Neurocardiac Control in Major Depression
Condition: Depression, Involutional
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Observational

Summary: 
      This study will examine how depression may influence the way the brain regulates heart
      function. Some researchers believe that depression may be a risk factor for some forms of
      heart disease.

      Right-handed healthy volunteers and patients with major depressive disorder who are between
      18 and 50 years of age may be eligible for this study. Female candidates must be
      premenopausal. Patients must currently be experiencing a major depressive episode. All
      candidates are screened with a medical history and physical examination, electrocardiogram,
      and blood and urine tests. They are interviewed about their psychiatric and medical history,
      current emotional state and sleep pattern, and family history of psychiatric disorders. They
      complete symptoms ratings scales for depression, anxiety, and negative thinking; history of
      alcohol and tobacco use; level of physical activity; socioeconomic status; overall level of
      functioning; and, for depressed patients, their depression type. Women candidates have their
      menstrual phase determined by the timing of their recent menstrual cycles and may undergo
      testing to determine the time of their ovulation.

      Participants undergo the following tests and procedures:

        -  12-minute walk/run test - This test measures the subject's general level of
           cardiorespiratory fitness. In a gymnasium in the NIH Clinical Center, the subject walks
           or runs as far as he or she can in 12 minutes. Blood pressure is measured before and
           after the exercise test, and heart rate is measured during exercise with a monitor worn
           around the chest.

        -  Magnetic resonance imaging (MRI) - A brain MRI scan is done to obtain pictures of the
           brain anatomy. Electrocardiogram leads are placed on the subject's chest to measure the
           electrical activity of the heart during the scanning session. The subject lies on a
           narrow bed in the scanner, which is a narrow metal cylinder about 6 feet long. The
           scanning session takes up to 90 minutes.

        -  Positron emission tomography (PET) - PET scanning produces images of the brain's blood
           flow. The subject is injected with a radiotracer (small amount of drug labeled with a
           radioactive substance) that is detected by a special camera to trace blood flow. During
           the scanning session, the subject lies still on a table. EKG leas are placed on the
           subject's chest to measure the electrical activity of the heart during the scan. A mask
           with holes for the eyes, ears, and mouth is placed over the subject's face to keep the
           head f...
    

Detailed description: 
      The presence of major depression, with or without pre-existing coronary artery disease,
      predicts increased mortality from myocardial infarction (MI) and sudden cardiac death (SCD).
      Decreased parasympathetic vagal outflow, especially in the presence of elevated cardiac
      sympathetic tone, has been proposed as a mechanism for the increased risk of SCD. Multiple
      lines of evidence suggests that fronto-limbic areas are actively engaged in the robust
      optimization of autonomic balance between sympathetic and parasympathetic cardiac outflow
      over a broad range of cognitive and physical demands. We propose that dysfunction of these
      forebrain neurocardiac networks in MDD mediates maladaptive cardiac autonomic control and the
      increased risk of cardiovascular mortality. In this model, neurocardiac control networks
      exhibit a systemic bias toward increased sympathetic relative to parasympathetic outflow.
      Increased amygdalar activity in MDD will promote this imbalance. Additionally, dysfunction in
      posterior orbitofrontal cortex (OFC) and ventral anterior cingulated cortex (ACC), areas
      associated with abnormal histopathological changes in MDD, will lead to reduced capacity for
      generating adaptive levels of cardioinhibitory, parasympathetic tone. This reduced capacity
      in depressives will be evidenced by abnormally large withdrawals of parasympathetic outflow,
      compared to healthy controls, as cognitive or physical demands increase. This dynamic model
      is potentially consistent with functional neuroimaging and post mortem histopathological
      findings in MDD and the knowledge gained through testing this protocol may ultimately
      elucidate how brain dysfunction in MDD mediates significantly increased clinical risk of
      spontaneous ventricular arrhythmias and sudden cardiac death.

      We propose to combine H (2) (15) O positron emission tomography (PET) and analysis of heart
      rate variability (HRV) in order to study in vivo the neural structures underlying normal
      forebrain control of cardiac autonomic function. We further aim to show whether regional
      functional abnormalities in amygdala, ventral anterior cingulate cortex, and orbitofrontal
      cortex-areas in which functional abnormalities have been identified in previous neuroimaging
      studies of major depressives-are associated with impaired modulation of cardiac autonomic
      function during major depression.
    

Keywords: PET; Heart Rate Variability; N-Back Task; Isometric Handgrip; MRI; Depression; MDD; Heart