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Biomedical subjects

M Hatzinger

Publications and source records attributed to M Hatzinger.

At least 37 records · Page 2Linked to original sources
PubMed2000

Neuropeptides and the hypothalamic-pituitary-adrenocortical (HPA) system: review of recent research strategies in depression.

Depressed patients show a variety of alterations in hypothalamic-pituitary-adrenocortical (HPA) system regulation which is reflected by increased pituitary-adrenocortical hormone secretion at baseline and a number of aberrant neuroendocrine function tests. The latter include the combined dexamethasone (DEX) suppression/corticotropin-releasing hormone (CRH) challenge test, in which CRH was able to override DEX induced suppression of ACTH and cortisol secretion. Whereas the abnormal HPA activation in these patients improved in parallel with clinical remission, persistent HPA dysregulation was associated with an increased risk of relapse. Moreover, healthy subjects at high genetic risk for depression also showed this phenomenon as a trait marker. In consequence, it has been concluded that HPA alteration and development as well as course of depression may be causally related. As evidenced from clinical and preclinical studies, underlying mechanisms of these abnormalities involve impairment of central corticosteroid receptor function which leads to enhanced activity of hypothalamic neurons synthesising and releasing vasopressin and CRH. These neuropeptides mediate not only neuroendocrine but also behavioural effects. Recent research provided evidence that CRH can induce depression-like symptoms in animals and that these signs are mediated through the CRH1 receptor subtype. Hence, therapeutical application of new compounds acting more specifically on the HPA system such as CRH1 receptor antagonists appear to be a promising approach for future treatment options of depression. In conclusion, research in neuroendocrinology provided new insights into the underlying pathophysiology of depression and, in consequence, may lead to the development of new therapeutic tools.

Adrenocorticotropic Hormone↗
PubMed1999

[Therapy refractory depression].

Patients who fail in an adequate trial of a standard antidepressant drug (corresponding to 150 mg/d imipramine over a minimal period of 4 weeks) are defined as treatment resistant. According to these guidelines a substantial number of patients is not sufficiently treated and, thus, should be reassessed for dosage and length of antidepressant medications. If patients fail to a sufficient treatment a response may be achieved if they are switched to an alternative drug and/or if biochemically differently acting antidepressants are combined. Furthermore, an increasingly popular approach to handle treatment resistance is the use of augmentation strategies. Among these, lithium and thyroid T3 are the most well studied with the most consistently positive results. As non-pharmacological augmentation approach partial sleep deprivation has proved to be effective in combination with antidepressant medication. Finally, patients who had no or only a partial response to several treatments with antidepressants may benefit from electroconvulsive therapy.

Antidepressive Agents↗
PubMed1998

Microsleep during partial sleep deprivation in depression.

BACKGROUND: Sleep deprivation (SD) exerts a beneficial effect on mood and sleep in about 60% of depressed patients usually followed by a relapse into depression after the recovery night. Short phases of sleepiness, especially naps in the early morning, may be responsible for this phenomenon. METHODS: To evaluate the effect of short, even ultrashort phases of sleep-microsleep (MS) during partial sleep deprivation (PSD) on mood, cognitive psychomotor performance (CPP), and sleep, an electroencephalograph (EEG) was continuously recorded over 60 hours in 12 patients with major depression. Subjective mood was assessed by a visual analogue scale and CPP by a letter cancellation test. RESULTS: The results illustrate that in depressed patients during PSD the amount of MS is increased, predominantly in the early morning, which was subjectively unrecognized and not observed by nursing staff. Patients with a low cumulative amount of MS during PSD improved significantly in mood, CPP, and sleep pattern compared to the patients with a high amount of MS who showed only slight changes. CONCLUSION: Therefore, accumulated MS may influence the SD-induced positive effects in depressed patients.

Adult↗
PubMed1998

Attenuated neuroendocrine responses to emotional and physical stressors in pregnant rats involve adenohypophysial changes.

1. The responsiveness of the rat hypothalamo-pituitary-adrenal (HPA) axis and hypothalamo-neurohypophysial system (HNS) to emotional (elevated plus-maze) and physical (forced swimming) stressors and to administration of synthetic corticotrophin-releasing hormone (CRH) was investigated during pregnancy and lactation. In addition to pregnancy-related adaptations at the adenohypophysial level, behavioural responses accompanying the neuroendocrine changes were studied. 2. Whereas basal (a.m.) plasma corticosterone, but not corticotrophin (adrenocorticotrophic hormone; ACTH), levels were increased on the last day (i.e. on day 22) of pregnancy, the stress-induced rise in both plasma hormone concentrations was increasingly attenuated with the progression of pregnancy beginning on day 15 and reaching a minimum on day 21 compared with virgin control rats. A similar attenuation of responses to both emotional and physical stressors was found in lactating rats. 3. Although the basal plasma oxytocin concentration was elevated in late pregnancy, the stress-induced rise in oxytocin secretion was slightly lower in day 21 pregnant rats. In contrast to vasopressin, oxytocin secretion was increased by forced swimming in virgin and early pregnant rats indicating a differential stress response of these neurohypophysial hormones. 4. The blunted HPA response to stressful stimuli is partly due to alterations at the level of corticotrophs in the adenohypophysis, as ACTH secretion in response to CRH in vivo (40 ng kg-1, i.v.) was reduced with the progression of pregnancy and during lactation. In vitro measurement of cAMP levels in pituitary segments demonstrated reduced basal levels of cAMP and a lower increase after CRH stimulation (10 nM, 10 min) in day 21 pregnant compared with virgin rats, further indicating reduced corticotroph responsiveness to CRH in pregnancy. 5. The reduced pituitary response to CRH in late pregnancy is likely to be a consequence of a reduction in CRH receptor binding as revealed by receptor autoradiography. [125I] CRH binding in the anterior pituitary was significantly reduced in day 11, 17 and 22 pregnant rats compared with virgin controls. 6. Anxiety-related behaviour of the animals as revealed by the time on and entries into the open arms of the elevated plus-maze was different between virgin and pregnant rats with decreased number of entries indicating increased anxiety with the progression of pregnancy (except on pregnancy day 18). The emotional behaviour, however, was not correlated with the neuroendocrine responses. 7. The results indicate that the reduced response of the HPA axis to stressors described previously during lactation is already manifested around day 15 of pregnancy in the rat and involves physiological adaptations at the adenohypophysial level. However, alterations in stressor perception at higher brain levels with the progression of pregnancy may also be involved.

Acclimatization↗
PubMed1997

Side effects of adjunct light therapy in patients with major depression.

Adjunct bright-light therapy has been suggested to augment antidepressant drug treatment in patients with non-seasonal major depression. Side effects of the combined therapy have not been investigated thus far. Therefore, somatic complaints and side effects of combined therapy were evaluated in 28 patients with major depression (DSM-III-R) randomly assigned to either trimipramine or trimipramine and serially applied adjunct bright-light therapy. Response rates were comparable in both treatment groups and rates of newly emergent side effects during treatment were generally low. The most prominent unfavourable side effects of adjunct bright-light therapy as compared with trimipramine monotherapy were aggravated sedation, persisting restlessness, emerging sleep disturbance and decreased appetite as well as the worsening of vertigo. Discriminant analysis revealed that the combination of trimipramine with bright light results in a different side effect profile compared with drug monotherapy.

Antidepressive Agents, Tricyclic↗
PubMed1997

[Techniques for bladder neck suspension with osseous screw fixation].

We investigated the technical feasibility and clinical results of bone fixation techniques in combination with needle suspension for correction of female stress urinary incontinence. In our experience the screw-like bone anchor, which is drilled into the public tubercle, represents a minimally invasive but very stable and reliable technique. However, the needle suspension fixed to the bone anchor turned out to be critical. Even though the suspension was fixed in the paraurethral tissue with a deep Z-stitch between the bladder neck and the midurethra, the 1-year recurrence rate was 76%. Our data showed that the suspension sutures pull through the paraurethral tissue because there is no paravesical scar formation as in open procedures. Modifications of the suspension technique (four-point suspension, simultaneous laparoscopic or digital dissection of the paravesical space, combination with sling procedures) revealed significantly improved short-term results. Therefore we conclude that after improvement of the suspension technique the bone anchor will represent a valid option for minimally invasive fixation of a bladder neck suspension.

Bone Screws↗
PubMed1997

Laparoscopy-assisted penile revascularization: a new method.

Analysis of more than 100 penile revascularizations using the Mannheim modification showed a success rate as high as 82% in properly selected patients. However, the dissection of the epigastric artery requires a relatively large incision, with the risk of postoperative bleeding, pain, and hernia formation. Therefore, we designed a laparoscopic approach for dissection of the epigastric vessels. From January 1995 to October 1996, we performed laparoscopy-assisted penile revascularization in 15 pharmacotesting nonresponders with erectile dysfunction. The first step is dissection of the penile vessels to minimize the occlusion time of the epigastric arteries. Thereafter, the extraperitoneal cavity is exposed using a balloon-trocar system inserted via a 15-mm suprapubic incision. A pneumoextraperitoneum is established, and two further cannulas are inserted (10 mm subumbilical, 5 mm in the lower abdomen contralateral to the desired epigastric artery). The dissection of the epigastric vessels starts caudally at the origin from the external iliac vessels and continues to the periumbilical area. All branches are dissected between clips, keeping the artery and vein together. For extraction of the artery, we insert another 5-mm port through the incision at the penile base. After desufflation of the extraperitoneal space and closure of the trocar wounds, microsurgical penile revascularization is performed using the previously described modification of the Hauri procedure. The mean operating time for laparoscopic dissection of epigastric artery was 120 minutes. No intraoperative complication occurred. One patient suffered from an inguinal hematoma. After a median follow-up of 12 month, 53% of patients showed spontaneous erections, and another 27% achieved a full erection with the aid of additional pharmacotherapy. Laparoscopic dissection of the epigastric arteries proved to be feasible, resulting in a considerable reduction of overall morbidity of penile revascularization without reducing the efficacy of the procedure.

Adult↗
PubMed1996

Neuroendocrine effects of a 20-mg citalopram infusion in healthy males. A placebo-controlled evaluation of citalopram as 5-HT function probe.

Pharmacokinetic measurements, neuroendocrine responses, and side effects profiles of intravenous infusions of 20 mg citalopram over 30 minutes during the early afternoon have been studied. Eight healthy male volunteers were enrolled in a placebo- (saline) controlled, single-blind, cross-over protocol. Plasma concentrations of the parent compound showed a double exponential decay. Demethyl and didemethyl metabolites were not detectable, but low concentrations of the propionic acid derivative of citalopram were found. Determination of the citalopram enantiomers yielded a balanced S(+)/R(-) ratio of 0.9 to 1.2. The endocrine response to the drug was characterized by significant increases in plasma prolactin and cortisol. Except for one subject, who developed pronounced side effects, human growth hormone showed a surge following saline that was inhibited following citalopram. Rectal temperature and heart rate were not affected and tolerability was favorable. Because of citalopram's extremely high selectivity for the presynaptic 5-hydroxytryptamine nerve terminals, the present data suggest that it might be a promising tool for the investigation of serotonergic function in the human brain in vivo.

Citalopram↗
PubMed1996

Combined dexamethasone/CRH test in rats: hypothalamo-pituitary-adrenocortical system alterations in aging.

Alterations of the hypothalamo-pituitary-adrenocortical (HPA) system are well-known phenomena in human aging as well as under stressful conditions and in psychiatric disorders. Among the various neuroendocrine function tests developed so far, the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test, in which DEX-pretreated subjects receive a single dose of CRH, has proved to be the most sensitive measure of subtle changes in HPA system regulation. To further explore the mechanisms underlying these neuroendocrine abnormalities in an animal model, a combined DEX/CRH test was established in young male Wistar rats. Five days before the experiment, the jugular vein was catheterized under halothane anesthesia for subsequent drug infusion and blood sampling. DEX (30 micrograms/kg) administered at 12.00 h, during the diurnal trough, suppressed the diurnal increase in circulating corticotropin (ACTH) and corticosterone between 18.00 and 20.00 h, during the acrophase. Subsequent CRH (50 ng/kg) infused at 20.00 h provoked a minimal escape from DEX suppression, indicated by a slight increase in ACTH and corticosterone secretion. Therefore, the combination of 30 micrograms/kg DEX given at 12.00 h followed by pituitary-adrenal system stimulation with 50 ng/kg CRH at 20.00 h was defined as the standard DEX/CRH test procedure and was then used in young (3-6 months) and aged male Wistar rats (20-24 months). After DEX treatment, basal ACTH levels between 18.00 and 20.00 h were significantly higher in aged than in young rats (77.6 +/- 23.2 vs. 19.9 +/- 0.9 pg/ml; p < 0.01), indicating resistance of the HPA system to the suppressive effect of DEX. In addition, the ACTH response to subsequent CRH was significantly higher in aged than in young animals (area under the concentration time curve: 3,670 +/- 2,230 vs. 294 +/- 112; p < 0.05). Thus, the HPA system appeared to be profoundly dysregulated in aged male Wistar rats. The elevated basal ACTH levels reflect glucocorticoid nonsuppression, suggesting negative feedback impairment. This is further supported by the elevated ACTH response to a subsequent CRH challenge, which, in addition, may indicate changes in the endogenous synergistic mechanisms of CRH with other corticotropic factors, for instance vasopressin. In summary, the DEX/ CRH test revealed HPA system alterations in aging and can be applied in future studies to further explore the mechanisms underlying the neuroendocrine disturbances during (psycho) pathological states.

Adrenal Cortex↗
PubMed1995

[Sleep disorders in chronic pain and generalized tendomyopathy].

Patients with a chronic pain syndrome often suffer from sleep disturbance. As both symptoms are frequent in the fibromyalgia syndrome, these patients in particular have been examined in this regard. No clear polysomnographic evaluation of the subjectively experienced sleep disturbance in these patients has been done so far. Therefore, we recorded the sleep EEG of 13 patients with a fibromyalgia syndrome in order to objectively characterize their sleep. Furthermore, we were interested in the relationship between the sleep alterations and pain intensity. In a subsequent placebo-controlled study based on pathophysiological considerations, we attempted to beneficially influence the sleep disturbance and the pain syndrome with the 5-HT2-receptor antagonist ketanserine, as this system has been proved to play a major role in the regulation of both sleep and pain. The results of our studies in patients with fibromyalgia show that the alteration of sleep is mainly characterized by a disturbance of sleep continuity associated with the experience of pain intensity. The application of 5-HT-receptor-antagonists may be a new strategy for the common treatment of sleep disturbance and the pain syndrome which needs to be evaluated in further studies. Duration of the patients' illness seems to be a predictive value in relation to intensity of the symptoms and the therapeutic outcome.

Adult↗
PubMed1995

[Sleep and addiction].

Sleep disorders and depressive symptoms are concomitant features in patients with addictive disorders. In this study, patients with addiction (alcohol and opioid, resp.) and with major depression (DSM-III-R) were examined with a sleep EEG and compared to age-matched controls. An age-dependent decrease of total sleep time and slow-wave sleep (SWS) was demonstrated. Sober patients with alcohol dependency showed a decrease of SWS, whereas patients with opioid dependency substituted with methadone showed a disorder of REM sleep (REM suppression). Depressive patients revealed a disturbance of sleep continuity and REM sleep (increased REM sleep). The neurobiological differentiation by sleep EEG is of interest for research and clinical practice.

Adolescent↗
PubMed1995

Effects of flumazenil on recovery sleep and hormonal secretion after sleep deprivation in male controls.

The effects of flumazenil, a benzodiazepine antagonist, on the sleep electroencephalogram (EEG) and neuroendocrine secretion in early morning recovery sleep (0500-0800 hours) following sleep deprivation (SD; 2300-0500 hours) were studied in seven healthy men. SD induced an increase in slow wave sleep (SWS), a decrease in sleep onset latency (SOL), an enhancement of EEG delta and theta power in non-rapid-eye-movement sleep, an increase in plasma human growth hormone (GH) concentration, and a decrease in plasma cortisol levels in recovery sleep (0500-0800 hours). Plasma GH, but neither plasma cortisol nor adrenocorticotrophic hormone (ACTH) concentration was attenuated during SD as compared to sleep (2300-0445 hours). The administration of flumazenil (3 x 1 mg intravenously) during recovery sleep resulted in an inhibition in SWS, an increase in stage 2 sleep, a selective reduction in delta and theta power, and a tendency to prolongation of SOL. Plasma GH concentration was decreased but plasma cortisol and ACTH remained unaffected. Since the SD-induced changes in sleep EEG and plasma GH secretion were antagonized by flumazenil, it is suggested that electrophysiological and hormonal effects of SD are mediated at least in part through GABAergic mechanisms.

Adrenocorticotropic Hormone↗
PubMed1995

Human plasma DSIP decreases at the initiation of sleep at different circadian times.

Nocturnal plasma delta sleep-inducing peptide-like immunoreactivity (DSIP-LI) was determined serially in seven healthy male subjects. Time courses during nocturnal sleep (2300-0800 h), nocturnal sleep deprivation (2300-0500 h), and morning recovery sleep (0500-0800 h) after sleep deprivation were compared. A significant decrease in plasma DSIP-LI was found at the transition from wakefulness to sleep in both evening sleep (2300 h) and morning recovery sleep (0500 h). Time courses were accompanied by physiological changes in sleep electroencephalographic slow-wave activity, and in plasma concentrations of cortisol and human growth hormone. No sleep stage specificity was found. It is concluded that DSIP is influenced by the initiation of sleep.

Adult↗
PubMed1995

Serial partial sleep deprivation as adjuvant treatment of depressive insomnia.

1. Sleep disturbance is a prominent symptom of major depression. Despite specific treatment with antidepressants, there is a substantial number of patients who improve in depressed mood but remain sleep disturbed. 2. Polysomnographic sleep (PSG) data and self reported sleep measures were assessed at baseline and after one week in 18 patients (35-65 years) randomly assigned to treatment with either trimipramine alone 200 mg/d (group 1) or trimipramine (200 mg/d) and additional serial partial sleep deprivation in the second half of the night (3x/week) (group 2). 3. In group 1 no marked changes between baseline and after treatment were found. 4. In group 2 the PSG data showed a significant increase of slow wave sleep and a compensatory decrease in stage 1. Sleep continuity improved in terms of numbers of awakenings, sleep onset latency and total sleep time. These changes were in parallel with the subjective estimation of sleep in group 2. 5. There was no significant difference in the Hamilton rating scale scores neither at baseline nor after treatment. 6. These observed effects on sleep following additional serial PSD therapy seem to occur independent from the antidepressive effect.

Adult↗