Synergistic effects of psychological and immune stressors on inflammatory cytokine and sickness responses in humans.

Activation of the innate immune system is commonly accompanied by a set of behavioural, psychological and physiological changes known as 'sickness behaviour'. In animals, infection-related sickness symptoms are significantly increased by exposure to psychosocial stress, suggesting that psychological and immune stressors may operate through similar pathways to induce sickness. We used a double-blind, randomised, placebo-controlled design to examine the effect of acute psychological stress on immune and subjective mood responses to typhoid vaccination in 59 men. Volunteers were assigned to one of four experimental conditions in which they were either injected with typhoid vaccine or saline placebo, and then either rested or completed two challenging behavioural tasks. Typhoid vaccine induced a significant rise in participants' serum levels of interleukin-6 (IL-6) and this response was significantly larger in the stress versus rest conditions. Negative mood increased immediately post-tasks, an effect also more pronounced in the vaccine/stress condition. In the vaccine/stress group, participants with larger IL-6 responses had heightened systolic blood pressure responses to tasks and elevated post-stress salivary levels of the noradrenaline metabolite 3-methoxy-phenyl glycol (MHPG) and cortisol. Our findings suggest that, as seen in animals, psychological and immune stressors may act synergistically to promote inflammation and sickness behaviour in humans.

Depressed mood, positive affect, and heart rate variability in patients with suspected coronary artery disease.

OBJECTIVE: To test associations between heart rate variability (HRV), depressed mood, and positive affect in patients with suspected coronary artery disease (CAD). Depression is associated with impaired HRV post acute cardiac events, but evidence in patients with stable coronary artery disease (CAD) is inconsistent. METHODS: Seventy-six patients (52 men, 24 women; mean age = 61.1 years) being investigated for suspected CAD on the basis of symptomatology and positive noninvasive tests, completed 24-hour electrocardiograms. The Beck Depression Inventory (BDI) was administered, and positive and depressed affect was measured over the study period with the Day Reconstruction Method (DRM). A total of 46 (60.5%) patients were later found to have definite CAD. HRV was analyzed, using spectral analysis. RESULTS: Typical diurnal profiles of HRV were observed, with greater normalized high frequency (HF) and lower normalized low frequency (LF) power in the night compared with the day. BDI depression scores were not consistently associated with HRV. But positive affect was associated with greater normalized HF power (p = .039) and reduced normalized LF power (p = .007) independently of age, gender, medication with beta blockers, CAD status, body mass index, smoking, and habitual physical activity level. In patients with definite CAD, depressed affect assessed using the DRM was associated with reduced normalized HF power and heightened normalized LF power (p = .007) independently of covariates. CONCLUSIONS: Relationships between depression and HRV in patients with CAD may depend on affective experience over the monitoring period. Enhanced parasympathetic cardiac control may be a process through which positive affect protects against cardiovascular disease.

Circadian rest-activity rhythm is altered in Parkinson's disease patients with hallucinations.

The sleep-wake cycle in Parkinson's Disease (PD) is profoundly disrupted, but less is known about circadian rhythm in PD and its relationship to other important clinical features. This study compared rest-activity rhythms in healthy older adults and PD patients with and without hallucinations. Twenty-nine older adults and 50 PD patients (27 with hallucinations, 23 without) were assessed using wrist-worn actigraphy for 5 days. Disease-related and cognitive data were also collected. PD patients demonstrated reduced amplitude of activity (F = 12.719, P < 0.01) and increased intradaily variability (F = 22.005, P < 0.001), compared to healthy older adults, independently of age, and cognitive status. Hallucinators showed lower interdaily stability (F = 7.493, P < 0.01) significantly greater activity during "night-time" (F = 6.080, P < 0.05) and significantly reduced relative amplitude of activity (F = 5.804, P < 0.05) compared to nonhallucinators, independently of clinical factors including motor fluctuations. PD patients with hallucinations display altered rest-activity rhythm characterized by an unpredictable circadian pattern across days, likely arising from damage to brainstem and hypothalamic sleep centers. Treatment of sleep and rest-activity rhythm disturbance is an important target in Parkinson's Disease.

Cortisol awakening response is elevated in acute coronary syndrome patients with type-D personality.

OBJECTIVE: Type-D or "distressed" personality and depression following admission for acute coronary syndrome (ACS) have been associated with poor clinical outcome. The biological pathways underpinning this relationship may include disruption of the hypothalamic-pituitary-adrenocortical (HPA) axis. We therefore assessed cortisol output in patients who had recently suffered from ACS. METHOD: Salivary cortisol was assessed eight times over a 24-h period in 72 patients within 5 days of admission for ACS. Depressive symptoms were measured with the Beck Depression Inventory (BDI), and type-D personality was measured with the Type-D Scale-16. Particular attention was given to cortisol awakening response (CAR), which was measured as the difference in cortisol between waking and peak responses 15-30 min later. RESULTS: Cortisol showed a typical diurnal pattern, with low levels in the evening, high levels early in the day, and CAR averaging 7.58+/-10.0 nmol/l. Cortisol was not related to the severity of ACS or underlying coronary artery disease or to BDI scores. The CAR was positively associated with type-D personality independently of age, gender, and body mass (P=.007). Linear regression showed that type-D personality accounted for 7.9% of the variance in CAR after age, sex, body mass, BDI, cortisol level on waking, and fatigue had been taken into account (P=.008). CONCLUSIONS: Type-D personality may be associated with disruption of HPA axis function in survivors of acute cardiac events and may contribute to heightened inflammatory responses influencing future cardiac morbidity.

Acute depressed mood as a trigger of acute coronary syndromes.

BACKGROUND: Some cases of acute coronary syndrome (ACS) may be triggered by emotional states such as anger, but it is not known if acute depressed mood can act as a trigger. METHODS: 295 men and women with a verified ACS were studied. Depressed mood in the two hours before ACS symptom onset was compared with the same period 24 hours earlier (pair-matched analysis), and with usual levels of depressed mood, using case-crossover methods. RESULTS: 46 (18.2%) patients experienced depressed mood in the two hours before ACS onset. The odds of ACS following depressed mood were 2.50 (95% confidence intervals 1.05 to 6.56) in the pair-matched analysis, while the relative risk of ACS onset following depressed mood was 4.33 (95% confidence intervals 3.39 to 6.11) compared with usual levels of depressed mood. Depressed mood preceding ACS onset was more common in lower income patients (p = .032), and was associated with recent life stress, but was not related to psychiatric status. CONCLUSIONS: Acute depressed mood may elicit biological responses that contribute to ACS, including vascular endothelial dysfunction, inflammatory cytokine release and platelet activation. Acute depressed mood may trigger potentially life-threatening cardiac events.

Frequency of distress and fear of dying during acute coronary syndromes and consequences for adaptation.

Experiencing an acute coronary syndrome (ACS) may provoke a range of negative emotional responses, including acute distress and fear of dying. The frequency of these emotional states has rarely been assessed. This study examined the presence and severity of the fear of dying and acute distress in 184 patients with ACS and analyzed its correlates and consequences. Intense distress and fear of dying was reported by 40 patients (21.7%) and moderate fear and distress by 95 patients (51.6%). Intense distress and fear was associated with female gender (odds ratio [OR] 2.49, 95% confidence interval [CI] 1.07 to 2.49), lower levels of education (OR 2.44, 95% CI 1.02 to 5.87), greater chest pain (OR 5.33, 95% CI 1.40 to 20.4), and emotional upset in the 2 hours before onset of ACS (OR 2.70, 95% CI 1.13 to 6.45). Having no acute distress or fear was more common in patients who exercised regularly (OR 3.32, 95% CI 1.35 to 8.18) and who did not initially attribute the chest pain to cardiac causes (OR 2.67, 95% CI 1.10 to 6.47). No association was found with cardiovascular disease history, objective measures of clinical severity, or with clinical presentation of ACS. Acute distress and fear of dying predicted greater depression and anxiety 1 week after ACS (p=0.006), and elevated levels of depression at 3 months (p=0.009), after adjustment for age, gender, and negative affect. In conclusion, distress and fear during the initial stages of an ACS may trigger subsequent depression and anxiety, thereby promoting poorer prognosis and greater morbidity with time.

Emotional face recognition deficits and medication effects in pre-manifest through stage-II Huntington's disease.

Facial emotion recognition impairments have been reported in Huntington's disease (HD). However, the nature of the impairments across the spectrum of HD remains unclear. We report on emotion recognition data from 344 participants comprising premanifest HD (PreHD) and early HD patients, and controls. In a test of recognition of facial emotions, we examined responses to six basic emotional expressions and neutral expressions. In addition, and within the early HD sample, we tested for differences on emotion recognition performance between those 'on' vs. 'off' neuroleptic or selective serotonin reuptake inhibitor (SSRI) medications. The PreHD groups showed significant (p<0.05) impaired recognition, compared to controls, on fearful, angry and surprised faces; whereas the early HD groups were significantly impaired across all emotions including neutral expressions. In early HD, neuroleptic use was associated with worse facial emotion recognition, whereas SSRI use was associated with better facial emotion recognition. The findings suggest that emotion recognition impairments exist across the HD spectrum, but are relatively more widespread in manifest HD than in the premanifest period. Commonly prescribed medications to treat HD-related symptoms also appear to affect emotion recognition. These findings have important implications for interpersonal communication and medication usage in HD.

Hostility and physiological responses to laboratory stress in acute coronary syndrome patients.

OBJECTIVE: Evidence suggests that emotional stress can trigger acute coronary syndromes in patients with advanced coronary artery disease (CAD), although the mechanisms involved remain unclear. Hostility is associated with heightened reactivity to stress in healthy individuals, and with an elevated risk of adverse cardiac events in CAD patients. This study set out to test whether hostile individuals with advanced CAD were also more stress responsive. METHODS: Thirty-four men (aged 55.9+/-9.3 years) who had recently survived an acute coronary syndrome took part in laboratory testing. Trait hostility was assessed by the Cook Medley Hostility Scale, and cardiovascular activity, salivary cortisol, and plasma concentrations of interleukin-6 were assessed at baseline, during performance of two mental tasks, and during a 2-h recovery. RESULTS: Participants with higher hostility scores had heightened systolic and diastolic blood pressure (BP) reactivity to tasks (both P<.05), as well as a more sustained increase in systolic BP at 2 h post-task (P=.024), independent of age, BMI, smoking status, medication, and baseline BP. Hostility was also associated with elevated plasma interleukin-6 (IL-6) levels at 75 min (P=.023) and 2 h (P=.016) poststress and was negatively correlated with salivary cortisol at 75 min (P=.034). CONCLUSION: Hostile individuals with advanced cardiovascular disease may be particularly susceptible to stress-induced increases in sympathetic activity and inflammation. These mechanisms may contribute to an elevated risk of emotionally triggered cardiac events in such patients.

Pre-hospital delay in patients with acute coronary syndrome: factors associated with patient decision time and home-to-hospital delay.

BACKGROUND: Pre-hospital delays in patients experiencing acute coronary syndromes (ACS) remain unacceptably long. AIMS: To examine simultaneously a wide range of clinical, sociodemographic and situational factors associated with total pre-hospital delay and its two components. METHODS: Pre-hospital delay data were collected from 228 patients with ACS using patient's medical notes and semi-structured interviews. Total pre-hospital delay (symptom onset to hospital admission) was divided into 2 components: decision time (symptom onset to call for medical help), and home-to-hospital delay (call for help to hospital admission). RESULTS: Shorter total pre-hospital delays and decision times were associated with ST segment myocardial infarction (STEMI), recognizing symptoms as cardiac in origin, being married, symptom onset outside the home and the presence of a bystander. Shorter home-to-hospital delays were more likely among younger patients, those experiencing an STEMI, and patients reporting a greater number of symptoms. Initial contact with emergency medical services was related to shorter total delays and decision times. CONCLUSIONS: Different factors were associated with shorter times in the 2 component phases. Greater understanding of the factors impacting on the component phases may help target interventions more effectively and reduce pre-hospital delays.

Causal beliefs, cardiac denial and pre-hospital delays following the onset of acute coronary syndromes.

Reducing pre-hospital delay is crucial in reducing mortality from acute coronary syndrome (ACS). Patient's causal beliefs and coping styles may affect symptom appraisal and help-seeking behavior. We examined whether patient's beliefs about the causes of their ACS and denial of impact were associated with pre-hospital delay. Pre-hospital delay data were collected from 177 patients with ACS. Retrospective causal beliefs and cardiac denial of impact were assessed using questionnaires. Factor analysis of causal beliefs produced 3 factors; beliefs in stress and emotional state, behavioral and clinical risk factors, and in heredity as causal influences. Patients with strong beliefs that stress and emotional state caused their ACS were more likely to have long pre-hospital delays (>130 min). There were no significant associations between pre-hospital delay and the other two causal belief factors. Patients with greater denial scores were also more likely to have long delays than those with low scores. These effects were independent of age, gender, education, previous myocardial infarction, history of depression and negative affectivity. Cognitive and emotional factors including patient's beliefs about causes and avoidant coping help to explain variations in pre-hospital delay.

Psychological and clinical predictors of return to work after acute coronary syndrome.

AIMS: Resumption of paid employment following acute coronary syndrome (ACS) is an important indicator of recovery, but has not been studied extensively in the modern era of acute patient care. METHODS AND RESULTS: A total of 126 patients who had worked before hospitalization for ACS were studied with measures of previous clinical history, ACS type and severity, clinical management, and sociodemographic characteristics. Depressed mood (Beck Depression Inventory) and type D personality were measured 7-10 days following admission. Among them, 101 (80.2%) had returned to work 12-13 months later. Failure to resume work was associated with cardiac factors on admission (heart failure, arrhythmia), cardiac complications during the intervening months, and depression scores during hospitalization. It was not related to age, gender, socioeconomic status, type of ACS, cardiac history, acute clinical management, or type D personality. In multivariate analysis, the likelihood of returning to work was negatively associated with depression, independently of clinical and demographic factors [adjusted odds ratio 0.90, CI 0.82-0.99, P=0.032]. CONCLUSION: Depressed mood measured soon after admission is a predictor of returning to work following ACS. The management of early depressed mood might promote the resumption of economic activity and enhance the quality of life of cardiac patients.

Patients' beliefs about the causes of heart disease: relationships with risk factors, sex and socio-economic status.

BACKGROUND: Patients' beliefs about the causes of their heart disease (causal attributions) are important to effective medical communication, psychological adaptation, and adherence to advice. We assessed the extent to which causal attributions relate to risk factors, sex and socio-economic status in men and women diagnosed with acute coronary syndrome. DESIGN: We conducted an interview and questionnaire study of 171 acute coronary syndrome patients assessed within 5 days of admission to three hospitals in the London area. METHOD: Patients rated beliefs in the role of 16 factors in causing their heart disease. Associations between attributions and risk factors were assessed, and differences in beliefs by sex and socio-economic status (defined by educational attainment) analysed. RESULTS: The most common attributions were to stress, smoking, high blood pressure, chance or bad luck, and heredity. Attributions were strongly associated with risk factors: 90% of smokers attributed heart disease to smoking, compared with 0% never smokers; 90.4% of hypertensives attributed heart disease to high blood pressure, 72.2% of patients with a positive family history to heredity, 85% of obese patients to being overweight, and 49% of sedentary patients to lack of exercise. Attributions to stress were related both to current mood and reports of recent life stress. There were few sex differences, but higher socio-economic status patients were more likely to attribute heart disease to heredity and genetic factors. CONCLUSIONS: Causal beliefs about heart disease are strongly associated with risk factors. Effective communication about modifiable risk factors may influence causal beliefs and stimulate lifestyle change, thereby promoting secondary prevention.

Pathophysiological processes underlying emotional triggering of acute cardiac events.

Acute negative emotional states may act as triggers of acute coronary syndrome (ACS), but the biological mechanisms involved are not known. Heightened platelet activation and hemodynamic shear stress provoked by acute stress may contribute. Here we investigated whether patients whose ACS had been preceded by acute anger, stress, or depression would show heightened hemodynamic and platelet activation in response to psychophysiological stress testing. We studied 34 male patients an average of 15 months after they had survived a documented ACS. According to an interview conducted within 5 days of hospital admission, 14 men had experienced acute negative emotion in the 2 h before symptom onset, and 20 men had not experienced any negative emotion. Hemodynamic variables and platelet activation were monitored during performance of challenging color-word interference and public speaking tasks and over a 2-h poststress recovery period. The emotion trigger group showed significantly greater increases in monocyte-platelet, leukocyte-platelet, and neutrophil-platelet aggregate responses to stress than the nontrigger group, after adjusting for age, body mass, smoking status, and medication. Monocyte-platelet aggregates remained elevated for 30 min after stress in the emotion trigger group. The emotion trigger group also showed poststress delayed recovery of systolic pressure and cardiac output compared with the nontrigger group. These results suggest that some patients with coronary artery disease may be particularly susceptible to emotional triggering of ACS because of heightened platelet activation in response to psychological stress, coupled with impaired hemodynamic poststress recovery.