Using narrower definitions of melancholia, i.e. CORE and (in particular) Newcastle, melancholic patients were impaired on mnemonic tasks and tasks of selective attention, and set-shifting while non-melancholic subjects were largely unimpaired in their cognitive performance. These differences may be due to impairment of specific neuroanatomical regions in narrowly defined melancholic patients, in particular the anterior cingulate.

OBJECTIVE Stress and depressive symptoms have been associated with impaired endothelial function as measured by brachial artery flow-mediated dilation (FMD), possibly through repeated and heightened activation of the sympathetic nervous system (SNS). Behavioral correlates of depression, such as satisfaction with leisure activities (i.e., leisure satisfaction), may also be associated with endothelial function via their association with depressive symptoms. This study examined the longitudinal associations between stress, depressive symptoms, leisure satisfaction, and endothelial function as measured by FMD. METHODS Participants were 116 elderly Alzheimer’s caregivers (mean age = 74.3 ± 8.1; 68% female; 87% Caucasian) who underwent three yearly assessments of FMD, stress, depressive symptoms, and leisure satisfaction. Mixed regression analyses were used to examine longitudinal relationships between constructs of interest. RESULTS A significant and positive association was found between leisure satisfaction and FMD (p = .050), whereas a negative relationship was found for stress (p = .017). Depressive symptoms were not associated with FMD (p = .432). Time (p < .001) and the number of years caregiving (p = .027) were also significant predictors of FMD, suggesting that FMD decreased over time and was worse the longer a participant had been a caregiver prior to study enrollment. CONCLUSIONS These results suggest that behavioral correlates of depression (i.e., engagement in pleasurable activities) may be related to endothelial function in caregivers, and behavioral treatments for depression may be particularly useful in improving cardiovascular outcomes in caregivers.

Objectives We examined the relationship between chronic caregiving stress and endothelial function. Background Evidence suggests that caregiving stress is associated with pathophysiologic processes related to atherosclerosis. Endothelial dysfunction is a possible underlying mechanism explaining the relationship between caregiving stress and cardiovascular morbidity. We investigated the relationship between chronic caregiving stress and endothelial dysfunction assessed by reactive hyperemia induced flow-mediated dilation (FMD). Methods Seventy eight elderly individuals participated in the study. Fifty-five were providing in-home care to a spouse with Alzheimer’s disease (AD) and 23 were married and living with a healthy, non-demented spouse. ANCOVA was used to examine relations between advancing dementia severity (Clinical Dementia Rating scores) and FMD and nitroglycerine-induced vasodilation of the brachial artery. Multiple linear regression was used to examine the relationship between years of caregiving and FMD. Results Clinical Dementia Rating (CDR) scores were significantly related to FMD (p = 0.033) with participants caring for a spouse with moderate-to-severe dementia showing significantly worse FMD than those caring for a spouse with mild dementia (p = 0.028) and non-caregivers (p = 0.032). Within the caregiver sample, years of caregiving was significantly related to FMD (r = −.465, p < .001). Conclusions These results suggest that the chronic stress of caregiving is associated with impaired endothelial function, which may be a potential mechanistic link between the observed increased risk for cardiovascular disease in elderly caregivers.

Epinephrine is the prototypical stress hormone. Its stimulation of all α and β adrenergic receptors elicits short-term systolic hypertension, hyperglycemia, and other aspects of the metabolic syndrome. Acute epinephrine infusion increases cardiac output and induces insulin resistance, but removal of the adrenal medulla has no consistent effect on blood pressure. Epinephrine is the most effective endogenous agonist at the β2 receptor. Transgenic mice that cannot make epinephrine and mice that lack the β2 receptor become hypertensive during exercise, presumably owing to the absence of β2-mediated vasodilatation. Epinephrine-deficient mice also have cardiac remodeling and poor cardiac responses to stress, but do not develop resting hypertension. Mice that cannot make epinephrine have a normal metabolism on a regular 14% fat diet but become hyperglycemic and insulin resistant when they eat a high fat diet. Vigorous exercise prevents diabetes in young mice and humans that overeat. However, exercise is a less effective treatment in older type 2 human diabetics and had no effect on glucose or insulin responses in older, diabetic mice. Sensitivity of the β2 receptor falls sharply with advancing age, and adrenal epinephrine release also decreases. However, treatment of older diabetic mice with a β2 adrenergic agonist improved insulin sensitivity, indicating that β2 subsensitivity can be overcome pharmacologically. Recent studies show that over the long term, epinephrine prevents hypertension during stress and improves glucose tolerance. The hyperglycemic influence of epinephrine is short-lived. Chronic administration of epinephrine and other β2 agonists improves cellular glucose uptake and metabolism. Overall, epinephrine counteracts the metabolic syndrome.

Objective To examine the impact of mood states on endothelial function, as measured noninvasively by brachial artery flow-mediated dilation (FMD). Substantial literature indicates that negative mood is linked to cardiovascular disease (CVD). However, the mechanisms underlying this relationship are not well defined. CVD is often preceded by dysfunction of the endothelium. Methods Healthy adults (n = 70; mean age, 36 years) completed the Profile of Mood States (POMS), which contains six subscales (depression/dejection; tension/anxiety; anger/hostility; confusion/bewilderment; fatigue/inertia; vigor/activity) that are used to compute a total mood disturbance score for overall psychological distress. FMD was calculated (maximum percentage change in brachial artery diameter) from ultrasound assessment of arterial diameter at baseline and for 10 minutes after occlusion. Results Regressions showed that increases in POMS total mood disturbance scores were associated with decreases in endothelial function. Mood disturbance explained 10% of the variance in FMD (p < .01), after controlling for age, sex, mean arterial pressure, body mass index, and socially desirable response bias. An exploratory set of separate regressions conducted to decompose the link between FMD and total mood disturbance revealed that the following POMS subscales were inversely correlated with FMD: depression/dejection, tension/anxiety, anger/hostility, fatigue/inertia (p’s < .05), and confusion/bewilderment (p < .01). Conclusions Mood disturbance could contribute to CVD via impaired vasodilation. These preliminary results show that even mild levels of adverse psychological states, particularly depressed, anxious, angry, confused, and fatigued states, might be linked to increased cardiovascular risk.