Chronic Insomnia Disorder

Neurological Disorder MONDO:0013600 Pathograph 7 Show in embeddings browser Sleep Disorder Neurological Disease

Chronic insomnia disorder is persistent difficulty initiating or maintaining sleep, or non-restorative sleep, together with significant daytime impairment, despite adequate opportunity to sleep. It is among the most prevalent disorders in medicine and among the least mechanistically understood. The best supported framework is hyperarousal: insomnia is not a deficiency of sleep drive but an excess of arousal that opposes it, and the excess is measurable across autonomic, neuroendocrine, neuroimmune, electrophysiological, and neuroimaging domains, at night AND during the day. That 24-hour character is the framework's strongest claim - a purely nocturnal sleep-generation failure would not predict daytime hyperarousal, and it is why patients so often describe fatigue without sleepiness, and why they perform poorly on objective sleepiness testing in the opposite direction to the hypersomnolence disorders. Recent work locates the vulnerability more specifically in circuits regulating emotion and arousal, rather than in the circadian or homeostatic sleep-regulating circuits, and a large genome-wide analysis is consistent with that: insomnia's genetic architecture correlates substantially with psychiatric traits and implicates striatal, hypothalamic, and claustrum neurons rather than the classical sleep-switch nuclei.

Ask OpenScientist

Ask a research question about Chronic Insomnia Disorder. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

1
Inheritance
5
Pathophys.
3
Phenotypes
2
Gaps
7
Pathograph
1
Genes
2
Medical Actions
🏷

Classifications

Harrison's Part
NEUROLOGIC
👪

Inheritance

1
Complex/Multifactorial HP:0010982
Substantially heritable, polygenic, with no Mendelian form. Risk arises from many small-effect common variants interacting with early-life stress, major life events, and perpetuating behavioural factors - the three-part vulnerability/stressor/perpetuation structure this entry's pathophysiology follows.
Polygenic inheritance
Show evidence (1 reference)
PMID:19481481 SUPPORT Other
"the interplay between a genetic vulnerability for an imbalance between arousing and sleep-inducing brain activity, psychosocial/medical stressors and perpetuating mechanisms"
States the multifactorial architecture - genetic vulnerability plus stressors plus perpetuation - that this inheritance block records.
?

Discussions and Knowledge Gaps

2
Is hyperarousal a mechanism or a description of the disorder's measurements?
KNOWLEDGE GAP gap_hyperarousal_framework_versus_lesion
Hyperarousal organises a large and consistent body of evidence, but it is close to being a restatement of what is measured rather than an explanation of it: to say a patient with insomnia is hyperaroused is not far from saying they cannot sleep. The framework earns its status from two things it does predict - daytime as well as nocturnal elevation, and the subjective-objective discrepancy - but it names no lesion, specifies no causal direction, and has not generated a treatment that acts on it specifically. The locus coeruleus / salience network model is the first proposal specific enough to falsify, and its authors present it as such. Until it or a rival is tested, this entry's central node should be read as the best available organising framework rather than as a mechanism.
Proposed experiments
Locus coeruleus responsiveness during REM sleep in insomnia
exp_lc_rem_responsiveness_insomnia
High-resolution functional imaging or pupillometric assay of locus coeruleus activity during REM sleep in patients with chronic insomnia disorder and matched controls, with salience-network connectivity and overnight change in emotional reactivity as covariates, directly testing the proposed model's central prediction that the locus coeruleus fails to go offline during REM sleep.
What does the persistent gap between reported and polysomnographic sleep measure?
KNOWLEDGE GAP gap_subjective_objective_discrepancy
Patients with chronic insomnia consistently report substantially worse sleep than polysomnography records, and the gap is large, reproducible, and unexplained. How it is read determines what the disorder is taken to be. If the polysomnogram is right, the primary abnormality is one of perception and the disorder is partly a misestimation; if the patient is right, the polysomnogram's scoring conventions are too coarse to capture the cortical arousal that persists within scored sleep - which is what the hyperarousal framework predicts. The second reading also implies that trials using polysomnographic endpoints are measuring the wrong quantity, which would explain why treatments improve reported sleep more than recorded sleep.
Proposed experiments
High-density EEG markers of within-sleep cortical arousal
exp_high_density_eeg_within_sleep_arousal
Simultaneous high-density EEG and standard polysomnography in patients with chronic insomnia and controls, quantifying high-frequency and local arousal activity within conventionally scored sleep epochs, and testing whether that activity - rather than scored sleep time - accounts for the subjective sleep estimate.

Pathophysiology

5
Predisposing Vulnerability in Emotion and Arousal Circuits
The trigger arm, and the level at which the disorder's causes actually sit. Insomnia is substantially heritable, and the largest genome-wide analysis - over 1.3 million individuals, 202 loci - shows enrichment not in circadian or homeostatic sleep machinery but in cortical and subcortical tissues and in striatal, hypothalamic, and claustrum neurons, with considerable genetic correlation with psychiatric traits. Early-life stress, major life events, and brain structural and functional variation contribute alongside. The integrated reading is that vulnerability lies in circuits regulating emotion and arousal rather than in circuits regulating sleep itself - which reframes insomnia as a disorder of arousal regulation that manifests during sleep, rather than as a disorder of sleep.
Show evidence (4 references)
PMID:30804565 SUPPORT Human Clinical
"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."
Identifies the implicated cell types, which are notably not the classical sleep-switch nuclei - the observation that motivates locating vulnerability in arousal and emotion circuits.
PMID:30804565 SUPPORT Human Clinical
"We found considerable genetic correlations with psychiatric traits and sleep duration, and modest correlations with other sleep-related traits."
The asymmetry is the point: insomnia's genetic architecture resembles psychiatric traits more than it resembles other sleep traits, which is direct support for the vulnerability being in emotion-arousal circuits.
PMID:32790576 SUPPORT Other
"the integrated findings suggest that the vulnerability to develop insomnia could rather be found in brain circuits regulating emotion and arousal than in circuits involved in circadian and homeostatic sleep regulation"
States the localisation claim this node encodes, and explicitly excludes the circadian and homeostatic circuits - which is also the basis for this entry's non-conformance to the circadian module.
+ 1 more reference
Persistent 24-Hour Physiological Hyperarousal
The central effector and the disorder's best-established abnormality. Elevated arousal is demonstrable across independent measurement domains - autonomic, neuroendocrine, neuroimmunological, electrophysiological, and neuroimaging - and the convergence across modalities is what makes it robust rather than any single finding. Its critical property is temporal: arousal is elevated during the day as well as at night. That distinguishes insomnia sharply from sleep deprivation, which produces daytime sleepiness, and explains the characteristic complaint of exhaustion without the ability to nap. A specific circuit-level account has been proposed - a locus coeruleus that is abnormally sensitive to, or abnormally driven by, salience-network input, remaining responsive even during REM sleep when it should be silent, so that the overnight adaptation to emotional distress that REM sleep normally provides fails and distress accumulates.
regulation of the sleep/wake cycle GO:0042749 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal regulation of the sleep/wake cycle, annotated with regulation of circadian sleep/wake cycle (GO:0042749). GO:0042749 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Show evidence (3 references)
PMID:19481481 SUPPORT Other
"Autonomous, neuroendocrine, neuroimmunological, electrophysiological and neuroimaging studies demonstrate increased levels of arousal in primary insomnia during both night and daytime."
Gives both the multi-modal convergence and the 24-hour character, which are the two properties this node rests on.
PMID:19481481 SUPPORT Other
"The current review provides substantial support for the concept that hyperarousal processes from the molecular to the higher system level play a key role in the pathophysiology of primary insomnia."
States the framework's central claim and the range of levels at which the evidence sits.
PMID:32790576 SUPPORT Other
"The model proposes that in people with a vulnerability to develop insomnia, the locus coeruleus is more sensitive to-or receives more input from-the salience network and related circuits, even during rapid eye movement sleep, when it should normally be sound asleep."
Cited as PARTIAL because the source explicitly presents this as a testable proposed model rather than an established finding; it is the most specific circuit-level account available and is curated as a proposal.
Perpetuating Behavioural and Cognitive Responses
A learned arm, and the one that turns an episode into a disorder. Once sleep has been disturbed, people respond in ways that are individually reasonable and collectively counterproductive: extending time in bed to "catch up", which dilutes sleep across a longer window and weakens the bed-sleep association; napping; monitoring the clock; and developing sleep-related worry and rumination that raise arousal precisely at bedtime. These perpetuating factors are why chronic insomnia frequently outlives the precipitant that started it, and - crucially - they are the specific targets of cognitive-behavioural therapy, which is why the most effective treatment for this disorder acts on the learned arm rather than on the physiological one.
Show evidence (2 references)
PMID:19481481 SUPPORT Other
"perpetuating mechanisms including dysfunctional sleep-related behavior, learned sleep preventing associations and other cognitive factors like tendency to worry/ruminate"
Names the three components of this node - behaviour, learned association, and cognitive factors - in the model's own terms.
PMID:19481481 SUPPORT Other
"primary insomnia may be conceptualized as a final common pathway resulting from the interplay between a genetic vulnerability for an imbalance between arousing and sleep-inducing brain activity, psychosocial/medical stressors and perpetuating mechanisms"
Establishes the three-part structure this entry's pathophysiology follows - vulnerability, stressor, and perpetuation - and frames the disorder as a final common pathway rather than a single lesion.
Failure of Sleep Initiation and Maintenance
The presenting abnormality: prolonged sleep-onset latency, wakefulness after sleep onset, early-morning awakening, or non-restorative sleep, in any combination and typically shifting between them over time. It is a failure of sleep against adequate opportunity, which is what separates it from insufficient sleep syndrome - the commonest cause of unrefreshing sleep in the population and not this disorder. A persistent discrepancy between subjective and objective measures is characteristic, with patients consistently reporting worse sleep than polysomnography records, and this is a feature of the disorder rather than an artefact to be corrected: it is consistent with the hyperarousal framework, in which cortical arousal persists into physiologically scored sleep.
sleep GO:0030431 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased sleep (GO:0030431). GO:0030431 is a biological process from the Gene Ontology. ↓ DECREASED
Show evidence (1 reference)
PMID:19481481 SUPPORT Other
"Primary insomnia is defined as difficulties in falling asleep, maintaining sleep or non-restorative sleep accompanied by significantly impaired daytime functioning in the absence of a specific physical, mental or substance-related cause."
Gives the definitional content of this node, including the requirement for daytime impairment that distinguishes the disorder from short sleep.
Daytime Impairment and Downstream Health Risk
The clinical endpoint, and the reason insomnia matters beyond the night. Daytime impairment is a diagnostic requirement, not an optional consequence. Beyond it, Mendelian randomisation in the large genetic study identified causal effects of insomnia on depression, diabetes, and cardiovascular disease - which is a stronger form of evidence than the observational associations usually cited, because it is less vulnerable to reverse causation, and matters most for depression, where the direction of effect has long been contested. It should still be read as a genetic-instrument inference and not as a demonstrated clinical effect of treating insomnia.
Show evidence (2 references)
PMID:30804565 SUPPORT Human Clinical
"Mendelian randomization identified the causal effects of insomnia on depression, diabetes, and cardiovascular disease, and the protective effects of educational attainment and intracranial volume."
Provides the causal-inference evidence for the downstream risks at this node, and the direction of effect for depression in particular.
PMID:32790576 SUPPORT Other
"Further supported by the clear mental health risks conveyed by insomnia"
Independently records the mental-health risk associated with the disorder, corroborating the Mendelian randomisation result above.

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Chronic Insomnia Disorder Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.

Phenotypes

3
Nervous System 2
Sleep-Onset Insomnia HP:0031354 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Sleep onset insomnia (HP:0031354), qualified as temporality chronic. HP:0031354 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:19481481 SUPPORT Other
"Primary insomnia is defined as difficulties in falling asleep, maintaining sleep or non-restorative sleep"
One of the three definitional presentations; no frequency band is asserted, since the three forms overlap and shift within individuals over time.
Daytime Functional Impairment OBLIGATE Insomnia HP:0100785 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Insomnia (HP:0100785), qualified as temporality chronic. HP:0100785 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:19481481 SUPPORT Other
"accompanied by significantly impaired daytime functioning in the absence of a specific physical, mental or substance-related cause"
OBLIGATE by definition: significant daytime impairment is part of the diagnostic definition, so every diagnosed patient has it.
Other 1
Sleep-Maintenance Insomnia HP:0031355 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Maintenance insomnia (HP:0031355), qualified as temporality chronic. HP:0031355 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:19481481 SUPPORT Other
"difficulties in falling asleep, maintaining sleep or non-restorative sleep accompanied by significantly impaired daytime functioning"
One of the three definitional presentations, curated with its daytime impairment requirement; no frequency band is asserted.
🧬

Genetic Associations

1
Polygenic architecture (202 loci, no established single gene)
relationship_type: SUSCEPTIBILITY
Show evidence (2 references)
PMID:30804565 SUPPORT Human Clinical
"We identify 202 loci implicating 956 genes through positional, expression quantitative trait loci, and chromatin mapping."
Establishes the scale of the polygenic architecture and the mapping methods behind the implicated gene set.
PMID:30804565 SUPPORT Human Clinical
"The meta-analysis explained 2.6% of the variance."
Cited as PARTIAL to bound the genetic arm: 202 loci in 1.3 million people account for a small fraction of variance, so no individual-level genetic prediction follows and no single gene may be curated as causal.
💊

Medical Actions

2
Cognitive Behavioural Therapy for Insomnia
Action: Behavioral counselingNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Behavioral counseling (NCIT:C181743). NCIT:C181743 is a clinical intervention from the NCI Thesaurus. Ontology label: Behavioral Counseling NCIT:C181743
First-line treatment, and mechanistically the best-matched: its components - sleep restriction, stimulus control, cognitive therapy, relaxation, sleep hygiene - map directly onto the perpetuating node, dismantling the learned associations and compensatory behaviours rather than sedating the arousal. Meta-analysis of randomised trials against inactive comparators shows clinically meaningful improvements in sleep-onset latency, wake after sleep onset, and sleep efficiency, with benefit sustained at later timepoints and no adverse outcomes reported - a profile no hypnotic matches. Note the trade-off the same data reveal: total sleep time improved by only about eight minutes and not significantly, so the treatment works by consolidating and re-associating sleep rather than by producing more of it.
Mechanism Target:
INHIBITS Perpetuating Behavioural and Cognitive Responses — Directly dismantles the learned associations, compensatory time-in-bed extension, and sleep-related worry that perpetuate the disorder.
Show evidence (3 references)
PMID:26054060 SUPPORT Human Clinical
"CBT-i is an effective treatment for adults with chronic insomnia, with clinically meaningful effect sizes."
Meta-analytic conclusion across 20 randomised trials supporting first-line status.
PMID:26054060 SUPPORT Human Clinical
"SOL improved by 19.03 (95% CI, 14.12 to 23.93) minutes, WASO improved by 26.00 (CI, 15.48 to 36.52) minutes, TST improved by 7.61 (CI, -0.51 to 15.74) minutes, and SE% improved by 9.91% (CI, 8.09% to 11.73%)"
Cited as PARTIAL because it qualifies the effect: latency, wakefulness after onset, and efficiency improve, while total sleep time does not significantly increase - the consolidation-not-quantity point in the description.
PMID:26054060 SUPPORT Human Clinical
"Approaches to CBT-i incorporated at least 3 of the following: cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation."
Enumerates the components, which is what allows the treatment to be mapped onto the perpetuating node rather than onto the arousal node.
Dual Orexin Receptor Antagonist (Suvorexant)
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: suvorexant CHEBI:82698 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses suvorexant (CHEBI:82698). CHEBI:82698 is a therapeutic agent from Chemical Entities of Biological Interest.
A hypnotic that reduces arousal drive by blocking orexin receptors, rather than by potentiating GABA-A as the benzodiazepine-receptor agonists do. It acts on the arousal node, which is the node the hyperarousal framework makes central, and is the pharmacological class best matched to that framework. Curated with an explicit caution: its efficacy does NOT indicate an orexin abnormality in these patients, and this entry does not conform to the orexin module on the strength of it. It reduces sleep-onset latency and increases sleep duration objectively and subjectively, with somnolence the commonest adverse effect and no strong rebound or withdrawal signal.
Mechanism Target:
INHIBITS Persistent 24-Hour Physiological Hyperarousal — Blockade of orexin receptors lowers arousal drive at the sleep opportunity, acting on the central effector node rather than on the learned arm.
Show evidence (2 references)
PMID:26937493 SUPPORT Human Clinical
"Suvorexant was shown to decrease sleep onset times and increase sleep duration, whether assessed objectively by polysomnography or subjectively by sleep diaries in primary insomnia patients."
Establishes efficacy on both objective and subjective measures, which matters in a disorder characterised by discrepancy between the two.
PMID:26937493 SUPPORT Human Clinical
"Further studies are required in patients with insomnia comorbid with depression and head-to-head studies with established hypnotics such as zolpidem and eszopiclone."
Cited as PARTIAL because it records what the evidence does not yet establish - comparative efficacy against existing hypnotics, and performance in the comorbid-depression population that is a large share of real patients.
🔬

Diagnosis

2
Clinical diagnosis against explicit criteria, with a sleep diary
Chronic insomnia disorder is a clinical diagnosis: persistent difficulty initiating or maintaining sleep with significant daytime impairment, despite adequate opportunity, for at least three months. A prospective sleep diary over one to two weeks is the core instrument. Which criteria are applied matters more here than in most disorders - see the prevalence record, where four standard criteria sets applied to the same 21,083-person cohort gave prevalences from 8.5% to 23.6%, the difference driven largely by whether daytime impairment is adequately required.
Show evidence (1 reference)
PMID:38718598 SUPPORT Human Clinical
"When looking at each symptom, we found over half the participants classified as having insomnia using the DSM-IV-TR and ICSD-3 criteria did not report having impaired daytime functioning at least three days per week."
Demonstrates that the daytime-impairment requirement is what separates the criteria sets, which is why this entry curates it as an obligate phenotype rather than an associated feature.
Polysomnography only to exclude another disorder
Polysomnography is not indicated for uncomplicated chronic insomnia and does not establish the diagnosis. It is used to exclude a comorbid sleep disorder - sleep-disordered breathing, periodic limb movements - when clinical features suggest one, or when the patient has not responded to adequate treatment. Expect a discrepancy between recorded and reported sleep if it is performed; that gap is characteristic of the disorder rather than evidence against it.
Show evidence (1 reference)
PMID:19481481 SUPPORT Other
"Primary insomnia is defined as difficulties in falling asleep, maintaining sleep or non-restorative sleep accompanied by significantly impaired daytime functioning in the absence of a specific physical, mental or substance-related cause."
The definition is clinical and exclusionary - "in the absence of a specific physical, mental or substance-related cause" - which is what makes polysomnography an exclusion tool rather than a diagnostic one.
📊

Prevalence

4
Tromso Study seventh survey, Norwegian adults aged 40-99 (DSM-5 criteria)
Point Prevalence 8500.0 per 100,000 >1 in 1,000
DSM-5 criteria applied to a 21,083-adult cohort. Curated as the primary record because DSM-5 is the most restrictive of the four criteria sets and the closest to the entity this entry curates - it requires daytime impairment, which is what this entry treats as an obligate phenotype. Recorded as its own record rather than as the low bound of a range: the spread across criteria sets is definitional, not a sampling interval, and encoding it as rate_low/rate_high would invite reading it as a confidence interval.
Show evidence (1 reference)
PMID:38718598 SUPPORT Human Clinical
"We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5 %, ICD-10 9.9 % and ICSD-3 20.0 %."
Gives all four criteria-dependent rates from a single cohort; the DSM-5 figure is the one this record carries.
Tromso Study seventh survey, Norwegian adults aged 40-99 (ICSD-3 criteria)
Point Prevalence 20000.0 per 100,000 >1 in 1,000
The same cohort scored against ICSD-3, the sleep-medicine classification, giving 20.0% - roughly 2.4-fold the DSM-5 figure. The difference is almost entirely the daytime-impairment requirement: over half of those meeting ICSD-3 or DSM-IV-TR criteria did not report impaired daytime functioning at least three days per week. Curated alongside the DSM-5 record so the criteria-dependence is visible as data rather than only as prose.
Show evidence (2 references)
PMID:38718598 SUPPORT Human Clinical
"We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5 %, ICD-10 9.9 % and ICSD-3 20.0 %."
Source of the ICSD-3 figure carried by this record.
PMID:38718598 SUPPORT Human Clinical
"When looking at each symptom, we found over half the participants classified as having insomnia using the DSM-IV-TR and ICSD-3 criteria did not report having impaired daytime functioning at least three days per week."
Identifies the daytime-impairment requirement as the source of the spread between criteria sets, which is what the note asserts.
Tromso Study seventh survey, Norwegian adults aged 40-99 (ICD-10 criteria)
Point Prevalence 9900.0 per 100,000 >1 in 1,000
The same cohort scored against ICD-10, giving 9.9% - close to the DSM-5 figure, and for the same reason: both require daytime consequences.
Show evidence (1 reference)
PMID:38718598 SUPPORT Human Clinical
"We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5 %, ICD-10 9.9 % and ICSD-3 20.0 %."
Source of the ICD-10 figure carried by this record.
Tromso Study seventh survey, Norwegian adults aged 40-99 (DSM-IV-TR criteria)
Point Prevalence 23600.0 per 100,000 >1 in 1,000
The same cohort scored against DSM-IV-TR, giving 23.6% - the highest of the four and nearly three times the DSM-5 figure. Curated so that the full criteria-dependent range is readable from structured fields rather than only from a snippet; DSM-IV-TR is superseded, so this record documents the historical estimate rather than a current one.
Show evidence (2 references)
PMID:38718598 SUPPORT Human Clinical
"We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5 %, ICD-10 9.9 % and ICSD-3 20.0 %."
Source of the DSM-IV-TR figure carried by this record.
PMID:38718598 SUPPORT Human Clinical
"Overall, this study suggests that insomnia prevalence may be overestimated if daytime symptoms are not adequately included in accordance with current guidelines."
Cited as PARTIAL because it qualifies this record rather than supporting it: the authors read the higher criteria-sets, this one included, as overestimates.
{ }

Source YAML

click to show
name: Chronic Insomnia Disorder
creation_date: "2026-08-24T00:00:00Z"
category: Neurological Disorder
parents:
- Sleep Disorder
- Neurological Disease
disease_term:
  preferred_term: insomnia
  term:
    id: MONDO:0013600
    label: insomnia
description: >-
  Chronic insomnia disorder is persistent difficulty initiating or maintaining
  sleep, or non-restorative sleep, together with significant daytime impairment,
  despite adequate opportunity to sleep. It is among the most prevalent
  disorders in medicine and among the least mechanistically understood. The best
  supported framework is hyperarousal: insomnia is not a deficiency of sleep
  drive but an excess of arousal that opposes it, and the excess is measurable
  across autonomic, neuroendocrine, neuroimmune, electrophysiological, and
  neuroimaging domains, at night AND during the day. That 24-hour character is
  the framework's strongest claim - a purely nocturnal sleep-generation failure
  would not predict daytime hyperarousal, and it is why patients so often
  describe fatigue without sleepiness, and why they perform poorly on objective
  sleepiness testing in the opposite direction to the hypersomnolence disorders.
  Recent work locates the vulnerability more specifically in circuits regulating
  emotion and arousal, rather than in the circadian or homeostatic
  sleep-regulating circuits, and a large genome-wide analysis is consistent with
  that:
  insomnia's genetic architecture correlates substantially with psychiatric
  traits and implicates striatal, hypothalamic, and claustrum neurons rather
  than the classical sleep-switch nuclei.
notes: >-
  ONTOLOGY CAVEAT, RECORDED DELIBERATELY. The bound term MONDO:0013600 carries a
  `MONDO:ambiguous` synonym qualifier upstream and cross-references both
  HP:0100785 (the phenotype) and NCIT:C28286. It is therefore the same class of
  term as the one flagged for Rickets in the curation guidance: a single label
  standing for both the symptom and the disorder. It is nonetheless the only
  MONDO term for the concept, and chronic insomnia disorder is a distinct
  clinical entity with its own diagnostic criteria and first-line treatment, so
  the entry is curated with the term bound and the ambiguity noted rather than
  omitted. Curators should not treat every KB use of HP:0100785 as an implicit
  reference to this entry.

  WHAT DOES NOT CONFORM, AND WHY IT MATTERS CLINICALLY. This entry deliberately
  does not conform to circadian_phase_misalignment. The discriminator is
  practical, not theoretical: in a circadian disorder, sleep is structurally
  normal when the patient is allowed to sleep at their own phase, whereas here
  sleep is disturbed at any phase. Delayed sleep-wake phase disorder is
  routinely misdiagnosed as sleep-onset insomnia, and the two have opposite
  treatments - timed light and melatonin versus cognitive-behavioural therapy -
  so the boundary is worth the discipline. Nor does the entry conform to
  orexin_arousal_instability, despite orexin's obvious relevance: dual orexin
  receptor antagonists are an effective insomnia treatment, but pharmacological
  responsiveness of a pathway is not evidence that the pathway is deranged, and
  no orexin-system abnormality has been shown in these patients. That treatment
  is curated as acting on the arousal node, not as evidence of an orexin lesion.

  THE HYPERAROUSAL MODEL IS A FRAMEWORK, NOT A MECHANISM. It organises a large
  and consistent body of measurement, but it does not specify a lesion, and the
  entry curates it accordingly - as the central effector with an explicit
  vulnerability arm above it, rather than as a trigger.
pathophysiology:
- name: Predisposing Vulnerability in Emotion and Arousal Circuits
  description: >-
    The trigger arm, and the level at which the disorder's causes actually sit.
    Insomnia is substantially heritable, and the largest genome-wide analysis -
    over 1.3 million individuals, 202 loci - shows enrichment not in circadian or
    homeostatic sleep machinery but in cortical and subcortical tissues and in
    striatal, hypothalamic, and claustrum neurons, with considerable genetic
    correlation with psychiatric traits. Early-life stress, major life events,
    and brain structural and functional variation contribute alongside. The
    integrated reading is that vulnerability lies in circuits regulating emotion
    and arousal rather than in circuits regulating sleep itself - which
    reframes insomnia as a disorder of arousal regulation that manifests during
    sleep, rather than as a disorder of sleep.
  role: trigger
  biological_scale: ORGANISM
  evidence:
  - reference: PMID:30804565
    reference_title: "Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      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.
    explanation: >-
      Identifies the implicated cell types, which are notably not the classical
      sleep-switch nuclei - the observation that motivates locating vulnerability
      in arousal and emotion circuits.
  - reference: PMID:30804565
    reference_title: "Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We found considerable genetic correlations with psychiatric traits and
      sleep duration, and modest correlations with other sleep-related traits.
    explanation: >-
      The asymmetry is the point: insomnia's genetic architecture resembles
      psychiatric traits more than it resembles other sleep traits, which is
      direct support for the vulnerability being in emotion-arousal circuits.
  - reference: PMID:32790576
    reference_title: "Brain mechanisms of insomnia: new perspectives on causes and consequences."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the integrated findings suggest that the vulnerability to develop insomnia
      could rather be found in brain circuits regulating emotion and arousal than
      in circuits involved in circadian and homeostatic sleep regulation
    explanation: >-
      States the localisation claim this node encodes, and explicitly excludes
      the circadian and homeostatic circuits - which is also the basis for this
      entry's non-conformance to the circadian module.
  - reference: PMID:30804565
    reference_title: "Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The meta-analysis explained 2.6% of the variance.
    explanation: >-
      Cited as PARTIAL to bound the genetic arm: 202 loci in 1.3 million people
      explain 2.6% of variance, so the genetics identify implicated circuits
      without accounting for individual risk.
  downstream:
  - target: Persistent 24-Hour Physiological Hyperarousal
    description: >-
      Sensitised emotion-arousal circuitry, interacting with stressors, produces
      a sustained elevation of arousal that is present day and night.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES

- name: Persistent 24-Hour Physiological Hyperarousal
  description: >-
    The central effector and the disorder's best-established abnormality.
    Elevated arousal is demonstrable across independent measurement domains -
    autonomic, neuroendocrine, neuroimmunological, electrophysiological, and
    neuroimaging - and the convergence across modalities is what makes it robust
    rather than any single finding. Its critical property is temporal: arousal is
    elevated during the day as well as at night. That distinguishes insomnia
    sharply from sleep deprivation, which produces daytime sleepiness, and
    explains the characteristic complaint of exhaustion without the ability to
    nap. A specific circuit-level account has been proposed - a locus coeruleus
    that is abnormally sensitive to, or abnormally driven by, salience-network
    input, remaining responsive even during REM sleep when it should be silent,
    so that the overnight adaptation to emotional distress that REM sleep
    normally provides fails and distress accumulates.
  role: central_effector
  biological_scale: ORGANISM
  biological_processes:
  - preferred_term: regulation of the sleep/wake cycle
    term:
      id: GO:0042749
      label: regulation of circadian sleep/wake cycle
    modifier: ABNORMAL
  evidence:
  - reference: PMID:19481481
    reference_title: "The hyperarousal model of insomnia: a review of the concept and its evidence."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Autonomous, neuroendocrine, neuroimmunological, electrophysiological and
      neuroimaging studies demonstrate increased levels of arousal in primary
      insomnia during both night and daytime.
    explanation: >-
      Gives both the multi-modal convergence and the 24-hour character, which are
      the two properties this node rests on.
  - reference: PMID:19481481
    reference_title: "The hyperarousal model of insomnia: a review of the concept and its evidence."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The current review provides substantial support for the concept that
      hyperarousal processes from the molecular to the higher system level play a
      key role in the pathophysiology of primary insomnia.
    explanation: >-
      States the framework's central claim and the range of levels at which the
      evidence sits.
  - reference: PMID:32790576
    reference_title: "Brain mechanisms of insomnia: new perspectives on causes and consequences."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The model proposes that in people with a vulnerability to develop insomnia,
      the locus coeruleus is more sensitive to-or receives more input from-the
      salience network and related circuits, even during rapid eye movement
      sleep, when it should normally be sound asleep.
    explanation: >-
      Cited as PARTIAL because the source explicitly presents this as a testable
      proposed model rather than an established finding; it is the most specific
      circuit-level account available and is curated as a proposal.
  downstream:
  - target: Failure of Sleep Initiation and Maintenance
    description: >-
      Arousal that persists into the sleep opportunity opposes sleep onset and
      permits repeated awakenings.
    causal_link_type: DIRECT
  - target: Perpetuating Behavioural and Cognitive Responses
    description: >-
      Disturbed sleep provokes compensatory behaviour and sleep-related worry,
      which are learned rather than physiological.
    causal_link_type: DIRECT

- name: Perpetuating Behavioural and Cognitive Responses
  description: >-
    A learned arm, and the one that turns an episode into a disorder. Once sleep
    has been disturbed, people respond in ways that are individually reasonable
    and collectively counterproductive: extending time in bed to "catch up",
    which dilutes sleep across a longer window and weakens the bed-sleep
    association; napping; monitoring the clock; and developing sleep-related
    worry and rumination that raise arousal precisely at bedtime. These
    perpetuating factors are why chronic insomnia frequently outlives the
    precipitant that started it, and - crucially - they are the specific targets
    of cognitive-behavioural therapy, which is why the most effective treatment
    for this disorder acts on the learned arm rather than on the physiological
    one.
  role: amplifier
  biological_scale: ORGANISM
  evidence:
  - reference: PMID:19481481
    reference_title: "The hyperarousal model of insomnia: a review of the concept and its evidence."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      perpetuating mechanisms including dysfunctional sleep-related behavior,
      learned sleep preventing associations and other cognitive factors like
      tendency to worry/ruminate
    explanation: >-
      Names the three components of this node - behaviour, learned association,
      and cognitive factors - in the model's own terms.
  - reference: PMID:19481481
    reference_title: "The hyperarousal model of insomnia: a review of the concept and its evidence."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      primary insomnia may be conceptualized as a final common pathway resulting
      from the interplay between a genetic vulnerability for an imbalance between
      arousing and sleep-inducing brain activity, psychosocial/medical stressors
      and perpetuating mechanisms
    explanation: >-
      Establishes the three-part structure this entry's pathophysiology follows -
      vulnerability, stressor, and perpetuation - and frames the disorder as a
      final common pathway rather than a single lesion.
  downstream:
  - target: Failure of Sleep Initiation and Maintenance
    description: >-
      Learned associations and sleep-related worry raise arousal at the sleep
      opportunity, reinforcing the failure that produced them.
    causal_link_type: DIRECT

- name: Failure of Sleep Initiation and Maintenance
  description: >-
    The presenting abnormality: prolonged sleep-onset latency, wakefulness after
    sleep onset, early-morning awakening, or non-restorative sleep, in any
    combination and typically shifting between them over time. It is a failure of
    sleep against adequate opportunity, which is what separates it from
    insufficient sleep syndrome - the commonest cause of unrefreshing sleep in
    the population and not this disorder. A persistent discrepancy between
    subjective and objective measures is characteristic, with patients
    consistently reporting worse sleep than polysomnography records, and this is
    a feature of the disorder rather than an artefact to be corrected: it is
    consistent with the hyperarousal framework, in which cortical arousal
    persists into physiologically scored sleep.
  role: effector
  biological_scale: ORGANISM
  biological_processes:
  - preferred_term: sleep
    term:
      id: GO:0030431
      label: sleep
    modifier: DECREASED
  evidence:
  - reference: PMID:19481481
    reference_title: "The hyperarousal model of insomnia: a review of the concept and its evidence."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Primary insomnia is defined as difficulties in falling asleep, maintaining
      sleep or non-restorative sleep accompanied by significantly impaired
      daytime functioning in the absence of a specific physical, mental or
      substance-related cause.
    explanation: >-
      Gives the definitional content of this node, including the requirement for
      daytime impairment that distinguishes the disorder from short sleep.
  downstream:
  - target: Daytime Impairment and Downstream Health Risk
    description: >-
      Disturbed sleep with sustained hyperarousal produces daytime functional
      impairment and, over time, downstream psychiatric and cardiometabolic risk.
    causal_link_type: DIRECT

- name: Daytime Impairment and Downstream Health Risk
  description: >-
    The clinical endpoint, and the reason insomnia matters beyond the night.
    Daytime impairment is a diagnostic requirement, not an optional consequence.
    Beyond it, Mendelian randomisation in the large genetic study identified
    causal effects of insomnia on depression, diabetes, and cardiovascular
    disease - which is a stronger form of evidence than the observational
    associations usually cited, because it is less vulnerable to reverse
    causation, and matters most for depression, where the direction of effect has
    long been contested. It should still be read as a genetic-instrument
    inference and not as a demonstrated clinical effect of treating insomnia.
  role: consequence
  biological_scale: ORGANISM
  evidence:
  - reference: PMID:30804565
    reference_title: "Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Mendelian randomization identified the causal effects of insomnia on
      depression, diabetes, and cardiovascular disease, and the protective effects
      of educational attainment and intracranial volume.
    explanation: >-
      Provides the causal-inference evidence for the downstream risks at this
      node, and the direction of effect for depression in particular.
  - reference: PMID:32790576
    reference_title: "Brain mechanisms of insomnia: new perspectives on causes and consequences."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Further supported by the clear mental health risks conveyed by insomnia
    explanation: >-
      Independently records the mental-health risk associated with the disorder,
      corroborating the Mendelian randomisation result above.
phenotypes:
- category: Neurological
  name: Sleep-Onset Insomnia
  description: >-
    Prolonged latency to sleep onset despite adequate opportunity and an
    appropriate sleep environment.
  phenotype_term:
    preferred_term: Sleep onset insomnia
    term:
      id: HP:0031354
      label: Sleep onset insomnia
    temporality: CHRONIC
  evidence:
  - reference: PMID:19481481
    reference_title: "The hyperarousal model of insomnia: a review of the concept and its evidence."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Primary insomnia is defined as difficulties in falling asleep, maintaining
      sleep or non-restorative sleep
    explanation: >-
      One of the three definitional presentations; no frequency band is asserted,
      since the three forms overlap and shift within individuals over time.
- category: Neurological
  name: Sleep-Maintenance Insomnia
  description: >-
    Repeated or prolonged awakenings after sleep onset, with difficulty returning
    to sleep.
  phenotype_term:
    preferred_term: Maintenance insomnia
    term:
      id: HP:0031355
      label: Maintenance insomnia
    temporality: CHRONIC
  evidence:
  - reference: PMID:19481481
    reference_title: "The hyperarousal model of insomnia: a review of the concept and its evidence."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      difficulties in falling asleep, maintaining sleep or non-restorative sleep
      accompanied by significantly impaired daytime functioning
    explanation: >-
      One of the three definitional presentations, curated with its daytime
      impairment requirement; no frequency band is asserted.
- category: Neurological
  name: Daytime Functional Impairment
  description: >-
    Fatigue, impaired attention and concentration, mood disturbance, and reduced
    performance attributable to the sleep disturbance. A required criterion
    rather than an associated feature, and characteristically experienced as
    fatigue without sleepiness.
  phenotype_term:
    preferred_term: Insomnia
    term:
      id: HP:0100785
      label: Insomnia
    temporality: CHRONIC
  frequency: OBLIGATE
  evidence:
  - reference: PMID:19481481
    reference_title: "The hyperarousal model of insomnia: a review of the concept and its evidence."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      accompanied by significantly impaired daytime functioning in the absence of
      a specific physical, mental or substance-related cause
    explanation: >-
      OBLIGATE by definition: significant daytime impairment is part of the
      diagnostic definition, so every diagnosed patient has it.
treatments:
- name: Cognitive Behavioural Therapy for Insomnia
  description: >-
    First-line treatment, and mechanistically the best-matched: its components -
    sleep restriction, stimulus control, cognitive therapy, relaxation, sleep
    hygiene - map directly onto the perpetuating node, dismantling the learned
    associations and compensatory behaviours rather than sedating the arousal.
    Meta-analysis of randomised trials against inactive comparators shows
    clinically meaningful improvements in sleep-onset latency, wake after sleep
    onset, and sleep efficiency, with benefit sustained at later timepoints and
    no adverse outcomes reported - a profile no hypnotic matches. Note the
    trade-off the same data reveal: total sleep time improved by only about eight
    minutes and not significantly, so the treatment works by consolidating and
    re-associating sleep rather than by producing more of it.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: Behavioral counseling
    term:
      id: NCIT:C181743
      label: Behavioral Counseling
  target_mechanisms:
  - target: Perpetuating Behavioural and Cognitive Responses
    treatment_effect: INHIBITS
    description: >-
      Directly dismantles the learned associations, compensatory time-in-bed
      extension, and sleep-related worry that perpetuate the disorder.
  evidence:
  - reference: PMID:26054060
    reference_title: "Cognitive Behavioral Therapy for Chronic Insomnia: A Systematic Review and Meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      CBT-i is an effective treatment for adults with chronic insomnia, with
      clinically meaningful effect sizes.
    explanation: >-
      Meta-analytic conclusion across 20 randomised trials supporting first-line
      status.
  - reference: PMID:26054060
    reference_title: "Cognitive Behavioral Therapy for Chronic Insomnia: A Systematic Review and Meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      SOL improved by 19.03 (95% CI, 14.12 to 23.93) minutes, WASO improved by
      26.00 (CI, 15.48 to 36.52) minutes, TST improved by 7.61 (CI, -0.51 to
      15.74) minutes, and SE% improved by 9.91% (CI, 8.09% to 11.73%)
    explanation: >-
      Cited as PARTIAL because it qualifies the effect: latency, wakefulness
      after onset, and efficiency improve, while total sleep time does not
      significantly increase - the consolidation-not-quantity point in the
      description.
  - reference: PMID:26054060
    reference_title: "Cognitive Behavioral Therapy for Chronic Insomnia: A Systematic Review and Meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Approaches to CBT-i incorporated at least 3 of the following: cognitive
      therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation.
    explanation: >-
      Enumerates the components, which is what allows the treatment to be mapped
      onto the perpetuating node rather than onto the arousal node.
- name: Dual Orexin Receptor Antagonist (Suvorexant)
  description: >-
    A hypnotic that reduces arousal drive by blocking orexin receptors, rather
    than by potentiating GABA-A as the benzodiazepine-receptor agonists do. It
    acts on the arousal node, which is the node the hyperarousal framework makes
    central, and is the pharmacological class best matched to that framework.
    Curated with an explicit caution: its efficacy does NOT indicate an orexin
    abnormality in these patients, and this entry does not conform to the orexin
    module on the strength of it. It reduces sleep-onset latency and increases
    sleep duration objectively and subjectively, with somnolence the commonest
    adverse effect and no strong rebound or withdrawal signal.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: suvorexant
      term:
        id: CHEBI:82698
        label: suvorexant
  target_mechanisms:
  - target: Persistent 24-Hour Physiological Hyperarousal
    treatment_effect: INHIBITS
    description: >-
      Blockade of orexin receptors lowers arousal drive at the sleep opportunity,
      acting on the central effector node rather than on the learned arm.
  evidence:
  - reference: PMID:26937493
    reference_title: "Suvorexant: efficacy and safety profile of a dual orexin receptor antagonist in treating insomnia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Suvorexant was shown to decrease sleep onset times and increase sleep
      duration, whether assessed objectively by polysomnography or subjectively
      by sleep diaries in primary insomnia patients.
    explanation: >-
      Establishes efficacy on both objective and subjective measures, which
      matters in a disorder characterised by discrepancy between the two.
  - reference: PMID:26937493
    reference_title: "Suvorexant: efficacy and safety profile of a dual orexin receptor antagonist in treating insomnia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Further studies are required in patients with insomnia comorbid with
      depression and head-to-head studies with established hypnotics such as
      zolpidem and eszopiclone.
    explanation: >-
      Cited as PARTIAL because it records what the evidence does not yet
      establish - comparative efficacy against existing hypnotics, and
      performance in the comorbid-depression population that is a large share of
      real patients.
genetic:
- name: Polygenic architecture (202 loci, no established single gene)
  notes: >-
    Insomnia is substantially heritable but has no Mendelian form and no
    established causal gene. The largest genome-wide analysis - 1,331,010
    individuals - identified 202 loci implicating 956 genes through positional,
    eQTL, and chromatin mapping, and the meta-analysis explained 2.6% of the
    variance. Curated as an architecture rather than as a gene list because no
    individual locus is established as causal and none is clinically actionable.
    The informative signal is where the enrichment sits: cortical and subcortical
    tissue and striatal, hypothalamic, and claustrum neurons, with considerable
    genetic correlation to psychiatric traits - which is what locates the
    vulnerability in emotion-arousal rather than sleep-regulatory circuits.
  relationship_type: SUSCEPTIBILITY
  evidence:
  - reference: PMID:30804565
    reference_title: "Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We identify 202 loci implicating 956 genes through positional, expression
      quantitative trait loci, and chromatin mapping.
    explanation: >-
      Establishes the scale of the polygenic architecture and the mapping methods
      behind the implicated gene set.
  - reference: PMID:30804565
    reference_title: "Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The meta-analysis explained 2.6% of the variance.
    explanation: >-
      Cited as PARTIAL to bound the genetic arm: 202 loci in 1.3 million people
      account for a small fraction of variance, so no individual-level genetic
      prediction follows and no single gene may be curated as causal.
inheritance:
- name: Complex/Multifactorial
  inheritance_term:
    preferred_term: Polygenic inheritance
    term:
      id: HP:0010982
      label: Polygenic inheritance
  description: >-
    Substantially heritable, polygenic, with no Mendelian form. Risk arises from
    many small-effect common variants interacting with early-life stress, major
    life events, and perpetuating behavioural factors - the three-part
    vulnerability/stressor/perpetuation structure this entry's pathophysiology
    follows.
  evidence:
  - reference: PMID:19481481
    reference_title: "The hyperarousal model of insomnia: a review of the concept and its evidence."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the interplay between a genetic vulnerability for an imbalance between
      arousing and sleep-inducing brain activity, psychosocial/medical stressors
      and perpetuating mechanisms
    explanation: >-
      States the multifactorial architecture - genetic vulnerability plus
      stressors plus perpetuation - that this inheritance block records.
diagnosis:
- name: Clinical diagnosis against explicit criteria, with a sleep diary
  description: >-
    Chronic insomnia disorder is a clinical diagnosis: persistent difficulty
    initiating or maintaining sleep with significant daytime impairment, despite
    adequate opportunity, for at least three months. A prospective sleep diary
    over one to two weeks is the core instrument. Which criteria are applied
    matters more here than in most disorders - see the prevalence record, where
    four standard criteria sets applied to the same 21,083-person cohort gave
    prevalences from 8.5% to 23.6%, the difference driven largely by whether
    daytime impairment is adequately required.
  evidence:
  - reference: PMID:38718598
    reference_title: "Prevalence of insomnia in a general adult population cohort using different diagnostic criteria: The seventh survey of the Tromsø study 2015-2016."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      When looking at each symptom, we found over half the participants
      classified as having insomnia using the DSM-IV-TR and ICSD-3 criteria did
      not report having impaired daytime functioning at least three days per week.
    explanation: >-
      Demonstrates that the daytime-impairment requirement is what separates the
      criteria sets, which is why this entry curates it as an obligate phenotype
      rather than an associated feature.
- name: Polysomnography only to exclude another disorder
  description: >-
    Polysomnography is not indicated for uncomplicated chronic insomnia and does
    not establish the diagnosis. It is used to exclude a comorbid sleep disorder
    - sleep-disordered breathing, periodic limb movements - when clinical
    features suggest one, or when the patient has not responded to adequate
    treatment. Expect a discrepancy between recorded and reported sleep if it is
    performed; that gap is characteristic of the disorder rather than evidence
    against it.
  evidence:
  - reference: PMID:19481481
    reference_title: "The hyperarousal model of insomnia: a review of the concept and its evidence."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Primary insomnia is defined as difficulties in falling asleep, maintaining
      sleep or non-restorative sleep accompanied by significantly impaired
      daytime functioning in the absence of a specific physical, mental or
      substance-related cause.
    explanation: >-
      The definition is clinical and exclusionary - "in the absence of a specific
      physical, mental or substance-related cause" - which is what makes
      polysomnography an exclusion tool rather than a diagnostic one.
prevalence:
- population: Tromso Study seventh survey, Norwegian adults aged 40-99 (DSM-5 criteria)
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 8500.0
  notes: >-
    DSM-5 criteria applied to a 21,083-adult cohort. Curated as the primary
    record because DSM-5 is the most restrictive of the four criteria sets and
    the closest to the entity this entry curates - it requires daytime
    impairment, which is what this entry treats as an obligate phenotype.
    Recorded as its own record rather than as the low bound of a range: the
    spread across criteria sets is definitional, not a sampling interval, and
    encoding it as rate_low/rate_high would invite reading it as a confidence
    interval.
  evidence:
  - reference: PMID:38718598
    reference_title: "Prevalence of insomnia in a general adult population cohort using different diagnostic criteria: The seventh survey of the Tromsø study 2015-2016."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5
      %, ICD-10 9.9 % and ICSD-3 20.0 %.
    explanation: >-
      Gives all four criteria-dependent rates from a single cohort; the DSM-5
      figure is the one this record carries.
- population: Tromso Study seventh survey, Norwegian adults aged 40-99 (ICSD-3 criteria)
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 20000.0
  notes: >-
    The same cohort scored against ICSD-3, the sleep-medicine classification,
    giving 20.0% - roughly 2.4-fold the DSM-5 figure. The difference is almost
    entirely the daytime-impairment requirement: over half of those meeting
    ICSD-3 or DSM-IV-TR criteria did not report impaired daytime functioning at
    least three days per week. Curated alongside the DSM-5 record so the
    criteria-dependence is visible as data rather than only as prose.
  evidence:
  - reference: PMID:38718598
    reference_title: "Prevalence of insomnia in a general adult population cohort using different diagnostic criteria: The seventh survey of the Tromsø study 2015-2016."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5
      %, ICD-10 9.9 % and ICSD-3 20.0 %.
    explanation: >-
      Source of the ICSD-3 figure carried by this record.
  - reference: PMID:38718598
    reference_title: "Prevalence of insomnia in a general adult population cohort using different diagnostic criteria: The seventh survey of the Tromsø study 2015-2016."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      When looking at each symptom, we found over half the participants
      classified as having insomnia using the DSM-IV-TR and ICSD-3 criteria did
      not report having impaired daytime functioning at least three days per week.
    explanation: >-
      Identifies the daytime-impairment requirement as the source of the spread
      between criteria sets, which is what the note asserts.
- population: Tromso Study seventh survey, Norwegian adults aged 40-99 (ICD-10 criteria)
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 9900.0
  notes: >-
    The same cohort scored against ICD-10, giving 9.9% - close to the DSM-5
    figure, and for the same reason: both require daytime consequences.
  evidence:
  - reference: PMID:38718598
    reference_title: "Prevalence of insomnia in a general adult population cohort using different diagnostic criteria: The seventh survey of the Tromsø study 2015-2016."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5
      %, ICD-10 9.9 % and ICSD-3 20.0 %.
    explanation: >-
      Source of the ICD-10 figure carried by this record.
- population: Tromso Study seventh survey, Norwegian adults aged 40-99 (DSM-IV-TR criteria)
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 23600.0
  notes: >-
    The same cohort scored against DSM-IV-TR, giving 23.6% - the highest of the
    four and nearly three times the DSM-5 figure. Curated so that the full
    criteria-dependent range is readable from structured fields rather than only
    from a snippet; DSM-IV-TR is superseded, so this record documents the
    historical estimate rather than a current one.
  evidence:
  - reference: PMID:38718598
    reference_title: "Prevalence of insomnia in a general adult population cohort using different diagnostic criteria: The seventh survey of the Tromsø study 2015-2016."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5
      %, ICD-10 9.9 % and ICSD-3 20.0 %.
    explanation: >-
      Source of the DSM-IV-TR figure carried by this record.
  - reference: PMID:38718598
    reference_title: "Prevalence of insomnia in a general adult population cohort using different diagnostic criteria: The seventh survey of the Tromsø study 2015-2016."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Overall, this study suggests that insomnia prevalence may be overestimated
      if daytime symptoms are not adequately included in accordance with current
      guidelines.
    explanation: >-
      Cited as PARTIAL because it qualifies this record rather than supporting
      it: the authors read the higher criteria-sets, this one included, as
      overestimates.
classifications:
  harrisons_chapter:
  - classification_value: NEUROLOGIC
    evidence:
    - reference: PMID:32790576
      reference_title: "Brain mechanisms of insomnia: new perspectives on causes and consequences."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        While insomnia is the second most common mental disorder, progress in our
        understanding of underlying neurobiological mechanisms has been limited.
      explanation: >-
        Classified under the nervous-system chapter as a disorder of brain
        arousal regulation; note the source's own framing as a mental disorder,
        which reflects the genuine overlap this entry's vulnerability node
        records.
discussions:
- discussion_id: gap_hyperarousal_framework_versus_lesion
  kind: KNOWLEDGE_GAP
  prompt: >-
    Is hyperarousal a mechanism or a description of the disorder's measurements?
  attaches_to:
  - pathophysiology#Persistent 24-Hour Physiological Hyperarousal
  rationale: >-
    Hyperarousal organises a large and consistent body of evidence, but it is
    close to being a restatement of what is measured rather than an explanation
    of it: to say a patient with insomnia is hyperaroused is not far from saying
    they cannot sleep. The framework earns its status from two things it does
    predict - daytime as well as nocturnal elevation, and the
    subjective-objective discrepancy - but it names no lesion, specifies no
    causal direction, and has not generated a treatment that acts on it
    specifically. The locus coeruleus / salience network model is the first
    proposal specific enough to falsify, and its authors present it as such. Until
    it or a rival is tested, this entry's central node should be read as the best
    available organising framework rather than as a mechanism.
  proposed_experiments:
  - experiment_id: exp_lc_rem_responsiveness_insomnia
    name: Locus coeruleus responsiveness during REM sleep in insomnia
    description: >-
      High-resolution functional imaging or pupillometric assay of locus
      coeruleus activity during REM sleep in patients with chronic insomnia
      disorder and matched controls, with salience-network connectivity and
      overnight change in emotional reactivity as covariates, directly testing
      the proposed model's central prediction that the locus coeruleus fails to
      go offline during REM sleep.
- discussion_id: gap_subjective_objective_discrepancy
  kind: KNOWLEDGE_GAP
  prompt: >-
    What does the persistent gap between reported and polysomnographic sleep
    measure?
  attaches_to:
  - pathophysiology#Failure of Sleep Initiation and Maintenance
  rationale: >-
    Patients with chronic insomnia consistently report substantially worse sleep
    than polysomnography records, and the gap is large, reproducible, and
    unexplained. How it is read determines what the disorder is taken to be. If
    the polysomnogram is right, the primary abnormality is one of perception and
    the disorder is partly a misestimation; if the patient is right, the
    polysomnogram's scoring conventions are too coarse to capture the cortical
    arousal that persists within scored sleep - which is what the hyperarousal
    framework predicts. The second reading also implies that trials using
    polysomnographic endpoints are measuring the wrong quantity, which would
    explain why treatments improve reported sleep more than recorded sleep.
  proposed_experiments:
  - experiment_id: exp_high_density_eeg_within_sleep_arousal
    name: High-density EEG markers of within-sleep cortical arousal
    description: >-
      Simultaneous high-density EEG and standard polysomnography in patients with
      chronic insomnia and controls, quantifying high-frequency and local
      arousal activity within conventionally scored sleep epochs, and testing
      whether that activity - rather than scored sleep time - accounts for the
      subjective sleep estimate.