Biomedical subjects

U Schweiger

Publications and source records attributed to U Schweiger.

At least 19 recordsLinked to original sources

PubMed2005

[Incorporation of multiple foreign bodies due to borderline personality disorder].

BACKGROUND: Autoaggressive behaviour is one of the pathognomonic characteristics in patients with borderline personality disorder. Clinical symptoms of such behaviour can be the self-induced incorporation of foreign bodies. In the head and neck area, this form of autoaggressivity causes primary or secondary infectious complications with different clinical manifestations. Below follows a description of diagnosis, therapy and follow-up of such a case, comparing our own findings with the corresponding literature. CASE REPORT: A 24-year-old woman with manifest borderline personality disorder was referred to the Department of Maxillofacial Surgery after developing a swelling in the infra-auricular region. After antibiotic therapy failed to reduce inflammatory symptoms, local revision was performed including excision of two metallic foreign bodies. Comprehensive radiological evaluation identified multiple foreign bodies in the head and neck region and lower arms. A total of 76 metallic foreign bodies was removed surgically. During early surgical follow-up and subsequent psychiatric treatment, the patient incorporated new foreign bodies. DISCUSSION: The case reported represents a pattern of foreign body incorporation which is unusual based on review of the literature but characteristic for patients with borderline personality disorder. Diagnostics and therapy require an individual concept which only can be implemented in close co-operation with psychiatrists. Secondary clinical benefit derived from surgical diagnostics and therapy as well as the possibility of autoaggressive relapse have to be taken into consideration.

Adult↗

PubMed2004

The need to revise the diagnostic criteria for anorexia nervosa.

Anorexia nervosa (AN) is a complex disorder of unclear etiology. We argue that the current DSM-IV criteria do not adequately describe the cardinal symptoms of this "eating disorder". Our reasoning is based on the lack of empirical evidence supporting the terminology of some of the criteria, which underlie the core of our current conceptualisation of AN. We propose alternative criteria which allow a better integration of biologically derived hypotheses addressing the nosology and the symptomatology of AN.

Adolescent↗

PubMed2004

The selfish brain: competition for energy resources.

The brain occupies a special hierarchical position in the organism. It is separated from the general circulation by the blood-brain barrier, has high energy consumption and a low energy storage capacity, uses only specific substrates, and it can record information from the peripheral organs and control them. Here we present a new paradigm for the regulation of energy supply within the organism. The brain gives priority to regulating its own adenosine triphosphate (ATP) concentration. In that postulate, the peripheral energy supply is only of secondary importance. The brain has two possibilities to ensure its energy supply: allocation or intake of nutrients. The term 'allocation' refers to the allocation of energy resources between the brain and the periphery. Neocortex and the limbic-hypothalamus-pituitary-adrenal (LHPA) system control the allocation and intake. In order to keep the energy concentrations constant, the following mechanisms are available to the brain: (1) high and low-affinity ATP-sensitive potassium channels measure the ATP concentration in neurons of the neocortex and generate a 'glutamate command' signal. This signal affects the brain ATP concentration by locally (via astrocytes) stimulating glucose uptake across the blood-brain barrier and by systemically (via the LHPA system) inhibiting glucose uptake into the muscular and adipose tissue. (2) High-affinity mineralocorticoid and low-affinity glucocorticoid receptors determine the state of balance, i.e. the setpoint, of the LHPA system. This setpoint can permanently and pathologically be displaced by extreme stress situations (chronic metabolic and psychological stress, traumatization, etc.), by starvation, exercise, infectious diseases, hormones, drugs, substances of abuse, or chemicals disrupting the endocrine system. Disorders in the 'energy on demand' process or the LHPA-system can influence the allocation of energy and in so doing alter the body mass of the organism. In summary, the presented model includes a newly discovered 'principle of balance' of how pairs of high and low-affinity receptors can originate setpoints in biological systems. In this 'Selfish Brain Theory', the neocortex and limbic system play a central role in the pathogenesis of diseases such as anorexia nervosa and obesity.

Adaptation, Physiological↗

PubMed2002

Smoking modulates neuroendocrine responses to ipsapirone in patients with panic disorder.

Reduced 5-HT1A-receptor responsiveness has been reported in patients with panic disorder(PD) and/or agoraphobia (PDA). Although many of these patients are regular smokers, it has not been examined whether psychological or neurobiological effects induced by the selective 5-HT1A-receptor agonist, ipsapirone, are affected by the smoking status of the patients. In order to clarify this question neuroendocrine challenges with oral doses of ipsapirone (0.3 mg/kg) and placebo were performed in 39 patients with PDA, and results were compared between patients who smoked (>10 cigarettes per day, n = 17) and patients who had been non-smokers for at least two years (n = 22). Patients who were smokers (but did not smoke during the challenge procedure) had significantly reduced baseline concentrations of cortisol and a significantly lower body temperature. In comparison to placebo, administration of ipsapirone was associated with significant increases of various psychological symptoms and plasma cortisol concentrations. The subgroup of PD patients who were smokers showed significantly higher cortisol responses to ipsapirone than non-smokers. In conclusion, smoking status has to be taken into account when assessing the responsiveness of 5-HT1A receptors in patients with psychiatric disorders. The prevention of smoking during challenge sessions might not be the ideal approach in heavy smokers, since sudden abstinence from smoking is likely to affect neurobiological and possibly psychological responses to ipsapirone.

Adult↗

PubMed2002

The neuroendocrine control of glucose allocation.

Here we propose that glucose metabolism can be understood on the basis of three concept-derived axioms: (I) A hierarchy exists among the glucose-utilizing organs with the brain served first, followed by muscle and fat. (II) Tissue-specific glucose transporters allocate glucose among organs in order to maintain brain glucose concentrations. (III) Exogenous carbohydrate supply compensates for glucose alterations that can temporarily occur in muscle and fat. Derived from the control theory, the simplest solution of allocating supply to 2 organs, e.g. brain and muscle, is a "fishbone"-structured model. We reviewed the literature, searching for neuroendocrine and metabolic mechanisms that can fulfill control functions in such a model: The tissue-specific glucose transporters are differentially regulated. GLUT 1, carrying glucose across the blood-brain-barrier, is independent of insulin. Instead, this trans-endothelial glucose transporter is rather dependent on potent regulators of blood vessel function like vascular endothelial growth factor - a pituitary counterregulatory hormone. GLUT 4, carrying glucose across the membranes of muscle and fat cells, depends on insulin. Thereby, insulin allocates glucose to muscle and fat. The hypothalamus-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS), and vascular endothelial growth factor allocate glucose to the brain. Multiple "sensors" (some of which have only recently been identified as ATP sensitive potassium channels) measure glucose or glucose equivalents at various sites of the body: the ventromedial hypothalamus, the lateral hypothalamus, portal vein, pancreatic beta cell, renal tubule, muscle and adipose tissue. Feedback pathways both from the brain and from muscle and fat are involved in regulating glucose allocation and exogenous glucose supply. The main feedback signal from the brain is found to be glucose, that from muscle and fat appears to be leptin. In fact, the literature search revealed two or more biological mechanisms for the function of each component in the model, finding glucose regulation highly redundant. This review focuses on "brain glucose" control. The concept of glucose allocation presented here challenges the common opinion of "blood glucose" being the main parameter controlled. According to the latter opinion, hyperglycemia in the metabolic syndrome is due to a putative defect located within the closed loop including the beta cell, muscle and fat cells. That traditional view leaves some peculiarities of e.g. the metabolic syndrome unexplained. The concept of glucose allocation, however, would predict that weight gain - with abundance of glucose in muscle and fat - increases feedback to the brain (via hyperleptinemia) which in turn results in HPA-axis and SNS overdrive, impaired insulin secretion, and insulin resistance. HPA-axis overdrive would account for metabolic abnormalities such as central adiposity, hyperglycemia, dyslipidemia, and hypertension, that are well known clinical aspects the metabolic syndrome. This novel viewpoint of "brain glucose" control may shed new light on the pathogenesis of the metabolic syndrome and type 2 diabetes.

Animals↗

PubMed2001

[Psychobiological aspects of anorexia nervosa].

In the long term anorexia nervosa has after toxicomania the second highest lethality of all psychiatric disorders. The genesis of this eating disorder may be found in a combination of biological, cultural, familial and intrapsychic factors. Long-term investigations have not only verified the seriousness of the prognosis of lethality but have also demonstrated that depressive illness, compulsive behaviour and addiction quite often supersede anorexia nervosa. It therefore seems justified to assume biological pathomechanisms as co-factors both in triggering the disease as well as in the chronification of this illness. Besides the discussion on a genetic disposition based on results of twin- and family research, psychobiological models of appetite and satiation behavior based on known neuropeptides and neurotransmitters are presented with regard to the development of anorexia nervosa.

Anorexia Nervosa↗

PubMed2000

Leptin suppresses semi-starvation induced hyperactivity in rats: implications for anorexia nervosa.

Semi-starvation induced hyperactivity (SIH) occurs in rodents upon caloric restriction. We hypothesized that SIH is triggered by the decline in leptin secretion associated with food restriction. To test this hypothesis, rats, which had established a stable level of activity, were treated with leptin or vehicle via implanted minipumps concomitantly to initiation of food restriction for 7 days. In a second experiment treatment was initiated after SIH had already set in. In contrast to the vehicle-treated rats, which increased their baseline activity level by 300%, the development of SIH was suppressed by leptin. Furthermore, leptin was able to stop SIH, after it had set in. These results underscore the assumed major role of leptin in the adaptation to semi-starvation. Because SIH has been viewed as a model for anorexia nervosa, we also assessed subjective ratings of motor restlessness in 30 patients with this eating disorder in the emaciated state associated with hypoleptinemia and after increments in leptin secretion brought upon by therapeutically induced weight gain. Hypoleptinemic patients ranked their motor restlessness higher than upon attainment of their maximal leptin level during inpatient treatment. Thus, hypoleptinemia might also contribute to the hyperactivity frequently associated with anorexia nervosa.

Animals↗

PubMed2000

Major depression and impaired glucose tolerance.

Hypercortisolism is a frequent endocrine sign in major depression and cortisol is a well-known anti-insulinergic hormone. Impaired oral glucose tolerance has already been described in major depression. However, thus far no information is available on spontaneous, circadian insulin secretion in patients. We studied 26 depressed inpatients along with 33 age- and sex-matched controls. Blood samples were collected at 30-minute intervals over a period of 26 hours (h) for estimation of cortisol, insulin and glucose. No differences in 24 h mean-insulin and glucose concentrations were detectable despite significantly reduced caloric consumption in patients. At the second morning a strictly standardized test meal of 2125 kjoule was given. Insulin and glucose responses to the test meal were significantly increased in hypercortisolemic patients compared to controls. Hence, patients with major depression have an impaired insulin sensitivity.

Analysis of Variance↗

PubMed2000

Lumbar bone mineral density in patients with major depression: evidence of increased bone loss at follow-up.

OBJECTIVE: This study investigated whether an increase in the loss of bone mineral density occurs with major depression. METHOD: The authors measured lumbar bone density with the use of quantitative computerized tomography in a longitudinal assessment of 18 depressed patients older than 40 years on hospital admission and 21 healthy women and men. The follow-up period lasted at least 24 months. RESULTS: A repeated measures analysis of variance model with depression and gender as factors showed that bone loss was greater for the depressed patients than for the comparison subjects and greater for men than for women. CONCLUSIONS: Major depression may be associated with increased bone loss, especially for men.

Absorptiometry, Photon↗

PubMed1999

Predictors of bone mineral density in patients with eating disorders.

OBJECTIVE: The objective of this study was to examine potential clinical predictors of bone density in patients with eating disorders. METHOD: We studied 137 women with anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified (NOS) after admission to the hospital. Clinical data of patients were collected by clinical interview and standardized questionnaires. Bone mineral density of the lumbar spine was measured by dual energy x-ray absorptiometry. RESULTS: Lumbar bone density was significantly correlated to present and past minimum weight even after correction for height and age. Other factors did not reach significance. CONCLUSION: Normalized present and past weight is the best predictor of lumbar bone density in patients with eating disorders. Factors like reduced caloric intake, binge eating, vomiting, menstrual status, and use of estrogen, laxatives, and nicotine seem to have no independent effect on bone density in this group of patients.

Absorptiometry, Photon↗

PubMed1998

The combined dexamethasone/corticotropin-releasing hormone stimulation test is more closely associated with features of diurnal activity of the hypothalamo-pituitary-adrenocortical system than the dexamethasone suppression test.

BACKGROUND: The dexamethasone suppression test (DST) is a widely used endocrine test in psychiatry, but was reported to not allow reliable inferences with regard to the basal activity of the hypothalamo-pituitary-adrenocortical (HPA) system. We compared the association of the standard DST and the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) challenge with parameters of diurnal cortisol profiles. METHODS: We performed a DEX/CRH challenge and 24-hour cortisol profiles in 25 depressed patients (mean age: 47.4 +/- 16.0 years) and 33 age-matched healthy controls (mean age: 51.4 +/- 19.3 years). RESULTS: A path analysis showed cortisol area under the curve (AUC) after CRH (= DEX/CRH status) to be dependent upon minimal 24-hour cortisol and evening frequency of pulsatile cortisol release. In contrast, postdexamethasone cortisol (= DST status) was related to 24-hour mean cortisol. Simple linear regressions supported an association of cortisol AUC with several parameters of the diurnal cortisol profiles, which was not true for the standard DST. CONCLUSIONS: We conclude that the combined DEX/CRH challenge test is more closely associated with the activity of the HPA system than the standard DST in healthy and depressed subjects.

Adrenocorticotropic Hormone↗

PubMed1998

Endurance training and its effect upon the activity of the GH-IGFs system in the elderly.

There is an age-associated decline in the activity of the GH-IGFs system. However, so far, it has not been studied, whether this decline in somatotrophic activity might be preventable by intensive exercising. We studied 11 elderly male (50-78 years) marathon runners and 10 age-matched male (52-73 years) sedentary controls to evaluate plasma concentrations of GH, total and free IGF-I and IGF-II and of IGF-binding protein-1 (IGFBP-1), IGFBP-2, IGFBP-3 and insulin. When comparing the two groups (runners vs controls) no differences were found in GH (1.0 +/- 1.2 vs 1.3 +/- 1.3 microg/l [mean +/- SD]), IGF-1 (115 +/- 23 vs 113 +/- 21 microg/l), IGF-II (961 +/- 192 vs 864 +/- 125 microg/l), free IGF-1 (227 +/- 80 vs 318 +/- 146 ng/l), free IGF-II (563 +/- 249 vs 492 +/- 108 ng/l), IGFBP-3 (2403 +/- 515 vs 2307 +/- 326 microg/l) or insulin (26 +/- 13 vs 27 +/- 18 mU/l). However, IGFBP-1 (4.44 +/- 2.61 vs 2.28 +/- 0.93 microg/l) and IGFBP-2 (493 +/- 143 vs 340 +/- 186 microg/l) were found to be significantly increased in marathon runners. In conclusion, our findings do not support the hypothesis that the age-associated decline in GH, IGF-1 and IGFBP-3 may be preventable by intensive endurance training. However, marathon running affects the regulation of the GH-IGFs system activity at the level of IGFBP-1 and -BP-2.

Aged↗

PubMed1998

Increased diurnal plasma concentrations of dehydroepiandrosterone in depressed patients.

Activation of the hypothalamus-pituitary-adrenocortical system is a biological core symptom of depression. Although the regulation of cortisol secretion is well studied in this condition, there is no information about the diurnal activity of dehydroepiandrosterone (DHEA) secretion. Therefore, we studied 24-h DHEA plasma concentrations (every 30 min) in severely depressed patients (n = 26) and healthy controls (n = 33). We found depression to significantly increase diurnal minimal and mean DHEA plasma concentrations, whereas there was no effect on the diurnal maximal plasma concentration and the diurnal amplitude of DHEA. In particular, we found a parallel increase in mean DHEA (5.8 +/- 3.6 vs. 3.4 +/- 1.9 nmol/L; P < 0.003), cortisol (286 +/- 65 vs. 184 +/- 29 nmol/L; P < 0.0001) and ACTH (7.14 +/- 2.06 vs. 5.72 +/- 1.36 pmol/L; P < 0.002) plasma concentrations. The novel finding of parallel increases in diurnal DHEA and cortisol plasma concentrations in depressed patients has important implications for the regulation of the hypothalamus-pituitary-adrenocortical system in conditions of chronic stress and for the rationale of DHEA treatment in depressed patients.

Adrenocorticotropic Hormone↗

PubMed1998

Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: response to amitriptyline treatment.

The effect of amitriptyline upon hypothalamic-pituitary-adrenal [HPA]-system-regulating neuropeptides (corticotropin-releasing hormone [CRH], vasopressin, somatostatin) was studied in a group of depressed elderly patients and controls. A first lumbar puncture was performed in 37 depressed in-patients. This was followed by a 6-week medication phase with amitriptyline. Upon its completion a second cerebrospinal fluid (CSF) sample was obtained in 18 of these 37 patients. In 25 healthy controls a first lumbar puncture was done eleven of these individuals agreed to take 75 mg/d amitriptyline for 6 weeks and to participate in the follow-up CSF study. Within the group of depressed patients amitriptyline led to a significant decrease of CSF CRH in treatment responders only (F1, 16 = 5.2; P < 0.02). Also, in normal controls CSF CRH concentration tended to decrease with amitriptyline treatment (t-test; P < 0.09). No effects of amitriptyline upon vasopressin or somatostatin were observed. In normal controls (r = 0.4; P < 0.02) and in patients (r = 0.4; P < 0.03) age correlated positively with baseline CSF somatostatin. A trend for CSF CRH to increase with aging was found only in controls (r = 0.3; P < 0.09); patients did not show a significant association here. Finally, CSF neuropeptide concentration at baseline did not differ between the group of depressed patients and healthy controls. Our study corroborates the evolving concept that antidepressants effect various components of the HPA system with the net result of a reduction in its activity. In addition, we found CSF CRH and CSF somatostatin concentrations to be better reflections of age than of depression and, finally, that during aging and during depression the HPA system changes in similar directions.

Adult↗

PubMed1997

Stochastic simulation of ligand-receptor interaction.

We have developed an algorithm for the stochastic simulation of ligand-receptor interactions based on 10(4)-10(5) fictitious binding sites. Reversible receptor binding was simulated by alternate random selection of sites, the first selection resulting in "occupation" if the selected site was "free," the second selection resulting in "dissociation" if the selected site was "occupied." We show that the mathematical formalism of mass action kinetics is predicted on purely statistical grounds. The model was extended by the introduction of two further selections, simulating a conformational change in the ligand-receptor complex ("receptor isomerization model"). All random selections were gauged separately by "probability barriers," taking the place of macroscopic kinetic rate constants. Simulation of gradual increases and gradual decreases of the fraction of occupied fictitious binding sites in the receptor isomerization model, using various combinations of "rate constants," resulted in biexponential time dependencies, in agreement with predictions from the integrated rate equations. Stochastic simulation of molecular processes is a powerful and versatile technique, providing the researcher with a means of studying mechanisms of increasing complexity.

Algorithms↗

PubMed1997

With aging in humans the activity of the hypothalamus-pituitary-adrenal system increases and its diurnal amplitude flattens.

There is compelling evidence for feedback disturbances in the hypothalamus-pituitary-adrenal system associated with human aging as assessed by challenge tests. However, reports about age-related changes in human basal activity are ambiguous and to date little is known about changes in the pulsatile features of the HPA system. To investigate these changes we studied twenty-two healthy male and eleven healthy female subjects ranging from 23 to 85 and 24 to 81 years respectively. 24-hour blood sampling with 30 minute sampling intervals was performed. From 18.00 to 24.00 hours blood was sampled every 10 minutes for analysis of pulsatile features of HPA activity. Statistical analysis revealed that age in particular had major effects upon basal HPA-system activity: there was a significant age-associated increase in minimal (p < 0.0001) and mean (p < 0.02) cortisol plasma concentrations, but no alteration in pulsatile features. We found no age-cortisol correlation during daytime, but were able to demonstrate a strong impact of age upon cortisol plasma levels from 20.00 to 1.30 hours. The diurnal amplitude of cortisol (p < 0.005) and ACTH (p < 0.006), relative to the 24-hour mean of the hormones, showed an age-associated decline. Additionally, the evening cortisol quiescent period (p < 0.01) was shortened in the elderly, suggesting increasingly impaired circadian function in aging. Our results suggest an increased basal activity and a flattened diurnal amplitude of the HPA system in the elderly.

Adult↗

PubMed1997

Insulin-like growth factor-I (IGF-I) plasma concentrations are increased in depressed patients.

There is some evidence that the somatotrophic system in depression, as assessed by basal growth hormone (GH) concentrations and by GH releasing hormone (GHRH) challenge, might be dysfunctional. However, the rather limited data have been inconclusive so far and plasma concentrations of both insulin-like growth factor-1 (IGF-I) and binding proteins (IGFBP 1 to IGFBP-6) have not been measured simultaneously in depressed patients. We studied 24 severely depressed patients and 33 healthy controls and estimated 24-hour mean plasma cortisol, six-hour evening mean plasma growth hormone (GH), morning plasma IGF-I, IGFBP 2 and 3 and GH-binding protein (GH-BP). Twenty-four-hour mean cortisol (306 +/- 69 vs. 196 +/- 30 nmol/l, p < .001) and IGF-I (157 +/- 40 vs. 120 +/- 33 micrograms/l, p < .01) plasma concentrations were found to be significantly increased in depressed patients, while there was no difference in GH or binding proteins between both groups. MANOVA analysis revealed age and diagnosis to have main effects upon plasma IGF-I. Especially young age and a diagnosis of major depression are associated with higher plasma IGF-I. After treatment only patients in remission had attenuated IGF-I plasma concentrations. We conclude that plasma IGF-I is increased in acutely depressed patients similar to other states of hypercortisolemia.

Adult↗

PubMed1997

Pulse-dosing and conventional application of doxepin: effects on psychopathology and hypothalamus-pituitary-adrenal (HPA) system.

It has been shown that a single pulse-dosing (PD) dose of clomipramine improves depressive symptoms. However, so far PD and conventional (CONV) application of antidepressants have never been directly compared for an extended period. We performed a double-blind study of PD and CONV application of doxepin (DOX) in depressed patients. After a 1-week placebo treatment, nine parents in the PD group received 250 mg of DOX every 6 days and placebo on the other days until day 39. Ten patients in the CONV group received increasing dosages of DOX until day 7 and 250 mg DOX on the other days for 39 days. Three dexamethasone (DEX)-suppression/corticotropin-releasing hormone (CRH)-stimulation tests were completed: (1)during the initial placebo period; (2)on day 9; and (3)on day 21. In the PD group, scores on the Hamilton Rating Scale for Depression (HAM-D) differed from baseline only after day 36 (17.1 +/- 7.0 vs. 22.7 +/- 2.8, p < 0.03). In the CONV group, however, HAM-D scores improved significantly after 2 days (22.8 +/- 7.2 vs. 26.5 +/- 5.7, p < 0.02) and continued to improve until day 39 (7.3 +/- 5.8). From day 25 to 39, there were significant differences between the HAM-D scores of the two groups. In the PD group, the decline of cortisol after DEX pretreatment was nonsignificant (NS) at both follow-up test occasions (35.9 +/- 40.7 vs. 24.0 +/- 20.7 vs. 23.6 +/- 26.6 micrograms/mL). In the CONV group, a significant decrease was observed at the second test (61.8 +/- 61.9 vs. 10.7 +/- 4.2 vs. 19.8 +/- 19 micrograms/mL, p < 0.05, respectively, NS). The area-under-the-curve cortisol response after CRH was attenuated in the PD group (5,667 +/- 2,910 vs. 1,883 +/- 2,178 vs. 2,239 +/- 2,583 [arbitrary unit], p < 0.01, respectively, p < 0.01) and in the CONV group (5,710 +/- 4,734 vs. 1,267 +/- 2,053 vs. 445 +/- 1,016 [arbitrary unit], NS, respectively, p < 0.02. We conclude that CONV application of DOX is clinically superior compared with PD and that both modes of application have attenuating effects on hypothalamus-pituitary-adrenal system activity.

Adult↗