[18F]PF-06445974 to Image PDE4B in Major Depressive Disorder Using PET
Background: Major depressive disorder (MDD) is a psychiatric condition. People with MDD have occasional bouts of depressive symptoms; these bouts are called major depressive episodes (MDEs). Researchers want to know if people having MDEs have lower levels of an enzyme called PDE4B in their brains. Primary
Objective: To determine whether PDE4B is reduced in the brains of individuals with MDD experiencing a major depressive episode (MDE). Secondary
Objectives: To determine the optimal length of scanning and the retest variability and reliability of \[18F\]PF-06445974, and whether PDE4B binding correlates with clinical rating scales. To measure if PDE4B radioligand binding can be blocked by taking apremilast.
Eligibility: People aged 18-70 years with MDD. Healthy volunteers are also needed.
Design: Participants will have up to 5 clinic visits. Participants will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. Some participants may have a psychiatric assessment; they will answer questions about their state of mind and related topics. Participants will have magnetic resonance imaging (MRI) of the brain. They will lie on a table that slides into a metal cylinder. Participants will have a positron emission tomography (PET) scan. A needle will be used to guide a thin plastic tube (catheter) into a vein in one arm. An experimental substance called a radioactive tracer (\[18F\]PF-06445974) will be injected through the catheter. Participants will lie on a table that slides into a doughnut-shaped machine. The scan will last up to 4 hours with a 15-minute break. Participants blood pressure, heart rate, and breathing will be monitored before, during, and after the PET scan. A second catheter will be inserted in the artery of the wrist so blood can be drawn during the scan. Some participants may return for a second PET scan; have a lung scan or receive apremilast. https://nimhcontent.nimh.nih.gov/start/surveys/?s=KE88DXXPLDFHHTF8
⁃ Patients: In order to be eligible for this study, MDD participants must meet all of the following criteria:
• 18 to 70 years of age.
• Female participants of childbearing potential must be using a medically acceptable means of contraception.
• Be in good general health as evidenced by medical history and physical examination. Stable medical conditions as assessed by their primary care provider (PCP) and/or in-house clinician are permitted to join the study.
• Each participant must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
• All participants must have undergone a screening assessment under protocol 01-M-0254, The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Participants .
• Participants must fulfill DSM-5 criteria for major depression (MDD) without psychotic features, as based on clinical assessment and structured diagnostic interview (SCID-P).
• Participants must have an initial score on the MADRS \>= 18 or HAM-D \>= 15 within one week of study entry.
• Participants must be experiencing an MDE lasting at least four weeks.
• All MDD participants must have a PCP or psychiatrist in the community.
• 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.
• 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:
• Aged 18 to 70 years old.
• Female participants of childbearing potential must be using a medically acceptable means of contraception.
• Able to provide informed consent.
• Be in good general health, as evidenced by medical history and physical examination, and have no cognitive impairment.
• 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 .
• 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.
• Agree to adhere to the lifestyle considerations.