Primary Objective: To identify reproducible neuroimaging signatures of OCDSecondary Objective: To link these neuroimaging signatures to specific cognitive functions and clinical profilesExploratory Aims: 1) To study how environmental factors may…
ID
Source
Brief title
Condition
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. clinical measures (on specific symptoms)
2. neurocognitive profiles (behaviour on neuropsychological tests)
3. neural correlates on regional brain volumes (e.g. cortical thickness,
surface area), white matter integrity (e.g. fractional anisotrophy), and
resting state network connectivity, using magnetic resonance imaging (MRI).
Secondary outcome
We will explore whether three factors (childhood trauma, socioeconomic status
(SES), and religiosity) moderate the link between our neuroimaging signatures
and clinical and cognitive profiles. We focus on childhood trauma and SES
because of their known effects on brain structure in healthy people, and their
potential to confound imaging data.
Background summary
OCD contributes to the global burden of disease. This project seeks to identify
reproducible brain signatures for OCD cognitive and clinical profiles, using
methods that are applicable to populations around the globe.
The phenotype of OCD is similar around the globe, including both core behaviors
(obsessions and compulsions) and individual variation (e.g., symptom
dimensions, age of onset, comorbidity). This is one reason why OCD is an
excellent test for identifying reproducible neuroimaging signatures that can be
linked to different cognitive and clinical profiles.
Brain circuit abnormalities have been identified in OCD subjects. We propose to
test their reproducibility in a large unmedicated sample and to validate them
by linking them to specific cognitive and clinical profiles.
Study objective
Primary Objective: To identify reproducible neuroimaging signatures of OCD
Secondary Objective: To link these neuroimaging signatures to specific
cognitive functions and clinical profiles
Exploratory Aims:
1) To study how environmental factors may moderate these brain-behavior
associations.
2) To study which neural correlates are markers of vulnerability (present in
both the OCD patients and their unaffected siblings), resilience (present in
the unaffected siblings but not the OCD patients), and disease (present in OCD
patients, but not the unaffected siblings)
3) To study the predictive value of neural correlates for naturalistic course
of disease at 1 year follow-up.
Study design
This cross-sectional multi-center study will run for 5 years, using harmonized
data collection across 5 sites worldwide. The design includes 3 domains of
profile assessment:
1) Demographic and clinical profiles, including assessment of environmental
factors
We will implement a standardized protocol at all sites to clinically assess
subjects. We will assess patients in their primary language. The clinical
protocol will include well-validated measures that have been used around the
globe and that tap different symptom domains.
The clinical measures to assess include:
a) Obsessive-Compulsive Profiles
* Total Severity: Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)102
* Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS)108
* Insight: Brown Assessment of Beliefs Scale (BABS)130
* Age of Onset: Structured Clinical Interview for DSM-5 (SCID)
* University of Sao Paulo Sensory Phenomenon Scale (USP-SPS)109
* Obsessive-Compulsive Personality Disorder (OCPD) assessment, based on SCID
b) Depression: Hamilton Depression Rating Scale (HAM-D)131
c) Anxiety: Hamilton Anxiety Rating Scale (HAM-A)132
d) Global Functioning: WHO Disability Assessment Schedule (WHODAS)134
e) History of Tic Disorders, using the structured interview (SCID)
f) Obsessive-Compulsive Inventory-Revised (OCI-R)
g) Autism: Autism Questionnaire (AQ)
h) Impulsivity: Impulsive-Compulsive Behaviors Checklist (ICBC)
i) Disgust: Disgust Propensity and Sensitivity Scale-Revised (DPSS-R)
2) Neuropsychological profiles
Neurocognitive tasks were chosen that: 1) probe the brain circuits and domains
of cognitive dysfunction that are implicated in OCD; 2) are consonant with the
NIMH*s RDoC matrix
(http://www.nimh.nih.gov/research-priorities/rdoc/nimh-research-domain-criteria-
rdoc.shtml); 3) can be standardized across sites (e.g., minimal reliance on
language and computerized); and 4) are in the public domain (e.g., NIH toolkit,
https://penncnp.med.upenn.edu, PhenXtoolkit).
These tasks will probe:
a) the dorsal *cognitive* CSTC circuit using the visual spatial N-BACK task to
assess the executive function of updating and the Tower of London task to
assess planning.
b) the ventral *cognitive* CSTC using the Stop-Signal Task to assess response
inhibition.
c) the ventral *reward* CSTC using a Temporal Discounting and Risk and Choice
task to assess capacity to delay reward, and the Habit task
d) the frontal-limbic circuitry using the Emotional Stroop task.
e) the sensorimotor CSTC using the Motor Sequence test.
3) Neural profiles
We will implement a standardized imaging protocol across all sites. At all
sites, the MRI will be performed within one week of the clinical and
neurocognitive assessments on a 3.0 Tesla whole-body scanner (GE MR750 [2
sites], Siemens Skyra [2 sites], and Philips Achieva [1 site]), all equipped
with a 32 channel phased-array head coil. Images will be acquired with
optimized and standardized sequences for:
a. high resolution 3D T1 weighted structural imaging with 1 mm isotropic
resolution and additional phase-sensitive inversion recovery (psir) T1 weighted
scan to optimize the segmentation in the subcortical areas
b. multi-shell diffusion tensor imaging (DTI) based on 73 high b-values: 25 in
the first shell (b1000), and 24 in the 2 higher shells (b2000 and b3000) with
2,5 mm isotropic resolution, and 7 unweighted (b=0 s/mm2) scans
c. rs-fMRI (10 minutes, eyes closed): 272 volumes with 3.3 mm isotropic
resolution.
Head motion will be monitored during scanning
At study start, we will harmonize data collection so that raw MRI data
(anatomical, DTI and rs-fMRI) can be optimally pooled. We will follow
established methods used in other multi-center MRI studies to reduce
between-scanner effects.
Study burden and risks
Participants will be measured at baseline during 3 assessment days (within a
timeframe of max. two weeks) of 4 hours for clinical/neuropsychological
assessments (psychiatric assessment (2 hours); self-report questionnaires (1
hour); neurocognitive assessment (2 hours)) and a 1 hour MRI scan session
within one week of the clinical/neuropsychological assessments. 1 year
follow-up session (Telephone) (0.5-1 hour)
There will be no direct benefit for the subjects to participate in the study.
However, participation is expected to result in increased insight in to
neurobiological background of the disorder, which will contribute subsequently
to the development of treatment alternatives. The risks can be considered
negligible. MRI is non-invasive imaging techniques. For subjects who are
sensitive to claustrophobia, the positioning in a MRI scanner might provoke
feelings of distress or in extreme situations panic attacks. In case a subject
feels uncomfortable in the scanner, it is possible to terminate the scanning
session at any moment without any consequence for the participant.
de Boelenlaan 1108
Amsterdam 1081HZ
NL
de Boelenlaan 1108
Amsterdam 1081HZ
NL
Listed location countries
Age
Inclusion criteria
1) OCD patients (n <= 250):
* Either gender, all ethnic/racial-cultural categories, and right-handed (based on the Edinburgh Handedness Inventory);
* Ages 18- 50;
* Meets current DSM-5 criteria for OCD, with both obsessions and compulsions;
* OCD is the principal psychiatric problem and severity of illness is at least moderate (i.e., a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of at least 16);
* Not on psychotropic medication (for at least 6 weeks; benzodiazepines / sleeping medication at least 1 week) and able to tolerate a treatment-free period;
* Capacity to provide informed consent;
* No current cognitive behavioral therapy (exposure in vivo with response prevention) for their OCD symptoms (last 6 weeks).;2) Healthy controls (n<=250):
* Either gender, all ethnic/racial-cultural categories;
* Ages 18-50;
* Capacity to provide informed consent.;3) Unaffected siblings (n<= 120-125):
* Either gender, all ethnic/racial-cultural categories;
* Ages 18-50;
* Capacity to provide informed consent;
* Sibling (first degree) of OCD participant.
Exclusion criteria
1) OCD patients:
* Lifetime diagnosis of a psychotic disorder, bipolar disorder, anorexia nervosa (note: binge eating and bulimia in past is OK, if not last 12 months), Tourette disorder or autism spectrum disorder with IQ < 80 (Asperger is OK, if OCD is primary);
* Current diagnosis (past 12 months) of any DSM-5 Substance-related and Addictive disorder (including nicotine) or chronic tic disorder, current diagnosis of Tourette Disorder. Note: Comorbid depressive or anxiety disorders and tics will be allowed if OCD is the principal diagnosis (i.e., most severe upon presentation and reason for seeking help).
* Active suicidal ideation;
* Females who are pregnant;
* Major medical or neurological problem (e.g., unstable hypertension, seizure disorder, head trauma (with loss of consciousness), neurocognitive disorder);
* Presence of metallic devices or dental braces (including retainers);
* IQ <80.;2) Healthy controls:
* Any current psychiatric diagnosis;
* Lifetime psychiatric diagnosis with the sole exception of major depressive disorder and anxiety disorders (Note: MDD and anxiety disorders OK only if not within the past 12 months);
* History and current use of psychotropic medication with the exception of sporadic sleeping drugs / benzodiazepines and only if not within the past week and not during study);
* OCD or tic disorder in a first- degree relative;
* Females who are pregnant;
* Major medical or neurological problem (e.g., unstable hypertension, seizure disorder, head trauma (with loss of consciousness));
* Presence of metallic devices or dental braces (including retainers with metal);
* IQ <80.;3) Unaffected siblings:
* Any current psychiatric diagnosis;
* Lifetime psychiatric diagnosis with the sole exception of major depressive disorder and anxiety disorders (Note: MDD and anxiety disorders OK only of not within the past 12 months);
* History and current use of psychotropic medication with the exception of sporadic sleeping drugs / benzodiazepines and only if not within the past week and not during study);
* Females who are pregnant;
* Major medical or neurological problem (e.g., unstable hypertension, seizure disorder, head trauma (with loss of consciousness));
* Presence of metallic devices or dental braces (including retainers with metal);
* IQ <80.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL61982.029.17 |