Validation of the German version of the Ford Insomnia Response to Stress Test.

The purpose of this study was to assess the psychometric properties of a German version of the Ford Insomnia Response to Stress Test with groups with and without sleep problems. Three studies were analysed. Data set 1 was based on an initial screening for a sleep training program (n = 393), data set 2 was based on a study to test the test-retest reliability of the Ford Insomnia Response to Stress Test (n = 284) and data set 3 was based on a study to examine the influence of competitive sport on sleep (n = 37). Data sets 1 and 2 were used to test internal consistency, factor structure, convergent validity, discriminant validity and test-retest reliability of the Ford Insomnia Response to Stress Test. Content validity was tested using data set 3. Cronbach's alpha of the Ford Insomnia Response to Stress Test was good (α = 0.80) and test-retest reliability was satisfactory (r = 0.72). Overall, the one-factor model showed the best fit. Furthermore, significant positive correlations between the Ford Insomnia Response to Stress Test and impaired sleep quality, depression and stress reactivity were in line with the expectations regarding the convergent validity. Subjects with sleep problems had significantly higher scores in the Ford Insomnia Response to Stress Test than subjects without sleep problems (P < 0.01). Competitive athletes with higher scores in the Ford Insomnia Response to Stress Test had significantly lower sleep quality (P = 0.01), demonstrating that vulnerability for stress-induced sleep disturbances accompanies poorer sleep quality in stressful episodes. The findings show that the German version of the Ford Insomnia Response to Stress Test is a reliable and valid questionnaire to assess the vulnerability to stress-induced sleep disturbances.

Sleep deprivation disrupts prepulse inhibition and induces psychosis-like symptoms in healthy humans.

Translational biomarkers, such as prepulse inhibition (PPI) of the acoustic startle response, are playing an increasingly important role in the development of antipsychotic drugs for schizophrenia and related conditions. However, attempts to reliably induce a PPI deficit by psychotomimetic drugs have not been successful, leaving an unmet need for a cross-species psychosis model sensitive to this widely studied surrogate treatment target. Sleep deprivation (SD) might be such a model as it has previously been shown to induce PPI deficits in rats, which could be selectively prevented with antipsychotic but not anxiolytic or antidepressant compounds. Here, in a first proof-of-concept study we tested whether SD induces a deficit in PPI and an increase in psychosis-like symptoms in healthy humans. In two counterbalanced sessions, acoustic PPI and self-reported psychosis-like symptoms (Psychotomimetic States Inventory) were measured in 24 healthy human volunteers after a normal night's sleep and after a night of total SD. SD decreased PPI (p = 0.001) without affecting the magnitude or habituation of the startle response (all p > 0.13). SD also induced perceptual distortions, cognitive disorganization, and anhedonia (all p < 0.02). Thus, extending previous rodent work, we conclude that SD, in combination with the PPI biomarker, might be a promising translational surrogate model for psychosis as this method represents a possibility to partially and reversibly mimic the pathogenesis of psychotic states.

Chronic and high alcohol consumption has a negative impact on sleep and sleep-associated consolidation of declarative memory.

BACKGROUND: The importance of sleep for memory consolidation has become a major focus of research. While it is known that abstaining alcohol-dependent patients often have sleep disorders and that there is some cognitive impairment during early abstention a possible interaction of disturbed sleep with overnight memory consolidation has not been addressed in a study as yet. METHODS: Twenty-four alcohol-dependent patients with a short abstention period (mean 21.9 +/- 7.6 days) were compared with 12 patients with an abstention period of several months (115.7 +/- 43.8 days). Groups did not differ with respect to daily alcohol consumption before treatment, duration of alcohol dependence, and age. Before sleep all patients learned a list of semantically associated word pairs and a face name association task to a fixed criterion (at least 60% of correct recall) and they performed a mirror tracing task. After a polysomnographically registered night the patients were tested for retention of the learned declarative material by cued recall and had to perform the mirror tracing task again. RESULTS: The groups did not differ with respect to sleep parameters or sleep-associated memory consolidation. Across both groups the duration of alcohol dependence correlated negatively with the amount of non-REM sleep and recall in the face name association task correlated negatively with daily alcohol consumption before abstention. Among the longer-term abstainers the duration of abstention correlated with the amount of slow wave sleep. CONCLUSIONS: Our data support the hypothesis that chronic and high alcohol consumption negatively affects sleep and declarative memory consolidation during the first months of abstention. Between an abstention period of a few weeks and of several months no change in sleep parameters and nightly memory consolidation could be demonstrated, however.

Midlife decline in declarative memory consolidation is correlated with a decline in slow wave sleep.

Sleep architecture as well as memory function are strongly age dependent. Slow wave sleep (SWS), in particular, decreases dramatically with increasing age, starting already beyond the age of 30. SWS normally predominates during early nocturnal sleep and is implicated in declarative memory consolidation. However, the consequences of changes in sleep across the life span for sleep-associated memory consolidation have not been evaluated so far. Here, we compared declarative memory consolidation (for word-pair associates) during sleep in young and middle-aged healthy humans. The age groups (18-25 vs. 48-55 yr) did not differ with regard to learning performance before retention periods that covered, respectively, the first and second half of nocturnal sleep. However, after early retention sleep, where the younger subjects showed distinctly more SWS than the middle-aged (62.3 +/- 3.7 min vs. 18.4 +/- 7.2 min, P < 0.001), retrieval of the word pairs in the middle-aged was clearly worse than in the young (P < 0.001). In contrast, declarative memory retention did not differ between groups after late sleep, where retention was generally worse than after early sleep (P = 0.005). Retention of declarative memories was the same in both age groups when sleep periods containing equal amounts of SWS were compared, i.e., across late sleep in the young and across early sleep in the middle-aged. Our results indicate a decline in sleep-associated declarative memory consolidation that develops already during midlife and is associated with a decrease in early nocturnal SWS.

Cortisol awakening response in abstinent alcohol-dependent patients as a marker of HPA-axis dysfunction.

Hypothalamo-pituitary-adrenocorticoid (HPA)-axis reactivity to psychosocial or pharmacological stimulants is diminished in alcohol-dependent patients during early abstinence but recovers after several months of abstention. In order to assess the physiological reactivity in the morning we used the cortisol awakening response (CAR) in saliva to compare 24 early abstainers (mean 21.9+/-7.6, range 10-36 days) with 12 alcohol-dependent patients with longer abstention periods (mean 116.8+/-45.7, range 59-230 days) and looked for an association with sleep, especially rapid eye movement (REM) sleep of the preceding night. Both groups did not differ with respect to age, duration of alcohol dependence, daily drinking dosage before detoxification, body mass index, depressivity, level of anxiety, daily cigarette consumption or sleep quality during the preceding 14 days. Sleep in the night before cortisol assessment did not differ with respect to total sleep time (412.4+/-35.9 vs. 407.0+/-38.7 min). Immediately upon awakening and 15, 30, 45 and 60 min later, specimens of salivary cortisol were collected. While starting from equal levels upon awakening longer abstaining patients with alcohol dependence showed a stronger CAR (ANOVA with repeated measurement, time x group effect: F=4.33, p<0.01) with distinctly higher cortisol levels 45 and 60 min after awakening (T=3.79, p<0.001 and T=3.06, p<0.005, respectively). Across both groups the time spent in REM-sleep only correlated with cortisol levels upon awakening (r=0.33, p<0.05). Our data indicate that CAR is a useful tool for investigating alterations in the HPA-axis regulation in abstaining alcohol-dependent patients.

Gender differences for ghrelin levels in alcohol-dependent patients and differences between alcoholics and healthy controls.

BACKGROUND: Ghrelin is a 28-amino acid gut-brain peptide, mainly secreted by the gastric mucosa. Its effects are linked to energy homeostasis and particularly seem to increase hunger and food intake. In recent years, studies suggested that appetite-regulating peptides, such as ghrelin play a relevant role in alcoholism. Since data published to date on the potential role of ghrelin as state and/or trait marker in alcoholism and the association with craving are controversial, we aimed at further elucidating these aspects. PATIENTS AND METHODS: One-hundred nine alcohol-dependent abstinent patients after withdrawal (27 f, 82 m), (ICD 10 F 10.25) and 45 healthy volunteers (12 f, 33 m) were included. Laboratory testing (Ghrelin RIA 90, Mediagnost Inc., Germany) was performed and several craving scales [Obsessive Compulsive Drinking Scale, Alcohol Urge Questionnaire and Visual Analogue Scale (VAS)] were applied at the beginning and at the end of the 3-week rehabilitation program. RESULTS: (1) Ghrelin levels are significantly higher in female alcohol-dependent patients as compared to controls, not, however, in men alcoholics. (2) In several statistical subanalyses, an association of craving and ghrelin was found. The results, however, remain heterogeneous. CONCLUSION: The data suggest gender-dependent ghrelin levels in alcohol-dependent patients. We therefore conclude, that it might be useful to perform statistical analyses gender-specific. With regard to a potential correlation of ghrelin and craving the results seem to depend on gender, duration of the abstinence period and the instrument used.

"Sex differences in a real academic stressor, cognitive appraisal and the cortisol response".

Women and men differ in their physiological and psychological stress response but only a few studies have analyzed this sex difference in a naturalistic setting and focused on cognitive stress appraisal. In the present study, the salivary cortisol concentration of 24 female and 22 male subjects was measured before and several times after an oral academic presentation given by themselves (stress condition) or given by a fellow student (control condition). Feelings of subjective stress and nervousness were assessed simultaneously to the saliva samples and a questionnaire for cognitive stress appraisal was conducted right before the oral presentation. In the stress condition, the presentation led to a significantly higher cortisol increase than in the control condition. Sex differences were shown concerning the subjective stress feelings, which were higher in women, whereas there were no sex differences in cortisol release. Women showed a disadvantageous cognitive appraisal compared to men in both conditions. There was an interaction effect of sex and condition: women reported to feel equally challenged in both conditions whereas men felt significantly more challenged by their own presentation than by the presentations of their fellow students. The result that men's cognitive appraisal was more influenced by an academic stressor than women's and that women felt subjectively more stressed whereas there was no difference concerning the cortisol response is discussed in consideration of evolutional and biological aspects.

Impaired declarative memory consolidation during sleep in patients with primary insomnia: Influence of sleep architecture and nocturnal cortisol release.

BACKGROUND: A central cognitive function of sleep is to consolidate newly acquired memories for long-term storage. Here, we investigated whether the overnight consolidation of declarative memory in patients with chronic sleep disturbances is impaired, owing to less slow wave sleep (SWS) and an increased cortisol release. METHODS: Polysomnographic recordings, serum cortisol concentrations, and overnight memory consolidation in 16 patients with primary insomnia were compared with those of 13 healthy control subjects. RESULTS: Patients displayed distinctly less overnight consolidation of declarative memory (p < .05), which was significantly correlated with SWS in the control subjects (r = .69) but with rapid eye movement (REM) sleep in the patients (r = .56), who had a diminished amount of SWS (p < .05). Increased cortisol levels in the middle of the night were associated with impaired retrieval of declarative memory after sleep for both control subjects (r = -.52) and patients (r = -.46). CONCLUSIONS: Primary insomnia is associated with a diminished sleep-related consolidation of declarative memory. Efficient overnight consolidation of declarative memory is associated with high amounts of SWS and low serum cortisol levels during the early part of the night. Where SWS is decreased, REM sleep might play a partly compensatory role in the consolidation of declarative memory.

Daytime naps improve procedural motor memory.

BACKGROUND AND PURPOSE: To investigate the impact of a short daytime nap on procedural and declarative memory consolidation. PATIENTS AND METHODS: Following a normal night's sleep, 34 young healthy subjects were randomly assigned to a nap or wake condition of about 45min in the early afternoon after learning procedural and declarative memory tasks. Subjects were controlled for alertness and cortisol secretion. RESULTS: The afternoon naps were dominated by sleep stage 2 but contained some slow wave sleep (SWS) and rapid eye movement (REM) sleep as well. Naps significantly improved procedural, but not declarative, memory. Females showed more improvement than males in the declarative memory tasks irrespective of nap or wake. There was no difference between groups with respect to cortisol secretion or alertness. CONCLUSIONS: A short nap is favorable for consolidation of procedural memory. The possibly confounding effect of gender should always be considered in research on sleep and memory.

The consumption of cigarettes, coffee and sweets in detoxified alcoholics and its association with relapse and a family history of alcoholism.

Thirty male alcohol dependent inpatients without concurrent depressive disorder, 13 of them with a positive family history of alcohol dependence in a first degree relative (PFH), were questioned about their desire and consumption habits with respect to cigarettes, coffee, and sweets while on a three-week inpatient treatment after detoxification from alcohol. Six weeks after discharge from hospital, the patients were reassessed for relapse. Eleven patients (36.6%) had relapsed at follow-up. Relapsers were younger than abstainers. The days until relapse correlated negatively with intensity of desire to drink alcohol, desire to smoke cigarettes, and with a higher consumption of cigarettes. PFH patients did not relapse earlier but they had a stronger desire to drink coffee and eat sweets and had a higher coffee consumption.

Sleep disturbances are correlated with decreased morning awakening salivary cortisol.

Morning and evening salivary cortisol levels were correlated with sleep parameters in 14 patients with primary insomnia and 15 healthy controls. Salivary cortisol was sampled immediately after awakening (T1), 15 min later (T2), and immediately before going to bed (T3) for 1 week at home. In parallel with this, subjects estimated parameters of sleep in a daily sleep log. Patients and controls were all non-smokers who did not differ regarding morning awakening time or bedtime. Cortisol after awakening was significantly decreased in primary insomnia. Salivary cortisol at the time of awakening correlated negatively with the subjective estimation of sleep quality, i.e. a low salivary cortisol level directly after awakening correlated with a higher frequency of nightly awakenings (r = -0.50), a diminished sleep quality (r = -0.34) and a decreased feeling of recovery after awakening (r = -0.35; all p < 0.05). Furthermore, awakening cortisol was negatively correlated with the Pittsburgh Sleep Quality Index (r = -0.43) and with a questionnaire on sleep-related cognitions with the subscales rumination in bed (r = -0.56 ) and focusing on sleep-related thoughts (r = -0.46; all p < 0.05).

Test-retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia.

OBJECTIVE: Psychometric evaluation of the Pittsburgh Sleep Quality Index (PSQI) for primary insomnia. METHODS: The study sample consisted of 80 patients with primary insomnia (DSM-IV). The length of the test-retest interval was either 2 days or several weeks. Validity analyses were calculated for PSQI data and data from sleep diaries, as well as polysomnography. To evaluate the specificity of the PSQI, insomnia patients were compared with a control group of 45 healthy subjects. RESULTS: In primary insomnia patients, the overall PSQI global score correlation coefficient for test-retest reliability was .87. Validity analyses showed high correlations between PSQI and sleep log data and lower correlations with polysomnography data. A PSQI global score > 5 resulted in a sensitivity of 98.7 and specificity of 84.4 as a marker for sleep disturbances in insomnia patients versus controls. CONCLUSION: The PSQI has a high test-retest reliability and a good validity for patients with primary insomnia.

Effectiveness of a cognitive behavioral self-help program for patients with primary insomnia in general practice - a pilot study.

OBJECTIVE: This study was conducted to evaluate the effectiveness of a cognitive behavioral self-help program (SHP) in combination with pharmacotherapy in patients with primary insomnia in general practice. PARTICIPANTS: Patients were recruited from 31 general practitioners (GPs) in the Hamburg area, who were randomly assigned to the two different study conditions. Eighty patients completed the study. They had suffered from insomnia for several years and showed a high impairment according to the Pittsburgh Sleep Quality Index. INTERVENTION: According to assignment of their GP the patients either received a progressively reduced 4-week pharmacotherapy or a combination of pharmacotherapy and a SHP consisting of six chapters on progressive muscle relaxation, cognitive relaxation, modified stimulus control, thought stopping, and cognitive restructuring. MEASURES AND RESULTS: After study enrollment patients had short weekly consultations with their GPs during treatment to receive sleep medication and questionnaires. They completed questionnaires measuring general sleep quality and sleep-disruptive beliefs and also sleep diaries before treatment, during treatment, immediately following treatment, and at a 6-week and 6-month follow-up time point. For collection of changes in mood the Beck Depression Inventory was used. The whole sample showed reductions of sleep onset latency and time awake after sleep onset. Total sleep time increased and mood improved. Patients additionally working with the SHP showed significantly more improvements in sleep quality and negative sleep-related cognitions like ruminating and focusing on sleep. Treatment effects were significant at the end of therapy and remained stable at the six-week and six-month follow-up. CONCLUSION: This study supports the use of a cognitive-behavioral SHP on primary insomnia in the setting of a general practice and should be investigated in more detail. Also, regular appointments and the utilization of sleep logs seem to have a positive influence on sleep disorders.

Skill memory escaping from distraction by sleep--evidence from dual-task performance.

BACKGROUND: Sleep facilitates off-line consolidation of memories, as shown for learning of motor skills in the absence of concomitant distractors. We often perform complex tasks focusing our attention mostly on one single part of them. However, we are equally able to skillfully perform other concurrent tasks. One may even improve performance on disregarded parts of complex tasks, which were learned implicitly. In the present study we investigated the role of sleep in the off-line consolidation of procedural skills when attention is diverted from the procedural task because of interference from a concurrent task. METHODOLOGY/PRINCIPAL FINDINGS: We used a dual-task paradigm containing (i) procedural serial reaction time task (SRTT), which was labeled as subordinate and unimportant and (ii) declarative word-pair association task (WPAT), performed concomitantly. The WPAT served as a masked distractor to SRTT and was strongly reinforced by the instructions. One experimental and three control groups were tested. The experimental group was re-tested after two nights of sleep (sleep group, SG). The first control group had sleep deprivation on the first post-learning night (nighttime-awake group, NA), the second control group was tested in the morning and then re-tested after 12-hours (daytime-awake group, DA); the third one had the same assignments as DA but with a subsequent, instead of a concomitant, WPAT (daytime-awake-subsequent-WPAT group, DAs). We found SRTT performance gains in SG but not in NA and DA groups. Furthermore, SG reached similar learning gains in SRTT as the DAs group, which gained in SRTT performance because of post-training interference from the declarative task. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that sleep allows off-line consolidation, which is resistant to deteriorating effects of a reinforced distractor on the implicit procedural learning and allowing for gains which are consistent with those produced when inhibited declarative memories of SRTT do not compete with procedural ones.

Urinary ethyl glucuronide (EtG) and ethyl sulphate (EtS) assessment: valuable tools to improve verification of abstention in alcohol-dependent patients during in-patient treatment and at follow-ups.

AIMS: The aims of this study were (i) to assess the effect of additional urinary ethyl glucuronide (EtG) and ethyl sulphate (EtS) assessment on diagnosed relapse rates in detoxified alcohol-dependent patients; and (ii) to compare dropout rates between EtG- and EtS-negative and -positive patients. DESIGN: Two studies on detoxified alcohol-dependent patients. If patients had no indication of relapse they were asked for a urinary sample at discharge from in-patient treatment 3, 6 and 12 weeks after discharge (study 1) and 1, 3 and 6 weeks after discharge (study 2), respectively. SETTING: Department of Psychiatry, University of Luebeck, Germany. PARTICIPANTS: A total of 107 and 32 detoxified alcohol-dependent patients having participated in a 3-week in-patient motivation enhancement programme. MEASUREMENT: Personal interviews, breathalyzer tests, assessment of urinary EtG and EtS with liquid chromatography-tandem mass spectrometry (LC-MS/MS analysis). FINDING: Urinary EtG and EtS were always positive at the same time. In the first study 13.5% of the patients were already positive before being discharged from hospital. At the follow-ups 3, 6 and 12 weeks after discharge 12.2, 19.4 and 28.0%, respectively, of the patients coming to the follow-up and denying relapse were positive on urinary EtG and EtS. In the second study, of those patients showing up for follow-up after 1 week and denying relapse, EtG and EtS were positive in four cases (17.4%). Only one EtG- and EtS-positive relapser (3.1%) came to the next follow-ups. In both studies the rates of detected relapses were significantly higher for early follow-ups if urinary EtG and EtS results were considered additionally. Dropout rates until the next follow-up were significantly higher among positive than EtG- and EtS-negative patients. CONCLUSION: Urinary EtG and EtS improve verification of abstinence in studies of alcohol-dependent patients.

Immediate as well as delayed post learning sleep but not wakefulness enhances declarative memory consolidation in children.

While there is mounting evidence for the importance of sleep for declarative memory consolidation in adults, so far this issue has not been investigated in children despite considerable differences in sleep duration and sleep architecture between children and adults. Here, 27 children (aged between 9 and 12yr) were examined on two conditions: on the Sleep-Wake condition, subjects learned word pairs in the evening and delayed recall was tested first in the next morning after sleep and then again in the following evening after daytime wakefulness. On the Wake-Sleep condition, learning took place in the morning and delayed recall was tested in the evening of the same day and again in the next morning after sleep. In both conditions retention of declarative memory was significantly increased only after an interval of sleep that either followed immediately after learning (as in the Sleep-Wake condition) or that followed after daytime wakefulness (as in the Wake-Sleep condition), respectively. The results support the hypothesis that sleep plays an active role in declarative memory consolidation even if delayed and further show for the first time the importance of sleep for declarative memory consolidation during childhood.

Onset and maintenance of psychiatric disorders after serious accidents.

The purpose of this study was to prospectively investigate the onset, course, and remission of psychiatric disorders in the first 6 months after a serious accident for consecutive patients in a hospital emergency department. Participants were 58 patients aged 18-65 who were assessed shortly after attending a hospital emergency department and were followed up 6 months afterwards. Patients were interviewed with regard to past and current psychiatric history using different instruments (e.g. SCID for DSM-IV). Prior to their accidents, 35% of all subjects had experienced one or more psychiatric disorders (lifetime prevalence). Shortly after the accident, the incidence of Acute Stress Disorder (7%), subsyndromal Acute Stress Disorder (12%), and adjustment disorder (1.5%) was increased as a reaction to the accident. At this time, 29% of all patients suffered from an acute psychiatric disorder. Six-months after the accident, 10% of the subjects met criteria for Major Depression, 6% for PTSD, 4% for subsyndromal PTSD, and 1.5% for Specific Phobia as newly developed disorders. The course of the psychiatric disorders shows that those patients who met criteria for any psychiatric diagnosis shortly after the accident ran a much higher risk for developing new or comorbid psychiatric disorders in the future.

Mildly disturbed hepatic and pancreatic function during early abstention from alcohol is associated with brain atrophy and with disturbed psychometric performance.

AIMS: To investigate the relation of liver status and pancreatic function to disorders of the central nervous system during early abstention from alcohol. METHODS: Sixty-seven alcohol-dependent patients (47 male) with a mean age of 42.3 +/- 12.5 years, were assessed by clinical history, abdominal sonography, computerized tomography of the brain and with neuropsychological and serum enzyme tests. Patients with sonographically diagnosed cirrhosis were excluded. RESULTS: Patients with fatty liver had more previous complicated detoxifications, but not more current signs of brain atrophy or impairment on neuropsychological tests. However, elevations in alpha amylase (AA), and gamma glutamyl transpeptidase (GGT) were associated with signs of cerebral atrophy. Higher serum GGT was related to impaired score on a number sequencing task (NST), and high AA with impairment on NST and on two tests of speed and perception. GGT and AA levels tended to be higher in older subjects. CONCLUSIONS: After detoxification from alcohol even mildly disturbed liver and pancreatic parameters, but not fatty liver itself, are associated with signs of brain atrophy and impaired psychometric performance. Age may be a confounding or contributing factor.

Short-term training increases diagnostic and treatment rate for insomnia in general practice.

OBJECTIVE: To evaluate the effect of short-term training of general practitioners (GPs) on their diagnosis and treatment of chronic insomnia. METHODS: A three-step randomized control group design was used: After baseline evaluation (T1) a group of 9 GPs underwent a training of half a day, while 7 GPs served as a control group. The diagnostic and therapeutic handling of insomnia patients was reevaluated under obligatory use of a structured diagnostic questionnaire (T2) and under optional use of it (T3). RESULTS: From 16 general practices, 4,754 patients were included. The frequency rate of insomnia was 19.3 %. The lowest diagnostic and treatment rate was found for insomnia patients without comorbidity (15 % at T1). Systematic non-pharmacological treatment was not offered by the GPs. At T2 the diagnosis rate increased significantly from 37.9 % (T1) to 71.5 % (T2, p = 0.038). It fell back to lower levels at T3 but remained better than at T1. At T3 non-pharmacological treatments and referral to a sleep expert were advised more often. CONCLUSION: Short-term training of GPs can significantly improve their diagnostic sensitivity and first-line treatment efforts against insomnia.