Major Depressive Disorder - Understanding The Link Between The Brain And The Heart

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.

Conditions

• Major Depressive Disorder

Interventions

DRUG

Participants will be prescribed an approved selective serotonin re-uptake inhibitor (SSRI) antidepressant.

The choice of SSRI will be based on clinical judgement and prescribed in line with standard dosing approved by the Therapeutic Goods Administration (TGA).

Sponsors & Collaborators

• The Alfred

  collaborator OTHER

• Monash Medical Centre

  collaborator OTHER

• Ballarat Health Services

  collaborator OTHER

• Baker Heart and Diabetes Institute

  lead OTHER

Principal Investigators

• Gavin Lambert · Baker IDI Heart & Diabetes Institute

• David Barton · Monash Medical Centre

• Abdul Khalid · Ballarat Health Services

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-05-31

Primary Completion

2020-12-31

Completion

2020-12-31

Countries

• Australia

Study Locations