This study will investigate the biological pathways involved in anti-depressant resistance that increase risk of cardiovascular disease in people with depression.

Rationale: Depression is known to be associated with the development of cardiovascular disease and poorer prognosis after cardiac events, however the mechanisms that mediate these links are poorly understood. Inflammatory and neuroendocrine processes are thought to play an important role in this relationship. In addition, antidepressants have been shown to improve cardiac outcomes and have anti-inflammatory effects, whilst inflammation has been shown to be elevated in patients who do not respond to treatment. Several possible biomarkers for antidepressant resistance have also been demonstrated to be cardiovascular risk markers. These include acute phase inflammatory markers, such as interleukin-6 (IL-6), and hypothalamic-pituitary-adrenal axis (HPA) dysregulation.

Design: This will be conducted alongside a larger pharmacological trial, PANDA, where participants will be recruited from primary care and randomized to sertraline (SSRI) or placebo. The RESIST study will compare inflammatory cardiovascular risk factors between depressed patients taking sertraline, depressed patients taking placebo and healthy controls. This will be achieved by investigating the pharmacological effect of antidepressants on gene expression, glucocorticoid and mineralocorticoid receptor function and regulatory T cell (Treg) profiles.

Inclusion Criteria:

• Depressed patients:

  • Meet ICD10 criteria from the Clinical Interview Schedule-Revised (CIS-R)

Exclusion Criteria:

• Depressed patients:

  • Are taking any anti-inflammatory drugs or drugs which interfere with HPA-axis function, endothelial function, circadian rhythm or any other pathways under investigation
  • Unable to read, understand and/or complete questionnaires
  • Other psychiatric disorders: psychosis, schizophrenia, bipolar disorder, mania, hypomania, dementia, and eating disorder
  • Vulnerable adults

• Healthy controls:

  • Have a history of depression
  • Are taking any anti-inflammatory drugs or drugs which interfere with HPA-axis function, endothelial function or circadian rhythm or any other pathways under investigation
  • Unable to read, understand and/or complete questionnaires
  • Other psychiatric disorders: psychosis, schizophrenia, bipolar disorder, mania, hypomania, dementia, and eating disorder
  • Vulnerable adults

Depressed patients will be recruited from the PANDA trial. Healthy controls will be recruited from primary care.