Circadian Phase in Bipolar Depression: Is it Delayed and Does it Normalize With Remission?
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Observational [Patient Registry]

Summary: 
      The overall aim of this project is to compare sleep patterns and melatonin profiles in
      individuals with bipolar disorder during depression and after remission. The hypothesis is
      that sleep time, rest-activity cycles and melatonin onset will be delayed during depression
      and become less delayed after remission.
    

Detailed description: 
      Bipolar disorder is a prevalent, disabling, and chronic mood disorder characterized by
      depressive symptoms that alternate with hypomanic, manic or mixed states. The depressive
      phase of this illness predominates and is associated with cognitive, occupational and social
      impairment, psychiatric comorbidity, and increased mortality from suicide and general medical
      problems. Clarification of the pathophysiology of this illness is important to improve
      treatment effectiveness.

      Various lines of evidence suggest that circadian factors play a role in the onset and
      maintenance of bipolar depression. Rhythmic clinical disturbances are found in the altered
      sleep-wake cycle, diurnal mood shifts, rest-activity changes, seasonal features, the cyclic
      pattern of relapse and remission and the polarity inversions that define this disorder.
      Chronotherapeutic treatments that act by modifying circadian phase have been shown to be
      effective in ameliorating the depressive symptoms of this illness. In addition to this
      circumstantial evidence, there is some more direct data implicating circadian dysfunction in
      bipolar depression. Genetic studies have documented associations between various circadian
      genes and bipolar illness. Actigraphic studies of activity levels have demonstrated
      illness-remission differences and phase advances in manic states. Though these latter studies
      employ more direct assessment methodologies, there are few articles that have attempted to
      investigate circadian processes in bipolar depression with the use of the core clock
      processes. These basic clock rhythms include core body temperature, cortisol levels and dim
      light melatonin onset. Because these physiological oscillations are less influenced by
      behavior and less prone to masking, they more accurately reflect the intrinsic timing of the
      central pacemaker.

      This study will use dim light melatonin onset and actigraphy to assess the status and changes
      in circadian phase between states of bipolar depression and their remission. Using a case
      control methodology, adult subjects will be evaluated during, and after remission from the
      depressive phase of bipolar disorder.

      General Aim

      The overall aim of this project is to compare the timing of dim-light melatonin onset and
      actigraphy-based activity patterns in adult patients with bipolar disorder in depressed vs
      remitted states. These markers will enable characterization of changes in circadian phase
      between illness and recovery. A case control design will enable the use of small sample sizes
      capable of identifying statistically significant changes in the timing of circadian rhythms
      in the two states of interest.

      Hypotheses

      It is predicted that the dim light melatonin onset and activity profile will be delayed in
      the depressed vs. the euthymic state of bipolar disorder. It is further anticipated that this
      phase delay will lessen when bipolar subjects achieve remission from their depression.

      Last, it is predicted that the circadian phase of the dim light melatonin onset and the
      activity profile will correlate, both being delayed in the depressive phase, and less delayed
      in euthymia.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Adults between 18 and 55 who are currently diagnosed with Bipolar Disorder.
      
Biospecimen description: 
      Saliva Samples
    
Keywords: Bipolar, Circadian, Melatonin