Chiara Baglioni

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.

Sleep and emotions: A focus on insomnia

Insomnia disorder is defined as difficulties in initiating/maintaining sleep and/or non-restorative sleep accompanied by decreased daytime functioning, persisting for at least four weeks. For many patients suffering from depression and anxiety, insomnia is a pervasive problem. Many of the aetiological theories of insomnia postulate that heightened emotional reactivity contributes to the maintenance of symptoms. This review focuses on the role of emotional reactivity in insomnia, and how the relationship between insomnia and depression and anxiety may be mediated by emotional reactivity. Furthermore, studies investigating the valence of emotions in insomnia are reviewed. Overall, there is empirical evidence that dysfunctional emotional reactivity might mediate the interaction between cognitive and autonomic hyperarousal, thus contributing to the maintenance of insomnia. Moreover, dysfunctions in sleep-wake regulating neural circuitries seem to be able to reinforce emotional disturbances. It seems plausible that dysfunctional emotional reactivity modulates the relationship between insomnia and depression and anxiety. Considering the interaction between sleep and emotional valence, poor sleep quality seems to correlate with high negative and low positive emotions, both in clinical and subclinical samples. Good sleep seems to be associated with high positive emotions, but not necessarily with low negative emotions. This review underlines the need for future research on emotions in insomnia.

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.

Comorbid Sleep Disorders in Neuropsychiatric Disorders Across the Life Cycle

The association between psychopathology and poor sleep has long been recognized. The current review focuses on the association between the most prevalent sleep disorders (insomnia, sleep-related breathing disorders and restless legs syndrome) and four major psychiatric disorders: alcohol dependence, schizophrenia, depression and anxiety disorders. Decreased total sleep time and increased sleep onset latency as measured by polysomnography as well an increase of the prevalence of insomnia has been reported in all of these psychiatric disorders. Furthermore, sleep disturbance is a risk factor for their development. Cognitive-behavioral therapy for insomnia has been shown to have a positive impact on both sleep and symptoms of depression and anxiety. Whether adequate treatment of sleep disorders can prevent the incidence of psychiatric disorders, remains to be investigated.

Is Chronic Insomnia a Precursor to Major Depression? Epidemiological and Biological Findings

Insomnia has been found to be a clinical predictor of subsequent depression. Nevertheless the biological processes underlying this causal relationship are yet not fully understood. Both conditions share a common imbalance of the arousal system. Patients with insomnia present fragmented REM sleep, which probably interferes with basal processes of emotion regulation. The interaction between the arousal and the affective system with the persistence of the disorder could slowly alter also the cognitive system and lead to depression. Although preliminary results seem to support this hypothesis, data are still too few to make valid conclusions.

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.

Insomnia Does Not Appear to be Associated With Substantial Structural Brain Changes

STUDY OBJECTIVES Sleep has been demonstrated to significantly modulate brain plasticity and the manifestation of mental disorders. However, previous studies on the effect of disrupted sleep on brain structure have reported inconsistent results. The goal of the current study was to investigate brain morphometry in a well-characterized large sample of patients with primary insomnia (PI) in comparison with good sleeper controls. DESIGN Automated parcellation and pattern recognition approaches were supplemented by voxelwise analyses of gray and white matter volumes to analyze magnetic resonance images. All analyses included age, sex, and total intracranial volume as covariates. SETTING Department of Psychiatry and Psychotherapy of the University of Freiburg Medical Center. PARTICIPANTS There were 28 patients with PI (10 males; 18 females; age 43.7 ± 14.2 y) and 38 healthy, good sleepers (17 males; 21 females; age 39.6 ± 8.9 y). INTERVENTIONS N/A. RESULTS No significant between-group differences were observed in any of the investigated brain morphometry variables. CONCLUSIONS Altered brain function in insomnia does not appear to have a substantial effect on brain morphometry on a macroscopic level.

Psychophysiological reactivity to sleep-related emotional stimuli in primary insomnia.

The present study examined psychophysiological reactivity to emotional stimuli related and non-related to sleep in people with primary insomnia (PPI) and in good sleepers (GS). Twenty-one PPI and 18 GS were presented with five blocks of neutral, negative, positive, sleep-related negative and sleep-related positive pictures. During the presentation of the pictures, facial electromyography (EMG) of the corrugator and the zygomatic muscles, heart rate (HR) and cardiac vagal tone (CVT) were recorded. Subjective ratings of the stimuli were also collected. We found that only PPI exhibited greater inhibition of the corrugator activity in response to sleep-related positive stimuli compared to the other blocks of stimuli. Furthermore, PPI rated the sleep-related negative stimuli as more unpleasant and arousing and showed higher CVT in response to all stimuli as compared to GS. Results were interpreted as indicating that PPI exhibit craving for sleep-related positive stimuli, and also hyper-arousability in response to sleep-related negative stimuli, as compared to GS. Our results suggest that psychological treatment of insomnia could benefit by the inclusion of strategies dealing with emotional processes linked with sleep processes.

EEG sigma and slow‐wave activity during NREM sleep correlate with overnight declarative and procedural memory consolidation

Previous studies suggest that sleep‐specific brain activity patterns such as sleep spindles and electroencephalographic slow‐wave activity contribute to the consolidation of novel memories. The generation of both sleep spindles and slow‐wave activity relies on synchronized oscillations in a thalamo‐cortical network that might be implicated in synaptic strengthening (spindles) and downscaling (slow‐wave activity) during sleep. This study further examined the association between electroencephalographic power during non‐rapid eye movement sleep in the spindle (sigma, 12–16 Hz) and slow‐wave frequency range (0.1–3.5 Hz) and overnight memory consolidation in 20 healthy subjects (10 men, 27.1 ± 4.6 years). We found that both electroencephalographic sigma power and slow‐wave activity were positively correlated with the pre–post‐sleep consolidation of declarative (word list) and procedural (mirror‐tracing) memories. These results, although only correlative in nature, are consistent with the view that processes of synaptic strengthening (sleep spindles) and synaptic downscaling (slow‐wave activity) might act in concert to promote synaptic plasticity and the consolidation of both declarative and procedural memories during sleep.