title: A novel neurological mechanism to explain the adverse effect of depression on coronary artery disease.
abstract: The strong antecedent effect of depression as a risk factor in the development of coronary artery disease (CAD) has been demonstrated in many robust epidemiological studies. However, the underlying causative mechanisms are incompletely understood: this hypothesis proposes one possibility. A variety of histological and radiological techniques have been used to demonstrate structural and functional abnormalities in the prefrontal cortex (PFC) of depressed subjects. In addition, this limbic region has been inextricably implicated in the modulation of autonomic tone. Cardio-specifically, stimulation of PFC has arrhythmogenic effects. Reciprocally, cardiac stress tests produce activation of this cortical region. These observations place PFC at the top of a hierarchical autonomic loop involved in sensing and modulating cardiac variables. Finally, the reduced heart rate variability, higher heart rates and elevated cerebrospinal fluid catecholamine levels in depressed patients, compared to non-depressed matched controls, suggest sympathetic overdrive in these patients. These observations lead the author to propose that a primary defect in the PFC of depressed subjects destabilises the autonomic neurocardiac axis, accounting for the proven adverse effect of depression on CAD. This novel neurological mechanism can help to develop other current theories and to design and trial future therapies to reduce the adverse effect of depression on coronary artery disease.
authors.affiliation: University of Oxford and John Radcliffe Hospital, Oxford OX3 9DU, UK. saroshirani@doctors.org.uk
authors.forename: Sarosh R
authors.initials: SR
authors.lastname: Irani
mesh_terms: D003324:Coronary Artery Disease / Q000209:etiology* / Q000503:physiopathology*; D003863:Depression / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012307:Risk Factors; D013564:Sympathetic Nervous System / Q000503:physiopathology*