This study consists of a naturalistic follow-up of subjects with Obsessive-Compulsive Disorder (OCD) that have participated in a global study investigating brain signatures of OCD funded by the National Institutes of Mental Health (RO1MH113250), with the following participant sites: the US (Columbia University, PI: Helen Blair Simpson), Brazil (University of Sao Paulo, PIs: Euripedes Miguel and Roseli G Shavitt), India (National Institutes of Mental Health, PI: Janardhan Reddy), The Netherlands (VU Amsterdam Medical Center, PI: Odile van den Heuvel), and South Africa (University of Cape Town, PI: Dan Stein; Stellenbosch University, PI: Christine Lochner). In this cross-sectional study, two-hundred and fifty unmedicated subjects with OCD (50 per site) will be assessed for clinical, neurocognitive and neuroimaging data. After completion of this study, participants willing to receive evidence-based treatments for OCD will be treated with the available resources in each site and will be assessed for treatment response status periodically, with a final assessment after 1 year of naturalistic follow-up. At this point, we will investigate baseline clinical, neurocognitive and neuroimaging variables associated with the treatment response status.

This study aims to investigate clinical, neurocognitive and neuroimaging variables associated with response to conventional treatments in adults with OCD.

Study design:

• 0-52 weeks: open-label trial of a selective serotonin reuptake inhibitor (SSRI) (preferably sertraline - easily available in the public network, usually well tolerated) up to the maximum recommended or tolerated dose (e.g., titration: start with 50mg/day, then add 50mg/day per week up to 200mg/day, if sertraline); patients who prefer to be treated with cognitive-behavioral therapy (CBT) will be given this option whenever CBT is available.
• treatment will be delivered under naturalistic conditions, tailored according to the needs, preference, and availability. Subjects will be called up for follow-up assessments at 3, 6, 9 and 12 months after baseline assessments. The instruments to be used at follow-up are the YBOCS and CGI scales.
• Response criteria: the definitions of a recent international expert consensus will be adopted (Mataix-Cols. et al., 2016). A positive response will be considered as at least 35% reduction in baseline Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores plus a Clinical Global Impression-Improvement (CGI-I) rating of 1 ("very much improved") or 2 ("much improved"), lasting for at least one week. We will also rate the CGI - severity. Partial response will correspond to a greater than 25% but less than 35% reduction in Y-BOCS scores plus a CGI-I rating of at least 3 ("minimally improved"), lasting for at least one week.

Subjects:

• All participants assessed for clinical, neurocognitive and neuroimaging data in the global brain signatures study who are willing to receive evidence-based treatment for OCD.

Assessments:

• Baseline: clinical, neurocognitive and neuroimaging protocols.

  1. Clinical: interviewer-delivered and self-report measures to determine: socio-demographic data, past medical history, psychiatric family history, psychiatric diagnoses, OCD symptom dimensions, the severity of OCD, insight into OCD, sensory phenomena, the severity of depression and anxiety symptoms, severity of compulsive-impulsive behaviors, level of disability
  2. Neurocognitive: executive function, emotional regulation, memory
  3. Neuroimaging: structural MRI, resting-state functional MRI (rs-fMRI), Diffusion Tensor Imaging (DTI)

• Months 3, 6, 9 and 12: YBOCS checklist and past week severity; CGI - improvement subscale, relative to baseline; CGI - severity subscale; assessments can be in person or by phone, by the same independent evaluator at the different time points

• 1 year: treatment history form, YBOCS severity and checklist, Impulsive-Compulsive Behaviors Checklist (ICBC), Obsessive-Compulsive Inventory-Revised (OCI-R), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), World Health Organization Disability Assessment Schedule (WHODAS), CGI.

Hypotheses (built from the literature): the following variables (as assessed at baseline) will show an association with response to treatment:

Clinical:

1. duration of untreated illness (Alarcon et al., 1993; Ravizza et al., 1995; Stein et al., 2001);
2. comorbidity: presence of comorbid social anxiety disorder (Carrasco et al., 1992), depressive disorders (Jakubovski et al., 2013); Post-Traumatic Stress Disorder (PTSD) (Shavitt et al., 2010);
3. level of insight (Erzegovesi et al., 2001);
4. symptom dimension: presence and severity of symmetry, contamination and hoarding dimensions (Alarcon et al., 1993; Ferrão et al., 2006; Mataix-Cols et al., 1999; Hazari et al., 2016)

Neurocognitive: decision making, verbal IQ (D'Alcante et al., 2012), verbal memory/learning (D'Alcante et al., 2012), inhibitory control and mental flexibility tasks (Flessner et al., 2010; Hazari et al., 2016).

Neuroimaging:

I. Structural: brain volumes in the orbitofrontal cortex, anterior cingulate, striatum, dorsolateral and dorsomedial prefrontal cortex (Yun et al., 2015), insula (Yun et al., 2015), thalamus, hippocampus, pituitary gland (Atmaca et al., 2016), amygdala (Szeszko et al., 2004), and cerebellum.

II. Structural connectivity (Diffusion Tensor Imaging - DTI): fractional anisotropy measures in the corpus callosum, the internal capsule, white matter in the area superolateral to the right caudate, bilateral cingulum, superior longitudinal fasciculus, and inferior longitudinal fasciculus (Cannistraro et al., 2007; Szeszko wt al., 2005; Yoo et al., 2007; Garibotto et al., 2010).

III. Functional connectivity (rs-fMRI): patterns of activation and connectivity in frontal-striatal (central executive), parietal, occipital, cerebellar, and insula-limbic (saliency) networks (Shin et al., 2014; Bhikram et al., 2016; Nakao et al., 2005; Sanematsu et al., 2010) IV. Exploratory: multimodal analyses of prediction

Analyses plan: parametric and non-parametric tests will be employed as indicated.

Inclusion Criteria:

• Principal DSM-5 diagnosis of OCD
• Y-BOCS ≥ 16
• No psychotropic meds for the last 6 weeks, with the exception of PRN sleeping meds (e.g., zolpidem or trazodone up to 50 mg) and benzos, as long as not within the past week or during study participation
• No CBT/EXRP focused on OCD within the past 6 weeks
• Capable of providing informed consent

Exclusion Criteria:

• Lifetime diagnosis of psychotic disorder, bipolar disorder, anorexia nervosa, autism spectrum disorder with IQ < 80, Tourette Disorder
• Current chronic tic disorder (current = in the past 12 months)
• Current substance-related and addictive disorders, including nicotine (current = in the past 12 months)
• Current binge-eating disorder or bulimia (current = in the past 12 months)
• Acute risk of suicide
• Female who is pregnant
• Major medical or neurological problems (including head injury with loss of consciousness) Presence of metallic devices or dental braces
• IQ < 80
• Cigarette use: more than 5 per day
• Alcohol use: more than 2 drinks per day for women and more than 3 drinks per day for men, Marijuana use: more than once per week