http://www.smhc.org.cn/uploadfiles/2014/09/20140929090442442.pdf

A Meta-Analysis of Cytokines in Major Depression

The Multi-Ethnic Study of Atherosclerosis was initiated in July 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease (CVD) in a population-based sample of 6,500 men and women aged 45-84 years. The cohort will be selected from six US field centers. Approximately 38% of the cohort will be White, 28% African-American, 23% Hispanic, and 11% Asian (of Chinese descent). Baseline measurements will include measurement of coronary calcium using computed tomography; measurement of ventricular mass and function using cardiac magnetic resonance imaging; measurement of flow-mediated brachial artery endothelial vasodilation, carotid intimal-medial wall thickness, and distensibility of the carotid arteries using ultrasonography; measurement of peripheral vascular disease using ankle and brachial blood pressures; electrocardiography; and assessments of microalbuminuria, standard CVD risk factors, sociodemographic factors, life habits, and psychosocial factors. Blood samples will be assayed for putative biochemical risk factors and stored for use in nested case-control studies. DNA will be extracted and lymphocytes will be immortalized for genetic studies. Measurement of selected subclinical disease indicators and risk factors will be repeated for the study of progression over 7 years. Participants will be followed through 2008 for identification and characterization of CVD events, including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, and congestive heart failure; therapeutic interventions for CVD; and mortality.

/pdf/multi-ethnic-study-of-atherosclerosis-objectives-and-design-2ly8fyhifg.pdf

Multi-Ethnic Study of Atherosclerosis: Objectives and Design

Because depression and painful symptoms commonly occur together, we conducted a literature review to determine the prevalence of both conditions and the effects of comorbidity on diagnosis, clinical outcomes, and treatment. The prevalences of pain in depressed cohorts and depression in pain cohorts are higher than when these conditions are individually examined. The presence of pain negatively affects the recognition and treatment of depression. When pain is moderate to severe, impairs function, and/or is refractory to treatment, it is associated with more depressive symptoms and worse depression outcomes (eg, lower quality of life, decreased work function, and increased health care utilization). Similarly, depression in patients with pain is associated with more pain complaints and greater impairment. Depression and pain share biological pathways and neurotransmitters, which has implications for the treatment of both concurrently. A model that incorporates assessment and treatment of depression and pain simultaneously is necessary for improved outcomes.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/216320/ira30040_2433_2445.pdf

Depression and pain comorbidity: a literature review.

Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.

Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.

https://stevebmd.files.wordpress.com/2011/04/cytokines-sing-the-blues2006.pdf

Cytokines sing the blues: inflammation and the pathogenesis of depression

This article reviews the challenge of diagnosing depression in patients with cancer. Major depression and depressive symptoms, although commonly encountered in medical populations, are frequently underdiagnosed and undertreated. This is especially true for patients with cancer in whom the diagnosis of major depression is clouded by neurovegetative symptoms that may be secondary to either cancer or depression. Well-established biological markers for major depression are proposed as diagnostic adjuncts in patients with cancer. Studies using biological markers in depressed patients with and without cancer are reviewed, and the implications of diminished immune function in depressed patients with cancer are discussed. The limited database on treatment of depression in patients with cancer also is reviewed. Treatment of depression in these patients improves their dysphoria and other signs and symptoms of depression, improves quality of life, and may improve immune function and survival time. Guidelines for future research are proposed.

Depression in Patients With Cancer: Diagnosis, Biology, and Treatment

Objective: This study iizvestigated whether depressed patients exhibit exaggerated platelet reactivity. Method: In vivo platelet activatioiz, secretioz, and dose-response aggregation were measured in 12 depressed patients and eight normal comparison subjects after overizight bed rest aizd following orthostatic challenge. Results: The depressed patients exhibited increased platelet activation at baseli,ze, demonstrated by increased binding of monoclonal antibody (moAb) annexin V protein reacting with prothrombinase complex binding sites. Followizg orthostatic challeizge, the depressed patients exhibited increases in binding of moAbs PACI a,zd anti-LIBS1 agaiizst actii'atedglycoprotein Jib/lila and GEI2 against P-selecti,z expressed 111)01? secretion. The normal comparison subjects exhibited increases in platelet activatioz only with GE I 2. Conclusions: Depressed patients exhibit enhazced baseline platelet activation and respozsiveness in comparisoz with normal subjects. Heightened susceptibility to platelet acti- vation flltlV he a mechanism b�' which depression is a significant risk factor for ischemic heart azd cerebrovascular disease and/or mortality after myocardial infarction. (AmJ Psychiatry 1996; 153:1313-1317)

Exaggerated platelet reactivity in major depression.

Objective: This study investigated whether cancer patients with and without major depression exhibit immune system abnormalities similar to those reported in medically healthy, depressed subjects without cancer. Method: The study subjects consisted of patients diagnosed with pancreatic, esophageal, or breast cancer. Other groups consisted of subjects with major depression (without cancer) and healthy comparison subjects. Subjects’ diagnoses were made with the Structured Clinical Interview for DSM-III-R. Severity of depression was measured with the Hamilton Depression Rating Scale. Plasma concentrations of interleukin-6 (IL-6) and postdexamethasone cortisol were measured. Results: Cancer patients with depression had markedly higher plasma concentrations of IL-6 than healthy comparison subjects and cancer patients without depression. Although significant correlations were found between Hamilton depression scale scores and plasma concentrations of postdexamethasone cortisol, no significant correlations were found between plasma IL-6 and postdexamethasone cortisol concentrations. Conclusions: Higher than normal plasma IL-6 concentrations were associated with a diagnosis of major depression in cancer patients. IL-6 may contribute to sickness behavior that has overlapping symptoms with major depression. (Am J Psychiatry 2001; 158:1252–1257) Cancer patients, who experience marked physiologic, economic, and psychological stressors, have long been observed to have elevated prevalence rates of major depression, compared with the general population (1). Among cancer patients, the highest prevalence rates are exhibited by patients with either oropharyngeal cancer (2–4) or pancreatic cancer (5–7). Prospective or crosssectional studies of patients with pancreatic cancer have documented a remarkable point prevalence rate of depression of 50% (5–8). Although a number of neurochemical, neuroendocrine, neuroanatomical, and neuroimmune alterations have been associated with unipolar depression, few of these psychobiologic alterations have been systematically investigated in cancer patients with depression.

https://ajp.psychiatryonline.org/doi/pdfplus/10.1176/appi.ajp.158.8.1252

Maryfrances R. Porter

Papers

Depression in Patients With Cancer: Diagnosis, Biology, and Treatment

Exaggerated platelet reactivity in major depression.

Higher Than Normal Plasma Interleukin-6 Concentrations in Cancer Patients With Depression: Preliminary Findings

Screening for depression.