Cerebrovascular Reactivity in Young Adults with Major Depressive Disorder

Abstract

Cerebral vasodilatory responsiveness is blunted in older adults (~70 yrs) with depressive disorders and thought to contribute to the link between depressive symptomology and increased risk for neurocognitive (e.g., dementia) and cerebral vascular (e.g., stroke) diseases. In young adults with major depressive disorder (MDD), peripheral vascular endothelial dysfunction is evident; however, to date, limited investigations have examined cerebral vasodilatory function in young otherwise healthy adults with MDD. We tested the hypothesis that cerebral vasodilatory responsiveness to a hypercapnic stimulus would be blunted in otherwise healthy young adults with MDD compared to healthy non‐depressed adults (HA). Four HA (22±2yrs) and 6 adults with MDD (23±2yrs; n=2 tested during a major depressive episode) participated. Beat‐to‐beat mean arterial pressure (MAP; finger photoplethysmography), middle cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound), internal carotid artery (ICA) diameter and blood flow (Doppler ultrasound), and end‐tidal carbon dioxide concentration (PETCO2; capnograph) were continuously measured during baseline (i.e., normocapnia) and rebreathing‐induced hypercapnia. Cerebral vascular conductance index (CVCi=MCAv•MAP−1) and ICA blood flow (Vmean•π(d•20−1)2•60) and conductance (CVC=ICA blood flow•MAP−1) were calculated at baseline and at the highest common magnitude of hypercapnia achieved by all subjects during rebreathing (ΔPETCO2 = 9 Torr). At baseline, there were no differences in any outcome variable between groups (all p>0.05). During hypercapnia, there were no group differences in the increase in MAP (Δ3±3 HA vs. Δ3±4 mmHg MDD; p=0.98). The increase in MCAv was blunted in adults with MDD (Δ33±4 HA vs. Δ23±7 cm•s−1 MDD; p=0.03). Both the absolute (Δ0.30±0.02 HA vs. Δ0.20±0.07 cm•s−1•mmHg−1 MDD; p=0.01) and relative (Δ42±7 HA vs. Δ26±9 %baseline MDD; p=0.01) increase in CVCi during hypercapnia were reduced in adults with MDD. There were no group differences in ICA diameter (Δ−0.04±0.22 HA vs. Δ0.05±0.17 mm MDD; p=0.51) or blood flow responses (Δ143±20 HA vs. Δ127±95 mL•min−1 MDD; p=0.49). Although the dilatory response in the ICA was ~50% less in adults with MDD, the increase in CVC was not significantly different between groups (Δ51±26 HA vs. Δ27±22 %baseline MDD; p=0.17). In adults with MDD, there was no relation between habitual physical activity and cerebral vasodilatory responsiveness (R2=0.09; p=0.57). These preliminary data suggest that cerebral vasodilatory reactivity to a hypercapnic stimulus may be blunted in young otherwise healthy adults with MDD, providing further support for the potential mechanistic link between cerebrovascular dysfunction and depression in increased neurocognitive and cerebral vascular disease risk.Support or Funding InformationHL133414 (JLG)