Elevated stress-hemoconcentration in major depression is normalized by antidepressant treatment: secondary analysis from a randomized, double-blind clinical trial and relevance to cardiovascular disease risk.

BACKGROUND: Major depressive disorder (MDD) is an independent risk factor for cardiovascular disease (CVD); the presence of MDD symptoms in patients with CVD is associated with a higher incidence of cardiac complications following acute myocardial infarction (MI). Stress-hemoconcentration, a result of psychological stress that might be a risk factor for the pathogenesis of CVD, has been studied in stress-challenge paradigms but has not been systematically studied in MDD. METHODS: Secondary analysis of stress hemoconcentration was performed on data from controls and subjects with mild to moderate MDD participating in an ongoing pharmacogenetic study of antidepressant treatment response to desipramine or fluoxetine. Hematologic and hemorheologic measures of stress-hemoconcentration included blood cell counts, hematocrit, hemoglobin, total serum protein, and albumin, and whole blood viscosity. FINDINGS: Subjects with mild to moderate MDD had significantly increased hemorheologic measures of stress-hemoconcentration and blood viscosity when compared to controls; these measures were correlated with depression severity. Measures of stress-hemoconcentration improved significantly after 8 weeks of antidepressant treatment. Improvements in white blood cell count, red blood cell measures and plasma volume were correlated with decreased severity of depression. CONCLUSIONS: Our secondary data analyses support that stress-hemoconcentration, possibly caused by decrements in plasma volume during psychological stress, is present in Mexican-American subjects with mild to moderate MDD at non-challenged baseline conditions. We also found that after antidepressant treatment hemorheologic measures of stress-hemoconcentration are improved and are correlated with improvement of depressive symptoms. These findings suggest that antidepressant treatment may have a positive impact in CVD by ameliorating increased blood viscosity. Physicians should be aware of the potential impact of measures of hemoconcentration and consider the implications for cardiovascular risk in depressed patients.

Effectiveness and tolerability of open label olanzapine in children and adolescents with Tourette syndrome.

OBJECTIVES: The primary aim of the study was to evaluate the effectiveness and tolerability of open-label olanzapine on motor and vocal tics in children and adolescents with Tourette syndrome (TS). Secondary aims included assessing the response of TS-associated disruptive behaviors to olanzapine exposure. METHOD: Twelve children and adolescents (mean age 11.3 +/- 2.4 years, range 7-14 years) with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) TS were enrolled in a single-site, 6-week, open-label, prospective, flexible-dose design in outpatients receiving monotherapy with olanzapine. Standardized ratings of tic symptoms, disruptive behaviors, and aggression were obtained, along with adverse events and safety data. RESULTS: Over the 6-week trial, olanzapine administration was associated with a significant decrease in total tic severity as measured by the Yale Global Tic Severity Scale (30% reduction by week 6; effect size 0.49). A significant majority of subjects were rated as "much improved" or "very much improved" on the Clinical Global Impressions-Improvement Scale (GCI-I) by both clinicians (67%; 8/12) and parents (64%; 7/11). Attention-deficit/hyperactivity disorder (ADHD) symptoms showed significant improvements from baseline for both inattention (33% decrease) and hyperactive/impulsivity (50% decrease) scores (effect sizes 0.44 and 0.43, respectively). Aggression was also decreased as assessed by fewer numbers of aggressive episodes on the Overt Aggression Scale (OAS). Little change in anxiety symptoms was noted. The most widely reported side effects were drowsiness/sedation and weight gain; adverse events were generally well tolerated. Mean weight gain of 4.1 +/- 2.0 kg was observed over the 6-week trial, a mean percent change of 8.4 +/- 4.4 (p < 0.001). CONCLUSIONS: Additional studies of the benefits of olanzapine treatment for tic control as well as the commonly associated co-morbid features of TS are indicated, especially if approaches to predict or minimize weight gain can be determined.

Effects of leptin on intake of specific micro- and macronutrients in a woman with leptin gene deficiency studied off and on leptin at stable body weight.

In this report, we examine the effects of leptin on the intake of specific macro- and micronutrients in a female patient with leptin gene deficiency. The patient was studied off and on leptin at stable body weight, within the normal to mildly overweight range. The data were obtained by detailed dietary assessments, measuring dietary intakes by weighed food and fluid consumption records, and analyzed using nutrition analysis software. Overall, significant differences were found in the off versus on leptin treatment periods in the following categories: (i) macronutrients: kilocalories, protein, carbohydrates, monounsaturated fats, MFA 18:1 oleic and total fiber; (ii) vitamins: vitamin C, pyridoxine and pantothenic acid; (iii) minerals: potassium, magnesium, copper and chromium; and amino acids: threonine, lysine and histidine. The nutritional data from this study indicates a direct link between the effects of leptin and ingestion of several specific micronutrients. The mechanisms underlying these effects warrant further investigation and study.