Major Depressive Disorder - Understanding The Link Between The Brain And The Heart
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 4

Summary: 
      There is strong evidence that patients with major depressive disorder (MDD) have an increased
      risk of developing coronary heart disease (CHD). This elevated risk is independent of
      standard risk factors such as smoking, obesity, high cholesterol, diabetes, and high blood
      pressure. The relative risk of developing CHD is proportional to the severity of depression
      (the more severe the depression, the more likely the development of CHD).

      The sympathetic nervous system (the part of your nervous system that makes your heart beat
      harder and faster) is responsible for our "flight and fight" response to a threatening
      situation. It has been determined that increased sympathetic nervous system activation occurs
      in approximately one in three untreated patients with MDD (with no underlying CHD). There is
      growing evidence linking elevated sympathetic activity to early stages of kidney dysfunction
      and an increased incidence of cardiovascular (heart and blood vessel) disease development
      (eg, heart attacks). Sympathetic nervous system activation over a prolonged period of time
      may also be associated with abnormal blood pressure regulation and the development of insulin
      resistance (an important feature of type 2 diabetes).

      It has been suggested that a certain gene, known as the serotonin transporter (5-HTT) gene,
      may be involved. In particular, work from our group indicates that a particular type of this
      gene, the short form (or "short" allele) may be important in linking MDD, sympathetic nervous
      activation, and increased cardiac risk.

      This study aims to examine the role of the 5-HTT gene on cardiovascular risk factors
      associated with elevated sympathetic activity in patients with MDD. Additionally, the study
      will examine the effect of serotonin re-uptake inhibitor (SSRI) therapy on these parameters.

      A clearer understanding of these systems and processes will allow for identification of
      patients with increased cardiac risk and development of risk reduction strategies. Such
      information is clinically significant given the link between cardiovascular disease and MDD.

      Hypothesis 1: That MDD patients carrying the s allele of the 5-HTT transporter have higher
      sympathetic activity than homozygous ll patients.

      Hypothesis 2: that MDD patients with elevated sympathetic activity display early signs of
      left ventricular hypertrophy (LVH) and diastolic dysfunction.

      Hypothesis 3: That MDD patients with high sympathetic activity have greater morning surges in
      blood pressure than patients with normal sympathetic activity.

      Hypothesis 4: That MDD patients with elevated sympathetic activity display early signs of
      insulin resistance.

      Hypothesis 5: That SSRI therapy, in particular in those who carry the s allele of the 5-HTT,
      has a favourable effect on blood pressure variability and morning surge in blood pressure,
      sympathetic stress reactivity, and markers of insulin resistance.
    


Intervention name(s): Participants will be prescribed an approved selective serotonin re-uptake inhibitor (SSRI) antidepressant.
Intervention type(s): Drug
Intervention description(s): The choice of SSRI will be based on clinical judgement and prescribed in line with standard dosing approved by the Therapeutic Goods Administration (TGA).
Intervention MeSH terms: Antidepressive Agents; Serotonin; Selective Serotonin Reuptake Inhibitors
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Major depressive disorder; Serotonin transporter; Sympathetic nervous system activation; Cardiovascular risk factors; Serotonin re-uptake inhibitor