Estrogen and autoimmune disease.

Estrogenic hormones possess both immunostimulating and immunosuppressive properties. In systemic lupus erythematosus (SLE), pregnancy is associated with disease flares. In some situations, exogenous estrogen predisposes to development of new SLE, flares of preexisting SLE, and thromboses in susceptible individuals. In contrast, treatment with exogenous estrogen protects postmenopausal rheumatoid arthritis (RA) patients from active RA and osteoporosis. The search for estrogen-like compounds with anti-inflammatory properties may expand treatment options in RA.

Plasma lipid-dependent and -independent effects of dietary soy protein and social status on atherogenesis in premenopausal monkeys: implications for postmenopausal atherosclerosis burden.

OBJECTIVE: : Atherosclerosis developed during premenopausal years predicts postmenopausal atherosclerosis burden. The objective of this study was to determine the effects of dietary soy protein isolate (SPI) and social status on atherogenesis and arterial gene expression in a premenopausal monkey model. DESIGN: : Socially housed premenopausal cynomolgus macaques (n = 84) were fed an atherogenic diet deriving protein from casein/lactalbumin or SPI (containing 1.88 mg isoflavones/g). After 36 months of diet consumption, iliac artery biopsies were assessed for atherosclerosis and expression of mRNA transcripts related to inflammation, macrophage and T-cell content, and estrogen receptors (ERs). RESULTS: : SPI reduced plaque size (P < 0.05), total plasma cholesterol, non-high-density lipoprotein cholesterol (HDLc), and the total plasma cholesterol/HDLc ratio (all P < 0.003), while increasing triglycerides (P < 0.006) and HDLc (P < 0.0001). Arterial mRNA for CD68 (P < 0.001), CD3 (P < 0.02), and CD4 (P < 0.001) and inflammatory markers monocyte chemotactic protein-1, intercellular adhesion molecule-1, and interleukin-6 (all P < 0.0001) were also lower in the group receiving SPI. For most outcomes, this effect remained even after adjustments for plaque size and plasma lipid concentrations. Arterial ER-alpha was inversely associated with atherosclerosis (P < 0.02) and increased with SPI (P < 0.001). Subordinate monkeys had lower ER-beta (P < 0.02) and higher interleukin-6 (P < 0.05) transcripts but did not differ from dominant monkeys in extent of atherosclerosis (P > 0.9). CONCLUSIONS: : Premenopausal consumption of SPI had plasma lipid-independent beneficial effects on the pathobiological processes involved in atherosclerotic plaque development, thus potentially establishing the basis for reduced postmenopausal complications. Dominant social status provided similar, albeit less extensive, benefits in risk markers.

Effects of dietary soy protein on iliac and carotid artery atherosclerosis and gene expression in male monkeys.

Male cynomolgus macaques (n=91) consumed an isoflavone (IF)-free, atherogenic control diet containing casein/lactalbumin for 5 months, then were randomized to three groups: control (n=30) continued on the control diet; low IF (n=30) received a mixture of unmodified and IF-depleted soy protein isolate (SPI) (0.94 mg IF/g protein, approximating a human intake of 75 mg/day); high IF (n=31) received unmodified SPI (1.88 mg IF/g protein, approximating a human intake of 150 mg/day) for 31 months. Iliac and carotid artery atherosclerosis, and arterial and hepatic mRNA transcripts related to inflammation and estrogen receptors (ER) were measured. Trend analysis identified a significant inverse relationship between dietary IF content and plaque area in the iliac (p<0.05) but not carotid arteries (p>0.13). No significant effect of diet on inflammatory gene or estrogen receptor expression was observed. Plaque area was positively correlated with the mRNA transcript levels for arterial MCP-1, ICAM-1, and the macrophage marker CD68 (all r>0.25, p<0.03), and negatively correlated with ER alpha and ER beta (all r<-0.23, p<0.03). Coronary artery plaque area appeared to be more closely associated with gene expression patterns of the iliac arteries than the carotid arteries. The data suggests benefits of dietary soy on atherosclerotic plaque development in males may be mediated through inflammation-independent pathways. The negative associations of arterial ER alpha expression with atherosclerosis lend support to a mechanistic role for estrogen receptors in atherosclerosis susceptibility which merits further study.

Rheumatoid arthritis: A review.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with primary manifestations in the diarthrodial (movable) joints. Methotrexate in weekly doses is the most widely used disease modifying agent. The recent development of biologic agents designed to shut off disease activity can be of great benefit to individuals who fail methotrexate therapy. New treatments such as tumor necrosis factor suppressants are effective in up to 80% of patients. It is extremely important to diagnose RA in its earliest stages so that patients may benefit from antimetabolites and biologics before permanent joint damage takes place.

Relationship of psychiatric history to pain reports in rheumatoid arthritis.

OBJECTIVE: The purpose was to examine the relationship of pre-existing psychiatric history to pain reports in a cohort of persons with RA and concomitant major depression who were receiving a trial of antidepressant medication. METHOD: RA patients (n = 41) with a current episode of major depression were divided into two subgroups comprised of those with a previous psychiatric history (PSY+) (n = 20) and those without a previous psychiatric history (PSY-) (n = 21). The groups were compared with regard to their responsiveness to a regimen of antidepressive medication on measures of depression, pain, coping, and life stress over a period of 15 months. RESULTS: Although depression scores for both the PSY+ and the PSY- groups decreased significantly from baseline to 15-month follow-up, the composite pain score was found to be significantly decreased only for the PSY- group. CONCLUSION: Psychiatric history appears to predispose persons with concomitant RA and major depression to report less pain reduction following antidepressive treatment than those persons without a psychiatric history.

Analyzing reliability of change in depression among persons with rheumatoid arthritis.

OBJECTIVE: To examine several methods of determining reliability of change constructs in depressive symptoms in patients with rheumatoid arthritis (RA) and to demonstrate the strengths, weaknesses, and uses of each method. METHODS: Data were analyzed from a cohort of 54 persons with RA who participated in a combined behavioral/pharmacologic intervention of 15 months duration. These longitudinal data were used to examine 3 methodologies for assessing the reliability of change for various measures of depression. The specific methodologies involved the calculations of reliable change, sensitivity to change, and reliability of the change score. RESULTS: The analyses demonstrated differences in reliability of change performance across the various depression measures, which suggest that no single measure of depression for persons with RA should be considered superior in all contexts. CONCLUSION: The findings highlight the value of utilizing reliability of change constructs when examining changes in depressive symptoms over time.

Health status, cognitive coping, and depressive symptoms: testing for a mediator effect.

OBJECTIVE: Research has established a link between health status and symptoms of depression in persons with rheumatoid arthritis (RA), but the effects of "cognitive coping" variables have not been extensively studied. We examined the mediator effect of a cognitive coping variable (Pain Control and Rational Thinking factor score from the Coping Strategies Questionnaire) over the course of a pharmacological intervention. METHOD: Data were analyzed from 54 persons with RA, all of whom met diagnostic criteria for major depression. Measures of depression, health status, and cognitive coping were collected at 4 different stages of a pharmacological (antidepressant) study as follows: (1) at baseline, (2) postintervention, (3) 6 month followup, and (4) 15 month followup. RESULTS: Results indicated that a direct relationship existed between health status and depression at all 4 time periods. However, this relationship was mediated by cognitive coping only at the postintervention and the 6 month followup. CONCLUSION: A cognitive coping variable was found to mediate the relationship between health status and depression, but only at moderate levels of depression.

Anxiety in rheumatoid arthritis.

OBJECTIVE: To examine the level of anxiety experienced by individuals with rheumatoid arthritis (RA). METHODS: Data from 2 previous studies were used to compare the level of anxiety (measured by the State-Trait Anxiety Inventory) in the following 4 subgroups: a general RA sample, a general osteoarthritis sample, a sample with both RA and major depression, and a normative sample of age-equivalent, working adults. Canonical correlations were used to examine associations between measures of anxiety and measures of both stress and depression. The relationship between anxiety and duration of RA was also explored. RESULTS: The general RA sample had state anxiety levels that were comparable to the normative sample, although trait anxiety levels were significantly higher (P < 0.001). In addition, individuals with RA who also met criteria for depression exhibited significantly higher levels of both state anxiety (P < 0.0001) and trait anxiety (P < 0.0001) than was observed in the normative sample. Canonical correlations revealed that measures of anxiety were correlated with both measures of depression (r = 0.83) and measures of stress (r = 0.50). Anxiety was not found to be significantly related to RA disease duration. CONCLUSION: These findings demonstrated that individuals with RA, especially if concomitantly depressed, tend to exhibit levels of anxiety that are generally higher than a normative group of age-equivalent, working adults. The substantial canonical correlations between anxiety and both depression and stress revealed that anxiety shares variance with these more frequently studied variables in RA. However, anxiety was not found to be related to RA disease duration.

Management of depression in rheumatoid arthritis: a combined pharmacologic and cognitive-behavioral approach.

OBJECTIVE: To examine the effectiveness of cognitive-behavioral and pharmacologic treatment of depression in rheumatoid arthritis (RA). METHODS: Subjects (n = 54) with confirmed diagnoses of both major depression and RA were randomly assigned to 1 of 3 groups: 1) cognitive-behavioral/pharmacologic group (CB-PHARM), 2) attention-control/pharmacologic group, or 3) pharmacologic control group. Measures of depression, psychosocial status, health status, pain, and disease activity were collected at baseline, posttreatment (10 weeks), 6-month followup, and 15-month followup. Data were analyzed to compare the treatment effectiveness of the groups; data also were aggregated to examine the effects of antidepressive medication over time. Lastly, a no-treatment control group was defined from a cohort of persons who declined participation. RESULTS: Baseline comparisons on demographic and dependent measures revealed a need to assess covariates on age and education; baseline scores on dependent measures also were entered as covariates. Analyses of covariance revealed no statistically significant group differences at postintervention, 6-month followup, or 15-month followup, except higher state and trait anxiety scores for the CB-PHARM group at the 15-month followup. In the longitudinal analyses of the effects of antidepressive medication, significant improvement in psychological status and health status were found at posttreatment, 6-month followup, and 15-month followup, but no significant improvements were shown for pain or disease activity. In addition, the comparison of the aggregated pharmacologic group with a no-treatment group revealed a statistically significant benefit for the 3 groups that received the antidepressive medication. CONCLUSION: In persons with RA, cognitive-behavioral approaches to the management of depression were not found to be additive to antidepressant medication alone, but antidepressant intervention was superior to no treatment.

Assessment of depression in rheumatoid arthritis: a modified version of the center for epidemiologic studies depression scale.

OBJECTIVE: The Center for Epidemiologic Studies Depression Scale (CES-D) is an instrument commonly used to assess depressive symptoms. Although the psychometric properties of the instrument are well established, the instrument's ability to identify confirmed cases of major depression has been unclear. The purpose of this study was to evaluate the ability of cutoff scores from both a full scale and a modified CES-D to detect major depression in people with rheumatoid arthritis (RA). METHOD: Data were analyzed from 457 persons with RA, including 91 who met criteria for major depression. RESULTS: Results indicated that, in general, a full scale cutoff score of 19 was the most efficient in identifying cases of major depression; the cutoff score of 19 outperformed a variety of other cutoff scores from the modified scale. Even the most efficient cutoff scores, however, demonstrated problems in accurately identifying people with depression. CONCLUSION: The CES-D, while potentially useful as a screening tool, should not be used to identify cases of major depression.