The Neurobiology of Depressive Illness

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.

Inclusion Criteria: Major depression Exclusion Criteria: heart disease diabetes hypertension psychosis significant suicidal risk dementia

Keating C, Dawood T, Barton DA, Lambert GW, Tilbrook AJ. Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder. BMC Psychiatry. 2013 Apr 29;13:124. doi: 10.1186/1471-244X-13-124.