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Sleep Initiation and Maintenance Disorders: HELP
Articles by Jeroen S. Benjamins
Based on 10 articles published since 2010
(Why 10 articles?)
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Between 2010 and 2020, Jeroen Benjamins wrote the following 10 articles about Sleep Initiation and Maintenance Disorders.
 
+ Citations + Abstracts
1 Review Insomnia heterogeneity: Characteristics to consider for data-driven multivariate subtyping. 2017

Benjamins, Jeroen S / Migliorati, Filippo / Dekker, Kim / Wassing, Rick / Moens, Sarah / Blanken, Tessa F / Te Lindert, Bart H W / Sjauw Mook, Jeffrey / Van Someren, Eus J W. ·Department of Sleep and Cognition, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Social, Health and Organizational Psychology, Utrecht University, Utrecht, The Netherlands; Department of Experimental Psychology, Utrecht University, Utrecht, The Netherlands. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Social Brain Lab, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Amsterdam, VU University, Amsterdam, The Netherlands; Department of Psychiatry, Neuroscience Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: e.van.someren@nin.knaw.nl. ·Sleep Med Rev · Pubmed #29066053.

ABSTRACT: Meta-analyses and systematic reviews have reported surprisingly few consistent insomnia-characteristics with respect to cognitions, mood, traits, history of life events and family history. One interpretation of this limited consistency is that different subtypes of insomnia exist, each with its own specific multivariate profile of characteristics. Because previously unrecognized subtypes will be differentially represented in individual studies and dilute effect sizes of subtype-dependent characteristics of importance, they are unlikely to be reported consistently in individual studies, let alone in meta-analyses. This review therefore aims to complement meta-analyses by listing previously reported psychometric characteristics of insomnia, irrespective of the degree of consistency over studies. The review clearly indicates that characteristics of insomnia may not be limited to sleep. Reports suggest that at least some individuals with insomnia may deviate from people without sleep complaints with respect to demographics, mental and physical health, childhood trauma, life events, fatigue, sleepiness, hyperarousal, hyperactivity, other sleep disorders, lifetime sleep history, chronotype, depression, anxiety, mood, quality of life, personality, happiness, worry, rumination, self-consciousness, sensitivity, dysfunctional beliefs, self-conscious emotion regulation, coping, nocturnal mentation, wake resting-state mentation, physical activity, food intake, temperature perception and hedonic evaluation. The value of this list of characteristics is that 1) internet has now made it feasible to asses them all in a large sample of people suffering from insomnia, and 2) statistical methods like latent class analysis and community detection can utilize them for a truly bottom-up data-driven search for subtypes. The supplement to this review provides a blueprint of this multivariate approach as implemented in the Sleep registry platform (www.sleepregistry.nl), that allows for bottom-up subtyping and fosters cross-cultural comparison and worldwide collaboration on insomnia subtype finding - and beyond.

2 Article Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways. 2019

Jansen, Philip R / Watanabe, Kyoko / Stringer, Sven / Skene, Nathan / Bryois, Julien / Hammerschlag, Anke R / de Leeuw, Christiaan A / Benjamins, Jeroen S / Muñoz-Manchado, Ana B / Nagel, Mats / Savage, Jeanne E / Tiemeier, Henning / White, Tonya / Anonymous16401124 / Tung, Joyce Y / Hinds, David A / Vacic, Vladimir / Wang, Xin / Sullivan, Patrick F / van der Sluis, Sophie / Polderman, Tinca J C / Smit, August B / Hjerling-Leffler, Jens / Van Someren, Eus J W / Posthuma, Danielle. ·Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands. · Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands. · Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. · UCL Institute of Neurology, Queen Square, London, UK. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Department of Social, Health and Organisational Psychology, Utrecht University, Utrecht, the Netherlands. · Department of Experimental Psychology, Helmholtz Institute, Utrecht University, Utrecht, the Netherlands. · Department of Clinical Genetics, Section of Complex Trait Genetics, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands. · Department of Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands. · 23andMe, Inc., Mountain View, CA, USA. · Department of Genetics, University of North Carolina, Chapel Hill, NC, USA. · Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA. · Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, The Netherlands. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience (an institute of the Royal Netherlands Academy of Arts and Sciences), Amsterdam, The Netherlands. · Departments of Psychiatry and Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam University Medical Center, Amsterdam, The Netherlands. · Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands. d.posthuma@vu.nl. · Department of Clinical Genetics, Section of Complex Trait Genetics, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands. d.posthuma@vu.nl. ·Nat Genet · Pubmed #30804565.

ABSTRACT: Insomnia is the second most prevalent mental disorder, with no sufficient treatment available. Despite substantial heritability, insight into the associated genes and neurobiological pathways remains limited. Here, we use a large genetic association sample (n = 1,331,010) to detect novel loci and gain insight into the pathways, tissue and cell types involved in insomnia complaints. We identify 202 loci implicating 956 genes through positional, expression quantitative trait loci, and chromatin mapping. The meta-analysis explained 2.6% of the variance. We show gene set enrichments for the axonal part of neurons, cortical and subcortical tissues, and specific cell types, including striatal, hypothalamic, and claustrum neurons. We found considerable genetic correlations with psychiatric traits and sleep duration, and modest correlations with other sleep-related traits. Mendelian randomization identified the causal effects of insomnia on depression, diabetes, and cardiovascular disease, and the protective effects of educational attainment and intracranial volume. Our findings highlight key brain areas and cell types implicated in insomnia, and provide new treatment targets.

3 Article Insomnia disorder subtypes derived from life history and traits of affect and personality. 2019

Blanken, Tessa F / Benjamins, Jeroen S / Borsboom, Denny / Vermunt, Jeroen K / Paquola, Casey / Ramautar, Jennifer / Dekker, Kim / Stoffers, Diederick / Wassing, Rick / Wei, Yishul / Van Someren, Eus J W. ·Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Amsterdam, Netherlands; Department of Integrative Neurophysiology and Department of Psychiatry, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam University Medical Centre, Amsterdam, Netherlands. Electronic address: t.blanken@nin.knaw.nl. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Amsterdam, Netherlands; Department of Social, Health and Organizational Psychology and Department of Experimental Psychology, Utrecht University, Utrecht, Netherlands. · Department of Psychological Methods, University of Amsterdam, Amsterdam, Netherlands. · Department of Methodology and Statistics, Tilburg School of Social and Behavioral Sciences, Tilburg University, Tilburg, Netherlands. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Amsterdam, Netherlands; Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Amsterdam, Netherlands. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Amsterdam, Netherlands; Spinoza Centre for Neuroimaging, Amsterdam, Netherlands. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Amsterdam, Netherlands; Department of Integrative Neurophysiology and Department of Psychiatry, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam University Medical Centre, Amsterdam, Netherlands. ·Lancet Psychiatry · Pubmed #30630691.

ABSTRACT: BACKGROUND: Insomnia disorder is the second most prevalent mental disorder, and it is a primary risk factor for depression. Inconsistent clinical and biomarker findings in patients with insomnia disorder suggest that heterogeneity exists and that subtypes of this disease remain unrecognised. Previous top-down proposed subtypes in nosologies have had insufficient validity. In this large-scale study, we aimed to reveal robust subtypes of insomnia disorder by use of data-driven analyses on a multidimensional set of biologically based traits. METHODS: In this series of studies, we recruited participants from the Netherlands Sleep Registry, a database of volunteers aged 18 years or older, who we followed up online to survey traits, sleep, life events, and health history with 34 selected questionnaires of which participants completed at least one. We identified insomnia disorder subtypes by use of latent class analyses. We evaluated the value of our identified subtypes of insomnia disorder by use of a second, non-overlapping cohort who were recruited through a newsletter that was emailed to a new sample of Netherlands Sleep Registry participants, and by assessment of within-subject stability over several years of follow-up. We extensively tested the clinical validity of these subtypes for the development of sleep complaints, comorbidities (including depression), and response to benzodiazepines; in two subtypes of insomnia disorder, we also assessed the clinical relevance of these subtypes by use of an electroencephalogram biomarker and the effectiveness of cognitive behavioural therapy. To facilitate implementation, we subsequently constructed a concise subtype questionnaire and we validated this questionnaire in the second, non-overlapping cohort. FINDINGS: 4322 Netherlands Sleep Registry participants completed at least one of the selected questionnaires, a demographic questionnaire, and an assessment of their Insomnia Severity Index (ISI) between March 2, 2010, and Oct 28, 2016. 2224 (51%) participants had probable insomnia disorder, defined as an ISI score of at least 10, and 2098 (49%) participants with a lower ISI score served as a control group. With a latent class analysis of the questionnaire responses of 2224 participants, we identified five novel insomnia disorder subtypes: highly distressed, moderately distressed but reward sensitive (ie, with intact responses to pleasurable emotions), moderately distressed and reward insensitive, slightly distressed with high reactivity (to their environment and life events), and slightly distressed with low reactivity. In a second, non-overlapping replication sample of 251 new participants who were assessed between June 12, 2017, and Nov 26, 2017, five subtypes were also identified to be optimal. In both the development sample and replication sample, each participant was classified as having only one subtype with high posterior probability (0·91-1·00). In 215 of the original sample of 2224 participants with insomnia who were reassessed 4·8 (SD 1·6) years later (between April 13, 2017, and June 21, 2017), the probability of maintaining their original subtype was 0·87, indicating a high stability of the classification. We found differences between the identified subtypes in developmental trajectories, response to treatment, the presence of an electroencephalogram biomarker, and the risk of depression that was up to five times different between groups, which indicated a clinical relevance of these subtypes. INTERPRETATION: High-dimensional data-driven subtyping of people with insomnia has addressed an unmet need to reduce the heterogeneity of insomnia disorder. Subtyping facilitates identification of the underlying causes of insomnia, development of personalised treatments, and selection of patients with the highest risk of depression for inclusion in trials regarding prevention of depression. FUNDING: European Research Council and Netherlands Organization for Scientific Research.

4 Article Overnight worsening of emotional distress indicates maladaptive sleep in insomnia. 2019

Wassing, Rick / Benjamins, Jeroen S / Talamini, Lucia M / Schalkwijk, Frans / Van Someren, Eus J W. ·Department of Sleep and Cognition, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. · Department of Social, Health and Organisational Psychology, Utrecht University, Utrecht, The Netherlands. · Department of Experimental Psychology, Helmholtz Institute, Utrecht University, Utrecht, The Netherlands. · Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands. · Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, The Netherlands. · Institute for Psychotherapy, Amsterdam, The Netherlands. · Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, The Netherlands. · Amsterdam UMC, Vrije Universiteit, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands. ·Sleep · Pubmed #30590834.

ABSTRACT: STUDY OBJECTIVES: Mechanisms underlying the distress of hyperarousal in people with insomnia remain enigmatic. We investigated whether insomnia impedes the overnight adaptation to emotional distress. METHODS: We induced the distressful self-conscious emotion of shame four times across three consecutive days by exposing 64 participants to their often embarrassingly out-of-tune singing, recorded earlier during a Karaoke session. Perceived physical, emotional, and social distress was assessed with the Experiential Shame Scale. RESULTS: Compared to exposures followed by wakefulness, exposures followed by sleep resulted in overnight relief of physical component of shame in normal sleepers, but in a striking opposite overnight worsening in people with insomnia. CONCLUSIONS: Our findings are the first to experimentally show that the benefits of sleep are not only lost when sleep is poor; people with insomnia experience a maladaptive type of sleep that actually aggravates physically perceived distress. Maladaptive sleep could shed new light on posttraumatic stress disorder (PTSD) and on diurnal mood fluctuation and the counterintuitive favorable effects of sleep deprivation in depression.

5 Article Attention deficit hyperactivity disorder symptom severity and sleep problems in adult participants of the Netherlands sleep registry. 2017

Vogel, Suzan W N / Bijlenga, Denise / Benjamins, Jeroen S / Beekman, Aartjan T F / Kooij, J J Sandra / Van Someren, Eus J W. ·PsyQ, Expertise Center Adult ADHD, Carel Reinierszkade 197, 2593 The Hague HR, The Netherlands. Electronic address: s.vogel@psyq.nl. · PsyQ, Expertise Center Adult ADHD, Carel Reinierszkade 197, 2593 The Hague HR, The Netherlands. · Department of Social, Health and Organisational Psychology, Department of Experimental Psychology, Utrecht University, Heidelberglaan 1, 3584 Utrecht CH, The Netherlands. · Department of Psychiatry, EMGO Institute for Health and Care Research, VU University Medical Center, A. J. Ernststraat 1187, 1081 Amsterdam HL, The Netherlands. · PsyQ, Expertise Center Adult ADHD, Carel Reinierszkade 197, 2593 The Hague HR, The Netherlands; Department of Psychiatry, EMGO Institute for Health and Care Research, VU University Medical Center, A. J. Ernststraat 1187, 1081 Amsterdam HL, The Netherlands. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 Amsterdam BA, The Netherlands; Departments of Psychiatry and Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University and Medical Center, De Boelelaan 1187, 1081 Amsterdam HV, The Netherlands. ·Sleep Med · Pubmed #29221785.

ABSTRACT: BACKGROUND: We examined whether current overall attention deficit hyperactivity disorder (ADHD), inattention, or hyperactivity symptom severities are associated with the current presence and persistent history of sleep problems. METHODS: N = 942 participants of the Netherlands Sleep Registry filled out online several validated questionnaires. Regression analyses were performed to assess the association between (1) current overall ADHD symptom severity and the current presence of sleep problems, (2) current ADHD symptom-severity groups and the persistent history of sleep problems, and (3) current inattention or hyperactivity symptom severities and the current presence of sleep problems. RESULTS: (1) Current overall ADHD symptom severity was associated with the odds of suffering from probable obstructive sleep apnea syndrome (OSAS), restless legs syndrome (RLS), periodic limb movement disorder (PLMD), insomnia disorder (ID) with predominant difficulties initiating sleep (DIS) and maintaining sleep (DMS), but not with the odds of suffering from narcolepsy or ID with predominant early-morning awakening (EMA). Current overall ADHD symptom severity was also associated with an extreme evening chronotype but not with short sleep. (2) The group with the most severe current ADHD symptoms was more likely to have a history of persistent OSAS, RLS, and ID. (3) The severity of symptoms of hyperactivity, but not of inattention, was specifically associated with probable RLS, PLMD, ID with DIS or DMS, and short sleep. Inattention symptom severity was only related to the probability of being an extreme evening chronotype. CONCLUSION: ADHD severity, especially the severity of hyperactivity, is associated with the current presence and persistent history of sleep problems.

6 Article The experienced temperature sensitivity and regulation survey. 2016

Van Someren, Eus J W / Dekker, Kim / Te Lindert, Bart H W / Benjamins, Jeroen S / Moens, Sarah / Migliorati, Filippo / Aarts, Emmeke / van der Sluis, Sophie. ·Department of Sleep and Cognition, Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Departments of Integrative Neurophysiology and Medical Psychology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University and Medical Center, Amsterdam, the Netherlands. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences , Amsterdam, The Netherlands. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Social, Health and Organizational Psychology, Department of Experimental Psychology, Utrecht University, Utrecht, The Netherlands. · Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam, Amsterdam, the Netherlands; Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany. · Department of Clinical Genetics, Section Complex Trait Genetics, VU Medical Center , Amsterdam, the Netherlands. ·Temperature (Austin) · Pubmed #27227080.

ABSTRACT: Individuals differ in thermosensitivity, thermoregulation, and zones of thermoneutrality and thermal comfort. Whereas temperature sensing and -effectuating processes occur in part unconsciously and autonomic, awareness of temperature and thermal preferences can affect thermoregulatory behavior as well. Quantification of trait-like individual differences of thermal preferences and experienced temperature sensitivity and regulation is therefore relevant to obtain a complete understanding of human thermophysiology. Whereas several scales have been developed to assess instantaneous appreciation of heat and cold exposure, a comprehensive scale dedicated to assess subjectively experienced autonomic or behavioral thermoregulatory activity has been lacking so far. We constructed a survey that specifically approaches these domains from a trait-like perspective, sampled 240 volunteers across a wide age range, and analyzed the emergent component structure. Participants were asked to report their thermal experiences, captured in 102 questions, on a 7-point bi-directional Likert scale. In a second set of 32 questions, participants were asked to indicate the relative strength of experiences across different body locations. Principal component analyses extracted 21 meaningful dimensions, which were sensitive to sex-differences and age-related changes. The questions were also assessed in a matched sample of 240 people with probable insomnia to evaluate the sensitivity of these dimensions to detect group differences in a case-control design. The dimensions showed marked mean differences between cases and controls. The survey thus has discriminatory value. It can freely be used by anyone interested in studying individual or group differences in thermosensitivity and thermoregulation.

7 Article Wake High-Density Electroencephalographic Spatiospectral Signatures of Insomnia. 2016

Colombo, Michele A / Ramautar, Jennifer R / Wei, Yishul / Gomez-Herrero, Germán / Stoffers, Diederick / Wassing, Rick / Benjamins, Jeroen S / Tagliazucchi, Enzo / van der Werf, Ysbrand D / Cajochen, Christian / Van Someren, Eus J W. ·Department of Sleep and Cognition, Netherlands Institute for Neuroscience (NIN), an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands. · Faculty of Biology, and Bernstein Center Freiburg, University of Freiburg, Freiburg, Germany. · Centre for Chronobiology, Psychiatric Hospital of the University of Basel (UPK), Basel, Switzerland. · Department of Clinical and Health Psychology, Department of Experimental Psychology, Utrecht University, Utrecht, The Netherlands. · Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, the Netherlands. · Departments of Integrative Neurophysiology and Psychiatry, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University and Medical Center, Amsterdam, the Netherlands. ·Sleep · Pubmed #26951395.

ABSTRACT: STUDY OBJECTIVES: Although daytime complaints are a defining characteristic of insomnia, most EEG studies evaluated sleep only. We used high-density electroencephalography to investigate wake resting state oscillations characteristic of insomnia disorder (ID) at a fine-grained spatiospectral resolution. METHODS: A case-control assessment during eyes open (EO) and eyes closed (EC) was performed in a laboratory for human physiology. Participants (n = 94, 74 female, 21-70 y) were recruited through www.sleepregistry.nl: 51 with ID, according to DSM-5 and 43 matched controls. Exclusion criteria were any somatic, neurological or psychiatric condition. Group differences in the spectral power topographies across multiple frequencies (1.5 to 40 Hz) were evaluated using permutation-based inference with Threshold-Free Cluster-Enhancement, to correct for multiple comparisons. RESULTS: As compared to controls, participants with ID showed less power in a narrow upper alpha band (11-12.7 Hz, peak: 11.7 Hz) over bilateral frontal and left temporal regions during EO, and more power in a broad beta frequency range (16.3-40 Hz, peak: 19 Hz) globally during EC. Source estimates suggested global rather than cortically localized group differences. CONCLUSIONS: The widespread high power in a broad beta band reported previously during sleep in insomnia is present as well during eyes closed wakefulness, suggestive of a round-the-clock hyperarousal. Low power in the upper alpha band during eyes open is consistent with low cortical inhibition and attentional filtering. The fine-grained HD-EEG findings suggest that, while more feasible than PSG, wake EEG of short duration with a few well-chosen electrodes and frequency bands, can provide valuable features of insomnia.

8 Article Slow dissolving of emotional distress contributes to hyperarousal. 2016

Wassing, Rick / Benjamins, Jeroen S / Dekker, Kim / Moens, Sarah / Spiegelhalder, Kai / Feige, Bernd / Riemann, Dieter / van der Sluis, Sophie / Van Der Werf, Ysbrand D / Talamini, Lucia M / Walker, Matthew P / Schalkwijk, Frans / Van Someren, Eus J W. ·Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, 1105 BA, Amsterdam, The Netherlands; r.wassing@nin.knaw.nl. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, 1105 BA, Amsterdam, The Netherlands; Department of Social, Health and Organizational Psychology, Experimental Psychology Section, Utrecht University, 3584 CS, Utrecht, The Netherlands; · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, 1105 BA, Amsterdam, The Netherlands; · Department of Clinical Psychology and Psychophysiology, University Medical Center Freiburg, 79104 Freiburg, Germany; · Department of Clinical Genetics, Complex Trait Genetics Section, Vrije Universiteit Medical Center, 1081 HV, Amsterdam, The Netherlands; · Department of Anatomy and Neurosciences, Vrije Universiteit Medical Center, 1007 MB, Amsterdam, The Netherlands; · Department of Psychology, University of Amsterdam, 1021 WX, Amsterdam, The Netherlands; · Department of Psychology, University of California, Berkeley, CA 94720-1650; · Institute for Psychotherapy, 1076 AP, Amsterdam, The Netherlands; · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, 1105 BA, Amsterdam, The Netherlands; Department of Medical Psychology, Vrije Universiteit Medical Center, 1081 HZ, Amsterdam, The Netherlands; Department of Integrative Neurophysiology, Neuroscience Campus, Vrije Universiteit, 1081 HV, Amsterdam, The Netherlands. ·Proc Natl Acad Sci U S A · Pubmed #26858434.

ABSTRACT: The mechanisms underlying hyperarousal, the key symptom of insomnia, have remained elusive, hampering cause-targeted treatment. Recently, restless rapid-eye-movement (REM) sleep emerged as a robust signature of sleep in insomnia. Given the role of REM sleep in emotion regulation, we hypothesized that restless REM sleep could interfere with the overnight resolution of emotional distress, thus contributing to accumulation of arousal. Participants (n = 1,199) completed questionnaires on insomnia severity, hyperarousal, self-conscious emotional distress, and thought-like nocturnal mentation that was validated to be a specific proxy for restless REM sleep (selective fragmentation: R = 0.57, P < 0.001; eye movement density: R = 0.46, P < 0.01) in 32 polysomnographically assessed participants. The experience of distress lasting overnight increased with insomnia severity (β = 0.29, P < 10(-23)), whereas short-lasting distress did not (β = -0.02, P = 0.41). Insomnia severity was associated with hyperarousal (β = 0.47, P < 10(-63)) and with the thought-like nocturnal mentation that is specifically associated with restless REM sleep (β = 0.31, P < 10(-26)). Structural equation modeling showed that 62.4% of the association between these key characteristics of insomnia was mediated specifically by reduced overnight resolution of emotional distress. The model outperformed all alternative mediation pathways. The findings suggest that restless REM sleep reflects a process that interferes with the overnight resolution of distress. Its accumulation may promote the development of chronic hyperarousal, giving clinical relevance to the role of REM sleep in emotion regulation in insomnia, depression, and posttraumatic stress disorder.

9 Article Effectiveness of internet-supported cognitive behavioral and chronobiological interventions and effect moderation by insomnia subtype: study protocol of a randomized controlled trial. 2015

Dekker, Kim / Benjamins, Jeroen S / Van Straten, Annemieke / Hofman, Winni F / Van Someren, Eus J W. ·Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands. k.dekker@nin.knaw.nl. · Department of Clinical and Health Psychology, Department of Experimental Psychology, Utrecht University, Heidelberglaan 1, 3584 CS, Utrecht, The Netherlands. j.s.benjamins@uu.nl. · Department of Clinical Psychology, VU University Amsterdam & EMGO Institute for Health Care and Research, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands. a.van.straten@vu.nl. · Department of Psychology, Brain and Cognition group, University of Amsterdamy, Weesperplein 4, 1018 XA, Amsterdam, The Netherlands. w.f.hofman@uva.nl. · Personal Health Institute International, Lobo-Braakensiekstraat 94, 1065 HP, Amsterdam, The Netherlands. w.f.hofman@uva.nl. · Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands. e.van.someren@nin.knaw.nl. · Departments of Integrative Neurophysiology and Medical Psychology, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University and Medical Center, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands. e.van.someren@nin.knaw.nl. ·Trials · Pubmed #26141682.

ABSTRACT: BACKGROUND: DSM-V criteria for insomnia disorder are met by 6 to 10% of the adult population. Insomnia has severe consequences for health and society. One of the most common treatments provided by primary caregivers is pharmacological treatment, which is far from optimal and has not been recommended since a 2005 consensus report of the National Institutes of Health. The recommended treatment is Cognitive Behavioral Therapy for Insomnia. Effectiveness, however, is still limited. Only a few studies have evaluated the effectiveness of chronobiological treatments, including the timed application of bright light, physical activity and body warming. Another opportunity for optimization of treatment is based on the idea that the people suffering from insomnia most likely represent a heterogeneous mix of subtypes, with different underlying causes and expected treatment responses. The present study aims to evaluate the possibility for optimizing insomnia treatment along the principles of personalized and stratified medicine. It evaluates the following: 1. The relative effectiveness of internet-supported cognitive behavioral therapy, bright light, physical activity and body warming; 2. Whether the effectiveness of internet-supported cognitive behavioral therapy for insomnia can be augmented by simultaneous or prior application of bright light, physical activity and body warming; and 3. Whether the effectiveness of the interventions and their combination are moderated by the insomnia subtype. METHODS/DESIGN: In a repeated measures, placebo-controlled, randomized clinical trial that included 160 people diagnosed with insomnia disorder, we are evaluating the relative effectiveness of 4 intervention weeks. Primary outcome is subjective sleep efficiency, quantified using a sleep diary. Secondary outcomes include other complaints of sleep and daytime functioning, health-related cost estimates and actigraphic objective sleep estimates. Compliance will be monitored both subjectively and objectively using activity, light and temperature sensors. Insomnia subtypes will be assessed using questionnaires. Mixed effect models will be used to evaluate intervention effects and moderation by insomnia subtype ratings. DISCUSSION: The current study addresses multiple opportunities to optimize and personalize treatment of insomnia disorder. TRIAL REGISTRATION: Netherlands National Trial Register NTR4010, 4 June 2013.

10 Article Orbitofrontal gray matter relates to early morning awakening: a neural correlate of insomnia complaints? 2012

Stoffers, Diederick / Moens, Sarah / Benjamins, Jeroen / van Tol, Marie-José / Penninx, Brenda W J H / Veltman, Dick J / Van der Wee, Nic J A / Van Someren, Eus J W. ·Department of Sleep and Cognition, Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences Amsterdam, Netherlands. ·Front Neurol · Pubmed #23060850.

ABSTRACT: Sleep complaints increase profoundly with age; prevalence estimates of insomnia in the elderly reach up to 37%. The three major types of nocturnal complaints are difficulties initiating (DIS) and maintaining (DMS) sleep and early morning awakening (EMA), of which the latter appears most characteristic for aging. The neural correlates associated with these complaints have hardly been investigated, hampering the development of rational treatment and prevention. A recent study on structural brain correlates of insomnia showed that overall severity, but not duration, of insomnia complaints is associated with lower gray matter (GM) density in part of the left orbitofrontal cortex (OFC). Following up on this, we investigated, in an independent sample of people not diagnosed with insomnia, whether individual differences in GM density are associated with differences in DIS, DMS, and EMA. Sixty five healthy participants (mean age = 41 years, range 18-56) filled out questionnaires and underwent structural magnetic resonance imaging. Three compound Z-scores were computed for questionnaire items relating to DIS, DMS, and EMA. Whole-brain voxel-based morphometry was used to investigate their association with GM density. Results show that participants with lower GM density in a region where the left inferior OFC borders the insula report more EMA, but not DIS or DMS. This is the first study to investigate structural brain correlates of specific sleep characteristics that can translate into complaints in insomniacs. The selective association of EMA with orbitofrontal GM density makes our findings particularly relevant to elderly people, where EMA represents the most characteristic complaint. It is hypothesized that low GM density in aforementioned orbitofrontal area affects its role in sensing comfort. An intact ability to evaluate comfort may be crucial to maintain sleep, especially at the end of the night when sleep is vulnerable because homeostatic sleep propensity has dissipated.