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Biomedical subjects

Mathias Berger

Publications and source records attributed to Mathias Berger.

At least 19 recordsLinked to original sources
PubMed2006

Sleep in obsessive compulsive disorder: polysomnographic studies under baseline conditions and after experimentally induced serotonin deficiency.

Several lines of evidence suggest that brain serotonergic systems may be disturbed in obsessive compulsive disorder (OCD). The serotonergic system strongly affects sleep and characteristic abnormalities of sleep are documented in depression. This study, therefore, aimed to investigate sleep structure of OCD patients in order to evaluate whether similar changes as in depression are present. Up to now, this issue has been addressed only in few studies with small numbers of patients. Sleep patterns of 62 unmedicated patients with primary OCD and 62 age- and sex-matched healthy controls were investigated by polysomnography. Additionally, the impact of tryptophan depletion on sleep was studied in a subgroup of 12 OCD patients and 12 controls. The OCD patients exhibited moderate, but significant disturbances of sleep continuity measures but no abnormalities of slow wave sleep or REM sleep, except a significant elevation of 1st REM density. Tryptophan depletion induced a worsening of sleep continuity, but no changes of REM sleep or slow wave sleep. Assuming that changes of sleep architecture indicate underlying neurobiological abnormalities, this study indicates that neurobiological disturbances are different in primary OCD as compared with primary depression.

Adult↗
PubMed2006

Differential effects of the muscarinic M1 receptor agonist RS-86 and the acetylcholine-esterase inhibitor donepezil on REM sleep regulation in healthy volunteers.

Broad evidence from preclinical and clinical research indicates that cholinergic neurotransmission contributes significantly to the generation of rapid eye movement (REM) sleep. However, a potential role of different acetylcholine receptor (AChR) subtypes for the regulation of three main aspects of REM sleep, (1) REM onset, (2) REM maintenance, and (3) generation of REMs, are not clear. In the present double-blind, randomized and placebo-controlled study, we investigated the differential effects of the M1 muscarinic AChR (mAChR) agonist RS-86 and the ACh-esterase inhibitor donepezil to further specify the AChR subtype function on REM sleep regulation in n = 20 healthy volunteers. We found that RS-86 selectively shortened REM latency (multivariate analysis of variance post hoc contrast p = 0.024 compared to placebo, not significant for donepezil) and that donepezil specifically enhanced the duration of REM sleep (% sleep period time, p = 0.000 compared to placebo; p = 0.003 compared to RS-86) and the number of REMs (p = 0.000 compared to placebo; p = 0.000 compared to RS-86). These results provide evidence that the onset of REM sleep is, in part, mediated by M1 mAChR activity, whereas the maintenance of REM sleep and the number of REMs are mediated by non-M1, but presumably M2 mAChR activity. These findings are of interest for the understanding of sleep regulation and of neuropsychiatric disorders, such as Alzheimer's dementia and depressive disorders, whose etiopathology may involve alterations in cholinergic neurotransmission.

Adult↗
PubMed2006

M1 muscarinic acetylcholine receptor agonism alters sleep without affecting memory consolidation.

Preclinical studies have implicated cholinergic neurotransmission, specifically M1 muscarinic acetylcholine receptor (mAChR) activation, in sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M1 mAChR agonist RS-86 on pre-post sleep memory consolidation. Twenty healthy human participants were tested in a declarative word-list task and a procedural mirror-tracing task. RS-86 significantly reduced rapid eye movement (REM) sleep latency and slow wave sleep (SWS) duration in comparison with placebo. Presleep acquisition and postsleep recall rates were within the expected ranges. However, recall rates in both tasks were almost identical for the RS-86 and placebo conditions. These results indicate that selective M1 mAChR activation in healthy humans has no clinically relevant effect on pre-post sleep consolidation of declarative or procedural memories at a dose that reduces REM sleep latency and SWS duration.

Adult↗
PubMed2006

Disease-modifying therapies in Alzheimer's disease: how far have we come?

Currently, there are no disease-modifying therapies available for Alzheimer's disease (AD). Acetylcholinesterase inhibitors and memantine are licensed for AD and have moderate symptomatic benefits. Epidemiological studies have suggested that NSAIDs, estrogen, HMG-CoA reductase inhibitors (statins) or tocopherol (vitamin E) can prevent AD. However, prospective, randomised studies have not convincingly been able to demonstrate clinical efficacy. Major progress in molecular medicine suggests further drug targets. The metabolism of the amyloid-precursor protein and the aggregation of its Abeta fragment are the focus of current studies. Abeta peptides are produced by the enzymes beta- and gamma-secretase. Inhibition of gamma-secretase has been shown to reduce Abeta production. However, gamma-secretase activity is also involved in other vital physiological pathways. Involvement of gamma-secretase in cell differentiation may preclude complete blockade of gamma-secretase for prolonged times in vivo. Inhibition of beta-secretase seems to be devoid of serious adverse effects according to studies with knockout animals. However, targeting beta-secretase is hampered by the lack of suitable inhibitors to date. Other approaches focus on enzymes that cut inside the Abeta sequence such as alpha-secretase and neprilysin. Stimulation of the expression or activity of alpha-secretase or neprilysin has been shown to enhance Abeta degradation. Furthermore, inhibitors of Abeta aggregation have been described and clinical trials have been initiated. Peroxisome proliferator activated receptor-gamma agonists and selected NSAIDs may be suitable to modulate both Abeta production and inflammatory activation. On the basis of autopsy reports, active immunisation against Abeta in humans seems to have proven its ability to clear amyloid deposits from the brain. However, a first clinical trial with active vaccination against the full length Abeta peptide has been halted because of adverse effects. Further trials with vaccination or passive transfer of antibodies are planned.

Alzheimer Disease↗
PubMed2005

Improving quality of care for depression: the German Action Programme for the implementation of evidence-based guidelines.

ISSUE: Depressive disorders are of great medical and political significance. The potential inherent in achieving better guideline orientation and a better collaboration between different types of care is clear. Throughout the 1990s, educational initiatives were started for implementing guidelines. Evidence-based guidelines on depression have been formulated in many countries. PURPOSE: This article presents an action programme for structural, educational, and research-related measures to implement evidence-based care of depressive disorders in the German health system. The starting points of the programme are the 'Guidelines Critical Appraisal Reports' of the 'Guideline Clearing House' and measures from the 'Competence Network on Depression and Suicidality' (CNDS) funded by the Federal Ministry of Education and Research. The article gives an overview of the steps achieved as recommended by the Guidelines Critical Appraisal Reports and the ongoing transfer process into the German health care system. RESULTS: The action programme shows that comprehensive interventions to develop and introduce evidence-based guidelines for depression can achieve benefits in the care of depression, e.g. in recognition, management, and clinical outcome. CONCLUSION: It was possible to implement the German Action Programme in selected care settings, and initial evaluation results suggest some improvements. The action programme provides preliminary work, materials, and results for developing a future 'Disease Management Programme' (DMP) for depression.

Depressive Disorder↗
PubMed2005

Chronotherapeutics (light and wake therapy) in affective disorders.

The Committee on Chronotherapeutics, delegated by the International Society for Affective Disorders (ISAD), makes the following recommendations after reviewing the evidence as of November 2004. (1) Wake therapy is the most rapid antidepressant available today: approximately 60% of patients, independent of diagnostic subtype, respond with marked improvement within hours. Treatment can be a single or repeated sleep deprivation, total (all night) or partial (second half of the night). Relapse can be prevented by daily light therapy, concomitant administration of SSRIs, lithium (for bipolar patients), or a short phase advance of sleep over 3 days following a single night of wake therapy. Combinations of these interventions show great promise. (2) Light therapy is effective for major depression--not only for the seasonal subtype. As an adjuvant to conventional antidepressants in unipolar patients, or lithium in bipolar patients, morning light hastens and potentiates the antidepressant response. Light therapy shows benefit even for patients with chronic depression of 2 years or more, outperforming their weak response to drugs. This method provides a viable alternative for patients who refuse, resist or cannot tolerate medication, or for whom drugs may be contraindicated, as in antepartum depression. (3) Given the urgent need for new strategies to treat patients with residual depressive symptoms, clinical trials of wake therapy and/or adjuvant light therapy, coupled with follow-up studies of long-term recurrence, are a high priority.

Clinical Trials as Topic↗
PubMed2005

Adherence to guidelines for treatment of depression in in-patients.

BACKGROUND: Adherence to treatment guidelines enhances treatment outcome. However, in clinical practice many patients with depression do not receive appropriate treatment. AIMS: To evaluate the treatment of depression in in-patients of German psychiatric hospitals with respect to treatment outcome and adherence to guidelines. METHOD: We recruited 1202 in-patients with depression from ten different hospitals. Quality data concerning treatment were collected at admission, during the treatment course and at discharge. RESULTS: The level of depression was significantly decreased and most patients were satisfied with treatment. Many aspects of the treatment routine adhered to guideline recommendations. Adherence to guidelines could be improved with respect to adjustment of antidepressant dosage, reduction of benzodiazepine prescription, enhanced use of electroconvulsive therapy and wider use of interpersonal therapy. CONCLUSIONS: The study reveals a high standard of psychiatric treatment of in-patients with depression. Nevertheless there is still room for improvement. Differences between hospitals in adherence to guidelines indicates the need for individual application of quality management tools.

Adult↗
PubMed2005

Impact of sleep-related complaints on depressive symptoms in patients with restless legs syndrome.

OBJECTIVE: Restless legs syndrome (RLS) is a distressing sensorimotor disorder with a 5% to 10% prevalence in the United States and Western Europe. The nocturnal occurrence of symptoms often leads to severe sleep disturbances. RLS has been reported to be associated with depression and anxiety. The aim of the present study was to investigate the relationship between RLS symptom severity, sleep disturbances, and depressive symptoms. METHOD: Questionnaire data from 100 consecutive patients with idiopathic RLS who had been investigated in our Sleep Disorders Unit from April 1999 to December 2004 were evaluated. Patients were untreated regarding RLS, depression, or sleep disturbances. Severity of RLS was assessed with the International RLS Study Group rating scale (IRLS). Depressive symptoms and subjective sleep quality were determined using the Beck Depression Inventory (BDI) and the Pittsburgh Sleep Quality Index (PSQI), respectively. RESULTS: IRLS scores indicated moderate-to-severe RLS symptoms in the population studied (mean +/- SD IRLS score = 23.6 +/- 6.7). The mean +/- SD BDI score was 9.3 +/- 5.6, with highest values on the "reduced sleep," "loss of energy," and "work difficulties" items, indicating predominating somatic symptoms of depression. Fourteen patients had a BDI score of 15 to 20 ("mild depression"), and 3 patients had a BDI score of 20 to 30 ("mild to moderate depression"). Overall, patients estimated their sleep quality as moderately impaired (mean +/- SD PSQI score = 10.9 +/- 3.7). Severity of RLS correlated with the impairment of subjective sleep quality (r = 0.281, p = .007) but not with self-rated depressive symptoms (r = 0.119, p = .237). CONCLUSION: RLS patients scored high on the somatic items of the BDI, particularly on those related to sleep disturbance, but not on the other items that mostly address cognitive symptoms. Our results indicate that RLS might be associated with some features of depression but not with the full spectrum of a depressive disorder. The relationship between the 2 disorders should be investigated in further studies.

Comorbidity↗
PubMed2004

Polysomnographic comparison between patients with primary alcohol dependency during subacute withdrawal and patients with a major depression.

Complex neurobiological models based on animal research have been formulated in an attempt to explain the cyclic pattern of nonREM and REM sleep. The "reciprocal interaction model" of nonREM and REM sleep regulation, which has been updated to incorporate new evidence is still the most convincing. Therefore it is reasonable to apply this model also to REM sleep abnormalities such as shortened REM latency and increased REM density, observed in patients with depression and alcohol dependency. In a retrospective analysis baseline data from 40 subjects with primary alcohol dependency are compared with a group of 40 patients diagnosed with major depression (diagnoses according to DSM-III-R) and healthy subjects. All alcohol dependent patients were examined in the sleep laboratory during subacute withdrawal at least 7 days off medication and after at least 14 days of abstinence. The patients with major depression (at least 7 days off psychoactive medication) and the healthy subjects had been examined previously by polysomnography during the last few years in the context of various studies and were assembled from our database to match the group of alcohol dependent patients with respect to age and sex. Alcohol dependent patients exhibited similar disturbances in sleep continuity and REM sleep as depressed patients in comparison to healthy controls while parameters of sleep architecture were even more strongly disturbed in alcohol dependence. While enhanced sensitivity of cholinergic receptors is the most likely explanation for the increase in "REM pressure" in depressives, this appears not to apply to alcoholics, who rather exhibit a decreased response to cholinergic stimulation. Thus, according to the reciprocal interaction model of nonREM- and REM sleep regulation and in contrast to the interpretation of the findings in depressed patients, an impaired aminergic rather than an increased cholinergic neurotransmission might be responsible for the increased REM sleep pressure in alcohol dependent patients. Alternatively or in addition the REM anomalies in alcoholic patients could also be due to adaptive regulatory processes during chronic alcohol consumption that lead to downregulation of GABA(A)- and upregulation of NMDA-receptors or their intracellular signalling and become apparent with alcohol withdrawal. Such adaptive counterregulation might also explain the alterations in slow wave sleep found in alcoholics that are even more pronounced in these patients than in patients with major depression.

Adult↗
PubMed2004

Identification of somatic and anxiety symptoms which contribute to the detection of depression in primary health care.

Somatic symptoms and anxiety symptoms are often disregarded in the detection of depression in primary care. The present investigation examined to what extent somatic and anxiety symptoms recorded with the Composite International Diagnostic Interview-Primary Health Care Version (CIDI-PHC) can improve the detection of depression as compared to the General Health Questionnaire-12-item version alone. Data from the World Health Organization study on Psychological Problems in General Health Care were used. The study sample consisted of primary care attenders from 15 centres from all over the world who underwent a psychiatric examination with the CIDI-PHC. Medically unexplained somatic symptoms (back pain, feelings of heaviness/lightness in parts of the body, periods of bodily weakness, seizures/convulsions, permanent tiredness, exhaustion after a minimum of effort) and-to a smaller extent-diverse anxiety symptoms (e.g. feelings of anxiousness/nervousness, feelings of tension, difficulties relaxing) significantly contributed to the detection of depression in a logistic regression analysis. The results confirm the observation that in primary care somatic symptoms play an important role in the manifestation of depressive disorders. The items investigated herein could prove beneficial for future depression screening instruments to improve the detection of depressive disorders in primary care.

Anxiety Disorders↗
PubMed2004

[Efficacy and therapeutic factors of interpersonal psychotherapy for depressed inpatients - results of a pilot study].

BACKGROUND: Despite the common use of combined therapy programs for the treatment of depression among inpatients, very few evaluations have been reported. OBJECTIVE: Evaluation of the efficacy and efficacy factors of a 6 week treatment program of IPT in combination with standard pharmacotherapy of depressed inpatients (IPT-S). METHOD: 28 inpatients with a major depression were treated with IPT-S. The first eight cases were evaluated regarding the therapy process using the cubus analysis. RESULTS: The treatment showed significant and stable changes on depression-specific and interpersonal measures. The most successful IPT therapies showed a pattern of intensive clarification - especially of interpersonal issues - in the first half of therapy followed by coping strategies. CONCLUSIONS: The preliminary results suggest that IPT-S is a useful and effective therapy concept that warrants further investigation.

Adolescent↗
PubMed2004

[Cost of care for depressive disorders in primary and specialized care in Germany].

Service utilization and total direct cost of care was assessed in 270 patients suffering from depressive disorder. Patients were recruited from primary care physicians or family doctors (n = 43) or psychiatrists (n = 23) in office practice, from three different regions in Germany (county of Düren and city of Aachen, Lörrach-county, city of Munich). A detailed catalogue of unit costs (including inpatient, outpatient and rehabilitative services) was used for calculating total cost of care on an individual basis. Service utilization and costs referred to 2001. Mean cost of total medical care of the study patients was euro 3849 (excluding cost of drugs for physical illness). The cost for treating depressive disorders and additional psychiatric co-morbidity (which is included into the total cost of care) was euro 2073 per patient and year. When cross-checking with ICD-10 criteria for depressive disorders, the original diagnosis by family doctors or psychiatrists could be confirmed in 186 patients of the total sample (n = 270), suggesting that there is a high amount of falsely diagnosed patients in primary and specialized care of depressive patients in Germany. Direct cost of the 186 confirmed patients was higher (total care cost: euro 4715, cost for treatment of depression and psychiatric co-morbidity: euro 2541) than in the total group and should be considered as reference cost, when discussing cost of care in depressive patients in Germany. Results suggest to analyse cost of care in depressive patients further and to discuss a more efficient allocation of health budgets in the field.

Adult↗
PubMed2004

Validation of polypharmacy process measures in inpatient schizophrenia care.

The influence of combining antipsychotics and different classes of psychotropic drugs on treatment outcome in schizophrenia remains unclear. As part of a comprehensive quality management program, we prospectively evaluated two schizophrenia polypharmacy performance measures in a cohort of 1,075 consecutively recruited individuals with schizophrenia in seven psychiatric hospitals. Multiple concurrent antipsychotic and overall psychotropic polypharmacy rates were noticeably high. In case-mix-adjustment models controlling for a variety of confounding baseline parameters, patients discharged with more than one antipsychotic had significantly poorer outcomes with respect to both mental state and social functioning. Prescription of more than three psychotropic agents did not adversely affect social functioning when patients taking more than three were compared to patients given fewer medications. Case-mix models suggest that antipsychotic polypharmacy, while used more often for individuals with chronic disease and more thought disturbance, is only partly a reaction to disease severity. The antipsychotic polypharmacy process measure may be used to identify treatment problems in order to find alternatives to polypharmacy. The measure can be easily assessed in a variety of settings and does not depend on the availability of case-mix data. The rising trend toward polypharmacy in schizophrenia care, which is not supported by current guideline recommendations, warrants critical appraisal.

Adolescent↗
PubMed2004

Impact of sleep deprivation and subsequent recovery sleep on cortisol in unmedicated depressed patients.

OBJECTIVE: One night of sleep deprivation induces a transient improvement in about 60% of depressed patients. Since depression is associated with abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis, the authors measured cortisol secretion before, during, and after therapeutic sleep deprivation for 1 night. METHOD: Fifteen unmedicated depressed inpatients participated in a combined polysomnographic and endocrine study. Blood was sampled at 30-minute intervals during 3 consecutive nights before, during, and after sleep deprivation. Saliva samples were collected at 30-minute intervals during the daytime before and after the sleep deprivation night. RESULTS: During the night of sleep deprivation, cortisol levels were significantly higher than at baseline. During the daytime, cortisol levels during the first half of the day were higher than at baseline in the patients who responded to sleep deprivation but not in the nonresponders. During recovery sleep, cortisol secretion returned to baseline values. CONCLUSIONS: This study demonstrated a significant stimulatory effect of 1 night of sleep deprivation on the HPA axis in unmedicated depressed patients. The results suggest that the short-term effects of antidepressant treatments on the HPA axis may differ from their long-term effects. A higher cortisol level after sleep deprivation might transiently improve negative feedback to the hypothalamus or interact with other neurotransmitter systems, thus mediating or contributing to the clinical response. The fast return to baseline values coincides with the short clinical effect.

Adult↗
PubMed2003

[Comprehensive ambulatory care quality management for patients with depressive disorders].

Depressive disorders are of great medical and political significance. Despite improvements in the treatment of depressive patients, the potential for guideline-oriented diagnosis and therapy as well as better co-operation between different levels of care is evident. This study is part of the German Research Network on Depression and Suicidality. The study is conducted in Southern Baden, North Rhine and Munich. The objective is to develop a quality management program for primary care physicians and psychiatrists. A comprehensive continuous medical education concept as well as quality management measures were developed, implemented and evaluated. A total of 66 physicians (43 primary care physicians and 23 psychiatrists) participated. They documented the diagnostic and treatment measures provided to depressive patients before and after the intervention that had been implemented in the intervention regions of Southern Baden and North Rhine. Effects regarding guideline orientation and implementation of stepped-care treatment are analysed with an intervention/control group design and prepost data measurement.

Ambulatory Care↗