Relationships between obsessive-compulsive disorder, depression and functioning before and after exposure and response prevention therapy.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is associated with impaired functioning and depression. Our aim was to examine relationships between OCD symptoms, depression and functioning before and after exposure and response prevention (ERP), a type of cognitive-behavioural therapy for OCD, specifically examining whether functioning, depression and other cognitive factors like rumination and worry acted as mediators. METHODS: Forty-four individuals with OCD were randomised to 4 weeks of intensive ERP treatment first (n = 23) or waitlist then treatment (n = 21). We used a bootstrapping method to examine mediation models. RESULTS: OCD symptoms, depression and functioning significantly improved from pre- to post-intervention. Functioning mediated the relationship between OCD symptoms and depression and the relationship between functioning and depression was stronger at post-treatment. Depression mediated the relationship between OCD symptoms and functioning, but only at post-intervention. Similarly, rumination mediated the relationship between OCD symptoms and depression at post-intervention. CONCLUSIONS: Our findings suggest that after ERP, relationships between depression and functioning become stronger. Following ERP, treatment that focuses on depression and functioning, including medication management for depression, cognitive approaches targeting rumination, and behavioural activation to boost functionality may be important clinical interventions for OCD patients.

New directions for patient-centred care in scleroderma: the Scleroderma Patient-centred Intervention Network (SPIN).

Systemic sclerosis (SSc), or scleroderma, is a chronic multisystem autoimmune disorder characterised by thickening and fibrosis of the skin and by the involvement of internal organs such as the lungs, kidneys, gastrointestinal tract, and heart. Because there is no cure, feasibly-implemented and easily accessible evidence-based interventions to improve health-related quality of life (HRQoL) are needed. Due to a lack of evidence, however, specific recommendations have not been made regarding non-pharmacological interventions (e.g. behavioural/psychological, educational, physical/occupational therapy) to improve HRQoL in SSc. The Scleroderma Patient-centred Intervention Network (SPIN) was recently organised to address this gap. SPIN is comprised of patient representatives, clinicians, and researchers from Canada, the USA, and Europe. The goal of SPIN, as described in this article, is to develop, test, and disseminate a set of accessible interventions designed to complement standard care in order to improve HRQoL outcomes in SSc.

Clinical correlates of sleep problems in systemic sclerosis: the prominent role of pain.

OBJECTIVE: Problems with sleep are common in patients with SSc and impact daily function. Little research, however, has examined factors associated with sleep disruption in SSc. Therefore, the objective of this study was to investigate socio-demographic and medical factors associated with sleep disruption in SSc. METHODS: Cross-sectional study of 70 patients from one Canadian Scleroderma Research Group site who were assessed with a 100-mm sleep disruption visual analogue scale (VAS). Patients also completed measures of pain and depressive symptoms and underwent clinical histories and medical examinations. Pearson's correlations were used to assess bivariate association of socio-demographic and medical variables with sleep VAS scores. Multivariable associations of socio-demographic (Step 1) and medical (Step 2) variables with sleep VAS scores were assessed using hierarchical multiple linear regression. RESULTS: The mean (s.d.) sleep disruption VAS score was 38.5 (29.9). In bivariate analyses, sleep disruption was associated with marital status (r = -0.24, P = 0.042), smoking (r = 0.27, P = 0.025), gastrointestinal symptoms (r = 0.27, P = 0.023), breathing problems (r = 0.31, P = 0.009), pain (r = 0.53, P < 0.001) and symptoms of depression (r = 0.34, P = 0.004). In multivariate analysis, only marital status (standardized ß = -0.24, P = 0.049) and pain (standardized ß = 0.50, P < 0.001) were significantly associated with sleep disruption. CONCLUSION: Sleep disruption scores were as high in SSc as in RA and higher than in the general population. Pain was robustly associated with sleep disruption. Additional research is needed on sleep in SSc so that well-informed sleep interventions can be developed and tested.

Sleep and inflammation: psychoneuroimmunology in the context of cardiovascular disease.

BACKGROUND: Poor sleep is prospectively linked to all-cause and cardiovascular mortality. Inflammatory processes may be an important biological mechanism linking poor sleep to cardiovascular disease. Such processes involve active participation of signaling molecules called cytokines in development of atherosclerotic plaques. PURPOSE: I review evidence from experimental sleep deprivation and clinical observational studies suggesting a bidirectional relationship between sleep and inflammatory cytokines. RESULTS: Findings from sleep deprivation studies indicate that sleep loss is associated with increases in these cytokines. Similarly, studies in clinical populations with sleep problems, such as primary insomnia patients and those diagnosed with major depression, also show elevations in these same cytokines. CONCLUSIONS: Bidirectional communication between the brain and the immune system is carried out through a complex network of autonomic nerves, endocrine hormones, and cytokines. Disturbed sleep appears to perturb the functioning of this network and therefore contribute to elevations in inflammatory mediators linked to cardiovascular disease.

Nocturnal levels of ghrelin and leptin and sleep in chronic insomnia.

Experimental sleep deprivation in healthy humans affects levels of ghrelin and leptin, two primary hormones involved in energy balance that regulate appetite and body weight. No study to date has examined levels of these hormones in patients with chronic insomnia. In this study, men diagnosed with primary insomnia using DSM-IV criteria (n=14) and age and body weight comparable healthy control men (n=24) underwent polysomnography. Circulating levels of ghrelin and leptin were measured at 2300h, 0200h and 0600h. As compared to controls, insomnia patients showed less total sleep time, stage 2 and REM sleep and decreased sleep efficiency and more stage 1 sleep than controls (p's<.05). Ghrelin levels across the night were significantly lower in insomnia patients (p<.0001). Leptin was not significantly different between the groups. In conclusion, decreased nocturnal ghrelin in insomnia is consistent with findings for nighttime levels in sleep deprivation studies in healthy sleepers. These findings suggest that insomnia patients have a dysregulation in energy balance that may play a role in explaining prospective weight gain in this population.

Improving sleep quality in older adults with moderate sleep complaints: A randomized controlled trial of Tai Chi Chih.

STUDY OBJECTIVES: To determine the efficacy of a novel behavioral intervention, Tai Chi Chih, to promote sleep quality in older adults with moderate sleep complaints. DESIGN: Randomized controlled trial with 16 weeks of teaching followed by practice and assessment 9 weeks later. The main outcome measure was sleep quality, as assessed by the Pittsburgh Sleep Quality Index (PSQI). SETTING: General community at 2 sites in the US between 2001 and 2005. PARTICIPANTS: Volunteer sample of 112 healthy older adults, aged 59 to 86 years. INTERVENTION: Random allocation to Tai Chi Chih or health education for 25 weeks. RESULTS: Among adults with moderate sleep complaints, as defined by PSQI global score of 5 or greater, subjects in the Tai Chi Chih condition were more likely to achieve a treatment response, as defined by PSQI less than 5, compared to those in health education (P < 0.05). Subjects in the Tai Chi Chih condition with poor sleep quality also showed significant improvements in PSQI global score (P < 0.001) as well as in the sleep parameters of rated sleep quality (P < 0.05), habitual sleep efficiency (P < 0.05), sleep duration (P < 0.01), and sleep disturbance (P < 0.01). CONCLUSIONS: Tai Chi Chih can be considered a useful nonpharmacologic approach to improve sleep quality in older adults with moderate complaints and, thereby, has the potential to ameliorate sleep complaints possibly before syndromal insomnia develops. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00118885.

Chronic stress and regulation of cellular markers of inflammation in rheumatoid arthritis: implications for fatigue.

OBJECTIVES: This study examined whether chronic interpersonal stress is associated with cellular markers of inflammation and regulation of these responses by in vitro doses of glucocorticoids in rheumatoid arthritis (RA) patients. The association between these markers of inflammation and fatigue was also tested. METHODS: Fifty-eight RA patients completed up to 30 daily ratings of the stressfulness of their interpersonal relations. Interleukin-6 (IL-6) production was analyzed in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cell cultures with and without varying concentrations of the glucocorticoid hydrocortisone. In addition, plasma levels of IL-6 and C-reactive protein (CRP) were analyzed, and subjective ratings of fatigue and pain were obtained on the day of blood sampling. RESULTS: Multilevel modeling showed that higher chronic interpersonal stress was associated with greater stimulated IL-6 production (p<0.05) as well as greater resistance to hydrocortisone inhibition of IL-6 production (p<0.05). These relations were not accounted for by demographic factors, body mass index, or steroid medication use. Stimulated production of IL-6, in turn, was associated with greater levels of self-reported fatigue, controlling for pain (p<0.05). Neither chronic stress ratings nor fatigue symptoms were related to plasma levels of IL-6 or CRP (ps>.05). CONCLUSIONS: Among RA patients, chronic interpersonal stress is associated with greater stimulated cellular production of IL-6 along with impairments in the capacity of glucocorticoids to inhibit this cellular inflammatory response. Moreover, these findings add to a growing body of data that implicate heightened proinflammatory cytokine activity in those at risk for fatigue symptoms.

Effects of mindfulness training on emotional and physiologic recovery from induced negative affect.

OBJECTIVE: Mindfulness training has been shown to improve psychological well-being and physical health. One proposed pathway for the positive effects of mindfulness training is through the development of new emotion regulation strategies, such as the ability to experience emotions by observing and accepting them without judgment. Theoretically, this should facilitate recovery from negative emotional states; however, this has rarely been examined empirically. The goal of the current study was to determine whether mindfulness training is associated with more efficient emotional and cardiovascular recovery from induced negative affect. METHODS: The current study tested emotional and cardiovascular recovery from induced negative affect during a personal recall task in women randomly assigned to 6-weeks of mindfulness training (n=39) compared to women assigned to a wait-list control condition (n=32). During baseline, task, and post-task rest, blood pressure and heart rate were monitored at fixed intervals and heart rate variability (HRV) and pre-ejection period (PEP) were monitored continuously. This study was embedded within a randomized trial that evaluated the effects of mindfulness training in a sample of younger breast cancer survivors, a group in need of access to effective psychosocial intervention as they can experience high stress, anxiety, and physical symptoms for many years in to survivorship. RESULTS: In response to the personal recall task, women in both the intervention and control groups showed significant increases in sadness, anxiety, and anger, with the intervention group reaching higher levels of sadness and anger than controls. Further, the intervention group showed a significantly steeper decline in sadness and anger, as well as steeper initial decline in diastolic blood pressure compared to women in the wait list control condition. Groups did not differ in their self-reported feelings of anxiety, or in blood pressure, heart rate, or pre-ejection period (PEP) responses to the task. The control group demonstrated an increase in heart rate variability (HRV) during the task (indexed by the root mean square of successive differences in heart rate; RMSSD) while the intervention group remained flat throughout the task. CONCLUSION: Compared to the control group, women in the intervention group experienced greater negative emotions when recalling a difficult experience related to their breast cancer, and demonstrated an efficient emotional and blood pressure recovery from the experience. This suggests that mindfulness training may lead to an enhanced emotional experience coupled with the ability to recovery quickly from negative emotional states.

Validation of a 3-factor scoring model for the Pittsburgh sleep quality index in older adults.

STUDY OBJECTIVES: The Pittsburgh Sleep Quality Index (PSQI) is widely used to assess subjective sleep disturbances in psychiatric, medical, and healthy adult and older adult populations. Yet, validation of the PSQI single-factor scoring has not been carried out. DESIGN: The PSQI was administered as a self-report questionnaire. Using a cross-validation approach, scores from the PSQI were analyzed with exploratory and confirmatory factor analyses. SETTING: San Diego, Denver, and Los Angeles community-based clinics. PARTICIPANTS: Community-dwelling depressed and nondepressed adults older that 60 years of age (N = 417) MEASUREMENTS AND RESULTS: Results yielded a 3-factor scoring model that obtained a measure of perfect fit and was significantly better fitted than either the original single-factor model or a 2-factor model. Components of the 3 factors were characterized by the descriptors sleep efficiency, perceived sleep quality, and daily disturbances. CONCLUSIONS: These findings validate the factor structure of the PSQI and demonstrate that a 3-factor score should be used to assess disturbances in three separate factors of subjective sleep reports.

Impairments in health functioning and sleep quality in older adults with a history of depression.

OBJECTIVES: To determine whether older adults with a history of depression show impairments in health functioning and sleep quality at a gradient between older adults with no history of depression and those with current major depression and to examine whether poor sleep quality contributes to declines in health functioning in addition to the contribution of depressive symptoms. DESIGN: Cross-sectional. SETTING: Three urban communities: Denver, Colorado, and Los Angeles and San Diego, California. PARTICIPANTS: Two hundred community-dwelling adults aged 60 and older who were never mentally ill, 143 with a history of major or minor depressive disorder in remission, and 67 with a current depressive disorder. MEASUREMENTS: Diagnosis, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; health functioning (Medical Outcomes Study 36-item Short-Form Health Survey); depressive symptom severity (Beck Depression Inventory); and sleep quality (Pittsburgh Sleep Quality Index). RESULTS: Older adults with a history of depression showed impairments in sleep quality and had lower levels of health functioning than controls; these impairments were at a gradient with declines in those with current depression. Poor sleep quality was independently associated with declines in health perception in older adults with and without depression. CONCLUSION: These findings have important health implications for older people who have a lifetime history of depression, given evidence that poor health functioning is a risk factor for depression recurrence as well as mortality. Moreover, in view of the association between sleep quality and health status, testing of interventions that target sleep quality might identify strategies to improve health functioning in older adults.

Tai Chi Chih acutely decreases sympathetic nervous system activity in older adults.

BACKGROUND: Aging is associated with increases of sympathetic nervous system activation implicated in the onset of hypertension and cardiovascular disease. The purpose of this study was to examine whether the practice of Tai Chi Chih (TCC), a movement-based relaxation practice, would acutely promote decreases of sympathetic activity in elderly persons. METHOD: The sample included two groups of older men and women (age > or = 60 years): TCC practitioners (n = 19) and TCC-naïve participants (n = 13). Participants were recruited after completing a 25-week randomized trial of TCC or health education. TCC practitioners performed TCC for 20 minutes, and TCC-naïve participants passively rested. Preejection period, blood pressure, and heart rate were measured before and after the task. A subsample (n = 8) returned for a second evaluation and performed videotape-guided stretching for 20 minutes to evaluate the effects of slow-moving physical activity on sympathetic activity. RESULTS: Results showed that TCC performance significantly decreased sympathetic activity as indexed by preejection period (p =.01). In contrast, there was no change in preejection period following passive rest or slow-moving physical activity. Neither blood pressure nor heart rate changed after TCC performance. DISCUSSION: This study is the first to our knowledge to assess the acute effects of TCC practice on sympathetic activity in older adults. TCC performance led to acute decreases in sympathetic activity, which could not be explained by physical activity alone. Further study is needed to determine whether the acute salutary effects of TCC on autonomic functioning are sustained with ongoing practice in older adults.

Inflammatory markers and sleep disturbance in major depression.

OBJECTIVE: This study was conducted to determine whether immune activation occurs in major depression, and to evaluate the associations between disordered sleep and markers of inflammation in patients with major depressive disorder. METHODS: All-night polysomnography was obtained in patients with acute Diagnostic and Statistical Manual of Mental Disorders, 4th edition major depressive disorder (n = 22) and age-, gender-, and body weight-matched comparison controls (n = 18). After the onset of sleep, nocturnal serum levels of interleukin-6 (IL-6), soluble intercellular adhesion molecule (sICAM), monocyte chemotactic protein (MCP-1), and IL-6 soluble receptor (IL-6sR) were sampled. RESULTS: As compared with matched controls, depressed patients showed significant (p <.05) nocturnal elevations of circulating levels of IL-6 and sICAM. Both sleep latency and rapid eye movement (REM) density had moderate correlations with IL-6 and sICAM (r's > or = 0.30). Backward regression analyses indicated that sleep latency (beta = 0.34, p <.05) and REM density (beta = 0.27, p = .09) were better predictors of IL-6 than depressive status. Similarly, sleep latency (beta = 0.27, p = .06) and REM density (beta = 0.32, p = .02) were also better predictors of sICAM. CONCLUSION: These findings support the hypothesis that sleep disturbance is associated with elevated levels of the inflammatory markers IL-6 and sICAM. This relationship was not accounted for by other confounding factors such as age and body weight. These findings suggest that the elevations in inflammatory markers found in depressive subjects may be partially the result of disturbances of sleep initiation found in this population.

Sympathoimmune anomalies underlying the response to stressful challenge in human immunodeficiency virus spectrum disease.

OBJECTIVE: This study examined immune, endocrine, and cardiovascular reactivity during stressful behavioral challenge in human immunodeficiency virus (HIV) seropositive (HIV+) and seronegative (HIV-) men and women and assessed whether immunocellular reactivity was differentially associated with concomitant alterations in sympathetic response. METHODS: The 133 HIV+ [84 asymptomatic, 49 symptomatic] and 92 HIV- subjects completed a speech stress reactivity protocol. RESULTS: Immunocellular reactivity to the speech stressor did not differ among asymptomatic and symptomatic HIV+ groups; however, relative to seronegatives, reactivity differences were present. Specifically, HIV+ subjects exhibited greater increases in total number of T cells, as well as in cytotoxic/suppressor T cells, activated T cells, and activated cytotoxic/suppressor T cells, and less increase in natural killer (NK) cell numbers. In addition, less stress-induced increase in NK cell cytotoxicity was observed along with greater suppression of the lymphoproliferative response to mitogen stimulation in the HIV+ group. Although no group differences in catecholamine reactivity were observed, the association of immunoreactivity with catecholamine responsiveness differed between serostatus groups. Specifically, the HIV+ subjects compared with HIV- subjects displayed greater lymphocytosis per unit change in norepinephrine; whereas NK cell reactivity was positively related to epinephrine responsiveness, but only in the HIV- group. These findings were present even after controlling for age and body mass, as well as other potential influences on immunocellular migration, such as cortisol levels and prevailing cardiac output. CONCLUSION: Early in HIV spectrum disease, functional abnormalities in the stress-induced migratory ability of specific immunocellular subsets are present that may reflect an underlying pathophysiological alteration in sympathoimmune communication.

Psychological distress is associated with decreased memory helper T-cell and B-cell counts in pre-AIDS HIV seropositive men and women but only in those with low viral load.

OBJECTIVE: Although some studies have demonstrated the association of psychological distress and diminished immune system function in HIV spectrum disease, other studies have yielded apparently conflicting findings; the lack of consideration of the role of HIV viral burden may be central to this controversy. This study examined whether HIV viral burden moderated the relationship between psychological distress and enumerative and functional immune measures in pre-AIDS HIV spectrum disease. METHODS: This cross-sectional study used factor analysis to derive a composite measure of psychological distress incorporating measures of dysphoria, anxiety, and perceived stress. Multiple regression analyses used distress as the predictor, immune measures as the outcome variables, with viral load as the moderator variable, while controlling for age, medication use, and HIV symptomatology. Subjects were 148 pre-AIDS, HIV seropositive men and women (89 asymptomatic, 59 symptomatic), aged 18 to 45 years. The main outcome measures were enumerative and functional immune measures. RESULTS: A model of psychological distress was derived using each of the proposed measures. Findings indicated that high distress was associated with decreased numbers of helper T (memory) cells and B cells, but only at low levels of viral burden after controlling for age, medication use, and HIV-related symptoms. CONCLUSIONS: These findings highlight the importance of assessing the role of HIV viral burden when examining distress-immunity relationships in HIV-infected individuals. The lack of association in those persons with high viral load suggests that, even before AIDS onset, disease-related processes are disrupting CNS and immune system communication.

Cognitive behavioral therapy vs. Tai Chi for late life insomnia and inflammatory risk: a randomized controlled comparative efficacy trial.

STUDY OBJECTIVES: To investigate the comparative efficacy of cognitive behavioral therapy (CBT), Tai Chi Chih (TCC), and sleep seminar education control (SS) on the primary outcome of insomnia diagnosis, and secondary outcomes of sleep quality, fatigue, depressive symptoms, and inflammation in older adults with insomnia. DESIGN: Randomized controlled, comparative efficacy trial. SETTING: Los Angeles community. PATIENTS: 123 older adults with chronic and primary insomnia. INTERVENTIONS: Random assignment to CBT, TCC, or SS for 2-hour group sessions weekly over 4 months with follow-up at 7 and 16 months. MEASUREMENTS: Insomnia diagnosis, patient-reported outcomes, polysomnography (PSG), and high-sensitivity C-reactive protein (CRP) levels. RESULTS: CBT performed better than TCC and SS in remission of clinical insomnia as ascertained by a clinician (P < 0.01), and also showed greater and more sustained improvement in sleep quality, sleep parameters, fatigue, and depressive symptoms than TCC and SS (all P values < 0.01). As compared to SS, CBT was associated with a reduced risk of high CRP levels (> 3.0 mg/L) at 16 months (odds ratio [OR], 0.26 [95% CI, 0.07-0.97] P < 0.05). Remission of insomnia was associated with lower levels of CRP (P < 0.05) at 16 months. TCC was associated with improvements in sleep quality, fatigue, and depressive symptoms as compared to SS (all P's < 0.05), but not insomnia remission. PSG measures did not change. CONCLUSIONS: Treatment of late-life insomnia is better achieved and sustained by cognitive behavioral therapies. Insomnia treatment and remission reduces a marker of inflammatory risk, which has implications for cardiovascular morbidity and diabetes observed with sleep disturbance in epidemiologic surveys.

A randomized controlled trial of a self-guided, multimedia, stress management and resilience training program.

BACKGROUND: Stress is a common and costly behavioral health issue. Technology-based behavioral health programs (e.g., computer or web-based programs) are effective for treating anxiety or depression. These programs increase availability of evidence-based interventions to individuals who are not able or willing to receive such in-person treatments. Stress management training has empirical support, but little data exists on its efficacy with stressed but healthy individuals, and there are no prior studies employing a self-guided, multimedia intervention. We conducted a randomized controlled trial of a self-guided, multimedia stress management and resilience training program (SMART-OP) with a stressed but healthy sample. METHODS: Participants (N = 66) were randomized to SMART-OP or an attention control (AC) group that received marketed videos and published material on stress management. Participants were evaluated on self-report measures and Trier Social Stress Test (TSST) performance. Analyses were based on study completers (N = 59). RESULTS: SMART-OP group reported significantly less stress, more perceived control over stress, and rated SMART-OP as significantly more useful than AC. During the TSST, the data suggests the SMART-OP group showed greater within-task α-amylase recovery at post-assessment. CONCLUSIONS: SMART-OP is highly usable and is a more effective and useful stress management training program than an educational comparison.

Assessing the scholarly impact of health psychology: a citation analysis of articles published from 1993 to 2003.

OBJECTIVE: We conducted a citation analysis to explore the impact of articles published in Health Psychology and determine whether the journal is fulfilling its stated mission. DESIGN: Six years of articles (N = 408) representing three editorial tenures from 1993-2003 were selected for analysis. MAIN OUTCOME MEASURES: Articles were coded for several dimensions enabling examination of the relationship of article features to subsequent citations rates. Journals citing articles published in Health Psychology were classified into four categories: (1) psychology, (2) medicine, (3) public health and health policy, and (4) other journals. RESULTS: The majority of citations of Health Psychology articles were in psychology journals, followed closely by medical journals. Studies reporting data collected from college students, and discussing the theoretical implications of findings, were more likely to be cited in psychology journals, whereas studies reporting data from clinical populations, and discussing the practice implications of findings, were more likely to be cited in medical journals. Time since publication and page length were both associated with increased citation counts, and review articles were cited more frequently than observational studies. CONCLUSION: Articles published in Health Psychology have a wide reach, informing psychology, medicine, public health and health policy. Certain characteristics of articles affect their subsequent pattern of citation.

Stress activation of cellular markers of inflammation in rheumatoid arthritis: protective effects of tumor necrosis factor alpha antagonists.

OBJECTIVE: Psychological stress is thought to aggravate disease activity in rheumatoid arthritis (RA), although the physiologic mechanisms are unclear. Tumor necrosis factor alpha (TNFalpha) is an inflammatory cytokine involved in the exacerbation of RA, and TNFalpha antagonists have emerged as efficacious treatments. The purpose of this study was to determine whether RA patients show increased monocyte production of TNFalpha following acute psychological stress and whether such responses are abrogated in RA patients taking TNFalpha antagonists. METHODS: A standardized stress task was administered to 3 groups of subjects: RA patients taking TNFalpha antagonists, RA patients not taking such medications, and healthy controls. Lipopolysaccharide-stimulated monocyte production of inflammatory cytokines was repeatedly measured using intracellular staining and flow cytometry. Subjective stress, cardiovascular responses, adrenocorticotropic hormone (ACTH) levels, and cortisol levels were also measured. RESULTS: The stress task induced increases in subjective stress, cardiovascular activity, and levels of ACTH and cortisol, with similar responses in the 3 groups. In addition, the stress task induced a significant increase (P < 0.001) in monocyte production of TNFalpha among RA patients who were not taking TNFalpha antagonists. However, monocyte production of TNFalpha did not change following psychological stress in RA patients taking TNFalpha antagonists or in healthy controls. CONCLUSION: Brief psychological stress can trigger increased stimulated monocyte production of TNFalpha in RA patients. The use of TNFalpha antagonists protects against stress activation of cellular markers of inflammation in RA patients.

Sex differences in monocyte expression of IL-6: role of autonomic mechanisms.

Sex differences in the prevalence of inflammatory disorders exist, perhaps due to sex differences in cellular mechanisms that contribute to proinflammatory cytokine activity. This study analyzed sex differences of monocyte intracellular expression of IL-6 and its associations with reproductive hormones and autonomic mechanisms in 14 matched pairs of men and women (n = 28). Monocyte intracellular IL-6 production was repeatedly assessed over two circadian periods. Sympathetic balance was estimated by heart rate variability and the ratio of power in the low-frequency (LF) to high-frequency (HF); vagal tone was indexed by the power of HF component. As compared to men, women showed greater monocyte expression of IL-6 across the circadian period. In addition, women showed lower sympathetic balance (LF/HF ratio), and greater levels of vagal tone (HF power). In women, but not men, sympathovagal balance was negatively associated with monocyte IL-6 expression, whereas vagal tone was positively associated with production of this cytokine. Levels of reproductive hormones were not related to monocyte IL-6 expression. The marked increase in monocyte expression of interleukin-6 in women has implications for understanding sex differences in risk of inflammatory disorders. Additionally, these data suggest that sex differences in sympathovagal balance or vagal tone may be a pathway to explain sex differences in IL-6 expression. Interventions that target autonomic mechanisms might constitute new strategies to constrain IL-6 production with impacts on inflammatory disease risk in women.