Psychosocial stress, interpersonal sensitivity, and social withdrawal in clinical high risk for psychosis: a systematic review.

Stress has repeatedly been implicated in the onset and exacerbation of positive symptoms of psychosis. Increasing interest is growing for the role of psychosocial stress in the development of psychosis symptoms in individuals at Clinical High Risk (CHR) for psychosis. A systematic review was therefore conducted to summarize the existing evidence base regarding psychosocial stress, interpersonal sensitivity, and social withdrawal in individuals at CHR for psychosis. An electronic search of Ovid (PsychINFO, EMBASE, MEDLINE, and GLOBAL HEALTH) was conducted until February 2022. Studies that examined psychosocial stress in CHR were included. Twenty-nine studies were eligible for inclusion. Psychosocial stress, interpersonal sensitivity, and social withdrawal were higher in CHR individuals compared to healthy controls and there was some evidence of their association with positive symptoms of psychosis. Two types of psychosocial stressors were found to occur more frequently with CHR status, namely daily stressors, and early and recent trauma, while significant life events did not appear to be significant. Greater exposure to psychosocial stress, emotional abuse, and perceived discrimination significantly increased risk of transition to psychosis in CHR. No studies examined the role of interpersonal sensitivity on transition to psychosis in CHR. This systematic review provides evidence for the association of trauma, daily stressors, social withdrawal, and interpersonal sensitivity with CHR status. Further studies investigating the impact of psychosocial stress on psychosis symptom expression in individuals at CHR and its effects on transition to psychosis are therefore warranted.

The association between psychosocial stress, interpersonal sensitivity, social withdrawal and psychosis relapse: a systematic review.

Psychosis is associated with a high risk of relapse, with 67% of clients relapsing within one year following a first episode. In light of the high personal, social, and healthcare costs of the illness, it is paramount to understand the risk factors associated with psychosis relapse. The current systematic review aims to critically review the role of psychosocial stress in psychosis relapse in individuals with an established psychotic disorder. This review systematically searched Ovid (PsycINFO, EMBASE, MEDLINE) literature databases from inception until 28th February 2022. Sixteen studies were eligible for inclusion. Most studies found that individuals with psychosis demonstrate high levels of psychosocial stress and are more likely to be socially withdrawn compared to healthy controls or other clinical presentations. Most studies reported a statistically significant association between psychosocial stress and psychosis relapse, as well as between social withdrawal and psychosis relapse. However, no studies examined the association between high levels of interpersonal sensitivity and psychosis relapse. Individuals with psychosis tend to experience high levels of psychosocial stress and social withdrawal, and these appear to increase the risk of psychosis relapse. Due to high levels of heterogeneity within the literature, we could only conduct a narrative synthesis of the findings. Future studies would benefit from employing a meta-analytic approach.

Trait anxiety and glucose metabolism in people without diabetes: vulnerabilities among black women.

AIMS: We examined whether the relationship between anxiety and indicators of glucose metabolism in people without diabetes varies by race and gender. METHODS: Participants were 914 adults (777 white, 137 black) without diabetes in the MIDUS (Midlife in the USA) II study. Glucose metabolism was characterized by fasting glucose, insulin, HOMA-IR (homeostasis model of assessment--insulin resistance), and HbA(1c). Hierarchical linear regressions stratified by race and gender examined whether anxiety was associated with glucose metabolism. RESULTS: After adjustment for potential confounders, positive relationships between anxiety and fasting glucose (P = 0.04), insulin (P = 0.01), and HOMA-IR (P = 0.02) but not HbA(1c), were observed in black women only. CONCLUSIONS: Our findings extend previous evidence for the links between psychosocial vulnerabilities and impaired glucose metabolism in black women, by documenting significant associations between anxiety and clinical indicators of glycaemic control among black women without diabetes. Thus, anxiety might constitute an intervention target in black women, a subgroup disproportionately affected by Type 2 diabetes, its complications, and premature mortality.

Effects of a stress management program on vital exhaustion and depression in women with coronary heart disease: a randomized controlled intervention study.

OBJECTIVES: Psychosocial factors, including depression and vital exhaustion (VE) are associated with adverse outcome in coronary heart disease (CHD). Women with CHD are poor responders to psychosocial treatment and knowledge regarding which treatment modality works in them is limited. This randomized controlled clinical study evaluated the effect of a 1-year stress management program, aimed at reducing symptoms of depression and VE in CHD women. DESIGN: Patients were 247 women, < or =75 years, recruited consecutively after a cardiac event and randomly assigned to either stress management (20 2-h sessions) and medical care by a cardiologist, or to obtaining usual health care as controls. Measurements at; baseline (6-8 weeks after randomization), 10 weeks (after 10 intervention sessions), 1 year (end of intervention) and 1-2 years follow-up. RESULTS: For VE, intention to treat analysis showed effects for time (P < 0.001) and time x treatment interaction (P = 0.005), reflecting that both groups improved over time, and that the decrease of VE was more pronounced in the intervention group. However, the level of VE was higher in the intervention group than amongst controls at baseline, 22.7 vs. 19.4 (P = 0.036) but it did not differ later. The change in depressive symptoms did not differ between the groups. CONCLUSIONS: CHD women attending our program experienced a more pronounced decrease in VE than controls. However, as they had higher baseline levels, due to regression towards the mean we cannot attribute the decrease in VE to the intervention. Whether the program has long-term beneficial effects needs to be evaluated.

Exercise and weight loss reduce blood pressure in men and women with mild hypertension: effects on cardiovascular, metabolic, and hemodynamic functioning.

BACKGROUND: Lifestyle modifications have been recommended as the initial treatment strategy for lowering high blood pressure (BP). However, evidence for the efficacy of exercise and weight loss in the management of high BP remains controversial. METHODS: One hundred thirty-three sedentary, overweight men and women with unmedicated high normal BP or stage 1 to 2 hypertension were randomly assigned to aerobic exercise only; a behavioral weight management program, including exercise; or a waiting list control group. Before and following treatment, systolic and diastolic BPs were measured in the clinic, during daily life, and during exercise and mental stress testing. Hemodynamic measures and metabolic functioning also were assessed. RESULTS: Although participants in both active treatment groups exhibited significant reductions in BP relative to controls, those in the weight management group generally had larger reductions. Weight management was associated with a 7-mm Hg systolic and a 5-mm Hg diastolic clinic BP reduction, compared with a 4-mm Hg systolic and diastolic BP reduction associated with aerobic exercise; the BP for controls did not change. Participants in both treatment groups also displayed reduced peripheral resistance and increased cardiac output compared with controls, with the greatest reductions in peripheral resistance in those in the weight management group. Weight management participants also exhibited significantly lower fasting and postprandial glucose and insulin levels than participants in the other groups. CONCLUSIONS: Although exercise alone was effective in reducing BP, the addition of a behavioral weight loss program enhanced this effect. Aerobic exercise combined with weight loss is recommended for the management of elevated BP in sedentary, overweight individuals.

Stress-induced laboratory blood pressure in relation to ambulatory blood pressure and left ventricular mass among borderline hypertensive and normotensive individuals.

Our primary aim in the present study was to investigate the association between blood pressure measured in the laboratory and in the ambulatory state in a group of middle-aged borderline hypertensive men and age-matched normotensive control subjects. In addition, we examined the relation between stress-induced blood pressure measurements and left ventricular mass. Blood pressure and heart rate were measured noninvasively during a standardized laboratory stress protocol and four times per hour throughout 24 hours. Borderline hypertensive subjects had significantly higher systolic and diastolic pressures than normotensive subjects during both the daytime (systolic pressure, 141.1 +/- 9.7 versus 130.9 +/- 8.6 mm Hg; diastolic pressure, 88.8 +/- 7.0 versus 79.4 +/- 6.2 mm Hg, P < .001) and nighttime (systolic pressure, 114.0 +/- 9.9 versus 107.1 +/- 8.3 mm Hg; diastolic pressure, 71.5 +/- 7.5 versus 64.6 +/- 7.2 mm Hg, P < .001). The borderline hypertensive group also displayed increased systolic pressure reactivity in the laboratory compared with the normotensive group. The groups did not differ significantly in left ventricular mass (index). In both borderline hypertensive and normotensive individuals, blood pressure levels during stress testing were closely related to ambulatory blood pressure levels (r = .51 to .82). Furthermore, stress-induced blood pressure levels were significantly correlated to left ventricular mass in borderline hypertensive (r = .33 to .40) but not normotensive subjects. Since stress-induced blood pressure levels were significantly associated with both ambulatory blood pressure levels and left ventricular mass in borderline hypertensive subjects, the addition of standardized stress testing to casual blood pressure measurements may improve risk estimation.

Effects of exercise and weight loss on mental stress-induced cardiovascular responses in individuals with high blood pressure.

The purpose of this study was to determine the effects of exercise and weight loss on cardiovascular responses during mental stress in mildly to moderately overweight patients with elevated blood pressure. Ninety-nine men and women with high normal or unmedicated stage 1 to stage 2 hypertension (systolic blood pressure 130 to 179 mm Hg, diastolic blood pressure 85 to 109 mm Hg) underwent a battery of mental stress tests, including simulated public speaking, anger recall interview, mirror trace, and cold pressor, before and after a 6-month treatment program. Subjects were randomly assigned to 1 of 3 treatments: (1) aerobic exercise, (2) weight management combining aerobic exercise with a behavioral weight loss program, or (3) waiting list control group. After 6 months, compared with control subjects, participants in both active treatment groups had lower levels of systolic blood pressure, diastolic blood pressure, total peripheral resistance, and heart rate at rest and during mental stress. Compared with subjects in the control group, subjects in the exercise and weight management groups also had greater resting stroke volume and cardiac output. Diastolic blood pressure was lower for the weight management group than for the exercise-only group during all mental stress tasks. These results demonstrate that exercise, particularly when combined with a weight loss program, can lower both resting and stress-induced blood pressure levels and produce a favorable hemodynamic pattern resembling that targeted for antihypertensive therapy.

Effects of exercise and weight loss on blood pressure during daily life.

PURPOSE: The objective of this study was to investigate the effects of exercise training and weight loss on blood pressure (BP) associated with physical activity and emotional stress during daily life. METHODS: One hundred twelve participants with unmedicated high normal or stage 1 to stage 2 hypertension were randomized to one of three conditions: a combined exercise and behavioral weight management group (WM), an exercise-only group (EX), or a wait list control group (CON). BP was assessed in the clinic and during 15 h of daytime ambulatory BP monitoring at baseline and after 6 months of treatment. RESULTS: Increased levels of physical activity and emotional distress measured during daily life were associated with increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and rate pressure product (RPP). After treatment, the WM group had significantly lower DBP, HR, and RPP responses during both high and low levels of physical activity and emotional distress compared with the CON group. The EX group had similar BP levels as the WM group, although the EX group had significantly lower BP than the CON group during low but not high levels of physical activity and emotional distress. CONCLUSION: These findings indicate that exercise, especially when combined with weight loss, reduces BP levels at rest and in situations that typically elevate BP such as intense physical activity and emotional distress.

Internal consistency and temporal stability of classically conditioned skin conductance responses.

The reliability of classically conditioned skin conductance responses was investigated. Temporal stability was determined in 28 subjects studied three weeks apart (study 1), and internal consistency in 223 subjects studied once (study 2). A discriminative classical conditioning paradigm using slides with a duration of 8 s served as conditioned stimuli (CS) for an aversive unconditioned noise stimulus (study 1) or a mild unconditioned electric shock stimulus (UCS) (study 2). Electrodermal responses were recorded during a habituation phase (4 trials), an acquisition phase, where CS+ was paired repeatedly with the UCS, while CS- never was (8 trials), and an extinction phase during which shocks were withheld (8 trials each). First interval responses were measured 1-4 s after CS- onset during all phases of the experiment. During the acquisition and extinction phases, second interval responses were scored 5-9 s after CS- onset while third interval responses were determined 1-4 s after CS- termination. Internal consistency was significant for the first (rxy range 0.96-0.90), second (rxy range 0.84-0.54) and third (rxy range 0.96-0.86) skin conductance interval response. Temporal stability was highest for the first interval response (rxy range 0.72-0.37) and lowest for the second interval response (rxy range 0.51-0.05). It is concluded that the first interval skin conductance response shows adequate internal consistency and temporal stability to assess individual differences in classical conditioning.

Psychosocial work characteristics and perceived control in relation to cardiovascular rewind at night.

This study examined the effects of psychosocial work characteristics on cardiovascular rewind at night. Ambulatory 24-hr recordings of blood pressure (BP) and heart rate (HR) of 75 borderline hypertensive and 74 normotensive men were related to diary ratings of perceived control (PC) and to scores of psychological demand (P), control (C), and social support (S) at work determined by an occupational classification system. Multiplicative interaction terms for job strain (P x C), isostrain (P x C x S), and Job Strain x Perceived Control (P x C x PC) were calculated. The P x C x PC interaction predicted diastolic BP at night but not at work. A delayed latency to attain the lowest systolic BP during the night was found for jobs with high job strain and isostrain. Low perceived control and social support were associated with higher HR at work and at night. A logistic regression analysis indicated that the interaction between P x C x PC and the body mass index was independently associated with borderline hypertension.

Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.

While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways implicated in variation of response to treatment. We profiled serum samples from healthy subjects pre- and postaspirin (14 days, 81 mg/day) using mass spectrometry. We established a strong signature of aspirin exposure independent of response (15/34 metabolites changed). In our discovery (N = 80) and replication (N = 125) cohorts, higher serotonin levels pre- and postaspirin correlated with high, postaspirin, collagen-induced platelet aggregation. In a third cohort, platelets from subjects with the highest levels of serotonin preaspirin retained higher reactivity after incubation with aspirin than platelets from subjects with the lowest serotonin levels preaspirin (72 ± 8 vs. 61 ± 11%, P = 0.02, N = 20). Finally, ex vivo, serotonin strongly increased platelet reactivity after platelet incubation with aspirin (+20%, P = 4.9 × 10(-4), N = 12). These results suggest that serotonin is implicated in aspirin response variability.

Purine pathway implicated in mechanism of resistance to aspirin therapy: pharmacometabolomics-informed pharmacogenomics.

Although aspirin is a well-established antiplatelet agent, the mechanisms of aspirin resistance remain poorly understood. Metabolomics allows for measurement of hundreds of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response. We defined the metabolic signature of aspirin exposure in subjects from the Heredity and Phenotype Intervention Heart Study. Many metabolites, including known aspirin catabolites, changed on exposure to aspirin, and pathway enrichment analysis identified purine metabolism as significantly affected by drug exposure. Furthermore, purines were associated with aspirin response, and poor responders had higher postaspirin adenosine and inosine levels than did good responders (n = 76; both P < 4 × 10(-3)). Using our established "pharmacometabolomics-informed pharmacogenomics" approach, we identified genetic variants in adenosine kinase associated with aspirin response. Combining metabolomics and genomics allowed for more comprehensive interrogation of mechanisms of variation in aspirin response--an important step toward personalized treatment approaches for cardiovascular disease.

Wine drinking is associated with increased heart rate variability in women with coronary heart disease.

OBJECTIVE: To test the hypothesis that alcohol consumption is positively related to heart rate variability (HRV) in women with coronary heart disease (CHD) and therefore that cardiac autonomic activity is potentially implicated in the mediation of the favourable effects of moderate drinking. DESIGN, SETTINGS, AND PATIENTS: Cross sectional study of female patients who survived hospitalisation for acute myocardial infarction or underwent a revascularisation procedure, percutaneous transluminal coronary angioplasty, or coronary artery bypass grafting. MAIN OUTCOME MEASURES: Ambulatory 24 hour ECG was recorded during normal activities. The mean of the standard deviations of all normal to normal intervals for all five minute segments of the entire recording (SDNNI) and the following frequency domain parameters were assessed: total power, high frequency power, low frequency power, and very low frequency power. A standardised questionnaire evaluated self reported consumption of individual alcoholic beverage types: beer, wine, and spirits. Other clinical characteristics, such as age, body mass index, smoking habits, history of diabetes mellitus, menopausal status, educational status, and treatment, were also assessed. RESULTS: Wine intake was associated with increased HRV in both time and frequency domains independently of other clinical covariates (for example, ln SDNNI was 3.89 among wine drinkers v 3.59 among wine non-drinkers in the multivariate model; p = 0.014). In contrast, consumption of beer and spirits and the total amount of alcohol consumed did not relate significantly to any of the HRV parameters. CONCLUSION: Intake of wine, but not of spirits or beer, is positively and independently associated with HRV in women with CHD. These results may contribute to the understanding of the complex relation between alcohol consumption and CHD.

Inflammatory markers and heart rate variability in women with coronary heart disease.

PURPOSE: Both heart rate variability (HRV) and inflammatory markers are carrying prognostic information in coronary heart disease (CHD), however, we know of no studies examining their relation in CHD. The aim of this study, therefore, was to assess the association between HRV and inflammatory activity, as reflected by the levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra) and C-reactive protein (CRP). SUBJECTS AND METHODS: Consecutive women patients who survived hospitalization for acute myocardial infarction, and/or underwent a percutaneous transluminal coronary angioplasty or a coronary artery bypass grafting were included and evaluated in a stable condition 1 year after the index events. An ambulatory 24-h ECG was recorded during normal activities. SDNN index (mean of the standard deviations of all normal to normal intervals for all 5-min segments of the entire recording) and the following frequency domain parameters were assessed: total power, high frequency (HF) power, low frequency (LF) power and very low frequency (VLF) power. Levels of high-sensitivity CRP were measured by nephelometry, IL-6 and IL-1ra concentrations were determined by enzyme immunoassay. RESULTS: Levels of IL-6 showed an inverse relation with HRV measures even after controlling for potential confounding factors. The P-values were 0.02, 0.04, 0.01, 0.03, 0.18 for the multivariate association with SDDN index, total power, VLF power, LF power and HF power respectively. In contrast, the inverse relationship between HRV measures and CRP or IL-1ra levels were weak and nonsignificant. Correlation coefficients for the relationship between IL-6 and HRV measures were both uni- and multivariately higher than for the relationship between HRV measures and any other factors evaluated in this study. CONCLUSION: Concentration of IL-6 showed a negative, independent association with HRV in women with CHD. Thus, increased inflammatory activity, as reflected by IL-6 levels, may represent a new auxiliary mechanism linking decreased HRV to poor prognosis in CHD.

Structural cardiac changes in relation to 24-h ambulatory blood pressure levels in borderline hypertension.

OBJECTIVES: To investigate left ventricular hypertrophy (LVH) in relation to 24-h ambulatory blood pressure (24-ABPM) and insulin levels in borderline hypertension. DESIGN: A case-control study. SUBJECTS: Borderline hypertensive men (diastolic blood pressure (DBP) 85-94 mmHg, n = 69) and age-matched normotensive controls (DBP < or = 80 mmHg, n = 69) from a population screening programme. MAIN OUTCOME MEASURES: Echocardiography (M-mode), insulin (RIA) and 24-APBM (Del Mar P-IV) levels. RESULTS: The borderline group showed a significant increase in septal thickness (10.4 +/- 1.5 vs. 9.7 +/- 1.5 mm, P < 0.01), peak systolic wall stress (218 +/- 38 vs. 202 +/- 38 10(3) dynes cm-2, P < 0.05) and a decrease in LV ejection time (28.4 +/- 2.5 vs. 29.5 +/- 2.1s, P < 0.01). The septum vs. posterior wall thickness ratio was significantly higher in the borderline group (1.13 +/- 0.14 vs. 1.06 +/- 0.14, P < 0.01). Casual BP levels did not correlate with LVH indices, while 24-ABPM systolic levels correlated strongly with LVH indices in the borderline group (r = 0.22-0.52, P < 0.05) but not in the normotensive group. Insulin levels correlates strongly with LVH indices in the normotensive group (r = 0.34-0.47, P < 0.01) but not the borderline, group. CONCLUSIONS: Signs of asymmetric LVH and altered ventricular function are already detectable in borderline hypertension. The data also suggest that early structural cardiac changes are related to ambulatory blood pressure profile, but not to casual blood pressure or trophic factors such as insulin.

Effectiveness of corneal neovascularization photothrombosis using phthalocyanine and a diode laser (675 nm).

We used chloroaluminum sulfonated phthalocyanine as a photo-sensitizer and a diode laser as a light source for induction of photothrombosis of corneal neovascularization. Corneal neovascularization was induced in 1 eye of each of 10 New Zealand white rabbits using intrastromal 6.0 silk sutures. After the intravenous injection of phthalocyanine in a dose of 4 mg per kg of body weight, photothrombosis was carried out using a diode laser emitting at 675 nm. The animals were followed up by both fluorescein angiography and slit-lamp photography for up to three months. At the end of the follow-up period the eyes were prepared for histology. After photothrombosis, thrombus formation was induced within new vessels demonstrating histological characteristics of both arterioles and venules. Most of the vessels disappeared or remained closed during the follow-up period. Recanalization of some of the thrombosed vessels occurred within the first 20 days after the operation. The combination of phthalocyanine and a 675 nm diode laser is effective for the induction of photothrombosis of corneal neovascularization.