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Biomedical subjects

Mark Cary

Publications and source records attributed to Mark Cary.

4 recordsLinked to original sources

Simvastatin causes changes in affective processes in elderly volunteers.

OBJECTIVES: To test for simvastatin-induced changes in affect and affective processes in elderly volunteers. DESIGN: Randomized, clinical trial. SETTING: The Geriatric Behavioral Psychopharmacology Laboratory at the University of Pennsylvania. PARTICIPANTS: Eighty older volunteers, average age 70, with high normal/mildly elevated serum cholesterol. INTERVENTION: Simvastatin up to 20 mg/d or placebo for 15 weeks. MEASUREMENTS: Daily diary records of positive and negative affects and of events and biweekly measures of depressive symptoms. Affect ratings were obtained using the Lawton positive and negative affect scales; independent raters coded the valences of events. RESULTS: Thirty-one of 39 subjects assigned to placebo and 33 of 41 receiving simvastatin completed the study. During biweekly assessments, four subjects on simvastatin and one on placebo experienced depressive symptoms, as manifest by Center for Epidemiological Studies Depression scale scores greater than 16 (exact P=.36). Diary data demonstrated significant effects on affective processes. For positive affect, there was a significant medication-by-time interaction that reflected decreases in positive affect in subjects receiving simvastatin, greatest in those patients whose final total cholesterol levels were below 148 mg/dL. For negative affect, there were significant medication-by-event, and medication-by-event-by-time interactions, reflecting a time-limited increase in the apparent effect of negative events. CONCLUSION: Simvastatin has statistically significant effects on affect and affective processes in elderly volunteers. The decrease in positive affect may be significant clinically and relevant to the quality of life of many patients.

Affect↗

The role of stress-induced cortisol in the relationship between depression and decreased bone mineral density.

BACKGROUND: This study was designed to test the hypothesis that cortisol mediates the relationship between bone density and depression in postmenopausal women. METHODS: Nineteen women aged 52-79 who had been assessed for bone mineral density by dual-energy x-ray absorptiometer (DEXA) were evaluated for depression and anxiety. Diurnal and stress-induced measures of salivary cortisol were obtained during the following week and at a laboratory session involving a speech task. RESULTS: Nine volunteers reported depression while 10 were never depressed. Ever depressed women had significantly lower total lumbar and right femur DEXA Z scores than never depressed (t(17) = 2.5, p = .019 and t(17) = 2.06, p = .05, respectively). Ever depressed women demonstrated a significant increase in salivary cortisol (area under the curve (AUC) = 27.83, SD = 37.64) compared to never depressed women (AUC = -13.34, SD = 19.55) (t(17) = -3.041, p = .007) during a psychological challenge. There were significant inverse relationships between salivary cortisol AUC values and bone density Z scores at every measured bone site. Mediation analyses suggest that 51 - 67% of the association between depression and bone density could be attributed to stress-induced changes in cortisol. CONCLUSIONS: Cortisol hypersecretion in response to stress may, in part, explain the impact of depression on bone density in post-menopausal women.

Absorptiometry, Photon↗

Association of resolution of major depression with increased natural killer cell activity among HIV-seropositive women.

OBJECTIVE: Depression is a potential risk factor for morbidity and mortality among patients with numerous medical conditions, including HIV disease, and it is also associated with decrements in immune function, such as natural killer (NK) cell activity. This study examined whether improvements in the diagnostic status of major depression are related to increases in NK cell activity among HIV-seropositive women. METHOD: HIV-seropositive women were recruited as part of a longitudinal cohort study and underwent comprehensive medical and psychiatric evaluations during a 2-year period. Fifty-seven women had complete NK cell activity and depression data measured at two time points and were examined for associations between changes in depression status and alterations in NK cell activity over time. RESULTS: Among the 57 HIV-seropositive women, improvements in the diagnostic status of depression and decreases in scores on the 17-item Hamilton Depression Rating Scale were significantly associated with increases in NK cell activity over time, as measured in lytic units. Eleven women (19.3%) had a major depression diagnosis that resolved over time, and this group also had a significant increase in cell activity measured in lytic units during this period. CONCLUSIONS: This study suggests that depression may impair certain aspects of innate cellular immunity relevant to delaying the progression of HIV disease and that these alterations are reversible with the resolution of a depressive episode. These findings support an examination of NK cell activity in assessments of the relationship between depression and morbidity and mortality in HIV disease.

Adult↗

Causal logistic models for non-compliance under randomized treatment with univariate binary response.

We propose a method for estimating the marginal causal log-odds ratio for binary outcomes under treatment non-compliance in placebo-randomized trials. This estimation method is a marginal alternative to the causal logistic approach by Nagelkerke et al. (2000) that conditions on partially unknown compliance (that is, adherence to treatment) status, and also differs from previous approaches that estimate risk differences or ratios in subgroups defined by compliance status. The marginal causal method proposed in this paper is based on an extension of Robins' G-estimation approach for fitting linear or log-linear structural nested models to a logistic model. Comparing the marginal and conditional causal log-odds ratio estimates provides a way of assessing the magnitude of unmeasured confounding of the treatment effect due to treatment non-adherence. More specifically, we show through simulations that under weak confounding, the conditional and marginal procedures yield similar estimates, whereas under stronger confounding, they behave differently in terms of bias and confidence interval coverage. The parametric structures that represent such confounding are not identifiable. Hence, the proof of consistency of causal estimators and corresponding simulations are based on two different models that fully identify the causal effects being estimated. These models differ in the way that compliance is related to potential outcomes, and thus differ in the way that the causal effect is identified. The simulations also show that the proposed marginal causal estimation approach performs well in terms of bias under the different levels of confounding due to non-adherence and under different causal logistic models. We also provide results from the analyses of two data sets further showing how a comparison of the marginal and conditional estimators can help evaluate the magnitude of confounding due to non-adherence.

Confounding Factors, Epidemiologic↗