The Neurobiology of Depressive Illness

Official Title: “The Neurobiology of Depressive Illness: Causes and Consequences of Altered Brain Monoaminergic Function”

We aim to determine why patients with depression are at an elevated risk for the development of coronary heart disease, and resolve whether the severity of a patient's depression has a counterpart in demonstrable abnormalities in brain chemistry. Studies will be completed in 28 patients with depression; both males and females. Patients will be studied both untreated and during administration of a selective serotonin re-uptake inhibitor (SSRI) antidepressant. They will be either newly diagnosed with depression, untreated patients suffering a recent relapse, or patients seeking to switch from a non-SSRI antidepressant due to non-response. The turnover of chemical messengers in the brain will be estimated by high internal jugular venous blood sampling and DNA will be isolated and examined from blood cells. Immune function will also be assessed. Whole body and cardiac sympathetic nervous activity will be determined, as well as microneurographic recording of muscle sympathetic nervous activity.

It is hypothesised that patients with depression and no existing demonstrable cardiac disease demonstrate:

Alterations in brain monoaminergic neurotransmitter turnover, resulting in sympathetic nervous activation and dysregulation of the baroreflex control to both the heart (vagal) and muscle vasoconstrictor sympathetic nerves; and Exhibit enhanced platelet reactivity predisposing them to thrombogenesis and myocardial ischaemia.

Therapeutic intervention with an SSRI will modify cardiac sympathetic function, baroreflex sensitivity or platelet reactivity in a fashion likely to reduce cardiac risk.

Intervention(s) in this Clinical Trial

• Drug: antidepressants primarily selective serotonin reuptake inhibitors
  • normal clinical dosages used according to clinical response as determined by a psychiatrist

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: intervention
  • there is no sham or placebo control arm It is a single arm study

Primary Measures

• level of sympathetic nervous system activity and its response to treatment
  • Time Frame: 12 weeks
    Safety Issue?: No

Secondary Measures

• clinical response to treatment
  • Time Frame: 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• Major depression

Exclusion Criteria:

• heart disease diabetes hypertension psychosis significant suicidal risk dementia

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Baker Heart Research Institute Other

Overall Clinical Trial Officials and Contacts

Murray A Esler, MBBS Phd Principal Investigator Baker Heart Research Insitute  

Overall Contact: David A Barton, MBBSFRANZCP 61393428946 david.barton@bigpond.com

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00168493

Study ID Number: NHMRC D-01

ClinicalTrials.gov Identifier: NCT00168493

Health Authority: Australia: National Health and Medical Research Council