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Biomedical subjects

Heidi Danker-Hopfe

Publications and source records attributed to Heidi Danker-Hopfe.

At least 19 recordsLinked to original sources
PubMed2006

The relationship between REM sleep and memory consolidation in old age and effects of cholinergic medication.

BACKGROUND: Recent findings in young adults suggest that rapid eye movement (REM) sleep plays a role in procedural memory consolidation. The significance of REM sleep for memory consolidation in old age has not yet been investigated. METHODS: Effects of REM sleep manipulation on declarative and procedural memory consolidation were investigated in 107 healthy older adults, ages 60-82 years. Rapid eye movement sleep deprivation was achieved by REM sleep awakenings and compared with non-REM sleep awakenings. Rapid eye movement sleep augmentation was realized physiologically by REM sleep rebound and pharmacologically by administering an acetylcholinesterase inhibitor in a double-blind, placebo-controlled design. Memory performance was tested by a paired associate list and a mirror tracing task at 9:30 pm and 7:30 am with sleep intervening between 11:00 pm and 7:00 am. RESULTS: Although REM sleep deprivation led to a significant reduction in total and phasic REM sleep, memory consolidation remained unaffected. Both REM sleep augmentation groups showed a significant increase in phasic REM sleep, whereas only pharmacological cholinergic REM sleep manipulation exerted a significant positive effect on procedural memory consolidation. CONCLUSIONS: Because only after cholinergic stimulation of phasic REM sleep procedural memory consolidation is improved, cholinergic activation seems to be a crucial component of REM sleep-related memory consolidation in old age.

Aged↗
PubMed2006

Nerve growth factor serum concentrations rise after successful cognitive-behavioural therapy of generalized anxiety disorder.

Generalized anxiety disorder (GAD) is a chronic stress disease with permanent physical tension and cognitive strain. Raised nerve growth factor (NGF) serum levels were reported as an acute stress reaction in soldiers before their first parachute jump even before the rise in cortisol. Taking GAD as a clinical model of chronic stress, we measured NGF in the serum of 22 patients with GAD before and after cognitive-behavioural therapy (CBT) and compared them to those of healthy normal controls. Treatment response was tested by the values of the State and Trait of Anxiety Inventory (STAI) and the Hamilton Anxiety Scale (HAM-A) as treatment outcome variables. The NGF values of patients and controls were similar at baseline (p=0.8941); however, with successful treatment, corresponding to a mean reduction in the HAM-A by more than 50% and a reduction in the clinical global impression scale (CGI) median from 4 to 1, the patients' NGF serum concentrations rose significantly (p=0.0006) which might correspond to an altered stress reaction, possibly contributing to good therapeutic response with CBT. There were 3 patients with a HAM-A decrease of less than 15%. In those patients NGF rose only marginally. Hence, the increase in serum NGF seems to indicate good treatment response.

Adolescent↗
PubMed2006

Serum neurotrophins--a study on the time course and influencing factors in a large old age sample.

The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are important mediators of brain and neuronal development, the maintenance of homeostatic conditions in the adult nervous system, and the complex interplay of central and peripheral physiological and pathophysiological factors. To date there are few studies examining blood concentrations of neurotrophic factors in large samples of healthy and diseased individuals and no published study specifically addresses peripheral BDNF and NGF levels in late life. Using improved highly sensitive and specific fluorometric two-site enzyme-linked immunosorbent assays we examined BDNF (n=465) and NGF (n=175) serum levels in a large cohort of elderly individuals (age range: 70-103 years). Neither BDNF nor NGF serum levels proved to be normally distributed, indicating that previously published studies with small sample sizes using parametric testing may be misleading. A significant correlation was found between BDNF and platelet count (r=0.344, p<0.01), age and BDNF protein (r=-0.101, p=0.029) and BDNF and NGF serum levels (r=0.152, p=0.04). No other major influencing factors were found including gender, depression, and dementia.

Age Factors↗
PubMed2006

Metabolic alterations in the dorsolateral prefrontal cortex after treatment with high-frequency repetitive transcranial magnetic stimulation in patients with unipolar major depression.

Neuroimaging studies suggest a specific role of anterior cingulate cortex (ACC) and left dorsolateral prefrontal cortex (DLPFC) in major depression. Stimulation of the latter by means of repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the past. The objective of the present study was to examine in vivo neurochemical alterations in both brain regions in 17 patients with unipolar major depression before and after 10 days of high-frequency (20Hz) rTMS of the left DLPFC using 3-tesla proton magnetic resonance spectroscopy. Six out of seventeen patients were treatment responders, defined as a 50% reduction of the Hamilton depression rating scale. No neurochemical alterations in the ACC were detected after rTMS. As compared to the non-responders, responders had lower baseline concentrations of DLPFC glutamate which increased after successful rTMS. Correspondingly, besides a correlation between clinical improvement and an increase in glutamate concentration, an interaction between glutamate concentration changes and stimulation intensity was observed. Our results indicate that metabolic, state-dependent changes within the left DLPFC in major depressive disorder involve the glutamate system and can be reversed in a dose-dependent manner by rTMS.

Adult↗
PubMed2006

Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS).

Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique which had recently been investigated as a putative antidepressant intervention. However, there is little agreement about clinically useful predictors of rTMS outcome. Therefore, the objective of the present study was to determine whether specific biographical, clinical, and psychopathological parameters are associated with the antidepressant response to rTMS in a large sample of 70 depressive patients. We performed a logistic regression analysis in 70 patients with major depressive disorder treated with rTMS of the left dorsolateral prefrontal cortex testing the predictive value of various domains of the depression syndrome as well as the variables episode duration, degree of treatment resistance, and CORE criteria. Response was defined as a 50% reduction of the initial Hamilton score (HAMD). After two weeks of treatment, 21% of the patients showed a response to rTMS. The binary logistic regression model correctly assigned 86.7% of the responders and 96.4% of the non-responders to their final response group. In the model, a high level of sleep disturbances was a significant predictor for treatment response to rTMS. Also, a low score of treatment resistance and a short duration of episode were positive predictors. These findings provide new evidence that especially pronounced sleep disturbances may be a significant clinical predictor of a response to rTMS. Prospective rTMS studies are necessary to validate the predictive value of the derived model.

Antidepressive Agents↗
PubMed2006

Adequate antipsychotic treatment normalizes serum nerve growth factor concentrations in schizophrenia with and without cannabis or additional substance abuse.

Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are important for the development and maintenance of neuron function. Neurodevelopment is thought to be impaired in schizophrenia, and vulnerable schizophrenic brains may be more sensitive to toxic influences. Thus, cannabis as a neurotoxin (and other substances) may be more harmful to schizophrenic brains than to non-schizophrenic brains, when used chronically. In a previous study we demonstrated an earlier disease onset and significantly higher serum NGF concentrations in drug-naïve schizophrenic patients with previous long-term cannabis abuse than in schizophrenics without cannabis abuse or cannabis abusers without schizophrenia. We therefore investigated whether this difference is still observed after treatment. Serum NGF measured in 114 treated schizophrenic patients (schizophrenia alone, n=66; schizophrenia plus cannabis abuse, n=42; schizophrenia plus multiple substance abuse, n=6) no longer differed significantly among those groups and from the control groups (healthy controls, n=51; cannabis controls, n=24; multiple substance controls, n=6). These results were confirmed by an additional prospective study in 28 patients suffering from schizophrenia (S) or schizophrenia with cannabis abuse (SC). Previously elevated serum NGF levels in the drug-naïve state, also differing between the groups (S: 83.44+/-265.25 pg/ml; SC: 246.89+/-310.24 pg/ml, S versus SC: p=0.03) dropped to 10.72+/-14.13 pg/ml (S) and 34.19+/-38.96 pg/ml (SC) (S versus SC, p>0.05), respectively, after adequate antipsychotic treatment. We thus conclude that antipsychotic treatment leads to recovery of neural integrity, as indicated by renormalized NGF values.

Adolescent↗
PubMed2005

Manipulating REM sleep in older adults by selective REM sleep deprivation and physiological as well as pharmacological REM sleep augmentation methods.

Experimental approaches to manipulate REM sleep within the cognitive neuroscience of sleep are usually based on sleep deprivation paradigms and focus on younger adults. In the present study, a traditional selective REM sleep deprivation paradigm as well as two alternative manipulation paradigms targeting REM sleep augmentation were investigated in healthy older adults. The study sample consisted of 107 participants, male and female, between the ages of 60 and 82 years, who had been randomly assigned to five experimental groups. During the study night, a first group was deprived of REM sleep by selective REM sleep awakenings, while a second group was woken during stage 2 NREM sleep in matched frequency. Physiological REM sleep augmentation was realized by REM sleep rebound after selective REM sleep deprivation, pharmacological REM sleep augmentation by administering an acetylcholinesterase inhibitor in a double-blind, placebo-controlled design. Deprivation and augmentation paradigms manipulated REM sleep significantly, the former affecting more global measures such as REM sleep minutes and percentage, the latter more organizational aspects such as stage shifts to REM sleep, REM latency, REM density (only pharmacological augmentation) and phasic REM sleep duration. According to our findings, selective REM sleep deprivation seems to be an efficient method of REM sleep manipulation in healthy older adults. While physiological rebound-based and pharmacological cholinergic REM sleep augmentation methods both failed to affect global measures of REM sleep, their efficiency in manipulating organizational aspects of REM sleep extends the traditional scope of REM sleep manipulation methods within the cognitive neuroscience of sleep.

Aged↗
PubMed2005

Evidence for impaired cortical inhibition in patients with unipolar major depression.

BACKGROUND: Several lines of evidence suggest that central cortical inhibitory mechanisms, especially associated with gamma-aminobutyric acid (GABA) neurotransmission, may play a role in the pathophysiology of major depression. Transcranial magnetic stimulation is a useful tool for investigating central cortical inhibitory mechanisms associated with GABAergic neurotransmission in psychiatric and neurological disorders. METHODS: By means of transcranial magnetic stimulation, different parameters of cortical excitability, including motor threshold, the cortical silent period, and intracortical inhibition/facilitation, were investigated in 20 medication-free depressed patients and 20 age- and gender-matched healthy volunteers. RESULTS: Silent period and intracortical inhibition were reduced in depressed patients, consistent with a reduced GABAergic tone. Moreover, patients showed a significant hemispheric asymmetry in motor threshold. CONCLUSIONS: This study provides evidence of reduced GABAergic tone and motor threshold asymmetry in patients with major depression.

Adult↗
PubMed2005

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex and cortical excitability in patients with major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex is a relatively non-invasive technique with putative therapeutic effects in major depression. However, the exact neurophysiological basis of these effects needs further clarification. Therefore, we studied the impact of ten daily sessions of left, dorsolateral prefrontal rTMS on motor cortical excitability, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials in 30 patients. As compared to the non-responders, responders (33%) showed changes in parameters pointing towards a reduced cortical excitability. These results suggest that repetitive transcranial magnetic stimulation of the dorsolateral, prefrontal cortex may have inhibitory effects on motor cortical neuronal excitability in patients with major depressive disorder. Furthermore, measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of antidepressant stimulation techniques like rTMS.

Adult↗
PubMed2005

An E-health solution for automatic sleep classification according to Rechtschaffen and Kales: validation study of the Somnolyzer 24 x 7 utilizing the Siesta database.

To date, the only standard for the classification of sleep-EEG recordings that has found worldwide acceptance are the rules published in 1968 by Rechtschaffen and Kales. Even though several attempts have been made to automate the classification process, so far no method has been published that has proven its validity in a study including a sufficiently large number of controls and patients of all adult age ranges. The present paper describes the development and optimization of an automatic classification system that is based on one central EEG channel, two EOG channels and one chin EMG channel. It adheres to the decision rules for visual scoring as closely as possible and includes a structured quality control procedure by a human expert. The final system (Somnolyzer 24 x 7) consists of a raw data quality check, a feature extraction algorithm (density and intensity of sleep/wake-related patterns such as sleep spindles, delta waves, SEMs and REMs), a feature matrix plausibility check, a classifier designed as an expert system, a rule-based smoothing procedure for the start and the end of stages REM, and finally a statistical comparison to age- and sex-matched normal healthy controls (Siesta Spot Report). The expert system considers different prior probabilities of stage changes depending on the preceding sleep stage, the occurrence of a movement arousal and the position of the epoch within the NREM/REM sleep cycles. Moreover, results obtained with and without using the chin EMG signal are combined. The Siesta polysomnographic database (590 recordings in both normal healthy subjects aged 20-95 years and patients suffering from organic or nonorganic sleep disorders) was split into two halves, which were randomly assigned to a training and a validation set, respectively. The final validation revealed an overall epoch-by-epoch agreement of 80% (Cohen's kappa: 0.72) between the Somnolyzer 24 x 7 and the human expert scoring, as compared with an inter-rater reliability of 77% (Cohen's kappa: 0.68) between two human experts scoring the same dataset. Two Somnolyzer 24 x 7 analyses (including a structured quality control by two human experts) revealed an inter-rater reliability close to 1 (Cohen's kappa: 0.991), which confirmed that the variability induced by the quality control procedure, whereby approximately 1% of the epochs (in 9.5% of the recordings) are changed, can definitely be neglected. Thus, the validation study proved the high reliability and validity of the Somnolyzer 24 x 7 and demonstrated its applicability in clinical routine and sleep studies.

Adult↗
PubMed2005

Age-related changes in sleep and memory: commonalities and interrelationships.

Aging is accompanied by changes on many different levels, including sleep and memory processes. In light of recent findings, which underline the importance of sleep for memory consolidation in young adults, the relationship between sleep and memory in older adults is of particular interest. This review takes a closer look at commonalities and interrelationships of the two aging trajectories in sleep and memory. A link between these two research domains on aging will be proposed and discussed on the basis of recent findings within the cognitive neuroscience of sleep.

Aged↗
PubMed2005

Motor cortical excitability in depressive patients after electroconvulsive therapy and repetitive transcranial magnetic stimulation.

Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex are brain stimulation techniques that are used as therapeutic interventions in major depression. However, the exact therapeutic mode of action needs further clarification. In this case report, we describe the impact of these stimulation techniques on motor cortical excitability, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials in 2 patients who received consecutively both rTMS and ECT. Both patients showed a decrease in motor cortical excitability after response to antidepressant brain stimulation, whereas parameters of motor cortical excitability remained unchanged after the first non-successful intervention. These results suggest that both ECT and rTMS may have an impact on parameters of motor cortical neuronal excitability. Furthermore, measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of different antidepressant stimulation techniques.

Adult↗
PubMed2004

Brain-derived neurotrophic factor serum concentrations are increased in drug-naive schizophrenic patients with chronic cannabis abuse and multiple substance abuse.

Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are critically implicated in development and maintenance of function of neurons. Neurodevelopment is reported to be impaired in schizophrenia and vulnerable schizophrenic brains may be more sensitive to toxic influences. Thus, cannabis as a neurotoxin, may be more harmful to schizophrenic brains than to non-schizophrenic brains when used chronically. And neurotoxic events may promote disease-onset and lead to exaggerated release of neurotrophins. We investigated 157 drug-naive first-episode schizophrenic patients and found significantly elevated BDNF serum concentrations (by up to 34%) in patients with chronic cannabis abuse (n = 35, p < 0.001) or multiple substance abuse (n = 20, p < 0.001) prior to disease onset. Drug-naive schizophrenic patients without cannabis consumption showed similar results to normal controls and cannabis controls without schizophrenia. Thus, raised BDNF serum levels are not related to schizophrenia and/or substance abuse itself but may reflect a cannabis-related idiosyncratic damage of the schizophrenic brain. In line with this hypothesis, disease onset was 5.2 years earlier in the cannabis-consuming group (p = 0.0111).

Adult↗
PubMed2004

Interrater reliability between scorers from eight European sleep laboratories in subjects with different sleep disorders.

Interrater variability of sleep stage scorings is a well-known phenomenon. The SIESTA project offered the opportunity to analyse interrater reliability (IRR) between experienced scorers from eight European sleep laboratories within a large sample of patients with different (sleep) disorders: depression, general anxiety disorder with and without non-organic insomnia, Parkinson's disease, period limb movements in sleep and sleep apnoea. The results were based on 196 recordings from 98 patients (73 males: 52.3 +/- 12.1 years and 25 females: 49.5 +/- 11.9 years) for which two independent expert scorings from two different laboratories were available. Cohen's kappa was used to evaluate the IRR on the basis of epochs and intraclass correlation was used to analyse the agreement on quantitative sleep parameters. The overall level of agreement when five different stages were distinguished was kappa = 0.6816 (76.8%), which in terms of kappa reflects a 'substantial' agreement (Landis and Koch, 1977). For different groups of patients kappa values varied from 0.6138 (Parkinson's disease) to 0.8176 (generalized anxiety disorder). With regard to (sleep) stages, the IRR was highest for rapid eye movement (REM), followed by Wake, slow-wave sleep (SWS), non-rapid eye movement 2 (NREM2) and NREM1. The results of regression analysis showed that age and sex only had a statistically significant effect on kappa when the (sleep) stages are considered separately. For NREM2 and SWS a statistically significant decrease of IRR with age has been observed and the IRR for SWS was lower for males than for females. These variations of IRR most probably reflect changes of the sleep electroencephalography (EEG) with age and gender.

Female↗
PubMed2004

Measurement of nerve growth factor serum concentration in a psychologically stressful situation in men.

Psychologically stressful events have been reported to elevate nerve growth factor (NGF) serum concentrations. NGF and cortisol serum concentrations were measured in 20 healthy male volunteers before (3 p.m.) and after (5 p.m.) an academic oral presentation and on a control day. Cortisol showed a significant overall change (p=0.001), i.e. cortisol serum concentrations were increased on the lecture day at 3 p.m. (p=0.007; 155%) and at 5 p.m. (p=0.001; 175%) as compared with the control day. In contrast to cortisol no significant differences among the four serum NGF measurements was detected (Chi-quadrat 2.94, df=3, p=0.401), i.e. the NGF serum concentrations remained unchanged on the lecture day at 3 p.m. (p=0.279) and at 5 p.m. (p=0.627) as compared with the control day. We conclude that NGF serum levels do not change during acute stress, at least after this type of stressor.

Acute Disease↗
PubMed2004

No association of a functional polymorphism in the serotonin transporter gene promoter and anxiety-related personality traits.

Serotonergic neurotransmission, which is involved in many psychiatric disorders, is mediated by the serotonin transporter protein. Gene coding for the serotonin transporter protein is designated SLC6A4, which has been differentially associated with anxiety-related behavioral traits and neuroticism in healthy subjects. To confirm the association between the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) and anxiety-related personality traits, we examined 228 healthy unrelated participants (age 38.6 +/- 12.8 years; 115 male, 113 female) of German origin, who were carefully examined with respect to psychiatric health. The self-ratable State-Trait Anxiety Inventory (STAI) and the NEO Five Factor Inventory (NEO-FFI) were performed. No significant association was observed between the 5-HTTLPR genotype and STAI 1 (state, chi2 = 0.82, p < 0.66, d.f. = 2), STAI 2 (trait, chi2 = 2.7, p < 0.25, d.f. = 2) and NEO-FFI scores of any of the 5 major axes, including neuroticism (chi2 = 3.35, p < 0.18, d.f. = 2) in all subjects. Given the small effect of this 5-HTT polymorphism on behaviour in previous studies, a lack of significant genotype differences in these tests could be due to considerable individual variability in these measures.

Adult↗