Cortical hyperarousal in individuals with frequent nightmares.

Nightmares are common among the general population and psychiatric patients and have been associated with signs of nocturnal arousal such as increased heart rate or increased high-frequency electroencephalographic (EEG) activity. However, it is still unclear, whether these characteristics are more of a trait occurring in people with frequent nightmares or rather indicators of the nightmare state. We compared participants with frequent nightmares (NM group; n = 30) and healthy controls (controls; n = 27) who spent 4 nights in the sleep laboratory over the course of 8 weeks. The NM group received six sessions of imagery rehearsal therapy (IRT), the 'gold standard' of cognitive-behavioural therapy for nightmares, between the second and the third night. Sleep architecture and spectral power were compared between groups, and between nights of nightmare occurrence and nights without nightmare occurrence in the NM group. Additionally, changes before and after therapy were recorded. The NM group showed increased beta (16.25-31 Hz) and low gamma (31.25-35 Hz) power during the entire night compared to the controls, but not when comparing nights of nightmare occurrence to those without. Moreover, low gamma activity in rapid eye movement sleep was reduced after therapy in the NM group. Our findings indicate, cortical hyperarousal is more of a trait in people with frequent nightmares within a network of other symptoms, but also malleable by therapy. This is not only a new finding for IRT but could also lead to improved treatment options in the future that directly target high-frequency EEG activity.

Contribution of Different Brain Disorders and Multimorbidity to Delirium Superimposed Dementia (DSD).

Delirium, an acute neuropsychiatric disorder characterized by a disturbance of attention and awareness, is often superimposed on dementia with its progressive cognitive decline. Despite the high frequency and clinical relevance of this condition, often called delirium-superimposed dementia (DSD), little is known about possible triggers. In this study using the GePsy-B databank, we investigated the impact of the underlying brain disorder and multimorbidity (MM) on DSD. MM was measured by CIRS and the number of ICD-10 diagnoses. Dementia was diagnosed by CDR, and delirium by DSM IV TR criteria. A total of 218 patients were diagnosed with DSD and these were compared to 105 patients with only dementia, 46 with only delirium, and 197 patients suffering from other psychiatric diseases, mainly depression. No significant differences between groups were found concerning CIRS scores. Based on CT scans, DSD cases were grouped into those with cerebral atrophy only (probably pure neurodegenerative), with brain infarction, or with white matter hyperintensities (WMH), but no between-group differences regarding the MM indices could be found. Regression analysis only revealed age and dementia stage as influencing factors. Conclusion: Our results suggest that neither MM nor morphologic changes in the brain are predisposing factors for DSD.

Assessment of Reward-Related Brain Function After a Single Dose of Oxytocin in Autism: A Randomized Controlled Trial.

Background: Autism spectrum disorder (ASD) is characterized by difficulties in social communication and interaction, which have been related to atypical neural processing of rewards, especially in the social domain. As intranasal oxytocin has been shown to modulate activation of the brain's reward circuit, oxytocin might ameliorate the processing of social rewards in ASD and thus improve social difficulties. Methods: In this randomized, double-blind, placebo-controlled, crossover functional magnetic resonance imaging study, we examined effects of a 24-IU dose of intranasal oxytocin on reward-related brain function in 37 men with ASD without intellectual impairment and 37 age- and IQ-matched control participants. Participants performed an incentive delay task that allows the investigation of neural activity associated with the anticipation and receipt of monetary and social rewards. Results: Nonsignificant tests suggested that oxytocin did not influence neural processes related to the anticipation of social or monetary rewards in either group. Complementary Bayesian analyses indicated moderate evidence for a null model, relative to an alternative model. Our results were inconclusive regarding possible oxytocin effects on amygdala responsiveness to social rewards during reward consumption. There were no significant differences in reward-related brain function between the two groups under placebo. Conclusions: Our results do not support the hypothesis that intranasal oxytocin generally enhances activation of reward-related neural circuits in men with and without ASD.

Sleep's role in updating aversive autobiographical memories.

Aversive autobiographical memories play a key role in the development and maintenance of many mental disorders. Imagery rescripting is a well-established psychotherapeutic intervention aiming to create a more adaptive version of an aversive memory by modifying its interpretation. Sleep has been shown to support reconsolidation of updated neutral memories. Here, we investigated in healthy participants whether a 90-min nap compared to wake supports the adaptive reconsolidation of autobiographical memories. Forty-four university students received a single 50-min imagery rescripting session. Thereafter, half of the participants took a 90-min nap, whereas the other half stayed awake. Subjective (arousal ratings, reports of emotions and dysfunctional cognitions) and heart rate (HR) responses to individual memory scripts were measured before the intervention (pre), after the 90-min retention interval (post 1) and 7 days later (post 2). Results demonstrate a significant decrease in distress of aversive memories pre to post imagery rescripting. The nap group showed less distressing dysfunctional cognitions along with a lower HR in response to the negative memory script as compared to the wake group at post 1. These differences were no longer evident 1 week later (post 2). Central sleep spindle density during the nap was correlated with the reduction in HR in response to the negative memory script from pre to post 1. Our results provide first evidence for sleep benefitting adaptive reconsolidation of aversive autobiographical memories. Future research should expand this approach to clinical populations and investigate precise conditions under which sleep may benefit psychotherapeutic interventions utilizing reconsolidation mechanisms.

Dysfunctional Overnight Memory Consolidation in Patients with Schizophrenia in Comparison to Healthy Controls: Disturbed Slow-Wave Sleep as Contributing Factor?

INTRODUCTION: Memory deficiency has been shown in schizophrenia patients, but results on the role of sleep parameters in overnight consolidation of associative verbal memory are still missing. Therefore, the aim of our study was to elucidate underlying processes of impaired sleep-related consolidation of associative word pairs in schizophrenia including standard sleep parameters as well as sleep spindle counts and spectral analysis. METHODS: Eighteen stably medicated schizophrenia patients and 24 healthy age-matched controls performed an associative declarative memory task before and after polysomnographic recordings. Part of the participants expected verbal associative memory testing in the morning, while the others did not. Furthermore, participants filled in self-rating questionnaires of schizophrenia-typical experiences (Eppendorf Schizophrenia Inventory [ESI] and Psychotic Symptom Rating Scale). RESULTS: Schizophrenia patients performed worse in verbal declarative memory in the evening as well as in overnight consolidation (morning compared to evening performance). While duration of slow-wave sleep was nearly comparable between groups, schizophrenia patients showed lower sleep spindle count, reduced delta power during slow-wave sleep, and reduced spindle power during the slow oscillation (SO) up-state. In healthy but not in schizophrenia patients, a linear relationship between overnight memory consolidation and slow-wave sleep duration as well as delta power was evident. No significant effect with respect to the expectation of memory retrieval was evident in our data. Additionally, we observed a negative linear relationship between total number of sleep spindles and ESI score in healthy participants. DISCUSSION/CONCLUSION: As expected, schizophrenia patients showed deficient overnight verbal declarative memory consolidation as compared to healthy controls. Reduced sleep spindles, delta power, and spindle power during the SO up-state may link sleep and memory deficiency in schizophrenia. Additionally, the absence of a linear relationship between sleep-related memory consolidation and slow-wave sleep as well as delta power suggests further functional impairments in schizophrenia. Note that this conclusion is based on observational data. Future studies should investigate if stimulation of delta waves during sleep could improve memory performance and thereby quality of life in schizophrenia.

[Psychotherapy of Sleep Disorders]. / Psychotherapie der Schlafstörungen.

Sleep disorders increase in prevalence and intensity with aging and often become chronic. Cognitive Behavioral Therapy of Insomnia (CBT-I) and the 3 P model of insomnia allows to differentiate between predisposing, precipitating and perpetuating factors influencing insomnia and to attenuate their effects. This treatment usually is the better alternative to long-term prescription of hypnotic medication. Its principles are outlined here.

Worsening of myasthenia due to antiepileptic, antipsychotic, antidepressant, and sedative medication: An estimation of risk based on reporting frequency.

BACKGROUND AND PURPOSE: Many drugs can worsen myasthenia symptoms. The clinician usually relies on cautionary lists compiled according to case reports. We intended to provide a quantitative basis for a risk comparison within the groups of antiepileptic, antidepressant, neuroleptic, and sedative drugs. METHODS: We extracted adverse drug reaction (ADR) counts (total and myasthenia related) for drugs from these groups and calculated the reporting odds ratio (ROR) within the drug groups from the World Health Organization pharmacovigilance database. For a given drug, the ROR was increased above 1 if the proportion of myasthenia-related ADRs for this drug was larger than the same proportion for the rest of drugs in that same group. If the 95% confidence interval of ROR was >1, this was taken as a signal for a higher risk of the given drug as compared to the average of the respective group. RESULTS: Gabapentin, sertraline, citalopram, lithium, and amisulpride had a signal for the ROR to be increased above 1 within their respective groups. Bupropion, desvenlafaxine, duloxetine, escitalopram, and paroxetine had ROR values <1. For all other drugs, 1 was within the ROR confidence interval. CONCLUSIONS: For gabapentin and lithium, the analysis of RORs confirmed case reports and cautionary lists. For a number of antidepressant drugs associated with a higher-than-average risk, no case reports exist substantiating our results. For these drugs, special attention should be paid to this risk. The remarkable difference between citalopram and escitalopram could prompt experimental work to confirm differential influence of the two preparations on neuromuscular transmission.

Simvastatin add-on to escitalopram in patients with comorbid obesity and major depression (SIMCODE): study protocol of a multicentre, randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%-60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity. METHODS AND ANALYSIS: This is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score <10), mean change in patients' self-reported Beck Depression Inventory (BDI-II) and mean change in high-density lipoprotein, low-density lipoprotein and total cholesterol from baseline to week 12. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226-EK 11) and by the relevant federal authority (Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences. TRIAL REGISTRATION NUMBERS: NCT04301271, DRKS00021119, EudraCT 2018-002947-27.

[Psychotherapy of Sleep Disorders]. / Psychotherapie der Schlafstörungen.

Sleep disorders increase in prevalence and intensity with aging and often become chronic. Cognitive Behavioral Therapy of Insomnia (CBT-I) and the 3P model of insomnia allows to differentiate between predisposing, precipitating and perpetuating factors influencing insomnia and to attenuate their effects. This treatment usually is the better alternative to long-term prescription of hypnotic medication. Its principles are outlined here.

[Multimorbidity in elder psychiatric patients]. / Multimorbidität bei älteren psychiatrischen Patienten.

Multimorbidity in older psychiatric patients. OBJECTIVE: Multimorbidity represents a great challenge in the medical care of older people. METHODS: This exploratory study was part of the Gerontopsychiatry study Berlin (Gepsy-B), an analysis of data on all 941 older inpatients (> 65 years) admitted to a psychiatric hospital within a period of 3 years. RESULTS: Nearly all patients (94,2 %) suffered from a chronic somatic disorder. The mean number of chronic somatic disorders was 2.70 + 1.39 and showed age dependency (r = 0.257, p < .001). The most prevalent disorders were cerebrovascular disorders (56.5 %), hypertension (54.8 %), chronic ischemic heart diseases or arrhythmias (52.2 %) and diabetes mellitus type II (37.5 %). Furthermore, many of the patients suffered from disabilities such as movement disorders (26.2 %), severe hearing loss (16.5 %), incontinence (15.1 %) or severely reduced vision (7.4 %). Organic brain disorders were more often associated with chronic somatic disorders or disabilities. CONCLUSIONS: Older patients treated for psychiatric disorders very often show somatic multimorbidity that probably limit treatment outcome.

[Alcohol Intoxication - a Psychiatric Emergency]. / Alkoholintoxikation ­ ein psychiatrischer Notfall.

Alcohol intoxication is the most common psychiatric cause of admission to German emergency rooms. Many of these patients refuse inpatient observation or treatment. Therefore, the physician in charge will have to decide on how to proceed. The capacity to consent has to be clarified, especially if the patient insists on being discharged. In this context, the risks of injuries, complicated alcohol withdrawal, and aggressive or suicidal behaviour have to be evaluated. In this article, the juridical aspects and the necessary mental and physical assessments, especially in case of discharge of the patient against medical advice, are presented. Essential aspects are summarized in checklists.

[Does multimorbidity in older psychiatric patients lead to higher transfer rates between psychiatric and somatic departments?] / Führt Multimorbidität bei älteren psychiatrischen Patienten gehäuft zu Verlegungen zwischen der Psychiatrie und somatischen Abteilungen?

OBJECTIVE: Multimorbidity is an increasing challenge in geriatric medicine, also in psychiatric patients. The question arises where an adequate treatment should be carried out. METHODS: This exploratory study was part of the Gerontopsychiatry study Berlin (Gepsy-B), an investigation of all admissions of older inpatients (>65 years) to a psychiatric hospital within 3 years. A total of 1266 admissions to a hospital in Berlin could be analyzed. RESULTS: Of the patients primarily admitted to the psychiatric department, 17.4% had to be transferred to a somatic department with a preponderance of patients with higher multimorbidity (11.7 ± 3.7 vs. 9.9 ± 3.8 somatic diagnoses, U­test p < 0.001). Of the patients 19.7% were transferred from somatic departments to the psychiatric department mainly due to delirium. They were also often multimorbid (mean number of somatic diagnoses: 11.7 + 3.7 vs. 10.3 + 3.8, U­test p < 0.001). CONCLUSION: Multimorbidity results in more frequent transfer of older patients in hospital.

[Risk Factors for Postoperative Delirium after Cardiac Surgery]. / Risikofaktoren des postoperativen Deliriums in der Herzchirurgie.

Background Delirium is a common psychiatric disorder after cardiac surgery and predisposes patients to increased mortality and morbidity. Its prevention requires knowledge of the risk factors involved. Objective What are preoperative risk factors for postoperative delirium after cardiac surgery? Methods Prospective longitudinal study of 241 elective cardiac surgical patients with preoperative assessment of potential risk factors and delirium assessment twice daily over five postoperative days. Results 13 % of the patients experienced delirium. Reduced cognitive performance (OR: 3.80; 95 % CI: 1.66 - 8.66), higher comorbidity (OR: 1.36; 95 % CI: 1.07 - 1.7) and higher age (OR: 1.08; 95 % CI: 1.02 - 1.13) increased the risk of delirium. Conclusion Delirium after cardiac surgery is common. It occurs in particular in patients with low cognitive performance, higher comorbidity and higher age.

[Alcohol withdrawal and its major complications]. / Der komplizierte Alkoholentzug: Grand-Mal-Anfälle, Delir und Wernicke-Enzephalopathie.

Delirium tremens is one of the most common complications of alcohol withdrawal. It is potentially lethal and therefore should be detected as early as possible and be monitored and treated intensively. The assessment of risk factors with the Luebeck Alcohol-Withdrawal Risk Scale short form (LARS-11) can help to predict the risk of severe withdrawal adequately. As delirium cannot be differentiated from Wernicke-Encephalopathy with sufficient certainty high parenteral doses of Vitamin B1 and Magnesium orally should be given in case of any severe withdrawal symptoms. According to guidelines delirium tremens should be treated with benzodiazepines besides adequate electrolyte and fluid substitution. Haloperidol is often additionally given to better control hallucinations. Delirium tremens usually subsides within 10 days of treatment.The article gives an overview of alcohol withdrawal with its different facets, its differential diagnoses, and the treatment options.

Impairment of sleep-related memory consolidation in schizophrenia: relevance of sleep spindles?

OBJECTIVES: Deficits in declarative memory performance are among the most severe neuropsychological impairments in schizophrenia and contribute to poor clinical outcomes. The importance of sleep for brain plasticity and memory consolidation is widely accepted, and sleep spindles seem to play an important role in these processes. The aim of this study was to test the associations of sleep spindles and picture memory consolidation in patients with schizophrenia and healthy controls. METHODS: We studied 16 patients with schizophrenia on stable antipsychotic medication (mean age ± standard deviation, 29.4 ± 6.4 years) and 16 healthy controls matched for age and educational level. Sleep was recorded and scored according to American Academy of Sleep Medicine (AASM) standard criteria. We performed a picture recognition paradigm and compared recognition performance for neutral and emotional pictures in sleep and wake conditions. RESULTS: Recognition accuracy was better in healthy controls than in patients with schizophrenia in the sleep and wake conditions. However, the memory-promoting effect of sleep was significantly lower in schizophrenia patients than in controls. Sleep spindle activity was reduced in patients, and sleep spindle density was correlated with sleep-associated facilitation of recognition accuracy for neutral pictures. CONCLUSION: Reduced sleep spindles seem to play an important role as a possible mechanism or biomarker for impaired sleep-related memory consolidation in patients with schizophrenia, and are a new target for treatment to improve memory functions and clinical outcomes in these patients.

The difficulty of staying awake during alpha/theta neurofeedback training.

Alpha/theta neurofeedback training is supposed to enhance cognitive performance as well as alleviate psychiatric disorders. Sleep during this training is regarded a confounding factor, although it is usually not controlled. Here, the amount of sleep, the impact of sleep on frequency results and the validity of subjective judgments of having fallen asleep were investigated. 40 healthy young subjects participated in 31 training units of real or mock feedback. It turned out that stage 2 sleep occurred in 10-14 % of training time, in 95 % of the subjects and in 1/3 of all training units. Sleep significantly influenced the theta/alpha ratio and theta but not alpha amplitudes. Only about 2/3 of the subjective judgements were correct and no more than 13 % of the participants could reliably identify sleep. These data demonstrate that sleep can easily occur during alpha/theta neurofeedback training and should be controlled by objective means.

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.