Overview

The proposed randomized, double-blind research study will use functional magnetic resonance neuroimaging using state-of-the-art HCP acquisition protocols and analytic pipelines, to identify predictors and correlates of response to an accepted first-line pharmacological treatment for obsessive-compulsive disorder.

Eligibility

Inclusion Criteria:

• Inclusion criteria for all groups will include: (i) Adults, Men and women will be included, in a 1:1 ratio; and efforts will be made to recruit racial and ethnic subgroups. Groups will be further matched on age, handedness; and later, in analysis, on educational status and smoking history.

        (ii) signed informed consent, approved by the Yale Human Investigations Committee; and
        (iii) ability and willingness to participate in all study procedures, including clinical
        assessments and fMRI scans.
          -  Additional inclusion criteria:
          -  OCD Participants:
             (i) a DSM diagnosis of OCD, established as detailed above; (ii) a baseline Y-BOCS of
             ≥16; (iii) no current psychoactive medication, with the exception of the occasional
             use of a PRN medication for sleep; (iv) treatment seeking, and clinically appropriate
             for fluoxetine pharmacotherapy; (v) for women of childbearing potential, not pregnant
             or intending to become pregnant, and willing to use reliable birth control over the
             course of the study, either prescribed contraceptive (oral contraceptive, injectable,
             or implant) or one barrier method (e.g. diaphragm with spermicide, intrauterine
             device, cervical cap). Women of childbearing potential must have a negative serum
             pregnancy test at screening and negative urine pregnancy tests at the study baseline
             and on each scan day appointment prior to the MRI scan.
          -  Healthy Control Participants:
             (i) no current DSM diagnosis (by clinician interview confirmed by SCID or MINI); (ii)
             no documented or clinically suspected family history in a first- or second- degree
             relative of OCD, Tourette syndrome, hoarding disorder, body dysmorphic disorder, or a
             compulsive grooming disorder.
        Exclusion Criteria:
          -  Exclusion criteria for all groups will include:
             (i) any unstable medical, psychiatric, or neurological condition (including active or
             otherwise problematic suicidality) that may necessitate urgent treatment; (ii) any
             substance use disorder within the past 6 months; (iii) use of psychotropic medications
             within the past 8 weeks, with the exception of occasional use of a sleep aid or
             analgesic; (iv) use of an as-needed sleep aid or prescription analgesic within 3 days
             of the scan; (v) any history of a primary psychotic disorder or of mania; (vi) any
             evidence of substance use on urine toxicology testing; (vii) any major neurological
             disease or history of major head trauma, including concussion with extended loss of
             consciousness; (viii) pregnancy; (ix) any metal in the body or other contraindication
             to MRI scanning; (x) severe claustrophobia, back pain, or other condition that may
             make an extended MR scan difficult or lead to excessive movement during the scan.
          -  Additional exclusion criteria:
          -  OCD Participants:
             (i) past allergy or adverse reaction to fluoxetine or another SSRI, or other clinical
             contraindication to fluoxetine pharmacotherapy; (ii) documented nonresponse to a past
             trial of fluoxetine of appropriate dose (≥40 mg/dy) and duration (≥12 weeks).
        (iii) Patients taking Coumadin or Monoamine oxidase inhibitors (MAOIs) will be excluded
        from the study.