенческое Attention Bias Modification Training
  The intervention is computer-based. The active and control treatments have two components. In one component of the active intervention, subjects are asked to indicate the identity of a letter that appears behind a neutral face, opposite from an angry face. In another component of the active intervention, subjects are asked to identify numbers that are hidden within a puzzle, in locations distal from angry faces. In both components of the active intervention, subjects implicitly learn to shift th
• Препарат Fluoxetine
  Randomized assignment.
• Поведенческое Cognitive Behavioral Therapy

Первичные конечные точки

• Pediatric Anxiety Rating Scale (PARS) [Срок оценки: Weekly]
• Clinical Global Improvement (CGI) Scale [Срок оценки: Weekly]

Вторичные конечные точки (1)

• Another secondary objective is to document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine. [Срок оценки: Changes in symptoms on PARS and changes after 8-12 weeks of treatment in patients]

Критерии участия

• INCLUSION CRITERIA:

ALL JUVENILE SUBJECTS

• Age: 8-17 (subjects who consent as 17-year-olds but turn 18 during the course of the study will be eligible to complete all procedures completed by other subjects who consent as 17-year-olds but do not turn 18).
• Consent: can give consent/assent (Parents will provide consent; minors will provide assent)
• IQ: all subjects will have IQ>70 (Assessment relies on either a WASI or assessment by trained clinical staff during the subject s screening visit. Completion of required activities during the screening visit requires an IQ above 70.)
• Language: all subjects will speak English (Tasks in this protocol have not been validated in languages other than English)

ALL ADULT SUBJECTS

• Age: 18-65
• Consent: can give consent
• IQ: all subjects will have IQ>70 (Assessment relies on either a WASI or assessment by trained clinical staff during the subject s screening visit. Completion of required activities during the screening visit requires an IQ above 70.)
• Language: all subjects will speak English (Tasks in this protocol have not been validated in languages other than English)

ALL SUBJECTS WITH AN ANXIETY DISORDER

• Diagnosis: Current Diagnosis of OCD, Social Phobia, Separation Anxiety, Generalized Anxiety Disorder, or Panic Disorder (Based on K-SADS (juveniles) or SCID (adults))
• Symptom Severity: Clinically significant, ongoing anxiety symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)
• Clinical Impairment: Clinically significant, ongoing distress or impairment from anxiety (This will be documented by clinician review with patients and their families during at least two visits with families.)

ALL PREVIOUSLY ENROLLED ADOLESCENT PATIENTS, CHILD AND ADULT HEALTHY VOLUNTEERS, AND ALL HEALTHY VOLUNTEERS TURNED PATIENTS

• Diagnosis: Current Diagnosis of OCD, Social Phobia, Separation Anxiety, Generalized Anxiety Disorder, or Panic Disorder; No current diagnosis (Based on K-SADS (juveniles) or SCID (adults))
• Clinical Impairment (as applicable): Clinically significant, ongoing symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)
• Symptom Severity (as applicable): Clinically significant, ongoing symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)

Критерии исключения

ALL SUBJECTS

• Any serious medical condition or condition that interferes with fMRI or M/EEG scanning, and for patients electing medication, any condition that increases risk of SSRI treatment. (All patients will complete a medical history. Healthy volunteer participants will be medication- free and have no current serious medical conditions, based on a review of their medical history. Subjects only will be excluded from the MRI portions of the study based on this exclusion criterion.)
• Pregnancy (Subjects only will be excluded from the MRI portions of the study based on this exclusion criterion.)
• Current use of any psychoactive substance; current suicidal ideation as indicated by the presence of intent for engaging in suicidal behaviors; 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, major depressive disorder (MDD), post-traumatic distress disorder, conduct disorder. (These factors may be affected by SSRI treatment, influencing ability to detect effects on anxiety/symptoms of depression. Of note, subjects who present with a diagnosis of MDD will not be eligible for inclusion at the outset of the study. However, youth with anxiety disorders frequently develop MDD when followed over time. Subjects will be allowed to remain in the study if they develop these diagnoses after enrollment.)
• Past or current history of mania, psychosis, or severe pervasive developmental disorder. (These factors may be affected by SSRI treatment, influencing ability to detect effects on anxiety/symptoms of depression. Of note, subjects who present with a diagnosis of MDD will not be eligible for inclusion at the outset of the study. However, youth with anxiety disorders frequently develop MDD when followed over time. Subjects will be allowed to remain in the study if they develop these diagnoses after enrollment.)
• Recent use of an SSRI with failure to respond or tolerate SSRI treatment at an adequate dose and duration. (This is designed to exclude subjects who have failed a trial of an SSRI for their current problem with anxiety. For previously enrolled participants, including patients and healthy volunteers, current use of an SSRI does not exclude participation from follow-up research tasks.)
• History of any (excepting nicotine-related and cannabis-related) DSM5-defined moderate to severe substance use disorder (or DSM-IV-defined substance dependence).

HEALTHY ADULT SUBJECTS

-Any current psychiatric diagnosis (Assessment relies on SCID)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• National Institutes of Health Clinical Center — Bethesda
• University of Maryland, College Park — College Park

Публикации

• Meigs JM, Kiderman M, Kircanski K, Cardinale EM, Pine DS, Leibenluft E, Brotman MA, Naim R. Sleepless nights, sour moods: daily sleep-irritability links in a pediatric clinical sample. J Child Psychol Psychiatry. 2024 Sep;65(9):1175-1183. doi: 10.1111/jcpp.13959. Epub 2024 Feb 14. PMID 38355141
• Byrne ME, Bernstein RA, Pine DS, Kircanski K. Ecological Momentary Assessment of Youth Anxiety: Evaluation of Psychometrics for Use in Clinical Trials. J Child Adolesc Psychopharmacol. 2023 Dec;33(10):409-417. doi: 10.1089/cap.2023.0025. Epub 2023 Dec 5. PMID 38052059
• Tseng WL, Naim R, Chue A, Shaughnessy S, Meigs J, Pine DS, Leibenluft E, Kircanski K, Brotman MA. Network analysis of ecological momentary assessment identifies frustration as a central node in irritability. J Child Psychol Psychiatry. 2023 Aug;64(8):1212-1221. doi: 10.1111/jcpp.13794. Epub 2023 Mar 28. PMID 36977629
• Linke JO, Haller SP, Xu EP, Nguyen LT, Chue AE, Botz-Zapp C, Revzina O, Perlstein S, Ross AJ, Tseng WL, Shaw P, Brotman MA, Pine DS, Gotts SJ, Leibenluft E, Kircanski K. Persistent Frustration-Induced Reconfigurations of Brain Networks Predict Individual Differences in Irritability. J Am Acad Child Adolesc Psychiatry. 2023 Jun;62(6):684-695. doi: 10.1016/j.jaac.2022.11.009. Epub 2022 Dec 21. PMID 36563874
• Newsome P, Ruiz SG, Gold AL, Pine DS, Abend R. Fear-potentiated startle reveals diminished threat extinction in pathological anxiety. Int J Psychophysiol. 2023 Jan;183:81-91. doi: 10.1016/j.ijpsycho.2022.11.011. Epub 2022 Nov 25. PMID 36442665
• Naim R, Shaughnessy S, Smith A, Karalunas SL, Kircanski K, Brotman MA. Real-time assessment of positive and negative affective fluctuations and mood lability in a transdiagnostic sample of youth. Depress Anxiety. 2022 Dec;39(12):870-880. doi: 10.1002/da.23293. Epub 2022 Nov 3. PMID 36325887
• Haller SP, Archer C, Jeong A, Jaffe A, Jones EL, Harrewijn A, Naim R, Linke JO, Stoddard J, Brotman MA. Changes in Internalizing Symptoms During the COVID-19 Pandemic in a Transdiagnostic Sample of Youth: Exploring Mediators and Predictors. Child Psychiatry Hum Dev. 2024 Feb;55(1):206-218. doi: 10.1007/s10578-022-01382-z. Epub 2022 Jul 6. PMID 35794298
• Scheinost D, Dadashkarimi J, Finn ES, Wambach CG, MacGillivray C, Roule AL, Niendam TA, Pine DS, Brotman MA, Leibenluft E, Tseng WL. Functional connectivity during frustration: a preliminary study of predictive modeling of irritability in youth. Neuropsychopharmacology. 2021 Jun;46(7):1300-1306. doi: 10.1038/s41386-020-00954-8. Epub 2021 Jan 21. PMID 33479511

Идентификаторы

NCT: NCT00018057 · 010192 · 01-M-0192

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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