Cerebrovascular Dysfunction is Related to Depressive Symptom Severity in Young Adults

Cerebral vasodilatory responsiveness is blunted in older adults (~70 yrs) with depressive disorders and is 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 present and graded in relation to the severity of depressive symptoms; however, to date, limited investigations have examined cerebral vasodilatory function in young otherwise healthy adults with MDD. PURPOSE: We tested the hypothesis that cerebral vasodilatory responsiveness to a hypercapnic stimulus would be blunted in young otherwise healthy adults with MDD compared to healthy non-depressed adults (HA). Further, we hypothesized, that the magnitude of impairment in cerebrovascular function would be related to depressive symptom severity. METHODS: Ten HA (7 women; 22±2yrs) and 10 adults with MDD (8 women; 22±2yrs; n=5 tested during a major depressive episode) participated. Depressive symptom severity was evaluated with the Patient Health History Questionnaire-9 (PHQ-9) in both HA and adults with MDD. Beat-to-beat mean arterial pressure (MAP; finger photoplethysmography), middle cerebral artery blood velocity (MCAv; transcranial 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) was calculated at baseline and at the highest common magnitude of hypercapnia achieved by all subjects during rebreathing (∆PETCO2 = 9 Torr). RESULTS: At baseline, there were no differences in MAP or CVCi between groups (both p\u3e0.05). During hypercapnia, there were no group differences in the increase in MAP (∆3±3 HA vs. ∆4±3 mmHg MDD; p=0.78). Further, neither the hypercapnia-induced increase in MCAv (∆29±7 HA vs. ∆26±8 cm•s-1 MDD; p=0.37) nor the increase in CVCi (∆39±12 HA vs. ∆30±12 %baseline MDD; p=0.13) were different between groups. However, greater severity of depressive symptoms was negatively related to cerebral vasodilatory responsiveness (R2=0.219, p=0.04). CONCLUSION: These preliminary data suggest that cerebral vasodilatory responsiveness to hypercapnia is not impaired in young adults with MDD, despite a negative relation between depressive symptom severity and the magnitude of hypercapnia-induced cerebral vasodilation

The Relation Between Cognitive Function and Cerebral Vasodilatory Reactivity in Young Adults with Major Depressive Disorder

Major depressive disorder (MDD) has been associated with an elevated risk of developing neurocognitive diseases (e.g., dementia). Although the precise neurobiological mechanisms remain incompletely understood, cerebrovascular dysfunction is thought to directly contribute, at least in part, to impairments in cognitive function. Cerebral vasodilatory reactivity to a hypercapnic stimulus is blunted in older adults with MDD compared to age-matched non-depressed adults. Further, impaired cerebral vasodilation has been linked to reduced cognitive activity in older adults with depression. However, to date, limited studies have examined the relation between cognitive function and cerebrovascular function in otherwise healthy young adults with MDD. PURPOSE: We tested the hypothesis that greater hypercapnia-induced cerebral vasodilation would be related to greater fluid cognitive ability (i.e., the capacity to process and integrate new information) in young adults with MDD. METHODS: Ten adults with MDD (non-medicated; age: 22±2 yrs: body mass index: 22.8±4.5 kg/m2; education level: all enrolled in a four-year university) participated. Cognitive function was assessed via the NIH Toolbox Cognitive Function Battery (iPad). A composite fluid cognitive ability score was derived from the specific tests within the battery that measure fluid ability [e.g., Flanker, Dimensional Change Cart Sort (DCCS)]; an age-correct standard T-score of 100 indicates ability that is average compared with national data. Beat-to-beat mean arterial pressure (MAP; finger photoplethysmography), middle cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound), and end-tidal carbon dioxide concentration (PETCO2; capnograph) were continuously measured during normocapnic baseline and during rebreathing-induced hypercapnia. The hypercapnia-induced (∆PETCO2=9 mmHg) increase in cerebral vascular conductance index (∆CVCi=MCAv/MAP) was used as an index of cerebral vasodilatory reactivity. RESULTS: Hypercapnia elicited an increase in CVCi in all subjects (mean: 30±12%; range: 18-60%). The age-corrected composite fluid cognitive ability standard score was 100±15 (range: 79-119). The increase in CVCi was not related to fluid cognitive ability (slope=-0.12±0.3; r2=0.02, p=0.67). In addition, the increase in CVCi was not related to either the age-corrected standard score for the Flanker task (slope=-0.38±0.4; r2=0.12, p=0.32) or for the DCCS task (slope=0.09±0.3; r2=0.02, p=0.72), both of which specifically measure executive function. CONCLUSION: These preliminary data suggest that cerebral vasodilatory reactivity to a hypercapnic stimulus is not related to fluid cognitive function in otherwise healthy college-aged adults with MDD

Effect of Acute Heat Exposure on the Pressor Response to a Voluntary Hypoxic Apnea: A Cross-tolerance Study

The pressor response induced by a voluntary hypoxic apnea is exaggerated in individuals with obstructive sleep apnea and is strongly correlated to sympathetic overactivity. Acute heat exposure alters neural control of blood pressure, but its effect on the pressor response to a voluntary hypoxic apnea has never been explored. PURPOSE: To test the hypothesis that acute heat exposure attenuates the pressor response to a voluntary hypoxic apnea, and thereby manifest as a form of physiological cross-tolerance. METHODS: Eight adults (3 females, 26 ± 2 yrs) were exposed to passive heat stress (water perfused suit) sufficient to increase body core temperature by 1.2 °C. Voluntary hypoxic apneas were performed in duplicate before acute heat exposure (pre-heat) and in recovery when body core temperature returned to ≤ 0.3 °C of baseline. Participants breathed gas mixtures of varying FiO2 (21%, 16%, and 12%; randomized) for 1 min followed immediately by a 15 s end-expiratory apnea. Beat-by-beat arterial blood pressure (Finometer) and arterial oxygen saturation (finger pulse oximetry) were measured throughout. The pressor response was calculated as the difference between baseline mean arterial pressure and the peak response following each apnea. RESULTS: The change in arterial oxygen saturation during each apnea did not differ from pre-heat to recovery (FiO2 21%, pre-heat 0 ± 1 % vs. recovery 0 ± 2 %; FiO2 16%, pre-heat -4 ± 1 % vs. recovery -4 ± 2 %; FiO2 12%, pre-heat -8 ± 3 % vs. recovery -10 ± 4 %; P = 0.3 for interaction). The pressor response to a voluntary apnea was attenuated in recovery from acute heat exposure across all concentrations of FiO2 (FiO2 21%, pre-heat 19 ± 8 mmHg vs. recovery 16 ± 8 mmHg; FiO2 16%, pre-heat 27 ± 8 mmHg vs. recovery 20 ± 8 mmHg; FiO2 12%, pre-heat 33 ± 11 mmHg vs. recovery 27 ± 13 mmHg; P = 0.02 for main effect of time). CONCLUSION: These data suggest that acute heat exposure induces a cross-tolerance effect such that the pressor response to a voluntary hypoxic apnea is reduced. Acute heat exposure could improve hypertension in adults with obstructive sleep apnea, secondary to altered chemoreflex function and sympathetic neural control, and provide additional therapeutic options for this population to improve cardiovascular health

Similarities in Vasoconstrictor Responsiveness to Exogenous Norepinephrine in the Cutaneous Circulation Between Young Black and White Men

Black (BL) men have an increased risk of hypertension and CVD compared to white (WH) men which is partially related to vascular dysfunction. In particular, elevated vascular resistance and increased sympathetic vascular transduction (SVT; greater constrictor and blood pressure responses for a burst of sympathetic nerve activity) may be a contributing factor. Previous reports indicate that BL men have exaggerated responses to a variety of stressors including cold pressor, orthostasis, and exercise; while also exhibiting increased SVT at rest. Additionally, rodent models indicate that oxidative stress contributes to heightened SVT. For example, hypertensive rats have elevated SVT which is attenuated following ascorbic acid (AA) administration such that the responses are similar to normotensive control rats. Additionally, administration of L-NAME; a nitric oxide synthase (NOS) inhibitor augments the constrictor response in healthy rats to the level of the hypertensive rats. These data suggest that oxidative stress and nitric oxide (NO) bioavailability may play a critical role in the heightened SVT in BL men. PURPOSE: To test the hypothesis that, BL men exhibit greater vasoconstrictor response to norepinephrine (NE; non-selective α-adrenoreceptor agonist) relative to WH men and exhibit a reduction in response with the administration of AA. METHODS: Four intradermal microdialysis membranes were inserted into the left forearm of 7 BL men and 6 WH men (mean ± SD; age: 22 ± 2 vs. 25 ± 4, respectively). Following 60-min of trauma resolution, each site was infused at a rate of 2µL/min with either lactated Ringer’s (control), AA (10mM), L-NAME (20mM) and a combination of AA+L-NAME (10mM and 20mM) for 30-min. After, local heaters were turned on to 33℃ for 10-min to reach a baseline skin blood flow. NE (100mM) was then co-administered at each site for 6-min. The response is presented as a percent reduction in cutaneous vascular conductance (CVC; flux/mean arterial pressure) from baseline (%CVCB). RESULTS: Following the administration of NE, BL and WH men exhibited a similar magnitude of vasoconstriction at all sites (control: -81.7± 8.2 vs. -76.8± 14.9%CVCB, AA: -82.0± 27.0 vs. -54.8 ± 67.0%CVCB, L-Name: -65.6 ± 17.1 vs. -66.7 ± 23.9%CVCB, AA +L-NAME:-78.2± 7.6 vs. -64.9 ± 16.0%CVCB ; p \u3e0.05). CONCLUSION: Contrary to our hypothesis, there appears to be no difference in the constrictor response between BL men and WH men and that oxidative stress and NO do not seem to play a role in this response