Study of Neuro-Cognitive Correlates of Pediatric Anxiety Disorders

Summary

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. ...

Timeline

Start

2001-10-02

Primary completion

2029-01-01

Completion

2029-01-01

Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Cardinale EM, Freitag GF, Brotman MA, Pine DS, Leibenluft E, Kircanski K. Phasic Versus Tonic Irritability: Differential Associations With Attention-Deficit/Hyperactivity Disorder Symptoms. J Am Acad Child Adolesc Psychiatry. 2021 Dec;60(12):1513-1523. doi: 10.1016/j.jaac.2020.11.022. Epub 2021 Jan 10.
• Linke JO, Abend R, Kircanski K, Clayton M, Stavish C, Benson BE, Brotman MA, Renaud O, Smith SM, Nichols TE, Leibenluft E, Winkler AM, Pine DS. Shared and Anxiety-Specific Pediatric Psychopathology Dimensions Manifest Distributed Neural Correlates. Biol Psychiatry. 2021 Mar 15;89(6):579-587. doi: 10.1016/j.biopsych.2020.10.018. Epub 2020 Nov 9.
• Smith AR, Haller SP, Haas SA, Pagliaccio D, Behrens B, Swetlitz C, Bezek JL, Brotman MA, Leibenluft E, Fox NA, Pine DS. Emotional distractors and attentional control in anxious youth: eye tracking and fMRI data. Cogn Emot. 2021 Feb;35(1):110-128. doi: 10.1080/02699931.2020.1816911. Epub 2020 Sep 21.
• Filippi CA, Sachs JF, Phillips D, Winkler A, Gold AL, Leibenluft E, Pine DS, Fox NA. Infant behavioral reactivity predicts change in amygdala volume 12 years later. Dev Cogn Neurosci. 2020 Apr;42:100776. doi: 10.1016/j.dcn.2020.100776. Epub 2020 Mar 21.
• Haller SP, Kircanski K, Stringaris A, Clayton M, Bui H, Agorsor C, Cardenas SI, Towbin KE, Pine DS, Leibenluft E, Brotman MA. The Clinician Affective Reactivity Index: Validity and Reliability of a Clinician-Rated Assessment of Irritability. Behav Ther. 2020 Mar;51(2):283-293. doi: 10.1016/j.beth.2019.10.005. Epub 2019 Nov 27.
• Smith AR, Nelson EE, Kircanski K, Rappaport BI, Do QB, Leibenluft E, Pine DS, Jarcho JM. Social anxiety and age are associated with neural response to social evaluation during adolescence. Dev Cogn Neurosci. 2020 Apr;42:100768. doi: 10.1016/j.dcn.2020.100768. Epub 2020 Feb 10.
• Abend R, Gold AL, Britton JC, Michalska KJ, Shechner T, Sachs JF, Winkler AM, Leibenluft E, Averbeck BB, Pine DS. Anticipatory Threat Responding: Associations With Anxiety, Development, and Brain Structure. Biol Psychiatry. 2020 May 15;87(10):916-925. doi: 10.1016/j.biopsych.2019.11.006. Epub 2019 Nov 15.
• Filippi CA, Subar AR, Sachs JF, Kircanski K, Buzzell G, Pagliaccio D, Abend R, Fox NA, Leibenluft E, Pine DS. Developmental pathways to social anxiety and irritability: The role of the ERN. Dev Psychopathol. 2020 Aug;32(3):897-907. doi: 10.1017/S0954579419001329.
• Abend R, Rosenfelder A, Shamai D, Pine DS, Tavor I, Assaf Y, Bar-Haim Y. Brain structure changes induced by attention bias modification training. Biol Psychol. 2019 Sep;146:107736. doi: 10.1016/j.biopsycho.2019.107736. Epub 2019 Jul 25.
• Cardinale EM, Kircanski K, Brooks J, Gold AL, Towbin KE, Pine DS, Leibenluft E, Brotman MA. Parsing neurodevelopmental features of irritability and anxiety: Replication and validation of a latent variable approach. Dev Psychopathol. 2019 Aug;31(3):917-929. doi: 10.1017/S095457941900035X. Epub 2019 May 8.
• Cardinale EM, Subar AR, Brotman MA, Leibenluft E, Kircanski K, Pine DS. Inhibitory control and emotion dysregulation: A framework for research on anxiety. Dev Psychopathol. 2019 Aug;31(3):859-869. doi: 10.1017/S0954579419000300. Epub 2019 Apr 10.
• Abend R, Swetlitz C, White LK, Shechner T, Bar-Haim Y, Filippi C, Kircanski K, Haller SP, Benson BE, Chen G, Leibenluft E, Fox NA, Pine DS. Levels of early-childhood behavioral inhibition predict distinct neurodevelopmental pathways to pediatric anxiety. Psychol Med. 2020 Jan;50(1):96-106. doi: 10.1017/S0033291718003999. Epub 2019 Jan 8.
• Tseng WL, Deveney CM, Stoddard J, Kircanski K, Frackman AE, Yi JY, Hsu D, Moroney E, Machlin L, Donahue L, Roule A, Perhamus G, Reynolds RC, Roberson-Nay R, Hettema JM, Towbin KE, Stringaris A, Pine DS, Brotman MA, Leibenluft E. Brain Mechanisms of Attention Orienting Following Frustration: Associations With Irritability and Age in Youths. Am J Psychiatry. 2019 Jan 1;176(1):67-76. doi: 10.1176/appi.ajp.2018.18040491. Epub 2018 Oct 19.
• Smith AR, Nelson EE, Rappaport BI, Pine DS, Leibenluft E, Jarcho JM. I Like Them...Will They Like Me? Evidence for the Role of the Ventrolateral Prefrontal Cortex During Mismatched Social Appraisals in Anxious Youth. J Child Adolesc Psychopharmacol. 2018 Nov;28(9):646-654. doi: 10.1089/cap.2017.0142. Epub 2018 May 24.
• Kircanski K, White LK, Tseng WL, Wiggins JL, Frank HR, Sequeira S, Zhang S, Abend R, Towbin KE, Stringaris A, Pine DS, Leibenluft E, Brotman MA. A Latent Variable Approach to Differentiating Neural Mechanisms of Irritability and Anxiety in Youth. JAMA Psychiatry. 2018 Jun 1;75(6):631-639. doi: 10.1001/jamapsychiatry.2018.0468.
• White LK, Sequeira S, Britton JC, Brotman MA, Gold AL, Berman E, Towbin K, Abend R, Fox NA, Bar-Haim Y, Leibenluft E, Pine DS. Complementary Features of Attention Bias Modification Therapy and Cognitive-Behavioral Therapy in Pediatric Anxiety Disorders. Am J Psychiatry. 2017 Aug 1;174(8):775-784. doi: 10.1176/appi.ajp.2017.16070847. Epub 2017 Apr 14.
• Gold AL, Jarcho JM, Rosen DK, Pine DS, Ernst M. Emotional and Nonemotional Conflict Processing in Pediatric and Adult Anxiety Disorders. J Child Adolesc Psychopharmacol. 2015 Dec;25(10):754-63. doi: 10.1089/cap.2015.0066. Epub 2015 Nov 6.
• Britton JC, Suway JG, Clementi MA, Fox NA, Pine DS, Bar-Haim Y. Neural changes with attention bias modification for anxiety: a randomized trial. Soc Cogn Affect Neurosci. 2015 Jul;10(7):913-20. doi: 10.1093/scan/nsu141. Epub 2014 Oct 24.

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