PET Whole Body Distribution Studies Using [11C]CUMI
Condition: Depression; Major Depression; Unipolar Depression; Anxiety Disorder; Anxiety Disorders
MeSH terms: Depression; Depressive Disorder; Anxiety Disorders
Study type: Observational

Summary: 
      Background:

        -  Researchers studying new treatments for major depressive disorder are looking at how
           medications to treat depression act on the brain chemical serotonin, which interacts
           with specific serotonin receptors on brain cells. New methods of studying serotonin
           receptors in the brain may help provide a better understanding of depression and
           treatment options.

        -  A new radioactive chemical called [11C]CUMI may be useful for studying serotonin
           receptors in the brain. By using positron emission tomography (PET) scanning to see how
           [11C]CUMI bonds with serotonin receptors, researchers will investigate whether [11C]CUMI
           can be used to study depression and how antidepressant medications work.

      Objectives:

      - To determine the usefulness of [11C]CUMI as a method of studying serotonin receptors in the
      brain.

      Eligibility:

      - Healthy individuals between 18 and 65 who have no history of psychiatric illness.

      Design:

        -  This study requires 8 outpatient visits to the NIH clinic.

        -  Visit 1: Participants will have a full physical examination and medical history, as well
           as a psychiatric evaluation and questions about alcohol and drug use. Other tests will
           include blood and urine samples and an electrocardiogram (EKG). Testing will take
           approximately 3 hours.

        -  Visit 2: Participants will have a magnetic resonance imaging (MRI) scan to evaluate
           brain function and activity.

        -  Visit 3: Participants will have a PET scan, in which a small amount of the radioactive
           chemical [11C]CUMI will be injected through an intravenous (IV) catheter, and will have
           another IV line put in place to draw regular blood samples during the scan. The scan
           will last approximately 4 hours.

        -  Visits 4-8: Participants will have regular blood tests after the scan between days 1-3
           and at about weeks 1, 2, 3, and 4. The blood tests will check muscle, heart, and liver
           function.
    

Detailed description: 
      Eighteen million people in the United States are currently suffering from Major Depressive
      Disorder, which is characterized by episodes of low mood, poor self attitude and poor
      vitality. Of those suffering from Major Depressive Disorder (MDD), only one third completely
      improve, but even among these cases, there is a waiting period of several weeks or more
      during which antidepressants take effect. Our inability to adequately treat MDD is evident in
      its being ranked number one in Disability Adjusted Life Years (DALY) among persons aged
      15-44. Given this profound burden, improving our understanding of the molecular basis of MDD
      is of utmost importance in the development of novel antidepressant medications.

      Serotoninergic neurotransmission is implicated in MDD, as demonstrated by the relative
      success of selective serotonin reuptake inhibitors (SSRIs). SSRIs block the reuptake of
      serotonin through the serotonin transporter, which then increases serotonin at the synaptic
      cleft. Serotonin then binds to 5-HT(1A) receptors, which are G-protein coupled receptors that
      are present both presynaptically and postsynaptically. Presynaptically, these receptors act
      as autoinhibitory receptors, triggering decreased firing rates and decreased serotonin
      release. This autoinhibitory mechanism is believed to be the reason why patients experience a
      delay in symptomatic improvement after initiation of SSRIs. Serotonin binding to postsynaptic
      receptors mediates symptomatic improvement of depression. Multiple positron emission
      tomography (PET) studies on 5-HT(1A) have been published. However, none of these studies use
      5-HT(1A) agonists, which are specific for the high affinity, G-protein coupled and active
      state of the 5-HT(1A) receptor. We would therefore like to establish the use of the 5-HT(1A)
      radiolabelled agonist, [(11)C]CUMI, here at NIH.

      The purpose of this study is to perform whole body PET studies in healthy volunteers in order
      to estimate radiation absorbed doses for [(11)C]CUMI. Future experiments will include studies
      on Major Depressive Disorder.
    

Time perspective: Prospective
Keywords: Serotonin 1A Receptor; Positron Emission Tomograhy (PET); Dosimetry; Healthy Volunteer; HV