SPECT evaluation of regional cerebral blood flow in major depressive disorder: Effect of therapy and relationship with endothelial dysfunction markers

Objectives Patients with major depression are usually treated with selective serotonin reuptake inhibitors(SSRIs)and could exhibit abnormal regional cerebral blood flow (rCBF) that is not fully understood. In a preliminary study we demonstrated that decreased rCBF is weakly associated with increased endothelial dysfunction (ED) via circulating endothelial cells (CECs) and soluble Intercellular Cell Adhesion Molecule (sICAM). The goal was to evaluate the effect of SSRIs therapy on rCBF and its association with ED markers in major depression.

Methods We included 31 untreated unipolar depressive patients (age 37.5±11 y.o.; 81% females) studied with 99mTc-ECD brain SPECT at baseline and 2 month post SSRIs therapy. We measured diminished rCBF extension and intensity (normal cutoff= 66% of maximal) and applied SPM5 software for group analysis comparison. We determined CECs and plasmatic sICAM at baseline and post-treatment. Hamilton scores (HAMD) were used to evaluate clinical response.

Results Global rCBF decrease was observed in all patients without significant frontal or prefrontal change post-therapy. Initial HAMD positively correlated with sICAM (r:0.617; p=0.01). Post therapy frontal cortex rCBF correlated with HAMD (r:0.40; p=0.015). Global brain rCBF at 2 months was also correlated with initial CECs (r:0.37; p=0.037). SPM5 demonstrated a significant and positive association in rCBF decrease in left amygdala, Brodmann area 25 and right striatum with HAMD and sICAM changes.

Conclusions We demonstrated association between ED markers, mood scores and brain perfusion in major depression. Abnormal rCBF and ED persist after 2 month therapy with adequate clinical response.

Research Support Grant 240/07 HCUC

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