Purpose of Review
Previous research has struggled with identifying clear-cut, objective counterparts to subjective distress in insomnia. Approaching this discrepancy with a focus on hyperarousal and ...dysfunctional affective processes, studies examining brain structures and neural networks involved in affect and arousal are reviewed and conclusions for an updated understanding of insomnia are drawn.
Recent Findings
Recent studies found that amygdala reactivity, morphometry and adaptation in insomnia are altered, indicating that processing of negative stimuli is intensified and more lasting. Also, patients with insomnia show aberrant connectivity in the default mode network (DMN) and the salience network (SN), which is associated with subjective sleep disturbances, hyperarousal, maladaptive emotion regulation and disturbed integration of emotional states. The limbic circuit is assumed to play a crucial role in enhanced recall of negative experiences.
Summary
There is reason to consider insomnia as a disorder of affect and arousal. Dysregulation of the limbic circuit might perpetuate impaired connectivity in the DMN and the SN. However, the interplay between the networks is yet to be researched.
A key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates of major depressive disorder (MDD). Identifying measurable indicators of ...brain processes associated with MDD could facilitate the detection of individuals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here, we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across six continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of large-scale data sharing for mental health research.
It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and ...investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent samples comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD; healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD.
Major depressive disorder is among the most burdening and costly chronic health hazards. Since its prognosis is poor and treatment effectiveness is moderate at best, prevention would be the strategy ...of first choice. Insomnia may be the best modifiable risk factor. Insomnia is highly prevalent (4-10%) and meta-analysis estimates ±13% of people with insomnia to develop depression within a year. Among people with insomnia, recent work identified three subtypes with a particularly high lifetime risk of depression. The current randomized controlled trial (RCT) evaluates the effects of internet-guided Cognitive Behavioral Therapy for Insomnia (CBT-I), Chronobiological Therapy (CT), and their combination on insomnia and the development of depressive symptoms.
We aim to include 120 participants with Insomnia Disorder (ID) of one of the three subtypes that are more prone to develop depression. In a two by two factorial repeated measures design, participants will be randomized to CBT-I, CT, CBT-I + CT or treatment as usual, and followed up for one year. The primary outcome is the change, relative to baseline, of the severity of depressive symptoms integrated over four follow-ups spanning one year. Secondary outcome measures include a diagnosis of major depressive disorder, insomnia severity, sleep diaries, actigraphy, cost-effectiveness, and brain structure and function.
Pre-selection of three high-risk insomnia subtypes allows for a sensitive assessment of the possibility to prevent the development and worsening of depressive symptoms through interventions targeting insomnia.
Netherlands Trial Register (NL7359). Registered on 19 October 2018.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Insomnia disorder comprises symptoms during night and day that strongly affect quality of life and wellbeing. Prolonged sleep latency, difficulties to maintain sleep and early morning ...wakening characterize sleep complaints, whereas fatigue, reduced attention, impaired cognitive functioning, irritability, anxiety and low mood are key daytime impairments. Insomnia disorder is well acknowledged in all relevant diagnostic systems: Diagnostic and Statistical Manual of the American Psychiatric Association, 5th revision, International Classification of Sleep Disorders, 3rd version, and International Classification of Diseases, 11th revision. Insomnia disorder as a chronic condition is frequent (up to 10% of the adult population, with a preponderance of females), and signifies an important and independent risk factor for physical and, especially, mental health. Insomnia disorder diagnosis primarily rests on self‐report. Objective measures like actigraphy or polysomnography are not (yet) part of the routine diagnostic canon, but play an important role in research. Disease concepts of insomnia range from cognitive‐behavioural models to (epi‐) genetics and psychoneurobiological approaches. The latter is derived from knowledge about basic sleep–wake regulation and encompass theories like rapid eye movement sleep instability/restless rapid eye movement sleep. Cognitive‐behavioural models of insomnia led to the conceptualization of cognitive‐behavioural therapy for insomnia, which is now considered as first‐line treatment for insomnia worldwide. Future research strategies will include the combination of experimental paradigms with neuroimaging and may benefit from more attention to dysfunctional overnight alleviation of distress in insomnia. With respect to therapy, cognitive‐behavioural therapy for insomnia merits widespread implementation, and digital cognitive‐behavioural therapy may assist delivery along treatment guidelines. However, given the still considerable proportion of patients responding insufficiently to cognitive‐behavioural therapy for insomnia, fundamental studies are highly necessary to better understand the brain and behavioural mechanisms underlying insomnia. Mediators and moderators of treatment response/non‐response and the associated development of tailored and novel interventions also require investigation. Recent studies suggest that treatment of insomnia may prove to add significantly as a preventive strategy to combat the global burden of mental disorders.
•Neuroimaging is a promising tool for better understanding of the shared pathophysiology of major depressive disorder and insomnia.•A link between the neural networks alterations, genetic and brain ...monoamine changes, is suggesting several common mechanisms on their pathophysiology.•Potentially, disruption of functional connectivity within and between the salience and default mode networks provide new insights into the link between major depressive disorder and insomnia, which needs further assessment in future.
Insomnia is a common symptom of Major Depressive Disorder (MDD) and genome-wide association studies pointed to their strong genetic association. Although the prevalence of insomnia symptoms in MDD is noticeable and evidence supports their strong bidirectional association, the number of available neuroimaging findings on patients of MDD with insomnia symptoms is limited. However, such neuroimaging studies could verily improve our understanding of their shared pathophysiology and advance corresponding theories.
Based on the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guideline, we have conducted a literature search using PubMed, EMBASE, and Scopus databases and systematically explored 640 studies using various neuroimaging modalities in MDD patients with different degrees of insomnia symptoms.
Despite inconsistencies, current findings from eight studies suggested structural and functional disturbances in several brain regions including the amygdala, prefrontal cortex and anterior cingulate cortex and insula. The aberrant functional connectivity within and between the main hubs of the salience and default mode networks could potentially yield new insights into the link between MDD and insomnia, which needs further assessment.
The number of studies reviewed herein is limited. The applied methods for assessing structural and functional neural mechanisms of insomnia and depression were variable.
Neuroimaging methods demonstrated the overlapping underlying neural mechanisms between MDD and insomnia. Future studies may facilitate better understanding of their pathophysiology to allow development of specific treatment.
Summary
Research into insomnia disorder has pointed to large‐scale brain network dysfunctions. Dynamic functional connectivity is instrumental to cognitive functions but has not been investigated in ...insomnia disorder. This study assessed between‐network functional connectivity strength and variability in patients with insomnia disorder as compared with matched controls without sleep complaints. Twelve‐minute resting‐state functional magnetic resonance images and T1‐weighed images were acquired in 65 people diagnosed with insomnia disorder (21–69 years, 48 female) and 65 matched controls without sleep complaints (22–70 years, 42 female). Pairwise correlations between the activity time series of 14 resting‐state networks and temporal variability of the correlations were compared between cases and controls. After false discovery rate correction for multiple comparisons, people with insomnia disorder and controls did not differ significantly in terms of mean between‐network functional connectivity strength; people with insomnia disorder did, however, show less functional connectivity variability between the anterior salience network and the left executive‐control network. The finding suggests less flexible interactions between the networks during the resting state in people with insomnia disorder.
The objective assessment of insomnia has remained difficult. Multisensory devices collecting heart rate (HR) and motion are regarded as the future of ambulatory sleep monitoring. Unfortunately, ...reports on altered average HR or heart rate variability (HRV) during sleep in insomnia are equivocal. Here, we evaluated whether the objective quantification of insomnia improves by assessing state-related changes in cardiac measures.
We recorded electrocardiography, posture, and actigraphy in 33 people without sleep complaints and 158 patients with mild to severe insomnia over 4 d in their home environment. At the microscale, we investigated whether HR changed with proximity to gross (body) and small (wrist) movements at nighttime. At the macroscale, we calculated day-night differences in HR and HRV measures. For both timescales, we tested whether outcome measures were related to insomnia diagnosis and severity.
At the microscale, an increase in HR was often detectable already 60 s prior to as well as following a nocturnal chest, but not wrist, movement. This increase was slightly steeper in insomnia and was associated with insomnia severity, but future EEG recordings are necessary to elucidate whether these changes occur prior to or simultaneously with PSG-indicators of wakefulness. At the macroscale, we found an attenuated cardiac response to sleep in insomnia: patients consistently showed smaller day-night differences in HR and HRV.
Incorporating state-related changes in cardiac features in the ambulatory monitoring of sleep might provide a more sensitive biomarker of insomnia than the use of cardiac activity averages or actigraphy alone.
Summary
In the past decades, actigraphy has emerged as a promising, cost‐effective, and easy‐to‐use tool for ambulatory sleep recording. Polysomnography (PSG) validation studies showed that ...actigraphic sleep estimates fare relatively well in healthy sleepers. Additionally, round‐the‐clock actigraphy recording has been used to study circadian rhythms in various populations. To this date, however, there is little evidence that the diagnosis, monitoring, or treatment of insomnia can significantly benefit from actigraphy recordings. Using a case–control design, we therefore critically examined whether mean or within‐subject variability of actigraphy sleep estimates or circadian patterns add to the understanding of sleep complaints in insomnia. We acquired actigraphy recordings and sleep diaries of 37 controls and 167 patients with varying degrees of insomnia severity for up to 9 consecutive days in their home environment. Additionally, the participants spent one night in the laboratory, where actigraphy was recorded alongside PSG to check whether sleep, in principle, is well estimated. Despite moderate to strong agreement between actigraphy and PSG sleep scoring in the laboratory, ambulatory actigraphic estimates of average sleep and circadian rhythm variables failed to successfully differentiate patients with insomnia from controls in the home environment. Only total sleep time differed between the groups. Additionally, within‐subject variability of sleep efficiency and wake after sleep onset was higher in patients. Insomnia research may therefore benefit from shifting attention from average sleep variables to day‐to‐day variability or from the development of non‐motor home‐assessed indicators of sleep quality.
Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently recognized heterogeneity within ...the insomnia population could obscure detection of involved brain circuits. The present study investigated whether structural brain connectivity deviations differ between recently discovered and validated insomnia subtypes.
Structural and diffusion weighted 3-Tesla MRI data of four independent studies were harmonized. The sample consisted of 73 controls without sleep complaints and 204 participants with insomnia grouped into five subtypes based on their fingerprint of mood and personality traits assessed with the Insomnia Type Questionnaire. Linear regression correcting for age and sex evaluated group differences in structural connectivity strength, indicated by fractional anisotropy, streamline volume density and mean diffusivity, and evaluated within three different atlases.
Insomnia subtypes showed differentiating profiles of deviating structural connectivity which concentrated in different functional networks. Permutation testing against randomly drawn heterogeneous subsamples indicated significant specificity of deviation profiles in four of the five subtypes: highly distressed, moderately distressed reward sensitive, slightly distressed low reactive and slightly distressed high reactive. Connectivity deviation profile significance ranged from p= 0.001 to p=0.049 for different resolutions of brain parcellation and connectivity weight.
Our results provide a first indication that different insomnia subtypes exhibit distinct profiles of deviations in structural brain connectivity. Subtyping of insomnia could be essential for a better understanding of brain mechanisms that contribute to insomnia vulnerability.
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