Overlapping Neural Circuits in Pediatric OCD

Overlapping Neural Circuits Implicated in Pediatric OCD

The purpose of this study is to examine the brain functioning of children and adolescent with OCD before and after treatment with Exposure and Response Prevention (EXRP) therapy.

Study Overview

• Status: Completed
• Conditions: Obsessive Compulsive Disorder
• Intervention / Treatment: Behavioral: CBT treatment for OCD based on Exposure & Response Prevention (EX/RP) and when indicated medication treatment

Detailed Description

The capacity to coordinate thoughts and actions to execute goal-directed behaviors (cognitive control) and the capacity to anticipate, respond to, and learn from reward (reward processing) are key processes for human behavior. Dysfunction in these processes has been hypothesized to contribute to repetitive thoughts and behaviors in many disorders, including obsessive-compulsive disorder (OCD), Tourette Syndrome (TS), and eating disorders. The investigators will use multimodal imaging to investigate neural circuits that support cognitive control and reward processing, using pediatric OCD as a model system. The short-term goal is to clarify how circuit-based abnormalities contribute to repetitive thoughts/behaviors; these data will inform future trans-diagnostic studies. The long-term goal is to identify control and reward circuit-abnormalities as targets for new trans-diagnostic treatments.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • NY State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Patient Inclusion Criteria:

• Participants must be 5-17 at the time of consent
• Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Diagnosis of OCD as the principal problem
• Not on psychotropic medication and not receiving current psychotherapy for OCD
• Written informed assent by the participants (8 and older) and consent by the parent
• Participants and a parent/guardian must be able to read and understand English

Patient Exclusion Criteria:

• DSM-IV current diagnosis of major depressive disorder, attention-deficit hyperactivity disorder, Tourette's/Tic Disorder, or substance/alcohol abuse
• DSM-IV lifetime diagnosis of psychotic disorder, bipolar disorder, eating disorder, pervasive developmental disorder, or substance/alcohol abuse
• Active suicidal ideation
• Females who are pregnant or nursing
• Major medical or neurological problems
• Presence of metallic device or dental braces
• IQ<80
• A current or past diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS)
• Individuals who are currently receiving CBT, other forms of psychotherapy, or psychotropic medications
• Individuals who have received a full course of CBT in the past
• A positive pregnancy test
• Positive urine screen for illicit drugs
• Inability of participant or parent/guardian to read or understand English

Healthy Control Inclusion Criteria:

• Participants must be 5-17 at the time of consent
• Written informed assent by the participants (8 and older) and consent by the parent
• Participants and a parent/guardian must be able to read and understand English

Healthy Control Exclusion Criteria:

• Any current or lifetime psychiatric diagnosis
• Active suicidal ideation
• Females who are pregnant or nursing
• Major medical or neurological problems
• Presence of metallic device or dental braces
• IQ<80
• A current or past diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS)
• A positive pregnancy test
• Positive urine screen for illicit drugs
• Inability of participant or parent/guardian to read or understand English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants With Obsessive-compulsive Disorder (OCD); Children and adolescents who meet DSM-IV diagnostic criteria for OCD and had clinically significant obsessive-compulsive symptoms (CY-BOCS score>15). Comorbid anxiety disorders, but no other lifetime psychiatric diagnoses, were permitted in the OCD group as long as OCD was the primary diagnosis. Participants were unmedicated and had not received a full course of CBT with exposure and response prevention for OCD prior to their participation in the study. Following baseline assessment and scan, patients with OCD underwent a course of manualized treatment of CBT with E/RP adapted for pediatric OCD delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI.	Behavioral: CBT treatment for OCD based on Exposure & Response Prevention (EX/RP) and when indicated medication treatment; CBT treatment consisted of 12-16 hour-long sessions. For exceptional cases not showing clinical improvement after six CBT treatment sessions, complementary pharmacological treatment (SSRI) was offered as part of our treatment protocol. CBT for OCD involves gradually exposing patients to anxiety provoking stimuli while having patients refrain from engaging in compulsive rituals and/or avoidance behaviors. There are three major components of CBT treatment for OCD, specifically: (1) exposure to anxiety provoking stimuli, (2) response prevention, and (3) cognitive techniques intended to decrease anxiety during the exposure and response prevention processes.
No Intervention: Healthy Control (HC) Participants; Healthy control (HC) participants matched on age and sex with the OCD group. HC participants had no lifetime psychiatric disorders. HC participants were assessed and scanned at baseline and again after 12-16 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Activation Associated With the Resolution of Cognitive Conflict	Task-based functional magnetic resonance imaging (fMRI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs) during their performance of a Simon Spatial Compatibility Task. In each trial, participants are presented with a leftward or rightward pointing arrow that is either congruent or incongruent with their position (left or right) on the screen. Participants are instructed to respond as quickly and accurately as possible to the direction in which the arrow was pointing by pressing a button on a response box using the index finger for left and the middle finger for right. Brain activation during the resolution of cognitive conflict is computed by contrasting blood-oxygen-level-dependent (BOLD) signal during Incongruent versus Congruent trials. BOLD signal is expressed in arbitrary units (A.U.s).	single time point: baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Connectivity	Functional magnetic resonance imaging (fMRI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs) at baseline and after approximately 16-20 weeks (i.e., post-treatment for the participants with OCD). The whole brain is divided in 352 brain regions comprised of 333 cortical surface (Gordon et al. Cereb Cortex 2016;26:288-303) and 19 subcortical (Fischl et al. Neuron 2002;53:341-55) parcellated regions. FC-strength (average of Fisher-r-to-Z transformed Pearson correlation coefficients) between each region was computed. Values >0 indicate regions are positively connected (synchronized), with larger values indicating stronger connection. Values <0 indicate regions are negatively connected (inversely synchronized), with more negative values stronger negative connection. A value of 0 indicates that the regions are not connected.	single time point: Baseline
Brain Gray Matter Thickness	Structural MRI will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs). Regional cortical thickness will be computed in the inferior frontal gyrus	Single time point: Baseline
Structural Connectivity (Streamline Counts)	Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs). A structural connectivity matrix is estimated for each participant using the standard MRtrix3 preprocessing pipeline, yielding 164x164 symmetrical streamline count matrix for each participant using the FreeSurfer segmentations/parcellations noted above (148 cortical, 14 subcortical regions, and the left and right cerebellum). Using this approach, streamline count between brain regions is proportional to the cross-sectional area of white matter fibers connecting those regions. Thus, streamline count is a biologically plausible metric of "structural connectivity" proposed to represent the communication 'bandwidth' between regions.	Single time point (baseline)

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Rachel Marsh, Ph.D., New York Psychiatric Institute

Publications and helpful links

General Publications

• Wang Z, Fontaine M, Cyr M, Rynn MA, Simpson HB, Marsh R, Pagliaccio D. Subcortical shape in pediatric and adult obsessive-compulsive disorder. Depress Anxiety. 2022 Jun;39(6):504-514. doi: 10.1002/da.23261. Epub 2022 Apr 29.
• Lv D, Ou Y, Wang Y, Ma J, Zhan C, Yang R, Chen Y, Shang T, Jia C, Sun L, Zhang G, Sun Z, Li J, Wang X, Guo W, Li P. Altered Functional Connectivity Strength at Rest in Medication-Free Obsessive-Compulsive Disorder. Neural Plast. 2021 Sep 8;2021:3741104. doi: 10.1155/2021/3741104. eCollection 2021.
• Cyr M, Pagliaccio D, Yanes-Lukin P, Fontaine M, Rynn MA, Marsh R. Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. Neuropsychopharmacology. 2020 Jun;45(7):1232-1240. doi: 10.1038/s41386-020-0613-3. Epub 2020 Jan 17. Erratum In: Neuropsychopharmacology. 2020 Mar 4;:
• Pagliaccio D, Cha J, He X, Cyr M, Yanes-Lukin P, Goldberg P, Fontaine M, Rynn MA, Marsh R. Structural neural markers of response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder. J Child Psychol Psychiatry. 2020 Dec;61(12):1299-1308. doi: 10.1111/jcpp.13191. Epub 2019 Dec 31.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: April 9, 2015
• First Submitted That Met QC Criteria: April 15, 2015
• First Posted (Estimated): April 20, 2015

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: OCD; Functional Magnetic Resonance Imaging (fMRI); Magnetic Resonance Imaging (MRI)
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Obsessive-Compulsive Disorder
• Other Study ID Numbers: 7006; R21MH101441 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES