Overview

Background

Researchers developed [11C]MC1, a radioligand for cyclooxygenase-2 (COX-2). COX-2 is an enzyme induced in the brain during inflammation. Researchers want to see the levels of COX-1 (measured as distribution volume VT) are elevated in the brain of two groups of mood disorders patients undergoing MDE relative to the control group.

Objective

To determine whether COX-1 and COX-2 are detectable in the brains of individuals with MDD experiencing a major depressive episode (MDE).

Eligibility

People aged 18-70 years with MDD and Healthy Volunteers aged 18 70 years.

Design

Group A: MDD participants will be studied with the same dose of [11C]MC1 before and after administration of 600 mg celecoxib; the study is neither randomized nor placebo-controlled. Group B: MDD participants, both medicated and unmedicated, will be studied with [11C]PS13 and compared to healthy volunteers..

https://nimhcontent.nimh.nih.gov/start/surveys/?s=TJW4RA4WN3LDD988

Eligibility

• INCLUSION CRITERIA:

        Patients: In order to be eligible for this study, MDD participants must meet all of the
        following criteria:
          1. Aged 18 to 70 years old.
          2. Female participants of childbearing potential must be using a medically acceptable
             means of contraception.
          3. Participants must be in good general health as evidenced by medical history and
             physical examination.
          4. Each participant must have a level of understanding sufficient to agree to all
             required tests and examinations and sign an informed consent document.
          5. All participants must have undergone a screening assessment under protocol 01M0254,
             The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Participants .
          6. Participants must fulfill DSM-5 criteria for major depression (MDD) without psychotic
             features, as based on clinical assessment and structured diagnostic interview
             (SCID-P).
          7. Participants must have an initial score on the MADRS greater than or equal to 18 or
             HAM-D greater than or equal to 15 within one week of study entry.
          8. Participants must be experiencing an MDE lasting at least four weeks.
          9. Unmedicated participants in both Groups must be medication-free for at least two weeks
             (5 weeks for aripirazole, brexpiprazole, fluoxetine) prior to first screen visit.
             Medications will not be discontinued for the purpose of this study.
         10. Participants must have their radial artery pulse checked for the presence of adequate
             ulnar collateral flow and the absence of any metal or foreign objects in both wrists.
         11. Participants must agree to adhere to the lifestyle considerations.
        Healthy Controls: In order to be eligible to participate in this study, control subjects
        must meet all of the following criteria:
          1. Aged 18 to 70 years old.
          2. Female participants of childbearing potential must be using a medically acceptable
             means of contraception.
          3. Able to provide informed consent.
          4. Be in good general health, as evidenced by medical history and physical examination,
             and have no cognitive impairment.
          5. Be enrolled in 01M0254, The Evaluation of Participants with Mood and Anxiety Disorders
             and Healthy Volunteers or 17M0181, Recruitment and Characterization of Healthy
             Research Volunteers for NIMH Intramural Studies .
          6. Have their radial artery pulse checked for the presence of adequate ulnar collateral
             flow and the absence of any metal or foreign objects in both wrists.
          7. Agree to adhere to the lifestyle considerations.
        EXCLUSION CRITERIA:
        Participants with MDD who meet any of the following criteria will be excluded from
        participation in this study:
          1. Clinically significant abnormalities on EKG or laboratory testing. This includes CBC
             and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen). Any lab
             value that is two-times the upper limit or even lower values in the investigator s
             judgment. Creatinine level >1.3 mg/dL.
          2. Participants must be free of all prohibited medications or at least two weeks (5 weeks
             for aripiprazole, brexpiprazole, fluoxetine) prior to screen visit. These medications
             include antidepressants, anti-inflammatory drugs (except for study medication
             celecoxib), antipsychotics, anxiolytics, psychotropic drugs not otherwise specified
             (including herbal products), and sedatives/hypnotics. Medicated participants in Group
             B may continue their therapy.
          3. Participants should not have taken Non-Steroidal Anti-Inflammatory Drug (NSAID)s for
             two weeks prior to the PET scan. Aspirin, corticosteroids (with the exception of
             topical steroids), or immunosuppressants (e.g. methotrexate) must not have been taken
             in the prior month.
          4. Current psychotic features or a diagnosis of schizophrenia or any other psychotic
             disorder as defined in the DSM-5.
          5. Participants with a history of DSM-5 substance use disorder (except for caffeinei or
             nicotine dependence) within the preceding three months. In addition, participants must
             not have substance use disorder or alcohol use disorder. However, alcohol or cannabis
             use by themselves are not exclusion criteria, unless that use impairs function of
             daily lfe.
          6. Participants who, in the investigator s judgment, pose a current serious suicidal or
             homicidal risk.
          7. Participants who have a history of aggressive behavior towards others.
          8. Participants who have an unstable medical condition that, in the opinion of the
             investigators, makes participation unsafe (e.g., an active infection or untreated
             malignancy).
          9. Participants seeking treatment or a change in treatment and may be referred to the
             community or to another research study.
         10. Are unable to travel to the NIH.
         11. Have recent exposure to radiation related to research (e.g., PET from other research)
             that, when combined with this study, would be above the allowable limits.
         12. Have an inability to lie flat and/or lie still on the camera bed for at least two
             hours, including claustrophobia, overweight greater than the maximum for the scanner,
             and uncontrollable behavioral symptoms, which will be screened by an interview with
             the participant during the screening visit.
         13. Are unable to have an MRI scan (e.g., because of pacemakers or other implanted
             electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on
             the wall of a large artery), metallic prostheses (including metal pins and rods, heart
             valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel
             fragments, or metal fragments in the eye.
         14. Pregnancy.
         15. HIV Infection.
         16. Be NIMH staff or an NIH employee who is a subordinate/relative/co-worker of the
             investigators.
        Healthy controls who meet any of the following criteria will be excluded from participation
        in this study:
          1. Clinically significant abnormalities on EKG or laboratory testing. This includes CBC
             and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen).
          2. Participants must be free of all prohibited medications or at least two weeks (5 weeks
             for aripiprazole, brexpiprazole, fluoxetine) prior to screen visit. These medications
             include antidepressants, anti-inflammatory drugs (except for study medication
             celecoxib), antipsychotics, anxiolytics, psychotropic drugs not otherwise specified
             (including herbal products), and sedatives/hypnotics.
          3. Participants should not have taken NSAIDs for two weeks prior to the PET scan.
             Aspirin, corticosteroids, or immunosuppressants (e.g. methotrexate) must not have been
             taken in the prior month.
          4. Participants with a history of DSM-5 substance use disorder (except for caffeine or
             nicotine dependence) within the preceding three months. In addition, participants must
             not have substance use disorder or alcohol use disorder. However, alcohol or cannabis
             use by themselves are not exclusion criteria, unless that use impairs function of
             daily life.
          5. Participants who have an unstable medical condition that, in the opinion of the
             investigators, makes participation unsafe (e.g., an active infection or untreated
             malignancy).
          6. Are unable to travel to the NIH.
          7. Have recent exposure to radiation related to research (e.g., PET from other research)
             that, when combined with this study, would be above the allowable limits.
          8. Have an inability to lie flat and/or lie still on the camera bed for at least two
             hours, including claustrophobia, overweight greater than the maximum for the scanner,
             and uncontrollable behavioral symptoms, which will be screened by an interview with
             the participant during the screening visit.
          9. Are unable to have an MRI scan (e.g., because of pacemakers or other implanted
             electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on
             the wall of a large artery), metallic prostheses (including metal pins and rods, heart
             valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel
             fragments, or metal fragments in the eye.
         10. Pregnancy.
         11. HIV Infection.
         12. Be NIMH staff or an NIH employee who is a subordinate/relative/co-worker of the
             investigators.
        EXCLUSION OF CHILDREN:
        Because this protocol has more than minimal risk from radiation exposure without
        possibility of direct benefit, inclusion of children is not appropriate.
        EXCLUSION OF PREGNANT OR BREASTFEEDING WOMEN:
        Pregnant women will be excluded because this protocol involves exposure to ionizing
        radiation. Lactating women will be excluded because radioisotopes may be excreted in milk.
        EXCLUSION OF PARTICIPANTS WHO ARE HIV POSITIVE:
        Persons with HIV infection are excluded because HIV infection itself may cause
        neuroinflammation, and we wish to specifically study the effect of depression on
        neuroinflammation.
        EXCLUSION OF NON ENGLISH SPEAKING PARTICIPANTS:
        Non-English-speaking participants will be excluded from participation in this study because
        neuropsychological testing is required by this protocol. This testing, which is critical
        for interpreting study results, has not been validated in other languages or when using a
        translator.