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Isabella Heuser

Publications and source records attributed to Isabella Heuser.

At least 37 records · Page 2Linked to original sources
PubMed2005

Suicide prevention by lithium SUPLI--challenges of a multi-center prospective study.

Several studies have shown that there is a significantly increased risk of suicide related mortality in patients with a positive history of suicide attempts. The SUPLI-Study is the first prospective, randomized, double blind, placebo controlled multi-center trial focusing on the proposed suicide preventive effects of lithium in patients with suicidal behavior but not suffering from bipolar disorder or recurrent major depressive disorder. Patients with a recent history of a suicide attempt are treated with lithium versus placebo during a 12 month period. The hypothesis is that lithium treatment will lead to a 50% reduction of suicidal behavior. The protocol of the study and preliminary results are presented.

Antipsychotic Agents↗
PubMed2004

Lipid metabolism and insulin resistance in depressed patients: significance of weight, hypercortisolism, and antidepressant treatment.

Major depression increases cardiovascular risk despite lower cholesterol levels. Little is known about effects of antidepressants on metabolic risk factors. We studied lipoprotein composition, insulin sensitivity (quantitative insulin sensitivity check index), and saliva cortisol in 78 depressed patients before and after 35 days of amitriptyline or paroxetin treatment. Data were analyzed by principal component factor analyses and analysis of variance (ANOVA). At baseline, quantitative insulin sensitivity check index was inversely correlated with cortisol (r = -0.46; P = 0.005) in normal weight patients, with body mass index in overweight patients (r = -0.50; P < 0.001). In overweight patients, hypercortisolemia correlated inversely with total and low density lipoprotein cholesterol (eg, cortisol at 4:00 PM and low density lipoprotein cholesterol: r = -0.49, P = 0.002). After treatment, quantitative insulin sensitivity check index was unchanged. Triglycerides increased in responders to amitriptyline only (P < 0.05). Parameters of cholesterol metabolism improved slightly without differences between treatment groups (eg, high density lipoprotein: pre 43.5 +/- 12.0; post 47.6 +/- 13.0 mg/dL; P = 0.01; low density lipoprotein triglycerides, a measure of low density lipoprotein atherogenicity: pre 458 +/- 120; post 415 +/- 130 mg/g; P < 0,01). The inverse correlation of cortisol and cholesterol, at least in the obese subgroup, proposes a mechanism for the known association of depression with low cholesterol. As determinants of plasma lipids in major depression, we identified body mass index, insulin sensitivity, and cortisol. Although uncontrolled, our data suggest that treatment of depression exerts a mainly beneficial effect on lipid regulation.

Adult↗
PubMed2004

Antidepressant treatment and dehydroepiandrosterone sulfate: different effects of amitriptyline and paroxetine.

BACKGROUND: There is evidence for activation of the hypothalamus-pituitary-adrenal system in depressed patients to be associated with increased secretion of adrenal androgens. However, there is only limited information about the effect of different classes of antidepressants on the course of adrenal androgens. METHODS: Dehydroepiandrosterone sulfate (DHEA-S) serum concentrations were measured in 80 patients being treated with amitriptyline (AMI) or paroxetine (PAROX) for a period of 35 days. RESULTS: Using analysis of variance with repeated measures, we found a significant effect of treatment upon DHEA-S serum concentrations that declined more in AMI-treated (before vs. after: 1.89+/-1.16 vs. 1.46 +/- 0.96 mg/l), compared to PAROX-treated patients (1.56+/-1.09 vs. 1.50+/-1.04 mg/l). CONCLUSIONS: Our results show changes in DHEA-S serum concentrations during antidepressant treatment to depend on medication.

Adult↗
PubMed2004

Combination therapy in Alzheimer's disease: a review of current evidence.

Treating dementia has become a major challenge in clinical practice. Presently, acetylcholinesterase inhibitors are the first-line drugs in the treatment of Alzheimer's disease (AD). These options are now complemented by memantine, which is approved for the treatment of moderate-to-severe AD. Altogether, a minimum of six agent classes already exist, all of which are approved for clinical use and are either already being tested or ready for phase III clinical trials for the treatment of AD. These include cholinesterase inhibitors, blockers of the NMDA receptor, antioxidants or blockers of oxidative deamination (including Gingko biloba), anti-inflammatory agents, neurotrophic factors (including hormone replacement therapy and drugs acting on insulin signal transduction) and antiamyloid agents (including cholesterol-lowering therapy). These approaches hold promise for disease modification and have a potential to be used as combination therapy for cognitive enhancement. Presently, only nine clinical studies have been published that have investigated the effects of a combination regimen on cognitive performance or AD. Among those, one study was conducted in elderly cognitively intact persons; the others involved patients with AD. Only five of the treatment studies followed a randomised, controlled design. Not all studies favoured the superior efficacy of combination therapy over monotherapy. Some studies, however, showed some evidence for synergistic combination effects of symptomatic therapy, including delay or prevention of disease progression in AD patients. In addition, six studies investigated the effects of AChE inhibitor in combination with antipsychotic or antidepressant therapy on behavioural aspects of AD symptomatology. In four of those studies there were indications that combination therapy had greater efficacy over monotherapy. The treatment of AD patients requires optimised options for all stages of illness based on the available drugs. There is a great need for further well designed studies on combination therapy in AD.

Alzheimer Disease↗
PubMed2004

Prevention and treatment of poststroke depression with mirtazapine in patients with acute stroke.

BACKGROUND AND OBJECTIVE: Poststroke depression is one of the most frequent complications of stroke, affecting approximately 20% to 40% of all patients. In spite of the importance of this neuropsychiatric disorder, little attention has been given to the prevention of poststroke depression. The purpose of this study was to examine whether prophylactic treatment with the antidepressant mirtazapine in patients with acute stroke given from day 1 after the incidence prevents poststroke depression. METHOD: Patients with ischemic stroke received either 30 mg mirtazapine or no antidepressant medication from day 1 after the stroke in an open, randomized study design. Data were collected from August 2001 to December 2002. Seventy patients were enrolled in the study and were reexamined on days 7, 44, 90, 180, 270, and 360 using neurologic, functional, and depression rating scales. Those poststroke patients who developed depression (DSM-IV criteria) but had been randomly assigned to the nontreatment group were given the antidepressant mirtazapine after the diagnosis of depression had been established. RESULTS: Forty percent (14/35) of the nontreated patients and only 5.7% (2/35) of the patients who were treated with mirtazapine developed poststroke depression. Altogether, 16 patients developed poststroke depression, 15 of whom remitted after initiation of treatment with mirtazapine. CONCLUSION: Mirtazapine significantly reduced the rate of poststroke depression in patients with acute stroke. The study also demonstrated that this antidepressant was highly effective in treating poststroke depression.

Aged↗
PubMed2003

[Prevention of dementias: state of the art].

Dementias of late life constitute a major public health challenge. Alzheimer disease (AD) is the most common form. Epidemiological studies suggest that the use of nonsteroidal anti-inflammatory drugs, wine and coffee consumption and regular physical activity may delay onset of AD or reduce rate of progression. Preclinical research in animals and epidemiological studies in humans have shown that estrogen substitution strategies and lipid lowering statins may be beneficial. Thus, despite the lack of prospective studies and, therefore, consensus, different pharmacological strategies for persons at high risk for Alzheimer's disease are discussed.

Aged↗
PubMed2003

Antidepressive treatment with amitriptyline and paroxetine: effects on saliva cortisol concentrations.

With regard to the course of basal human hypothalamus-pituitary-adrenal (HPA) system activity, there is a lack of data for comparing different classes of antidepressants. Ninety-four patients were included in a study comparing standardized treatment with paroxetine (PAROX) and amitriptyline (AMI) after a drug-free period of at least 6 days. Saliva for measurement of cortisol concentrations was obtained daily at 0800, 1600, and 2200 during the 6 days of drug-free washout and 35 days of active treatment. The course of HPA system activity and psychopathology, as assessed by the Hamilton Depression Scale, was compared by means of repeated-measurement analyses of variance (ANOVA-rm). Only AMI responders-not PAROX responders or nonresponders to either antidepressant-had a significant decline in saliva cortisol concentrations. In hypercortisolemically depressed patients, treatment with AMI may be preferable to PAROX in order to lower HPA system activity.

Amitriptyline↗
PubMed2003

Circadian blood pressure regulation in hospitalized depressed patients and non-depressed comparison subjects.

BACKGROUND: Neuroendocrine dysregulation and disturbed sleep, frequently seen in major depression, may interfere with circadian blood pressure regulation. DESIGN AND METHODS: Using a portable device, 24 h blood pressure profiles were registered in 69 depressed in-patients and 26 hospitalized, non-depressed comparison subjects. The use of antihypertensive medication was considered to be indicative of known arterial hypertension. Mean systolic and diastolic blood pressure levels were compared between the group of depressed patients not taking antihypertensive medication and the healthy comparison subjects, both for the entire 24 h of measurement, and for the daytime and night-time periods. In a subgroup of patients, circadian blood pressure follow-up data were obtained after 5 weeks of antidepressant therapy. RESULTS: Depressed patients not receiving antihypertensive medication (n=52) had higher mean 24 h systolic blood pressure levels than non-depressed comparison subjects (125.5+/-14.7 versus 119.6+/-13.3 mmHg, P<0.05). Subgroup analysis revealed that this difference could be almost exclusively attributed to patients on hypnotic medication; this subgroup also had a high day/night blood pressure change ('dip'). In depressed patients using antihypertensive agents (n=17), circadian blood pressure levels pointed to a suboptimal control of hypertension. In the subgroup with follow-up measurements, circadian blood pressure levels had not changed after 5 weeks of antidepressant therapy. CONCLUSION: Circadian blood pressure monitoring identified a subgroup of depressed patients characterized by higher mean systolic blood pressure levels, the use of hypnotics and a high day/night blood pressure change.

Adult↗
PubMed2003

Effect of ambulatory blood pressure measurement on sleep in patients with a major depressive episode.

BACKGROUND: To assess the effects of ambulatory blood pressure measurement (ABPM) upon sleep in mentally depressed patients with near absence of deep (stage 3 and 4) sleep. METHODS: Twelve depressed patients aged 50.5+/-13.5 (21-item Hamilton Depression Rating Scale: 23.8+/-5.1) were studied on three consecutive nights in the sleep laboratory. In a random order, blood pressure was measured with a portable device over 24 h on either day 2 or 3. Polysomnographic data were analysed according to the criteria of Rechtschaffen and Kales. RESULTS: Compared to the control night, there was a significant increase of awakenings during the ABPM night. However, total sleeping time as well as sleep efficiency remained unchanged. Percentage of nocturnal decrease in both systolic and diastolic blood pressure was unrelated to the number of arousals. CONCLUSION: In depressed patients with severe disturbances of sleep architecture, ABPM did not lead to a prolongation of time awake or decrease in sleep efficiency.

Adult↗
PubMed2003

Treatment with the selective muscarinic m1 agonist talsaclidine decreases cerebrospinal fluid levels of A beta 42 in patients with Alzheimer's disease.

The amyloid beta-peptides A beta 40 and A beta 42 are highly amyloidogenic constituents of brain beta-amyloid plaques in Alzheimer's disease (AD). Lowering their formation may be achieved by modulating the activities of proteases that cleave the amyloid precursor protein (A beta PP), including alpha- beta-, and gamma-secretases. Talsaclidine is a functionally selective muscarinic m1 agonist that stimulates non-amyloidogenic alpha-secretase processing in vitro. We compared cerebrospinal fluid (CSF) levels of A beta 40 and A beta 42 measured by ELISA before and at the end of 4 weeks of treatment with talsaclidine. The medication was administered in a double-blind, placebo-controlled, and randomized clinical study to 40 patients with AD. Talsaclidine (n = 34) decreased CSF levels of A beta 42 by a median of 19% (p < 0.001) as compared to baseline. The mean difference between CSF levels of A beta 42 before and after treatment with talsaclidine (n = 34) was -46 +/- 73 (SD) pg/ml as compared to 0 +/- 8 (SD) pg/ml with placebo (n = 6) (p < 0.05). CSF levels of A beta 40 increased during treatment with placebo (n = 6) while they remained stable during treatment with talsaclidine (n = 31) (1.118 +/- 1.710 ng/ml, and -0.170 +/- 0.967 ng/ml, respectively; p < 0.05). These data show that treatment with the m1 agonist talsaclidine reduced A beta peptides, and particularly A beta 42, in AD patients, suggesting it as a potential amyloid lowering therapy of AD.

Aged↗
PubMed2002

Steroid synthesis inhibition with ketoconazole and its effect upon the regulation of the hypothalamus-pituitary-adrenal system in healthy humans.

Steroid synthesis inhibitors are commonly used in the treatment of patients with Cushing's disease, but may also improve psychopathology in hypercortisolemic depressed patients. Since glucocorticoids exert a negative feedback at pituitary and supra-pituitary levels, the inhibition of steroid synthesis may lead to increased expression of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). We studied the effect of treatment with 800 mg ketoconazole (3 weeks) upon the concentrations of basal plasma cortisol in the evening, corticosteroid-binding globulin (CBG), dehydroepiandrosterone-sulfate (DHEA-S), and ACTH as well as the concentrations of cortisol, CRH, and AVP in cerebrospinal fluid (CSF) at 8.30 h in 10 healthy, male volunteers. While we found cortisol plasma concentrations to be unchanged, we noted a significant increase in ACTH (post: 45.1+/-43.5; pre: 14.2+/-5.2 pmol/l; F(1,8)=9.78, p<0.02) and CBG concentrations (post: 38.8+/-4.3; pre: 31.9+/-4.2 microg/l), but DHEA-S plasma concentrations declined (post: 1.75+/-1.83; pre: 2.75+/-2.80 mg/l; F(1,8)=7.9, p<0.03). CRH concentrations in CSF were unchanged after treatment (post: 62.5+/-15.9; pre: 63.7+/-13.9 pg/ml), while there was a trend for AVP concentrations to rise during treatment (post: 2.52+/-1.18; pre: 1.92+/-0.96 pg/ml; paired t=-1.9, p<0.1). Cortisol CSF concentrations declined in the elderly (pre: 52.5+/-23.2; post: 26.7+/-4.6 nmol/l), but not in the young subgroup (pre: 15.6+/-11.3; post: 27.7+/-9.4 nmol/l). We thus conclude that the treatment of healthy controls with steroid-synthesis inhibitors does not lead to a major increase in CRH secretion.

Adult↗
PubMedDate not supplied

MR spectroscopy in Alzheimer's disease: gender differences in probabilistic learning capacity.

Degenerative alterations of cortical and subcortical regions in Alzheimer disease (AD) can be estimated by the extent of brain metabolite changes as measured by magnetic resonance spectroscopic imaging (MRSI). A neuropsychological assessment may correlate with metabolite levels and could evaluate underlying degenerative processes. Probabilistic-related classification learning, which represents one form of procedural learning, is associated with the neostriatum. The present study was aimed at examining the correlation of spectroscopic imaging in subcortical regions with the evaluation of specific neuropsychological findings. Twenty-two patients with Alzheimer's disease were compared to 15 healthy elderly control subjects. Proton MRSI of the basal ganglia (BG) and thalamus region was performed for detection of N-acetylaspartate (NAA), trimethylamine (TMA) and creatine ((P)Cr). In addition, a probabilistic-related classification learning task (Weather Prediction Task (WT)) was applied. We observed that in patients a high TMA signal in the basal ganglia region was correlated with a poorer performance in the probabilistic learning task (Spearman rank order correlation (SROC)=-0.6, P<0.009). Although Alzheimer's patients, as a group, did not differ from controls with regard to probabilistic learning capacity (PLC), male AD patients, as compared to male controls, displayed an impairment in the task performance by 28% (P<0.03) and showed a 16% elevation in TMA signaling (P<0.04). The altered metabolite signals and ratios in combination with the cognitive performance might suggest gender-related neuronal degeneration and dysfunction within subcortical regions in AD.

Aged↗
PubMedDate not supplied

Stress and the brain.

Stress is a risk factor for a variety of illnesses, involving the same hormones that ensure survival during a period of stress. Although there is a considerable ambiguity in the definition of stress, a useful operational definition is: "anything that induces increased secretion of glucocorticoids". The brain is a major target for glucocorticoids. Whereas the precise mechanism of glucocorticoid-induced brain damage is not yet understood, treatment strategies aimed at regulating abnormal levels of glucocorticoids, are worth examining.

Aging↗
PubMedDate not supplied

Hypercortisolemic depression is associated with increased intra-abdominal fat.

OBJECTIVE: Similar to patients with a metabolic syndrome, patients with major depression are at increased risk of developing cardiovascular disorders. Interestingly, both disorders share a specific endocrine syndrome that promotes the accumulation of visceral fat, which again is considered a marker of increased cardiovascular morbidity and mortality. METHODS: Intra-abdominal fat was measured in 22 postmenopausal depressed women and 23 age-matched healthy women by computer tomography at the level of lumbar vertebrae 1 (L1) and 4 (L4). Saliva was taken in patients and control subjects at 08:00 hours over a period of 7 drug-free days for the measurement of free cortisol. In patients only we performed an oral glucose tolerance test. RESULTS: Compared with control subjects, depressed patients with elevated free cortisol concentrations showed similar visceral fat depots at L1 (113.0 +/- 41.6 vs. 94.3 +/- 53.2 cm(2)). Hypercortisolemic depressed patients also showed greater fat depots in this area (74.5 +/- 55.5 cm(2), p =.04) than the normocortisolemic patients. However, a comparison of all patients with control subjects revealed no difference in fat accumulation at either L1 or L4. Finally, glucose concentrations during the glucose tolerance test were higher in hypercortisolemic than in normocortisolemic patients, whereas their insulin levels showed only a tendency toward being increased. CONCLUSIONS: Hypercortisolemic depressed patients suffer from resistance to insulin and increased visceral fat. The fact that hypercortisolemia reverses depression-related fat loss, particularly in the visceral area, might partially explain why major depression can be considered a risk factor for cardiovascular disorders.

Abdomen↗