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| ID | Type | Description | Link |
|---|---|---|---|
| R21MH101441 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Participants With Obsessive-compulsive Disorder (OCD) | Experimental | 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. |
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| Healthy Control (HC) Participants | No Intervention | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CBT treatment for OCD based on Exposure & Response Prevention (EX/RP) and when indicated medication treatment | Behavioral | 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. |
| 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 |
| 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. |
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Patient Inclusion Criteria:
Patient Exclusion Criteria:
Healthy Control Inclusion Criteria:
Healthy Control Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rachel Marsh, Ph.D. | New York Psychiatric Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NY State Psychiatric Institute | New York | New York | 10032 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35485920 | Derived | 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. | |
| 34539777 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 (March & Mulle, 1998) delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI. 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. |
| FG001 | 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 . |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 (March & Mulle, 1998) delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI. 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Only participants with usable fMRI data were included in these analyses. One participant with OCD and 4 HC participants were excluded because of missing fMRI data. | Posted | Mean | Standard Deviation | Arbitrary units | single time point: baseline |
Approximately 16-20 weeks for each participant (over 6 years and 6 months for the entire study).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 (March & Mulle, 1998) delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI. 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Rachel Marsh | New York State Psychiatric Institute | 646-774-5774 | rachel.marsh@nyspi.columbia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 24, 2017 | Sep 27, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009771 | Obsessive-Compulsive Disorder |
| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| D001523 | Mental Disorders |
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|
| 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) |
| 31952071 | Derived | 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. |
| 31889307 | Derived | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Full Scale Intelligence Quotient (FSIQ) | The FSIQ is a score derived from administration of 4 selected subtests (vocabulary, similarities, block design, and matrix reasoning) from the Wechsler Abbreviated Intelligence Scale - Second Edition (WASI-II), to provide a measure of global level of general cognitive and intellectual functioning. Standard scores are normed with a population mean of 100 and standard deviation of 15. Interpretation of Standard Score Ranges in terms of Performance: >129=Superior;120-129=Very High; 110-119=Bright Normal Performance; 90-109=Average; 80-89=Low Average; 70-79=Borderline Mental Functioning. | Mean | Standard Deviation | T-Score |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | 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 (March & Mulle, 1998) delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI. 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. |
| OG001 | 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. |
|
|
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| Secondary | 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. | Only participants with usable fMRI data were included in these analyses. Three participants with OCD and 4 HC participants were excluded because of missing fMRI data. | Posted | Mean | Standard Deviation | arbitrary units | single time point: Baseline |
|
|
|
|
| Secondary | 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 | Posted | Mean | Standard Deviation | mm | Single time point: Baseline |
|
|
|
|
| Secondary | 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. | Only participants with usable DTI data were included in these analyses. Three participants with OCD and 2 HC participants were excluded because of missing DTI data. | Posted | Mean | Standard Deviation | streamlines | Single time point (baseline) | streamlines | streamlines |
|
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|
|
| 0 |
| 28 |
| 0 |
| 28 |
| 0 |
| 28 |
| EG001 | 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. | 0 | 27 | 0 | 27 | 0 | 27 |
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Direction of the comparison: HC>OCD
| Superiority |
We selected 'arbitrary units' as the unit of measure here because we are looking at connectivity strengths |
| Separate cross-lagged panel models were computed in the OCD group for the three functional connections that differed significantly across groups at baseline (see Statistical Analysis 1). These models were constructed using IBM SPSS Amos (v.23) to test for directional relationships between OCD symptoms and FC pre- to post-treatment in the OCD patients. CY-BOCS total scores at each time point were used as the OCD symptoms measure. | Regression, Linear | <.05 | Slope | -.521 | 2-Sided | Other |
| Superiority |
only participants were assigned to groups (OCD, HC) and we measured streamline count in these participants to index structural connectivity |