Auditory stimulation in-phase with slow oscillations to enhance overnight memory consolidation in patients with schizophrenia?

Sleep-dependent memory consolidation is disturbed in patients with schizophrenia, who furthermore show reductions in sleep spindles and probably also in delta power during sleep. The memory dysfunction in these patients is one of the strongest markers for worse long-term functional outcome. However, therapeutic interventions to normalise memory functions, e.g., with medication, still do not exist. Against this backdrop, we investigated to what extent a non-invasive approach enhancing sleep with real-time auditory stimulation in-phase with slow oscillations might affect overnight memory consolidation in patients with schizophrenia. To this end, we examined 18 patients with stably medicated schizophrenia in a double-blinded sham-controlled design. Memory performance was assessed by a verbal (word list) and a non-verbal (complex figure) declarative memory task. In comparison to a sham condition without auditory stimuli, we found that in patients with schizophrenia, auditory stimulation evokes an electrophysiological response similar to that in healthy participants leading to an increase in slow wave and temporally coupled sleep spindle activity during stimulation. Despite this finding, patients did not show any beneficial effect on the overnight change in memory performance by stimulation. Although the stimulation in our study did not improve the patient's memory, the electrophysiological response gives hope that auditory stimulation could enable us to provide better treatment for sleep-related detriments in these patients in the future.

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.

REM density is associated with treatment response in major depression: Antidepressant pharmacotherapy vs. psychotherapy.

Major depression is one of the most common psychiatric illnesses. Interestingly, a few studies have indicated the existence of depression subgroups, which respond differently to the available treatment options. Previously, sleep abnormalities have been suggested to indicate amenability to different treatment regimens. Thereby, especially REM-sleep parameters seem to play a prominent role, and REM-sleep dysregulation has been repeatedly discussed as a potential endophenotype of depression. With that said, estimating therapy outcome in order to choose the best line of treatment is of utmost importance to patients suffering from depression. The present study looks deeper into these clues by investigating the capability of polysomnographic sleep parameters to predict treatment response in depressed patients to either pharmacotherapy or psychotherapy. Moderately to severely depressed patients (n = 38) were randomly assigned to either psychotherapy (i.e. interpersonal psychotherapy) or pharmacotherapy (i.e., monotherapy with selective serotonin reuptake inhibitors, SSRI, or selective serotonin noradrenalin reuptake inhibitors, SSNRI). Prior to treatment, all patients underwent polysomnography in the sleep laboratory. After treatment, responders and non-responders of both treatment groups were compared regarding their baseline sleep parameters. Higher baseline REM density, i.e. the amount of rapid eye movements during REM sleep, predicted better response to antidepressant pharmacotherapy. In the psychotherapy group, the effect seemed reversed but was not statistically significant. No other sleep parameter predicted treatment response. Our findings support the notion that REM-sleep dysregulation is indeed indicative of a distinct endophenotype of depression and that pharmacotherapy with SSRI/SSNRI might be superior to psychotherapy in these patients.

Bed-Sharing in Couples Is Associated With Increased and Stabilized REM Sleep and Sleep-Stage Synchronization.

BACKGROUND/OBJECTIVES: Sharing the bed with a partner is common among adults and impacts sleep quality with potential implications for mental health. However, hitherto findings are contradictory and particularly polysomnographic data on co-sleeping couples are extremely rare. The present study aimed to investigate the effects of a bed partner's presence on individual and dyadic sleep neurophysiology. METHODS: Young healthy heterosexual couples underwent sleep-lab-based polysomnography of two sleeping arrangements: individual sleep and co-sleep. Individual and dyadic sleep parameters (i.e., synchronization of sleep stages) were collected. The latter were assessed using cross-recurrence quantification analysis. Additionally, subjective sleep quality, relationship characteristics, and chronotype were monitored. Data were analyzed comparing co-sleep vs. individual sleep. Interaction effects of the sleeping arrangement with gender, chronotype, or relationship characteristics were moreover tested. RESULTS: As compared to sleeping individually, co-sleeping was associated with about 10% more REM sleep, less fragmented REM sleep (p = 0.008), longer undisturbed REM fragments (p = 0.0006), and more limb movements (p = 0.007). None of the other sleep stages was significantly altered. Social support interacted with sleeping arrangement in a way that individuals with suboptimal social support showed the biggest impact of the sleeping arrangement on REM sleep. Sleep architectures were more synchronized between partners during co-sleep (p = 0.005) even if wake phases were excluded (p = 0.022). Moreover, sleep architectures are significantly coupled across a lag of ± 5min. Depth of relationship represented an additional significant main effect regarding synchronization, reflecting a positive association between the two. Neither REM sleep nor synchronization was influenced by gender, chronotype, or other relationship characteristics. CONCLUSION: Depending on the sleeping arrangement, couple's sleep architecture and synchronization show alterations that are modified by relationship characteristics. We discuss that these alterations could be part of a self-enhancing feedback loop of REM sleep and sociality and a mechanism through which sociality prevents mental illness.

Slow-wave sleep predicts long-term social functioning in severe mental illness.

Sleep's relevance for long-term social functioning in psychiatric disorders has been widely overlooked so far. Here, we investigate social functioning in a transdiagnostic sample of 31 patients with severe mental illness, namely schizophrenia (n = 15) or major depression (n = 16), in relation to their polysomnographic sleep characteristics 6 (± 2.4) years earlier. In addition, cognitive performance at follow-up and clinical characteristics (i.e., severity of disorder-related symptoms and number of hospitalizations between baseline and follow-up) are assessed. Multiple regression analysis results in a model with slow-wave sleep (SWS) and number of hospitalizations as significant predictors accounting for 50% (R2 = 0.507; p <0.001) of the variance in social functioning. SWS remains a significant predictor of long-term social functioning throughout a series of refining analyses which also identify baseline functioning as an additional significant predictor, whereas diagnosis is non-significant. Also, the effect of SWS on social functioning is not mediated by number of hospitalizations as assessed by a bootstrapped mediation analysis. We thus conclude that duration of slow-wave sleep is a powerful predictor of long-term social outcome in psychiatric disorders. Also, we discuss the relevance of verbal memory, symptom severity, and diagnostic category for social functioning. Future studies should test this finding by using a prospective design, a bigger sample, optimized predictor variables, and a more diverse set of diagnoses. Moreover, it should be explored whether or not treating sleep disturbances in psychiatric illnesses independently improves long-term social functioning.

"Are We in Sync with Each Other?" Exploring the Effects of Cosleeping on Heterosexual Couples' Sleep Using Simultaneous Polysomnography: A Pilot Study.

The present study aimed to explore dynamic and interactive aspects of cosleep in heterosexual couples. The sample consisted of eight young healthy adults who belonged to four heterosexual couples with a good relationship quality and a history of cosleeping. All individuals underwent simultaneous polysomnography in a sleep laboratory for four nights in which they slept individually and with their partner. Also, a sleep protocol of subjective sleep measures was completed. Statistical analyses included cross recurrence quantification analysis to assess synchronization during sleep. Cosleeping was associated with better subjective sleep quality, increased total sleep time, sleep efficiency, total slow wave sleep, and REM sleep. Sleep stages were more synchronized during cosleep independent of awakenings. Cardiorespiratory measures remained unchanged. The results indicate that young healthy couples in good relationships benefit from cosleeping on a subjective and objective level. Combining simultaneous polysomnography and cross recurrence quantification analysis is a promising method to study dynamic and interactive aspects of cosleep possibly leading to deeper understanding of the role of sleep for sociality, the nature of REM sleep, and the partner as a social zeitgeber. Moreover, clinical implications may arise from these findings.

Sleep recordings in individuals with borderline personality disorder before and after trauma therapy.

Most individuals diagnosed with borderline personality disorder (BPD) have been exposed to severe and traumatic stressors and thus frequently present with symptoms of a posttraumatic stress disorder (PTSD). Severe sleep disturbances often accompany these complex cases, but changes of sleep parameters during therapy and the impact of sleep on treatment response have barely been studied. Narrative Exposure Therapy (NET) is an evidence-based approach for the treatment of trauma-related psychological disorders. To investigate the effect of NET on sleep in patients with BPD and comorbid PTSD, we screened 45 inpatients and outpatients who met the inclusion criteria of both diagnoses according to DSM-IV and who had a minimum of 2 weeks' stable medication. Patients were allocated to NET (N = 13) or treatment as usual (TAU; N = 8) in blocks. Polysomnographies and psychological questionares were performed before, directly and 6 months after the last therapy session. The aim of this pilot study was to investigate the effectiveness of trauma therapy by NET on sleep quantity (total sleep time) and sleep continuity (sleep efficiency and awakenings) in patients with comorbid BPD and PTSD. Participants of the NET group compared with those who received TAU showed an increased reduction in sleep latency from baseline to the end of therapy and a reduction in arousals over time. Patients with longer pre-treatment total sleep time and pre-treatment REM sleep duration showed a better outcome of NET with respect to PTSD symptoms. NET seems not lead to a change in sleep for the worse during therapy and seems to improve sleep as good as treatment as usual. Furthermore, our results provide evidence of an influence of sleep structure at baseline on treatment success later on.

Sleep at baseline and after electroconvulsive therapy in patients with major depression.

Sleep in major depressive disorder is frequently altered and possibly indicative for treatment outcomes. For example, increased rapid eye movement (REM-) sleep density seems to predict worse treatment outcomes of psychotherapy. We therefore investigated pre-treatment sleep and sleep changes after termination of electroconvulsive therapy (ECT). Sleep was polysomnographically recorded. The analysed sample consisted of 15 inpatients with ages ranging from 30 to 80 (mean 59 years). ECT was applied two times a week up to 7 weeks. Stable remission of depressive symptoms was defined by a score in the Hamilton Rating Scale of Depression <8 at six months after ECT. The main results were an increase in sleep efficiency and a decrease in the number of awakenings within the course of ECT in the entire patient group. Significant increases in slow wave sleep and REM sleep duration and a significant decrease in REM density were only seen in stable remitters and not in non-remitters. In pre-treatment baseline sleep a higher REM density of the first REM sleep period was significantly associated with better ECT outcome. In conclusion, REM density of the first REM sleep period seems to be an interesting candidate as putative predictor of stable treatment outcome of ECT.

The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy.

Narcolepsy with cataplexy is a sleep dysregulation disorder with alterations of REM sleep, i.e., sleep onset REM periods and REM sleep instability. Deficient orexin-A (hypocretin-1) signaling is assumed to be a major cause of narcolepsy with cataplexy. In this study we investigated fourteen subjects with narcolepsy with cataplexy in a within-subject, random-order crossover, placebo-controlled design. Patients received double-blinded intranasal orexin-A (435 nmol) or sterile water (placebo) in the morning. Administration was preceded by an adaptation night and followed by a modified maintenance of wakefulness test, attention testing and a second full night of polysomnographic recording. We found comparable sleep behavior during the adaptation nights between both conditions. After orexin-A administration patients had less wake-REM sleep transitions and a decreased REM sleep duration. In the subsequent night, patients showed an increased N2 duration. In the test of divided attention, patients had fewer false reactions after orexin-A administration. Our results support orexin-A to be a REM sleep stabilizing factor and provide functional signs for effects of orexin-A on sleep alterations and attention in narcolepsy with cataplexy.

Declarative memory performance is associated with the number of sleep spindles in elderly women.

OBJECTIVE: Recent evidence suggests that the sleep-dependent consolidation of declarative memory relies on the nonrapid eye movement rather than the rapid eye movement phase of sleep. In addition, it is known that aging is accompanied by changes in sleep and memory processes. Hence, the purpose of this study was to investigate the overnight consolidation of declarative memory in healthy elderly women. SETTING: Sleep laboratory of University. PARTICIPANTS: Nineteen healthy elderly women (age range: 61-74 years). MEASUREMENTS: We used laboratory-based measures of sleep. To test declarative memory, the Rey-Osterrieth Complex Figure Test was performed. RESULTS: Declarative memory performance in elderly women was associated with Stage 2 sleep spindle density. Women characterized by high memory performance exhibited significantly higher numbers of sleep spindles and higher spindle density compared with women with generally low memory performance. CONCLUSION: The data strongly support theories suggesting a link between sleep spindle activity and declarative memory consolidation.

Olfactory dysfunction in patients with narcolepsy with cataplexy is restored by intranasal Orexin A (Hypocretin-1).

Until recently, olfactory dysfunction was an unknown feature of narcolepsy. Orexin A, also called hypocretin-1, is abnormally decreased or undetectable in the cerebrospinal fluid of narcoleptic patients with cataplexies. As hypothalamic orexin-containing neurons project throughout the entire olfactory pathway, from the olfactory mucosa to the olfactory cortex, disturbed orexinergic transmission may crucially be involved in impaired olfactory performance of narcolepsy patients. In our study we analysed the olfactory performance (threshold, discrimination, identification and sum score of these measurements, the TDI score) of narcoleptic patients with cataplexies (n = 10) and of age-, gender-, BMI- and smoker/non-smoker-matched healthy controls (n = 10). We then in a double-blind, randomized, placebo-controlled cross-over design applied orexin A intranasally to seven of the patients and measured 2-phenyl-ethyl alcohol (PEA) single-staircase odour detection thresholds. Compared to the controls, patients showed significantly lower scores for olfactory threshold (patients: median 8.0, range 4.0-10.5; controls: median 9.4, range 7.5-13.3; P < 0.05), discrimination (patients: median 12.5, range 10-15; controls: median 15.0, range 12-16; P < 0.005), identification (patients: median 13.0, range 10-16; controls: median 14.0, range 13-16; P < 0.05) and TDI score (patients: median 33.4, range 30-36; controls: median 38.4, range 35-43; P < 0.0001). In all patients, the PEA olfactory threshold score increased after administration of orexin A (median 11.5, range 6.5-13.25) compared to placebo (median 7.75, range 6.25-11.25; P < 0.05). Our results support the hypothesis that mild olfactory dysfunction is an intrinsic symptom of narcolepsy with cataplexies. The observation that intranasal orexin A restores olfactory function is in favour of this hypothesis. Furthermore, our data support that the pathophysiological mechanism underlying olfactory dysfunction in narcolepsy is the lack of CNS orexin.