Stress-related reduction in personal mastery is associated with reduced immune cell beta2-adrenergic receptor sensitivity

Background: A growing body of literature suggests that caregiving burden is associated with impaired immune system functioning, which may contribute to elevated morbidity and mortality risk among dementia caregivers. However, potential mechanisms linking these relationships are not well understood. The purpose of this study was to investigate whether stress-related experience of depressive symptoms and reductions in personal mastery were related to alterations in ss2-adrenergic receptor sensitivity.Methods: Spousal Alzheimer's caregivers (N = 106) completed measures assessing the extent to which they felt overloaded by their caregiving responsibilities, experienced depressive symptoms, and believed their life circumstances were under their control. We hypothesized that caregivers reporting elevated stress would report increased depressive symptoms and reduced mastery, which in turn would be associated with reduced ss2- adrenergic receptor sensitivity on peripheral blood mononuclear cells (PBMC), as assessed by in vitro isoproterenol stimulation.Results: Regression analyses indicated that overload was negatively associated with mastery (beta = -0.36, p = 0.001) and receptor sensitivity (beta = -0.24, p = 0.030), whereas mastery was positively associated with receptor sensitivity (beta = 0.29, p = 0.005). Finally, the relationship between overload and receptor sensitivity diminshed upon simultaneous entry of mastery. Sobel's test confirmed that mastery significantly mediated some of the relationship between overload and receptor sensitivity (z = -2.02, p = 0.044).Conclusions: These results suggest that a reduced sense of mastery may help explain the association between caregiving burden and reduced immune cell ss2-receptor sensitivity.

[Erectile dysfunction in depression and under treatment with antidepressants -- current treatment options]

Erectile dysfunction (ED) is a common problem in the general population, but also a symptom of both treated and untreated depression. As a side effect of antidepressant medication, erectile dysfunction appears to be one of the principal reasons for discontinuing antidepressant treatment. Avoiding or switching antidepressants is problematic, as this may lead to an increase in depressive symptoms. Our review shows that oral phosphodiesterase inhibitors are an option in treating both ED resulting from depression and from antidepressant medication.

Depression, the metabolic syndrome and cardiovascular risk

BACKGROUND: The relationship between depression and the metabolic syndrome is unclear, and whether metabolic syndrome explains the association between depression and cardiovascular disease (CVD) risk is unknown. METHODS: We studied 652 women who received coronary angiography as part of the Women's Ischemia Syndrome Evaluation (WISE) study and completed the Beck Depression Inventory (BDI). Women who had both elevated depressive symptoms (BDI > or =10) and a previous diagnosis of depression were considered at highest risk, whereas those with one of the two conditions represented an intermediate group. The metabolic syndrome was defined according to the ATP-III criteria. The main outcome was incidence of adverse CVD events (hospitalizations for myocardial infarction, stroke, congestive heart failure, and CVD-related mortality) over a median follow-up of 5.9 years. RESULTS: After adjusting for demographic factors, lifestyle and functional status, both depression categories were associated with about 60% increased odds for metabolic syndrome compared with no depression (p = .03). The number of metabolic syndrome risk factors increased gradually across the three depression categories (p = .003). During follow-up, 104 women (15.9%) experienced CVD events. In multivariable analysis, women with both elevated symptoms and a previous diagnosis of depression had 2.6 times higher risk of CVD. When metabolic syndrome was added to the model, the risk associated with depression only decreased by 7%, and both depression and metabolic syndrome remained significant predictors of CVD. CONCLUSIONS: In women with suspected coronary artery disease, the metabolic syndrome is independently associated with depression but explains only a small portion of the association between depression and incident CVD.

[Diagnosis and therapy of depression in the heart disease patient]

Even though depressions and depressive symptoms are frequently observed in patients with medical diseases, their psychological problems are often neither diagnosed nor treated. Diagnosis of mood state might be easy in isolated cases yet it often is not since the precise nature of normal mood cannot be expressed in quantitative terms. Furthermore, depression can only be diagnosed based on the doctor's clinical appraisal and the patient's own description of his/her complaints. There is no gold standard on which depressive symptoms can be based on--and further on, depression is not a diagnosis. Instead, it is a syndrome that calls for differential diagnoses before treatment can be offered. Diagnosing depressive comorbidity in patients with medical complaints is even more difficult because of the overlap between symptoms of depression and accompanying symptoms of the somatic illness e.g. lack of energy. Although depressive states have been known to be a risk factor for the prognosis of patients with coronary heart disease for a long time, there is a paucity of research about the therapy these patients undergo due to the fact that tricyclic anti-depressants can have cardiotoxic effects on patients with heart disease. The treatment of depression in these patients has become a much lower risk since the introduction of serotonin reuptake inhibitors. There is widespread evidence that depressive comorbidity has a negative impact on the prognosis of medical disorders. Despite the complex nature of diagnosing depression, proper diagnosis and treatment is increasingly important in internal medicine and especially cardiology.

Nondermatomal somatosensory deficits in patients with chronic pain disorder: clinical findings and hypometabolic pattern in FDG-PET

Patients with chronic pain disorders often show somatosensory disturbances that are considered to be functional. This paper aims at a more precise clinical description and at a documentation of functional neuroimaging correlates of this phenomenon. We examined 30 consecutive patients with unilaterally accentuated chronic pain not explained by persistent peripheral tissue damage and ipsilateral somatosensory disturbances including upper and lower extremities and trunk. The patients were assessed clinically and with conventional brain CT or MRI scan. In the last 11 patients functional neuroimaging was carried out (18-fluordeoxyglucose positron emission tomography=FDG-PET). Depressive symptoms were assessed with the Hamilton depression scale (HAMD-17) and pain intensity was rated with a visual analogue scale for pain (VAS). All patients suffered from mild to moderate depressive symptoms. All patients had experienced a prolonged antecedent phase of severe emotional distress; most of them remembered a "trigger episode of somatic pain" on the affected side. Somatosensory deficits were a replicable hyposensitivity to touch and heat perception of nondermatomal distribution. Conventional imaging procedures (brain CT or MRI scans) showed no structural changes. However, in 11 patients functional imaging with FDG-PET showed a significant hypometabolic pattern of changes in cortical and subcortical areas, mainly in the post-central gyrus, posterior insula, putamen, and anterior cingulate cortex. In summary, pain-related nondermatomal somatosensory deficits (NDSDs) are a phenomenon involving biological as well as psychosocial factors with replicable neuroperceptive clinical findings and a complex neurodysfunctional pattern in the FDG-PET.

The relationship between pain intensity and severity and depression in older people: exploratory study

BACKGROUND: Pain and depression are known to be associated in later life, and both have a negative effect on physical performance both separately and in combination. The nature of the relationships between pain intensity and depression in elderly persons experiencing pain is less clear. The objectives of this study were to explore which factors are associated with depressed mood in older people experiencing pain, and to test the hypothesis that older people experiencing pain are at risk of depressed mood according to the severity or frequency of their pain. In addition we explored whether other potentially modifiable factors might increase the risk of depressed mood in these persons. METHODS: The study is a secondary analysis of baseline data for four hundred and six community-dwelling non-disabled people aged 65 and over registered with three group practices in suburban London who had experienced pain in the past 4 weeks. Intensity and frequency of pain was measured using 24 item Geriatric Pain Measure (GPM) and the presence of depressive symptoms using the 5 item Mental Health Inventory. Risk for social isolation was measured using the 6 item Lubben Social Network scale and instrumental activities of daily living (IADL) were also measured. RESULTS: Overall 76 (19%) had depressed mood. Pain frequency and severity were not statistically significantly associated with depressed mood in this population. In multivariate analyses, significant predictors of the presence of depressive symptoms were difficulties with basic ADLs (OR 2.8, 95% CI 1.1.7.8), risk for social isolation (OR 4.1, 95% CI 1.8-9.3), and basic education only (OR 2.2, 95% CI 1.1-4.4). CONCLUSION: Older people experiencing pain are also likely to experience depression. Among those experiencing pain, social network and functional status seem to be more important predictors of depressive symptoms than the severity of pain. Further studies should evaluate whether improvement of social network and functional status might reduce depressive symptoms in older patients.

Comparative efficacy of seven psychotherapeutic interventions for patients with depression: a network meta-analysis

BACKGROUND Previous meta-analyses comparing the efficacy of psychotherapeutic interventions for depression were clouded by a limited number of within-study treatment comparisons. This study used network meta-analysis, a novel methodological approach that integrates direct and indirect evidence from randomised controlled studies, to re-examine the comparative efficacy of seven psychotherapeutic interventions for adult depression. METHODS AND FINDINGS We conducted systematic literature searches in PubMed, PsycINFO, and Embase up to November 2012, and identified additional studies through earlier meta-analyses and the references of included studies. We identified 198 studies, including 15,118 adult patients with depression, and coded moderator variables. Each of the seven psychotherapeutic interventions was superior to a waitlist control condition with moderate to large effects (range d = -0.62 to d = -0.92). Relative effects of different psychotherapeutic interventions on depressive symptoms were absent to small (range d = 0.01 to d = -0.30). Interpersonal therapy was significantly more effective than supportive therapy (d = -0.30, 95% credibility interval [CrI] [-0.54 to -0.05]). Moderator analysis showed that patient characteristics had no influence on treatment effects, but identified aspects of study quality and sample size as effect modifiers. Smaller effects were found in studies of at least moderate (Δd = 0.29 [-0.01 to 0.58]; p = 0.063) and large size (Δd = 0.33 [0.08 to 0.61]; p = 0.012) and those that had adequate outcome assessment (Δd = 0.38 [-0.06 to 0.87]; p = 0.100). Stepwise restriction of analyses by sample size showed robust effects for cognitive-behavioural therapy, interpersonal therapy, and problem-solving therapy (all d>0.46) compared to waitlist. Empirical evidence from large studies was unavailable or limited for other psychotherapeutic interventions. CONCLUSIONS Overall our results are consistent with the notion that different psychotherapeutic interventions for depression have comparable benefits. However, the robustness of the evidence varies considerably between different psychotherapeutic treatments.

A longitudinal study on delirium in nursing homes

OBJECTIVE To investigate the evolution of delirium of nursing home (NH) residents and their possible predictors. DESIGN Post-hoc analysis of a prospective cohort assessment. SETTING Ninety NHs in Switzerland. PARTICIPANTS Included 14,771 NH residents. MEASUREMENTS The Resident Assessment Instrument Minimum Data Set and the Nursing Home Confusion Assessment Method were used to determine follow-up of subsyndromal or full delirium in NH residents using discrete Markov chain modeling to describe long-term trajectories and multiple logistic regression analyses to determine predictors of the trajectories. RESULTS We identified four major types of delirium time courses in NH. Increasing severity of cognitive impairment and of depressive symptoms at the initial assessment predicted the different delirium time courses. CONCLUSION More pronounced cognitive impairment and depressive symptoms at the initial assessment are associated with different subsequent evolutions of delirium. The presence and evolution of delirium in the first year after NH admission predicted the subsequent course of delirium until death.

Predictors of temporary and permanent work disability in patients with inflammatory bowel disease: results of the swiss inflammatory bowel disease cohort study

BACKGROUND Inflammatory bowel disease can decrease the quality of life and induce work disability. We sought to (1) identify and quantify the predictors of disease-specific work disability in patients with inflammatory bowel disease and (2) assess the suitability of using cross-sectional data to predict future outcomes, using the Swiss Inflammatory Bowel Disease Cohort Study data. METHODS A total of 1187 patients were enrolled and followed up for an average of 13 months. Predictors included patient and disease characteristics and drug utilization. Potential predictors were identified through an expert panel and published literature. We estimated adjusted effect estimates with 95% confidence intervals using logistic and zero-inflated Poisson regression. RESULTS Overall, 699 (58.9%) experienced Crohn's disease and 488 (41.1%) had ulcerative colitis. Most important predictors for temporary work disability in patients with Crohn's disease included gender, disease duration, disease activity, C-reactive protein level, smoking, depressive symptoms, fistulas, extraintestinal manifestations, and the use of immunosuppressants/steroids. Temporary work disability in patients with ulcerative colitis was associated with age, disease duration, disease activity, and the use of steroids/antibiotics. In all patients, disease activity emerged as the only predictor of permanent work disability. Comparing data at enrollment versus follow-up yielded substantial differences regarding disability and predictors, with follow-up data showing greater predictor effects. CONCLUSIONS We identified predictors of work disability in patients with Crohn's disease and ulcerative colitis. Our findings can help in forecasting these disease courses and guide the choice of appropriate measures to prevent adverse outcomes. Comparing cross-sectional and longitudinal data showed that the conduction of cohort studies is inevitable for the examination of disability.

Cortisol levels and history of depression in acute coronary syndrome patients

BACKGROUND: Depressed mood following an acute coronary syndrome (ACS) is a risk factor for future cardiac morbidity. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with depression, and may be a process through which depressive symptoms influence later cardiac health. Additionally, a history of depression predicts depressive symptoms in the weeks following ACS. The purpose of this study was to determine whether a history of depression and/or current depression are associated with the HPA axis dysregulation following ACS. METHOD: A total of 152 cardiac patients completed a structured diagnostic interview, a standardized depression questionnaire and a cortisol profile over the day, 3 weeks after an ACS. Cortisol was analysed using: the cortisol awakening response (CAR), total cortisol output estimated using the area under the curve method, and the slope of cortisol decline over the day. RESULTS: Total cortisol output was positively associated with history of depression, after adjustment for age, gender, marital status, ethnicity, smoking status, body mass index (BMI), Global Registry of Acute Cardiac Events (GRACE) risk score, days in hospital, medication with statins and antiplatelet compounds, and current depression score. Men with clinically diagnosed depression after ACS showed a blunted CAR, but the CAR was not related to a history of depression. CONCLUSIONS: Patients with a history of depression showed increased total cortisol output, but this is unlikely to be responsible for associations between depression after ACS and later cardiac morbidity. However, the blunted CAR in patients with severe depression following ACS indicates that HPA dysregulation is present.

The EVIDENT-trial: protocol and rationale of a multicenter randomized controlled trial testing the effectiveness of an online-based psychological intervention

BACKGROUND: Depressive disorders are among the leading causes of worldwide disability with mild to moderate forms of depression being particularly common. Low-intensity treatments such as online psychological treatments may be an effective way to treat mild to moderate depressive symptoms and prevent the emergence or relapse of major depression. METHODS/DESIGN: This study is a currently recruiting multicentre parallel-groups pragmatic randomized-controlled single-blind trial. A total of 1000 participants with mild to moderate symptoms of depression from various settings including in- and outpatient services will be randomized to an online psychological treatment or care as usual (CAU). We hypothesize that the intervention will be superior to CAU in reducing depressive symptoms assessed with the Personal Health Questionnaire (PHQ-9, primary outcome measure) following the intervention (12 wks) and at follow-up (24 and 48 wks). Further outcome parameters include quality of life, use of health care resources and attitude towards online psychological treatments. DISCUSSION: The study will yield meaningful answers to the question of whether online psychological treatment can contribute to the effective and efficient prevention and treatment of mild to moderate depression on a population level with a low barrier to entry. TRIAL REGISTRATION: Trial Registration Number: NCT01636752.

Association between hospice care and psychological outcomes in Alzheimer's spousal caregivers.

CONTEXT Dementia care giving can lead to increased stress, physical and psychosocial morbidity, and mortality. Anecdotal evidence suggests that hospice care provided to people with dementia and their caregivers may buffer caregivers from some of the adverse outcomes associated with family caregiving in Alzheimer's Disease (AD). OBJECTIVES This pilot study examined psychological and physical outcomes among 32 spousal caregivers of patients with AD. It was hypothesized that caregivers who utilized hospice services would demonstrate better outcomes after the death of their spouse than caregivers who did not utilize hospice. METHODS The charts of all spousal caregivers enrolled in a larger longitudinal study from 2001 to 2006 (N=120) were reviewed, and participants whose spouse had died were identified. Of these, those who received hospice care (n=10) were compared to those who did not (n=22) for various physiological and psychological measures of stress, both before and after the death of the care recipient. An Analysis of Covariance (ANCOVA), with postdeath scores as the dependent variable and pre-death scores as covariates, was used for all variables. RESULTS Significant group differences were found in postdeath depressive symptoms (HAM-D; F(1,29)=6.10, p<0.05) and anxiety symptoms (HAM-A; F(1,29)=5.71, p<0.05). Most psychological outcome variables demonstrated moderate effect sizes with a Cohen's d of>0.5 between groups. CONCLUSIONS These data suggest that hospice enrollment may ameliorate the detrimental psychological effects in caregivers who have lost a spouse with Alzheimer's Disease. Based on these pilot data, further prospective investigation is warranted.

A randomized clinical trial of Behavioral Activation (BA) therapy for improving psychological and physical health in dementia caregivers: results of the Pleasant Events Program (PEP).

Dementia caregiving is associated with elevations in depressive symptoms and increased risk for cardiovascular diseases (CVD). This study evaluated the efficacy of the Pleasant Events Program (PEP), a 6-week Behavioral Activation intervention designed to reduce CVD risk and depressive symptoms in caregivers. One hundred dementia family caregivers were randomized to either the 6-week PEP intervention (N = 49) or a time-equivalent Information-Support (IS) control condition (N = 51). Assessments were completed pre- and post-intervention and at 1-year follow-up. Biological assessments included CVD risk markers Interleukin-6 (IL-6) and D-dimer. Psychosocial outcomes included depressive symptoms, positive affect, and negative affect. Participants receiving the PEP intervention had significantly greater reductions in IL-6 (p = .040), depressive symptoms (p = .039), and negative affect (p = .021) from pre- to post-treatment. For IL-6, clinically significant improvement was observed in 20.0% of PEP participants and 6.5% of IS participants. For depressive symptoms, clinically significant improvement was found for 32.7% of PEP vs 11.8% of IS participants. Group differences in change from baseline to 1-year follow-up were non-significant for all outcomes. The PEP program decreased depression and improved a measure of physiological health in older dementia caregivers. Future research should examine the efficacy of PEP for improving other CVD biomarkers and seek to sustain the intervention's effects.

Psychological adaptation to spousal loss in old age: The role of personality

Spousal loss is an inevitable critical life event for most individuals in old age, mostly associated with a negative impact on various well-being measures, ie. lower life satisfaction, higher rates of loneliness and depressive symptoms compared to married peers. While the negative effects on well-being are well documented in literature, the modifying factors accounting for the large variability in adaptation to loss are discussed controversially. The potential relevance of personality in the adaptation process has rarely been examined and findings regarding the role of time since loss are contradictory. Based on a vulnerability-stress-model this contribution aims a) to compare psychological well-being of bereaved individuals with married counterparts and b) to investigate the protective effects of different personality traits (Big Five, resilience), and the role of time since loss for adaptation in terms of life satisfaction, loneliness and depression. Data from a questionnaire study about the loss of a spouse in middle and old age in the German- and French-speaking parts of Switzerland are reported. The study is part of the Swiss National Centre of Competence in Research LIVES (Swiss National Science Foundation). The sample consists of 351 widowed persons (39% men, widowed since 0 - 5 years), and 605 married controls (50% men), aged 60 - 89 years. Group comparisons reveal the detrimental effect of spousal bereavement on all indicators of psychological adaptation. Results from hierarchical regression analyses show furthermore, that the effect of spousal loss on all psychological outcomes is moderated by personality traits. Separate analyses with the group of bereaved individuals suggest, that the protective effect of personality varies by the time passed since loss. Our results contribute to a better understanding of the variability in psychological adaptation to spousal loss in old age and give hints for counselling practice.

Comparative Behavioral and Neural Effects of Tryptophan and Catecholamine Depletion in Remitted Depression

Background: Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catechominergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or catecholamine neurotransmission hold the potential to optimize the prescriber’s selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Methods: Using identical neuroimaging procedures with [18F] fluorodeoxyglucose positron emission tomography after tryptophan depletion (TD) and catecholamine depletion (CD), subjects with remitted depression were compared to healthy controls in a double-blind, randomized, crossover design. Results: While TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex (PCC). While we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. Conclusions: In conclusion, this study showed that serotonin and catecholamines play common and differential roles in the pathophysiology of depression.