p11 Protein Levels in Patients With Major Depressive Disorder Treated With Citalopram
Condition: Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Observational

Summary: 
      This study will compare levels of p11 protein in people with and without major depressive
      disorder (MDD) and examine if p11 levels in patients are affected by treatment with
      citalopram (Celexa).

      Healthy normal volunteers and patients with chronic or recurrent major depression between 18
      and 65 years of age may be eligible for this study.

      Participants undergo the following tests and procedures:

      Healthy Volunteers

        -  Psychiatric interview and medical examination, questions about family history

        -  Blood draw

      Patients with MDD

      Phase 1 - Evaluation and Discontinuation of Medications

        -  Physical examination, electrocardiogram, blood tests

        -  Gradual antidepressant medication withdrawal, followed by 2- to 6-week drug-free period.
           If needed, medicines for anxiety and difficulty sleeping may be prescribed.

      Phase 2 Citalopram Treatment

        -  Start daily citalopram treatment

        -  Evaluations at the start of phase 2 and every week for 8 weeks with following
           procedures:

        -  Symptoms ratings interview and questionnaires

        -  Review of side effects and new medications

        -  Blood pressure and pulse measurements

        -  Blood and urine tests

      At the end of the study, plans are developed for long-term treatment and transfer of care to
      the patient s own physician.

      ...
    

Detailed description: 
      Major depressive disorder (MDD) is a serious, debilitating, life-shortening illness that
      affects many persons of all ages and backgrounds. While treatments are effective for a
      significant portion of patients with MDD, progress in developing more effective treatments is
      lagging. Furthermore, with regards to existing antidepressant medications, there are yet no
      reliable predictors of the likelihood of remission, response or non-response with an initial
      trial of an antidepressant medication. Identifying factors that are likely to predict
      response would have the advantage of personalizing treatment to a particular individual; that
      is selecting the antidepressant medication that is most likely to give the greatest
      probability of having a favorable outcome.

      The serotonin system has been implicated in the pathophysiology of depression and mechanism
      of action of existing effective antidepressant treatments. Fourteen different serotonin
      receptors have been identified to date. One of them, 5-HT1B, plays an important role in
      regulating serotonin neurotransmission. Recently, p11 (a member of the S100 family of
      proteins) was found to interact with 5-HT1B receptors (Svenningsson et al 2006; Svenningsson
      and Greengard 2007). p11 mRNA levels are markedly reduced in the forebrain in helpless
      H/Rouen mice and the level of p11 mRNA was down-regulated in the anterior cingulate cortex
      from depressed patients. p11 mRNA is distributed in an anatomical pattern that closely
      resembled that of 5-HT1B receptor mRNA, including cortex, hippocampus, hypothalamus and raphe
      nuclei. Chronic administration of the antidepressants imipramine, tranylcypromine, and
      citalopram significantly increase the level of p11 in cortex. Finally, we have found that
      chronic treatment with fluoxetine increases p11 in peripheral mononuclear cells in monkeys.

      We will now study whether the blood cell levels of p11 differ between healthy individuals and
      patients suffering from unipolar depression. Moreover, we will study whether the levels of
      p11 are affected by treatment with the selective serotonin reuptake inhibitor, citalopram.
      Complementary work will continue at other laboratories to better characterize the role of p11
      in the pathophysiology of depression (e.g., animal studies, post-mortem studies).

      In addition, we will also acquire a battery of magnetic resonance imaging (MRI) scans in a
      subset of 45 more homogeneous depressed subjects, and 45 matched healthy controls at baseline
      and at 8 weeks. There is a growing body of evidence implicating morphometric and physiologic
      abnormalities, measureable by MRI, in the pathophysiology of major depressive disorder. We
      will assess both baseline differences between depressed subjects and healthy controls,
      treatment effects, and search for possible MRI markers predicting treatment response.

      This is an open label study which will be performed at the National Institute of Mental
      Health. In all, 82 adult subjects with major depressive disorder, between the ages of 18 and
      65 years, will be recruited from the community. In addition, we will perform p11 measurements
      in blood cells from 64 healthy control subjects.
    

Keywords: Depression; Depression Treatment; Unipolar Depression; Citalopram; Serotonin; Major Depression; Healthy Volunteer; HV