Christoph Nissen

Insomnia as a predictor of depression: A meta-analytic evaluation of longitudinal epidemiological studies

BACKGROUND In many patients with depression, symptoms of insomnia herald the onset of the disorder and may persist into remission or recovery, even after adequate treatment. Several studies have raised the question whether insomniac symptoms may constitute an independent clinical predictor of depression. This meta-analysis is aimed at evaluating quantitatively if insomnia constitutes a predictor of depression. METHODS PubMed, Medline, PsycInfo, and PsycArticles databases were searched from 1980 until 2010 to identify longitudinal epidemiological studies simultaneously investigating insomniac complaints and depressed psychopathology. Effects were summarized using the logarithms of the odds ratios for insomnia at baseline to predict depression at follow-up. Studies were pooled with both fixed- and random-effects meta-analytic models in order to evaluate the concordance. Heterogeneity test and sensitivity analysis were computed. RESULTS Twenty-one studies met inclusion criteria. Considering all studies together, heterogeneity was found. The random-effects model showed an overall odds ratio for insomnia to predict depression of 2.60 (confidence interval [CI]: 1.98-3.42). When the analysis was adjusted for outliers, the studies were not longer heterogeneous. The fixed-effects model showed an overall odds ratio of 2.10 (CI: 1.86-2.38). LIMITATIONS The main limit is that included studies did not always consider the role of other intervening variables. CONCLUSIONS Non-depressed people with insomnia have a twofold risk to develop depression, compared to people with no sleep difficulties. Thus, early treatment programs for insomnia might reduce the risk for developing depression in the general population and be considered a helpful general preventive strategy in the area of mental health care.

Does REM sleep contribute to subjective wake time in primary insomnia? A comparison of polysomnographic and subjective sleep in 100 patients

Primary insomnia (PI) is characterized by low subjective sleep quality which cannot always be verified using polysomnography (PSG). To shed light on this discrepancy, subjective estimates of sleep and PSG variables were compared in patients with PI and good sleeper controls (GSC). 100 patients with PI (age: 42.57 ± 12.50 years, medication free for at least 14 days) and 100 GSC (41.12 ± 13.99 years) with a sex distribution of 46 men and 54 women in each group were included. Both PSG and questionnaire variables showed clear impairments of sleep quality in PI compared with GSC. The arousal index within total sleep time was increased, which was mainly because of a strong increase within rapid eye movement (REM) sleep. Subjectively, more PI than GSC subjects estimated wake times longer than obtained from PSG. Linear modeling analysis of subjective wake time in terms of PSG parameters revealed that in addition to PSG defined wake time, REM sleep time contributed significantly to subjective wake time. This REM sleep contribution was larger for PI than for GSC subjects. The findings suggest that REM sleep‐related processes might contribute to subjectively disturbed sleep and the perception of waking time in patients with PI.

Heart rate and heart rate variability in subjectively reported insomnia

According to epidemiological studies, insomnia is associated with cardiovascular mortality. However, it is yet to be determined whether this link is mediated by known cardiovascular risk factors. The current study aimed at investigating the association between primary insomnia, defined as subjectively reported sleep disturbance in the absence of any other pathology or substance intake, and alterations in polysomnographically determined nocturnal heart rate (HR) and heart rate variability (HRV). A total of 4 581 nocturnal short‐term electrocardiographic recordings (5 min each) from 104 participants (58 with primary insomnia, 46 healthy controls) were evaluated for HR as well as for time and frequency domain measures of HRV. In the primary insomnia group, we found a lower wake‐to‐sleep HR reduction and a lower standard deviation of RR intervals (SDNN) compared to healthy controls. However, between‐group differences in resting HR were not found, and previous results of an increase in sympathovagal balance and a decrease in parasympathetic nocturnal activity in objectively determined insomnia could not be confirmed in our sample of self‐report insomnia patients. When restricting our analyses to insomnia patients with objectively determined short sleep duration, we found reduced parasympathetic activity as indicated by decreased high frequency power of HRV, as well as decreased root mean square of successive RRI differences (RMSSD) and percentage of successive RRIs that differ by more than 50 ms (pNN50) values. A lower wake‐to‐sleep HR reduction and alterations in HRV variables might, at least partially, mediate the increased rates of cardiovascular morbidity and mortality observed in insomnia patients.

The neurobiology, investigation, and treatment of chronic insomnia

Chronic insomnia is defined by difficulties in falling asleep, maintaining sleep, and early morning awakening, and is coupled with daytime consequences such as fatigue, attention deficits, and mood instability. These symptoms persist over a period of at least 3 months (Diagnostic and Statistical Manual 5 criteria). Chronic insomnia can be a symptom of many medical, neurological, and mental disorders. As a disorder, it incurs substantial health-care and occupational costs, and poses substantial risks for the development of cardiovascular and mental disorders, including cognitive deficits. Family and twin studies confirm that chronic insomnia can have a genetic component (heritability coefficients between 42% and 57%), whereas the investigation of autonomous and central nervous system parameters has identified hyperarousal as a final common pathway of the pathophysiology, implicating an imbalance of sleep-wake regulation consisting of either overactivity of the arousal systems, hypoactivity of the sleep-inducing systems, or both. Insomnia treatments include benzodiazepines, benzodiazepine-receptor agonists, and cognitive behavioural therapy. Treatments currently under investigation include transcranial magnetic or electrical brain stimulation, and novel methods to deliver psychological interventions.

S3-Leitlinie Nicht erholsamer Schlaf/Schlafstörungen

Somnologie 2017 · 21:2–44 DOI 10.1007/s11818-016-0097-x Online publiziert: 27. Februar 2017

Learning as a Model for Neural Plasticity in Major Depression

BACKGROUND The neuroplasticity hypothesis of depression proposes that a dysfunction of neural plasticity-the basic ability of living organisms to adapt their neural function and structure to external and internal cues-might represent a final common pathway underlying the biological and clinical characteristics of the disorder. This study examined learning and memory as correlates of long-term synaptic plasticity in humans to further test the neuroplasticity hypothesis of depression. METHODS Learning in three tasks, for which memory consolidation has been shown to depend on local synaptic refinement in areas of interest (hippocampus-dependent declarative word-pair learning, amygdala-dependent fear conditioning, and primary-cortex-dependent visual texture discrimination), was assessed in 23 inpatients who met International Classification of Disease, 10th Revision, criteria for severe unipolar depression and 35 nondepressed comparison subjects. RESULTS Depressed subjects showed a significant deficit in declarative memory consolidation and enhanced fear acquisition as indicated by skin conductance responses to conditioned stimuli, in comparison with nondepressed subjects. Depressed subjects demonstrated impaired visual discrimination at baseline, not allowing for valid group comparisons of gradual improvement, the plasticity-dependent phase of the task. CONCLUSIONS The results of the study are consistent with the neuroplasticity hypothesis of depression, showing decreased synaptic plasticity in a dorsal executive network that comprises the hippocampus and elevated synaptic plasticity in a ventral emotional network that includes the amygdala in depression. Evaluation of further techniques aimed at modulating synaptic plasticity might prove useful for developing novel treatments for major depressive disorder.

Sleep-related memory consolidation in primary insomnia.

It has been suggested that healthy sleep facilitates the consolidation of newly acquired memories and underlying brain plasticity. The authors tested the hypothesis that patients with primary insomnia (PI) would show deficits in sleep‐related memory consolidation compared to good sleeper controls (GSC). The study used a four‐group parallel design (n = 86) to investigate the effects of 12 h of night‐time, including polysomnographically monitored sleep (‘sleep condition’ in PI and GSC), versus 12 h of daytime wakefulness (‘wake condition’ in PI and GSC) on procedural (mirror tracing task) and declarative memory consolidation (visual and verbal learning task). Demographic characteristics and memory encoding did not differ between the groups at baseline. Polysomnography revealed a significantly disturbed sleep profile in PI compared to GSC in the sleep condition. Night‐time periods including sleep in GSC were associated with (i) a significantly enhanced procedural and declarative verbal memory consolidation compared to equal periods of daytime wakefulness in GSC and (ii) a significantly enhanced procedural memory consolidation compared to equal periods of daytime wakefulness and night‐time sleep in PI. Across retention intervals of daytime wakefulness, no differences between the experimental groups were observed. This pattern of results suggests that healthy sleep fosters the consolidation of new memories, and that this process is impaired for procedural memories in patients with PI. Future work is needed to investigate the impact of treatment on improving sleep and memory.

The reorganisation of memory during sleep

Sleep after learning promotes the quantitative strengthening of new memories. Less is known about the impact of sleep on the qualitative reorganisation of memory, which is the focus of this review. Studies have shown that, in the declarative system, sleep facilitates the abstraction of rules (schema formation), the integration of knowledge into existing schemas (schema integration) and creativity that requires the disbandment of existing patterns (schema disintegration). Schema formation and integration might primarily benefit from slow wave sleep, whereas the disintegration of a schema might be facilitated by rapid eye movement sleep. In the procedural system, sleep fosters the reorganisation of motor memory. The neural mechanisms of these processes remain to be determined. Notably, emotions have been shown to modulate the sleep-related reorganisation of memories. In the final section of this review, we propose that the sleep-related reorganisation of memories might be particularly relevant for mental disorders. Thus, sleep disruptions might contribute to disturbed memory reorganisation and to the development of mental disorders. Therefore, sleep-related interventions might modulate the reorganisation of memories and provide new inroads into treatment.

Increased EEG sigma and beta power during NREM sleep in primary insomnia.

The hyperarousal model of primary insomnia suggests that a deficit of attenuating arousal during sleep might cause the experience of non-restorative sleep. In the current study, we examined EEG spectral power values for standard frequency bands as indices of cortical arousal and sleep protecting mechanisms during sleep in 25 patients with primary insomnia and 29 good sleeper controls. Patients with primary insomnia demonstrated significantly elevated spectral power values in the EEG beta and sigma frequency band during NREM stage 2 sleep. No differences were observed in other frequency bands or during REM sleep. Based on prior studies suggesting that EEG beta activity represents a marker of cortical arousal and EEG sleep spindle (sigma) activity is an index of sleep protective mechanisms, our findings may provide further evidence for the concept that a simultaneous activation of wake-promoting and sleep-protecting neural activity patterns contributes to the experience of non-restorative sleep in primary insomnia.

The microstructure of sleep in primary insomnia: An overview and extension

The present review was undertaken to summarize studies elucidating sleep microstructural differences in chronic insomnia. The etiology of insomnia is still unknown, whereas the hyperarousal concept has gained much attention with respect to pathophysiology. According to this model, insomnia is characterized by significant hyperarousal on an autonomous and central nervous level. Objective findings derived from polysomnography frequently show much less severe differences to good sleepers than subjective sleep complaints assessed by self-rating questionnaires. However, using more fine-grained methods to characterize the electrophysiology of sleep in insomnia, rather distinct differences between the sleep of good sleepers and patients with insomnia have been noted. These methods include the spectral analysis of the sleep EEG, micro-arousal and CAP (cyclic alternating pattern) analysis as well as the assessment of event-related potentials (ERPs) during night-sleep. The application of these methods shows stronger correlations with the subjective experience of disturbed sleep than standard sleep EEG scoring. An overview of the relevant empirical evidence is presented, previous investigations are extended and a theoretical synthesis within the framework of the hyperarousal concept of insomnia is attempted.