[Treatment of depression in coronary heart disease]. / Behandlung der Depression bei koronarer Herzerkrankung.

Depression and coronary heart disease (CHD) are leading causes of disability and show a high comorbidity. Furthermore, depression is an independent risk factor for an unfavorable course and increased mortality in patients with CHD. In contrast, successful treatment of depression can reduce the risk of cardiac events. Currently, there are several treatment options for the management of depression in CHD, including self-management strategies, psychotherapy, pharmacotherapy and collaborative care models. This article provides an overview of the epidemiology of depression in CHD, the mechanisms of association and the current state of evidence with respect to the different treatment options.

[Cardiac and metabolic risk factors in severe mental disorders. Task of a prevention manager]. / Kardiale und metabolische Risikofaktoren bei schweren psychischen Erkrankungen. Aufgaben eines Präventionsmanagers.

People with severe mental disorders have a reduction in life expectancy of 13-30 % compared with the general population. This severe disadvantage is primarily due to an increased prevalence of cardiac and metabolic disorders, especially coronary heart disease (CHD) and type 2 diabetes mellitus and are the result of untoward health behavior characterized by smoking, low levels of physical activity and unhealthy dietary habits. Obesity, arterial hypertension and lipid disorders are also associated with this behavior and further increase the risk of CHD and type 2 diabetes. Thus, people with mental disorders constitute a population with a high risk of cardiovascular events. Appropriate measures for prevention and therapy are urgently indicated but rarely applied. This article presents new organizational structures to overcome this deficit with a prevention manager playing a central role in organizing and applying preventive and therapeutic care. Results from cardiology and diabetic medicine have shown the effectiveness of pooling this responsibility. The measure has the potential to reduce the increased mortality of people with severe mental disorders.

Changes of serum concentrations of brain-derived neurotrophic factor (BDNF) during treatment with venlafaxine and mirtazapine: role of medication and response to treatment.

INTRODUCTION: Depression, stress and antidepressant treatment have been found to modulate the expression of brain-derived neurotrophic factor (BDNF). Recent research suggests that serum BDNF concentration is reduced in depression and that antidepressant treatment leads to an increase in serum BDNF concentration. METHODS: We studied depressed patients receiving a randomized antidepressant treatment with either mirtazapine (n=29) or venlafaxine (n=27) for 28 days in a prospective design. Changes in the concentrations of serum neurotrophins in response to antidepressant treatment were assessed. RESULTS: There was a significant "treatment" by "medication" interaction effect on BDNF serum concentrations that indicated a decline of BDNF in venlafaxine-treated patients (7.82±3.75-7.18±5.64 ng/mL), while there was an increase in mirtazapine-treated patients (7.64±6.23-8.50±5.37 ng/mL). There was a trend for a "treatment" by "remission" interaction with a favourable clinical course being related to increasing serum BDNF. DISCUSSION: Changes in BDNF serum concentrations as a result of antidepressant therapy depend on the antidepressant and potentially on the clinical course.

Assessment of cardiovascular disease risk in patients with schizophrenia spectrum disorders in German psychiatric hospitals: results of the pharmacoepidemiologic CATS study.

PURPOSE: Patients with severe mental illness are at high risk for metabolic and cardiac disorders. Thus, monitoring of cardiovascular risks is imperative and schedules for screening for lipids, glucose, body mass index (BMI), waist-hip ratio and blood pressure have been developed. We intended to analyze screening for metabolic disorders in German patients with schizophrenia spectrum disorders in routine psychiatric care. METHODS: We included 674 patients with any F2 diagnosis in out- and inpatient settings and analyzed metabolic screening procedures as practiced under conditions of usual care. RESULTS: Except BMI (54 %), all other values were documented only in a minority of patients: waist circumference (23 %), cholesterol (28 %), fasting glucose (19 %), triglycerides (25 %) and blood pressure (37 %). We found evidence for less than perfect quality of blood pressure measures. The group of patients who met the individual metabolic syndrome ATP III criteria was comparable to the US CATIE trial. CONCLUSIONS: We conclude that frequency and quality of metabolic monitoring in German in- and outpatients settings are not in accordance with the respective recommendations. Similar to previous reports we found evidence for a high prevalence of metabolic disturbances in German patients with schizophrenia spectrum disorders.

Insulin secretion and sensitivity after single-dose amisulpride, olanzapine or placebo in young male subjects: double blind, cross-over glucose clamp study.

INTRODUCTION: Increased risks of weight gain and diabetes mellitus have been reported for schizophrenic patients under long-term treatment with several atypical antipsychotic drugs including olanzapine. Among other antipsychotic drugs, treatment with the selective dopamine D2 and D3 receptor antagonist amisulpride has been implicated with a lower risk for metabolic complications. PATIENTS AND METHODS: In this study we compared the acute, non-adiposity related effects of a single dose of olanzapine, amisulpride and placebo on insulin sensitivity and secretion in 10 healthy subjects in a randomised, double blind cross-over design. Subjects underwent euglycemic-hyperinsulinemic and hyperglycemic clamp tests using an automated clamp device. C-peptide and pro-insulin levels were determined using highly specific immuno-assays. RESULTS: Insulin sensitivity was not significantly different between both verum medications and placebo. However, C-peptide secretion during hyperglycemic clamp was significantly higher after administration of amisulpride than after olanzapine or placebo. This was true both for the early phase and for the second phase of insulin secretion (C-peptide at 0, 5,10 and 30 min: amisulpride 1.49±0.49; 4.22±1.45; 3.19±1.22; 5.33±1.85; olanzapine 1.35±0.47; 3.84±1.37; 2.72±0.91; 4.28±1.96; placebo 1.72±0.82; 3.59±1.19; 2.71±1.02; 4.54±1.42 ng/mL, mean±SD; ANOVA p=0.043). Pro-insulin levels did not differ significantly between groups. DISCUSSION: A low dose of the D2/D3 antagonist amisulpride, but not olanzapine appears to acutely increase pancreatic insulin secretion in healthy controls. Stimulation of ß-cells could be a protective factor against the development of diabetes mellitus.

[Stress, mental disorders and coronary heart disease]. / Stress, psychische Erkrankungen und koronare Herzkrankheit.

There are numerous associations between stress, mental disorders and coronary heart disease (CHD). Exposure to an acute stressor leads to activation of the hypothalamus-pituitary-adrenal and sympathoadrenal systems and chronic stressors are associated with sustained functional changes of these systems. Experiencing acute and chronic stress is paralleled by an increased incidence of mental disorders with the most consistent evidence on the triggering of major depressive episodes. Various mental disorders, including depression, anxiety and schizophrenia, are associated with an increased risk of CHD. Furthermore, acute and chronic stressors have been identified as risk factors or triggers of acute coronary syndromes. Thus therapeutic strategies aim at reducing subjective stress experience, therapy of mental disorders and treatment of cardiac risk factors known to be more prevalent in increased stress states and mental disorders.

[Antidepressant therapy in coronary artery disease]. / Antidepressive Therapie bei koronarer Herzkrankheit.

Depression is considered an independent risk factor for coronary artery disease (CAD) and other vascular conditions. Moreover, comorbid depressive disorder in CAD patients carries an increased risk of cardiac events and mortality. Among survivors of acute myocardial infarction, up to 20% meet diagnostic criteria for major depression, the presence of which carries a fivefold increased risk of cardiac death within 6 months. Heart patients with depressive comorbidity require particular care for both adequate treatment of their affective disorder and reduction of their cardiac risk. Antidepressant treatment must follow established guidelines; special care is needed to avoid cardiac side effects. In this review, we discuss the pathophysiological and prognostic significance of comorbid depression in CAD and weigh risks and benefits of available treatment options - particularly different drug classes and psychotherapy - in light of recent study results.

Valproic acid and all trans retinoic acid differentially induce megakaryopoiesis and platelet-like particle formation from the megakaryoblastic cell line MEG-01.

Both, the activity of transcription factors as well as epigenetic alterations in defined DNA regions regulate cellular differentiation processes. Hence, neuronal differentiation from neural progenitor cells is promoted by the transcription factor all trans retinoic acid (ATRA) and the histone deacetylase inhibitor valproic acid (VPA). VPA has also been shown to be involved in differentiation of tumor cells and to greatly improve the reprogramming of human somatic cells to induced pluripotent stem cells. Here we have investigated the impact of ATRA and VPA on the differentiation of megakaryoctes and platelets from the megakaryocyte progenitor cell line MEG-01. Our results show that treatment with ATRA (10⁻¹¹ M) and VPA (2 × 10⁻³ M) induces megakaryopoiesis of MEG-01 cells as estimated by polyploidy, formation of characteristic proplatelets and elevated expression of the megakaryocytic markers CD41 and CD61. The resulting megakaryocytes stayed viable for more than 3 weeks and shed platelet-like particles positive for CD41, CD61 and CD42b into the supernatant. Platelet-like particles responded to thrombin receptor activating peptide (TRAP-6) with increased externalization of P-selectin. Thus, ATRA and VPA proved to be efficient agents for the gentle induction of megakaryopoiesis and thrombopoiesis of MEG-01 cells providing the possibility to study molecular events underlying megakaryopoiesis and human platelet production over longer time periods.

Does night-time cortisol excretion normalize in the long-term course of depression?

INTRODUCTION: While there is extensive literature on HPA system activity in acutely depressed patients, there is only limited information about the presence of hypercortisolemia during the interepisode interval of affective disorders. We hypothesized an increase in HPA system activity in depressed patients compared to controls, and proposed that night-time cortisol excretion during follow-up will depend on clinical outcome. METHODS: We measured night-time cortisol excretion in 27 patients during an acute episode of major depression as well as a 20-week follow-up. 40 healthy subjects served as control group. RESULTS: During the acute episode depressed patients showed increased levels of night-time cortisol excretion compared to healthy controls. Both, patients with full and sustained remission (n=8) as well as patients with incomplete remission or relapse (n=19) showed declining cortisol excretion in night-time urine during follow-up. At the end of follow-up cortisol excretion did not differ between patients with affective disorder and healthy controls. DISCUSSION: Irrespective of residual depressive symptoms, HPA system activity declines after the generally investigated acute depressive episode.

No major effect of orciprenaline and propranolol upon ACTH-induced cortisol secretion.

Preclinical research suggests adrenal beta-adrenergic receptors to be involved in the regulation of steroid synthesis. In a group of healthy male volunteers, we compared ACTH-induced cortisol and dehydroepiandrosterone (DHEA) secretion after pre-treatment with orciprenaline, propranolol or placebo. Neither baseline nor ACTH-induced steroid secretion differed between these conditions. Our data do not support the hypothesis that the adrenal beta-receptor plays a major role in steroid secretion in humans.

Increased platelet aggregability in major depression?

There is compelling evidence that depression constitutes an independent risk factor for cardiovascular morbidity and mortality. As exaggerated platelet reactivity is associated with an increased risk of intra-arterial thrombus formation, we studied platelet aggregability in patients with major depression both before and after 5 weeks of anti-depressant therapy as well as in healthy control subjects. Twenty-two depressed patients and 24 healthy control subjects participated in the study. Washed and rediluted platelets were stimulated with the agonists collagen and thrombin in three concentration steps. Depression was associated with a higher aggregability after stimulation with thrombin in the intermediate concentration and with collagen at the low concentration, with ceiling effects for the other concentrations. After 5 weeks of anti-depressant therapy, aggregability was somewhat less exaggerated, although this effect did not reach statistical significance. We thus conclude that major depression is associated with increased platelet aggregability, which seems to persist even under a marked improvement in depressive symptomatology. This effect may contribute to the increased cardiovascular morbidity in depressed patients.

Platelet counts in depressed patients treated with amitriptyline or paroxetine.

OBJECTIVE: To assess whether therapy with two widely used antidepressants influences platelet counts. SUBJECTS AND METHODS: In 90 patients hospitalized for treatment of a major depressive episode according to DSM-IV, platelet counts were performed after a 6 d antidepressant-free run-in period and again after 35 d of active standardized treatment with amitriptyline (n = 40) or paroxetine (n = 50). RESULTS: There was a trend for platelet counts to increase during treatment with amitriptyline (from 245.5 +/- 68.6 to 256.8 +/- 69 cells x 10(9) L(-1), P < 0.06); no change was observed during treatment with paroxetine (from 232.6 +/- 58.3 to 234.6 +/- 68.9 cells x 10(9) L(-1), n.s). CONCLUSION: Treatment with amitriptyline tends to be associated with elevated platelet counts. The cause for this increase is not known, but may be relevant in terms of patients' long-term thromboembolic risk.

Flattened circadian cortisol rhythm in type 2 diabetes.

INTRODUCTION: While altered cortisol concentrations have been observed in subjects with type 2 diabetes their circadian cortisol profile is unknown. PATIENTS AND METHODS: Using a cross-sectional design, we studied 63 ambulatory individuals with type 2 diabetes and 916 non-diabetic control subjects of the Cooperative Research in the Region of Augsburg (KORA)-F3 study. Circadian cortisol profiles were derived from saliva cortisol concentrations, determined on a regular weekday upon wake-up (F0), as well as ½ h (F½), 8 (F8) and 14 h (F14) after wake-up. RESULTS: Diabetic subjects exhibited a flattened circadian cortisol profile (rm-ANOVA: F[3,654]=3.41, p=0.02), with lower morning and higher afternoon and evening cortisol concentrations. CONCLUSION: We observed a flattened circadian cortisol rhythm in subjects with type 2 diabetes, providing evidence for a specific HPA system dysfunction.

[An interdisciplinary unit for major psychiatric/somatic comorbidity: concept and 22 years of experience]. / Interdisziplinäre Station für psychisch Kranke mit erheblichen somatischen Komorbiditäten: Konzept und Erfahrungen von 1985-2007.

In this article we describe in detail a specialised facility geared toward caring for patients presenting with major psychiatric and somatic comorbidity. Located in a psychiatric hospital, an important feature of the treatment offered in this unit is that psychiatric/psychotherapeutic and somatic care are provided by the same team members. Working in this unit places high demands on the medical team, which must be competent in both fields, especially during emergency situations. Due to the severity of the patients' symptomatology, the unit requires more staff than regular psychiatric wards. Frequent psychiatric diagnoses necessitating the transfer of patients to this ward include delirium associated with internal/neurologic disorders or occurring postoperatively, and affective syndromes and dementia due to general medical conditions. Somatic disorders frequently requiring treatment in this ward include acute cardiovascular syndromes, liver or renal failure, infections, and conditions arising postoperatively or following trauma.

[Dysfunction of the hypothalamus-pituitary-adrenal system--background variable of relevant cardiovascular risk factors?--description of a cooperative project]. / Dysfunktion des Hypothalamus-Hypophysen-Nebennierenrinden-Systems -- Hintergrundvariable relevanter kardiovaskulärer Risikofaktoren? -- Beschreibung eines kooperativen Projektes.

The present project is based on findings showing that important risk factors for the development of coronary heart disease are frequently associated with a dysregulation in stress-responsive systems. Accordingly, the observed dysfunction in these systems might represent a background variable with a significant effect on the development and course of coronary heart disease. Examining a random population sample we aim at testing the hypothesis whether cardiac risk factors such as arterial hypertension, type 2 diabetes, visceral obesity and depression might be associated with a dysfunction in a major stress-responsive system, namely the hypothalamic-pituitary-adrenal (HPA) system. Assessment of the functional status of this system will be carried out by measuring cortisol concentrations in saliva at four set measurement times throughout a normal day while subjects continue to carry out their usual activities. This methodology enables us to characterize HPA system activity with regard to basal tone, reactivity to a specific stressor, circadian rhythm and overall activity. Our study population includes 1250 subjects aged 50 to 70 years taken from a representative sample of the general public of the city of Augsburg, Germany (KORA F3). Through close cooperation within the framework of the present project we will be able to examine neuroendocrine issues in association with detailed demographic and clinical data of a representative population sample.