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Biomedical subjects

Ulrich Voderholzer

Publications and source records attributed to Ulrich Voderholzer.

At least 19 recordsLinked to original sources

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↗

Periodic leg movements in sleep and periodic limb movement disorder: prevalence, clinical significance and treatment.

Periodic leg movements in sleep (PLMS) are a frequent finding in polysomnography. The prevalence of PLMS is estimated to be 4-11% in adults. In childhood, PLMS rarely occur although medical conditions like sleep apnea syndrome or neuropsychiatric disorders can lead to high rates of PLMS. In the elderly, PLMS are also common in subjects without sleep disturbances. In sleep studies, PLMS are found most frequently in restless legs syndrome (RLS) and often occur in narcolepsy, sleep apnea syndrome and REM sleep behavior disorder. Some patients with otherwise unexplained insomnia or hypersomnia reveal an elevated number of PLMS, a condition defined as periodic limb movement disorder (PLMD). PLMS were found also in various medical and neurological disorders that do not primarily affect sleep. A summary of these is presented. In sleep disorders related to dopaminergic dysfunction such as RLS, PLMS are considered to be a symptom of the disease. In other disorders like primary insomnia, the clinical relevance of PLMS is still being controversially discussed. Studies with findings both pro and contra are referred. To date, only a few studies have evaluated the efficacy of therapeutic substances in reducing PLMS in PLMD patients. Their results need to be confirmed in controlled randomized trials.

Aged↗

Neuropsychological impairment in obsessive-compulsive disorder--improvement over the course of cognitive behavioral treatment.

A large body of studies demonstrates mild cognitive dysfunction in patients with Obsessive Compulsive Disorder (OCD). Few trials have investigated whether this dysfunction can be improved by treatment. Thirty unmedicated inpatients with OCD were administered a comprehensive neuropsychological test battery before and after 12 weeks of cognitive behavioral therapy (CBT). Thirty-nine carefully matched healthy controls were tested twice within the same interval. At baseline, patients exhibited significant impairments on several tests which normalized at follow-up. A significant group x time interaction was found for tests of nonverbal memory, set shifting and flexible, self guided behavior. Major responders improved significantly more than minor responders on the Rey-Osterrieth Figure immediate and delayed recall. Results suggest that cognitive dysfunction in OCD can improve in the course of treatment. We hypothesize that particularly cognitive behavioral treatment enables OCD patients to think and act in a more flexible way that helps them to develop more effective cognitive strategies.

Adult↗

Impaired sleep-related memory consolidation in primary insomnia--a pilot study.

STUDY OBJECTIVES: To compare sleep-related consolidation of procedural memory in patients with primary insomnia and healthy controls. DESIGN: Controlled comparison pilot study. SETTING: Sleep Laboratory of the Department of Psychiatry and Psychotherapy, University of Freiburg, Germany. PATIENTS OR PARTICIPANTS: Seven patients with primary insomnia and 7 sex-, age-, and IQ-matched healthy controls. INTERVENTIONS: Subjects spent 1 night in the sleep laboratory with polysomnographic monitoring. Performance on a mirror tracing task was measured before and after sleep. MEASUREMENTS AND RESULTS: Polysomnography revealed a trend toward disturbed sleep in the patients, compared with the control group, without reaching significance. Performance in the mirror tracing task before sleep did not differ between the groups. Both groups performed significantly better in the retest condition after sleep. Healthy controls showed an improvement of 42.8% +/- 5.8% in the mirror tracing draw time, whereas patients with insomnia showed an improvement of 20.4% +/- 14.8% (multivariate analyses of variance test session x group interaction: F(3,10) = 10.9, p = .002). CONCLUSIONS: These preliminary findings support the view that sleep-associated consolidation of procedural memories may be impaired in patients with primary insomnia.

Adult↗

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↗

Increased nocturnal interleukin-6 excretion in patients with primary insomnia: a pilot study.

The aim of the present study was to investigate whether there is a difference in evening/nocturnal interleukin-6 (IL-6) serum excretion in patients with primary insomnia compared to controls. We hypothesized that in insomniac patients, the excretion of evening/nocturnal IL-6 is enhanced, like observed in aged adults and after sleep deprivation in healthy subjects. We studied IL-6 serum concentrations in 11 patients (two males and nine females) with primary insomnia and 11 age and gender-matched healthy controls. Sleep was monitored polysomnographically for three consecutive nights. The measurement of IL-6 (from 19:00 h to 09:00 h) in 2-h intervals were performed prior to and during the last laboratory night. Polysomnographically determined sleep parameters and subjective ratings of sleep demonstrated clear-cut impairments of sleep in the insomniac group. Nocturnal IL-6 secretion was significantly increased (p<.05) in insomniac patients for the whole measurement period (mean area under the curve+/-SD: 27.94+/-14.15 pg/ml x 2h) compared to controls (16.70+/-7.64 pg/ml x 2h). Total IL-6 secretion correlated inversely with subjectively perceived sleep quality and amount of slow wave sleep in the insomniac patients. Amount of Wake Time correlated positively with IL-6 excretion in insomniacs. The results of the present study demonstrate significantly increased nocturnal IL-6 secretion in insomniacs. It might be speculated that chronic primary insomnia with polysomnographically documented sleep impairments activates the production of IL-6 analogous to sleep deprivation studies in healthy subjects. This might also implicate a higher risk for inflammatory and cardiovascular diseases in patients with chronic insomnia.

Adult↗

Spectral analysis of sleep EEG in patients with restless legs syndrome.

OBJECTIVE: Conventional analyses of sleep EEG recordings according to standard criteria indicate severe sleep disturbances in patients with restless legs syndrome (RLS). Spectral analysis of sleep EEG may be a sensitive tool to detect functional alterations of sleep mechanisms beyond the visual scoring of polysomnographic records. We analysed sleep EEG spectral power differences between RLS patients and healthy subjects. Furthermore, we studied the relationship of sleep EEG spectral power to the occurrence of periodic leg movements in sleep (PLMS) and arousal events. METHODS: Sleep EEGs from 20 patients with idiopathic RLS and of 20 age and sex matched healthy subjects were investigated. The spectral analysis was carried out on the same 30s epochs for which sleep stages had been determined. As a first step, whole-night spectral power excluding epochs with an arousal or with a PLMS was compared separately for REM and NREM sleep between RLS and healthy subjects. In a second step, we evaluated the spectral effects of PLMS, PLMS with associated arousals and isolated arousals relative to epochs of sleep without such events in both groups. In this part of the analysis, we only included the epochs of sleep stage 2 (the main and most stable non-REM sleep stage) and of REM sleep. RESULTS: Spectral power of all sleep epochs (excluding arousals and PLMS) did not differ between patients with RLS and healthy subjects. As expected, arousals and PLMS-associated arousals resulted in a significant increase in higher-frequency activity (alpha, beta1, beta2 and gamma bands) in both groups. Spectral power in epochs with PLMS alone did not significantly differ from spectral power in epochs without PLMS and without arousal in any of the groups. CONCLUSIONS: We found no evidence for an altered cortical activity in sleep stage 2 and REM sleep epochs in RLS patients compared to that in healthy controls if epochs with arousals were not considered. Furthermore, while PLMS associated with an arousal have a high impact on EEG spectra, the effect of a PLMS without arousal seems to be minor and transient. SIGNIFICANCE: Our data suggest that RLS related symptoms may intermittently disrupt sleep but do not appear to involve a persistent disturbance of the basic sleep generating patterns.

Adult↗

Increased delta power and discrepancies in objective and subjective sleep measurements in borderline personality disorder.

BACKGROUND: Previous studies have shown depression-like sleep abnormalities in borderline personality disorder (BPD). However, findings in BPD are not unequivocal for REM dysregulation, as well as for a decrement of slow wave sleep and sleep continuity disturbances. Earlier findings in sleep EEG abnormalities in BPD may have been confounded by concomitant depressive symptoms. METHODS: Twenty unmedicated female BPD patients without current comorbid major depression and 20 sex- and age-matched control subjects entered the study. Conventional polysomnographic parameters and for the first time sleep EEG spectral power analysis was performed on two sleep laboratory nights. Subjective sleep parameters were collected by sleep questionnaires in order to assess the relationship between objective and subjective sleep measurements. RESULTS: BPD patients showed a tendency for shortened REM latency and significantly decreased NonREM sleep (stage 2). Spectral EEG analysis showed increased delta power in total NREM sleep as well as in REM sleep in BPD patients. Subjective ratings documented drastically impaired sleep quality in BPD patients for the two weeks before the study and during the two laboratory nights. CONCLUSION: Not-depressed BPD patients only showed tendencies for depression-like REM sleep abnormalities. Surprisingly, BPD patients displayed higher levels of delta power in the sleep EEG in NREM sleep than healthy control subjects. There was a marked discrepancy between objective and subjective sleep measurements, which indicates an altered perception of sleep in BPD. The underlying psychological and neurobiological mechanisms of these alterations are still unclear and need to be clarified in future studies including interventions on a pharmacological and cognitive-behavioral level.

Adolescent↗

Sleep in adults with attention-deficit/hyperactivity disorder: a controlled polysomnographic study including spectral analysis of the sleep EEG.

STUDY OBJECTIVES: Previous studies in children with attention-deficit/hyperactivity disorder and attention deficit disorder (ADHD/ADD) have shown impaired sleep quality with increased nocturnal motor activity. However, polysomnographic findings are not unequivocal. Up to now, in adults with ADHD, only 1 case-control polysomnographic study with small sample size has been performed. We investigated objective and subjective sleep quality in adultADHD, including an electroencephalogram spectral power analysis. DESIGN: Single-blind comparative study. SETTING: University medical center. PARTICIPANTS: Twenty adult unmedicated ADHD patients without current comorbid major depression, drug abuse, or comorbid axis-II disorder and 20 sex- and age-matched control subjects. INTERVENTIONS: N/A. MEASUREMENTS: Conventional polysomnographic parameters and sleep electroencephalogram spectral power analysis was calculated for the 2 laboratory nights. Subjective sleep parameters were estimated by sleep questionnaires to assess the relationship between objective and subjective sleep measurements. RESULTS: Adult ADHD patients showed increased nocturnal motor activity (as indicated by heightened indexes of periodic leg movements in sleep), which was significantly inversely correlated with subjective total sleep time. Although ADHD patients displayed significantly increased objective total sleep time, the subjective ratings documented impaired sleep quality in those with ADHD. Other polysomnographic sleep patterns and spectral electroencephalogram parameters did not differ between ADHD patients and normal controls. CONCLUSIONS: Similar to children, adults with ADHD show increased nocturnal motor activity. Otherwise, sleep does not seem to be impaired in ADHD patients. However, the dissociation between objective and subjective sleep parameters points to a misinterpretation of sleep quality in patients with ADHD.

Adult↗

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↗

Variability of periodic leg movements in various sleep disorders: implications for clinical and pathophysiologic studies.

STUDY OBJECTIVES: Periodic leg movements in sleep (PLMS) are a frequent phenomenon in various sleep disorders. The pathophysiology of PLMS is still not understood, but recent studies indicate a hypoactivity of the dopaminergic system in subjects with PLMS. In the present study, we investigated the intrasubject variance of PLMS from one night to the other because a fluctuation in the number of PLMS may influence the outcome of pharmacologic and pathophysiologic studies. DESIGN: Retrospective observational study. SETTING: Data collection occurred in the sleep disorders unit. PATIENTS: Sleep electroencephalogram and PLMS data of 115 patients with PLMS monitoring over 2 consecutive nights were evaluated retrospectively. Patients were grouped into the following diagnostic categories: restless legs syndrome, insomnia secondary to a psychiatric disorder, primary insomnia, sleep apnea syndrome, and narcolepsy or idiopathic hypersomnia. INTERVENTIONS: N/A. RESULTS: In 27% of the entire patient population, we found a considerable variability of the PLMS index (difference between nights > 10/hour) and, in 19% of patients, variability of the PLMS arousal index (difference between nights > 5/hour) across the 2 investigated nights. The intraindividual variance occurred most frequently and to the highest extent in patients with RLS. CONCLUSIONS: The variability of PLMS indexes should considered if the PLMS recording is performed in support of the clinical diagnosis or in the interpretation of studies investigating drug efficacy. Furthermore, the variability of PLMS may be an indicator of an instability of the dopaminergic system that should be taken into account in studies investigating central nervous system dopaminergic activity.

Circadian Rhythm↗

Clinical outcome in patients with obsessive-compulsive disorder after discontinuation of SRI treatment: results from a two-year follow-up.

BACKGROUND: Combined treatment with serotonin-reuptake inhibitors (SRI) and cognitive-behavioral therapy (CBT) is a common therapy approach for obsessive-compulsive disorder (OCD). However, it is a matter of debate whether discontinuation of SRI after combined treatment leads to relapse. METHOD: Seventy-four consecutively admitted patients suffering from OCD were included in the study. Thirty-seven patients were treated with CBT alone, and 37 patients received combined CBT and SRI treatment. Of these latter patients, seventeen discontinued SRI treatment during the follow-up period (1 and 2 years after inpatient treatment). OCD symptom severity was determined by Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and mood was assessed by Hamilton Depression Rating Scale (HDRS). RESULTS: During the initial treatment, scores for Y-BOCS (p < 0.001), HDRS (p < 0.001) and the Global Assessment of Functioning Scale (GAF) (p < 0.001) improved significantly in all groups. Reassessment two years later revealed that a) OCD symptom severity and depression scores were similar between the groups and b) discontinuation of SRI did not prompt by a recurrence of symptoms. CONCLUSIONS: We interpret our results as suggesting that discontinuation of SRI treatment may be considered in formerly combined treated OCD patients after stable remission.

Adult↗

Neuropsychological performance in obsessive-compulsive disorder: a critical review.

There is growing evidence for neuropsychological dysfunction in obsessive-compulsive disorder (OCD) related to an underlying frontal lobe and/or basal ganglia dysfunction. The following paper is a systematical review of the existing literature on cognitive impairment in OCD patients. Fifty studies were surveyed with regard to methodological aspects and cognitive impairments found in OCD patients. In addition, the impact of confounding variables such as psychotropic medication, co-morbidity or severity of symptoms on neuropsychological functioning as well as effects of treatment are discussed. OCD is often related to memory dysfunction that seems to be associated with impaired organization of information at the stage of encoding. Several other executive functions are also commonly disturbed, though results are inconsistent. The results of our study suggest that some cognitive deficits seem to be common in OCD, but future studies should focus more on possible confounding variables such as co-morbidity or psychotropic medication.

Attention↗

Object alternation test--is it sensitive enough to detect cognitive dysfunction in obsessive-compulsive disorder?

A computerized version of the object alternation test (OAT) was employed in unmedicated obsessive-compulsive disorder (OCD) patients and matched healthy controls. OCD patients performed normally on the OAT but scored below controls on a task assessing visuo-spatial working memory. The results challenge the concept of the OAT as a sensitive instrument for orbitofrontal dysfunction in OCD.

Adult↗

Do periodic leg movements influence patients' perception of sleep quality?

BACKGROUND AND PURPOSE: Periodic leg movements in sleep (PLMS) are a common finding in various sleep disorders. Whether PLMS are an epiphenomenon or are causally related to the presence of sleep-wake disturbances is still being debated. We investigated the relationship of the occurrence of PLMS to patients' perception of sleep quality during a night of polysomnography in various sleep disorders. METHODS: The retrospective evaluation included PLMS recordings over two nights of 78 consecutive patients diagnosed with a restless legs syndrome, primary insomnia or insomnia associated with a psychiatric disorder. The subjects' perception of sleep during the polysomnography night was assessed by the subscale 'sleep quality' of the validated self-rating sleep questionnaire SFA (SFA-SQ). RESULTS: SFA-SQ scores correlated with the PLMS index (number of PLMS per hour of sleep) only in patients with restless legs syndrome during the first of the two nights investigated (r=-0.464, P<0.01). PLMS appear to have a low impact on the subjects' perception of sleep quality. The correlation of subjective sleep quality to PLMS index in the first of the two investigated nights in RLS patients may reflect an adaptation effect. CONCLUSION: The results of our study favor the hypothesis that PLMS most likely are not the primary cause of sleep disturbances in these patient groups.

Adult↗

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↗