Regional Brain Perfusion Is Associated with Endothelial Dysfunction Markers in Major Depressive Disorder

Abstract

Background: Major depressive disorder (MDD) is an important independent risk factor for cardiovascular disease. Cumulative data suggest that depressive patients exhibit derangement in regional cerebral blood flow (rCBF), although underlying mechanisms remain mostly unknown. Endothelial dysfunction (ED), defined as different forms of abnormal endothelial activity, plays a key role in the pathogenesis of vascular disease. ED is associated with several clinical conditions characterized by high cardiovascular risk. Diverse ED markers have been found in mood disorders. Purpose: To evaluate the association between rCBF and peripheral ED markers in MDD patients, at baseline and after selective serotonin receptor inhibitors (SSRIs) therapy. Patients and Methods: Twenty-seven untreated unipolar MDD patients in their first episode were evaluated with the Hamilton Depression Rating Scale (HAM-D) and brain perfusion SPECT at baseline and after 2 months of SSRIs. Statistical Parametric Mapping (SPM) was employed to evaluate rCBF; circulating endothelial cells (CECs), plasma soluble intercellular adhesion molecule (sICAM), and high-sensitivity C-reactive protein (hsCRP) were used as independent covariates. Results: Baseline CECs and sICAM were increased in MDD patients compared with matching controls (p = 0.0001) and hsCRP (p = 0.03). HAM-D scores (21 items) and CECs diminished after SSRI therapy in MDD patients (p < 0.0001). There was a significant rCBF decrease, mainly in deep central structures. HAM-D change was associated with rCBF decrease at the left amygdala, right striatum levels, and Brodmann area 25. CEC change was associated with rCBF at deep brain level and sICAM with large rCBF areas at the left caudate and tectum; hsCRP was associated, to a lesser extent, with the left dorsal striatum and mesencephalic tectum. Conclusion: ED markers in patients with MDD are associated with significant changes in rCBF which are features of depression. These findings suggest that systemic damage/activation of the endothelium may contribute to the abnormal rCBF observed in MDD patients.