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6
Pathophys.
4
Phenotypes
11
Pathograph
2
Treatments
4
Differentials
2
Datasets
4
Trials
1
Deep Research

Pathophysiology

6
Traumatic Stress Exposure
Exposure to psychologically threatening or horrific traumatic events is the initiating environmental context required for PTSD.
response to stress link ⚠ ABNORMAL
Show evidence (1 reference)
DOI:10.1192/bja.2024.27 SUPPORT Other
"Given ongoing debate, the article proposes that trauma exposure is best defined in future iterations of the DSM and ICD as exposure to one or more psychologically threatening or horrific experiences that are overwhelming."
The diagnostic review supports traumatic exposure as the initiating context for PTSD assessment.
Polygenic Susceptibility to PTSD after Trauma
Common-variant genetic liability increases the probability of probable PTSD after traumatic injury, but does not by itself cause PTSD without a trauma context. PTSD genetic liability overlaps with genetic risk for other neurodegenerative conditions including REM sleep behavior disorder, suggesting shared genetic mechanisms underlying trauma response and neurodegenerative risk.
Show evidence (3 references)
DOI:10.1038/s41398-023-02313-9 SUPPORT Human Clinical
"We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients."
Prospective trauma-center cohort data support inherited liability as a post-trauma PTSD risk modifier.
DOI:10.1038/s41398-023-02313-9 SUPPORT Human Clinical
"The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80–7.65) than in the lowest PTSD-PRS quintile."
A PTSD polygenic risk score predicted probable PTSD after mild traumatic brain injury.
PMID:42168223 SUPPORT Human Clinical
"While not supporting a causal relationship, genetic analyses revealed a significant association between PTSD and iRBD, consistent with the exploratory imaging substudy. These findings suggest that individuals genetically at risk for PTSD may also be at higher risk for iRBD."
Genome-wide genetic analyses support shared genetic predisposition between PTSD and isolated REM sleep behavior disorder, with implications for understanding both psychiatric and neurodegenerative disease mechanisms.
Epigenetic Stress-Response Regulation
Trauma and other environmental stressors are associated with epigenetic mechanisms affecting HPA-axis, neurotrophic, neurotransmitter, and immune systems relevant to PTSD.
chromatin organization link ⚠ ABNORMAL
Show evidence (2 references)
DOI:10.1159/000541822 SUPPORT Human Clinical
"Studies show that environmental stressors can induce various epigenetic changes that shape the PTSD phenotype."
Review evidence supports environmentally induced epigenetic regulation as a PTSD susceptibility and phenotype mechanism.
DOI:10.1159/000541822 SUPPORT Human Clinical
"This review investigated gene methylation changes in association with PTSD, including those related to the hypothalamic-pituitary-adrenal axis, brain-derived neurotrophic factor, neurotransmitters, and immune system functioning, as well as the role of histones and regulatory noncoding RNAs."
The reviewed molecular systems map directly to HPA, neurotransmission, and immune pathophysiology nodes.
HPA-Axis Regulation Alteration
PTSD is associated with altered hypothalamic-pituitary-adrenal axis regulation, including lower morning and 24-hour cortisol in meta-analysis, though moderator patterns are inconsistent.
response to stress link ⚠ ABNORMAL
hypothalamus link pituitary gland link adrenal gland link
Show evidence (1 reference)
PMID:30790632 SUPPORT Human Clinical
"Morning and 24 h cortisol were significantly lower in PTSD than in controls (g = -0.21; 95% CI: -0.42-(-0.01); g = -0.31; CI: -0.60-(-0.03))."
Meta-analysis supports lower cortisol measures in PTSD compared with controls.
Neuroimmune Activation
PTSD is associated with peripheral inflammatory markers and immune-system changes that may affect brain circuits involved in fear, anxiety, and emotion regulation.
microglial cell link astrocyte link
inflammatory response link ↑ INCREASED cytokine production link ↑ INCREASED cytokine-mediated signaling pathway link ⚠ ABNORMAL
amygdala link hippocampal formation link prefrontal cortex link
Show evidence (2 references)
PMID:35927237 SUPPORT Human Clinical
"some individuals with PTSD also exhibit elevated concentrations of inflammatory markers, including C-reactive protein, interleukin-6, and tumor necrosis factor-α."
Review evidence supports inflammatory-marker elevation in a subset of individuals with PTSD.
PMID:31991875 SUPPORT Human Clinical
"Major findings included elevated levels of serum proinflammatory cytokines in individuals with PTSD across various trauma types, as compared with those without PTSD."
Structured review evidence supports increased proinflammatory cytokines across trauma contexts.
Threat-Circuit and Fear-Extinction Dysregulation
Altered amygdala, hippocampal, and prefrontal cortical function affects threat detection, emotional regulation, fear reactivity, and traumatic memory processing.
neuron link
learning link ⚠ ABNORMAL memory link ⚠ ABNORMAL modulation of chemical synaptic transmission link ⚠ ABNORMAL
amygdala link hippocampal formation link prefrontal cortex link
Show evidence (1 reference)
PMID:31991875 SUPPORT Human Clinical
"particular brain regions may be identifiable as neural correlates of PTSD, including the prefrontal cortex, hippocampus, and amygdala of the brain."
Review evidence supports amygdala-hippocampal-prefrontal circuitry as a PTSD-relevant neurobiological substrate.

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Post-Traumatic Stress 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

4
Nervous System 2
Hyperarousal and Anxiety Anxiety (HP:0000739)
Show evidence (1 reference)
DOI:10.1192/bja.2024.27 SUPPORT Other
"the clinical presentation of PTSDs; psychological models of PTSDs; how to approach assessment and differential diagnosis"
The diagnostic review supports clinical presentation and assessment of PTSD symptom clusters, including arousal and threat-related symptoms.
Depressive Symptoms Depression (HP:0000716)
Show evidence (1 reference)
DOI:10.1136/gpsych-2023-101438 SUPPORT Human Clinical
"We estimated a prevalence of 23.70% (95% CI 19.50% to 28.40%) for PTSD symptoms and 25.60% (95% CI 20.70% to 31.10%) for depressive features among war-afflicted civilians."
Meta-analysis supports frequent depressive features in a high-risk PTSD context.
Other 2
Intrusive Re-experiencing
Show evidence (1 reference)
DOI:10.1159/000541822 SUPPORT Human Clinical
"PTSD is characterized by nightmares, flashbacks and avoidance of stressors."
Review abstract supports nightmares and flashbacks as PTSD symptom features.
Avoidance of Trauma Reminders
Show evidence (1 reference)
DOI:10.1159/000541822 SUPPORT Human Clinical
"PTSD is characterized by nightmares, flashbacks and avoidance of stressors."
The abstract identifies avoidance as a core PTSD symptom feature.
💊

Treatments

2
Trauma-focused psychotherapy
Action: cognitive behavior therapy MAXO:0000883
First-line trauma-focused psychotherapies for PTSD include exposure therapy such as prolonged exposure, cognitive processing therapy, trauma-focused cognitive behavioral therapy, EMDR, and narrative exposure therapy.
Target Phenotypes: Intrusive re-experiencing Avoidance of trauma reminders Anxiety
Show evidence (2 references)
PMID:26574151 SUPPORT Human Clinical
"Evidence supports efficacy of exposure therapy (high SOE) including the manualized version Prolonged Exposure (PE); cognitive therapy (CT), cognitive processing therapy (CPT), cognitive behavioral therapy (CBT)-mixed therapies (moderate SOE); eye movement desensitization and reprocessing (EMDR)..."
Systematic review evidence supports trauma-focused psychotherapy options including PE, CPT, CBT-based therapies, EMDR, and narrative exposure therapy for adults with PTSD.
PMID:35044471 SUPPORT Human Clinical
"This randomized clinical trial found that although PE was statistically more effective than CPT, the difference was not clinically significant, and improvements in PTSD were meaningful in both treatment groups."
A large randomized trial supports both prolonged exposure and cognitive processing therapy as effective PTSD psychotherapies.
Serotonergic antidepressant pharmacotherapy
Action: Pharmacotherapy NCIT:C15986
Agent: sertraline paroxetine venlafaxine
SSRI and SNRI pharmacotherapy can be used for PTSD symptom reduction, including sertraline, paroxetine, and venlafaxine.
Target Phenotypes: Anxiety
Show evidence (1 reference)
PMID:34992738 SUPPORT Human Clinical
"For individual monotherapy agents compared to placebo in two or more studies, we found small statistically significant evidence for the antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the antipsychotic quetiapine."
Systematic review and meta-analysis evidence supports several antidepressant monotherapies for reducing PTSD symptom severity, including paroxetine, sertraline, and venlafaxine.
🔀

Differential Diagnoses

4

Conditions with similar clinical presentations that must be differentiated from Post-Traumatic Stress Disorder:

Acute stress disorder Not Yet Curated MONDO:0003763
Overlapping Features Acute stress disorder is considered when trauma-related symptoms occur in the immediate post-trauma period before persistence thresholds for PTSD are met.
Show evidence (1 reference)
DOI:10.1002/jts.23013 SUPPORT Other
"The 2023 Department of Veterans Affairs /Department of Defense Clinical Practice Guideline for Management of Posttraumatic Stress Disorder and Acute Stress Disorder is described herein."
The guideline covers PTSD and acute stress disorder together, supporting the distinction in post-trauma assessment.
Adjustment disorder Not Yet Curated MONDO:0003265
Overlapping Features Adjustment disorder can follow stressors and cause distress or impairment, but does not require the full PTSD trauma and symptom-cluster profile.
Show evidence (1 reference)
DOI:10.1192/bja.2024.27 PARTIAL Other
"A range of topics relevant to assessment are discussed, including: the complex relationship between trauma and PTSDs; DSM-5-TR PTSD and ICD-11 PTSD and complex PTSD diagnoses and the similarities and differences between them; the clinical presentation of PTSDs; psychological models of PTSDs; how..."
The abstract supports differential-diagnosis assessment, but does not specifically name adjustment disorder.
Overlapping Features Depressive symptoms frequently co-occur in trauma-exposed populations and can overlap with PTSD negative mood and cognition symptoms.
Show evidence (1 reference)
DOI:10.1136/gpsych-2023-101438 SUPPORT Human Clinical
"This meta-analysis aims to estimate the prevalence of post-traumatic stress disorder (PTSD) and depressive symptoms among civilians residing in armed conflict-affected regions."
The meta-analysis supports close assessment of depressive symptoms in PTSD-prone trauma contexts.
Substance use disorder Not Yet Curated MONDO:0002494
Overlapping Features Substance use disorder commonly co-occurs with PTSD and can complicate symptom attribution, treatment planning, and outcomes.
Show evidence (1 reference)
DOI:10.1002/jts.23049 SUPPORT Human Clinical
"Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) co-occur at high rates, with research showing that up to nearly 60% of individuals with PTSD also suffer from an alcohol and/or drug use disorder."
Co-occurrence at high rates supports assessment for SUD during PTSD differential and comorbidity evaluation.
📊

Related Datasets

2
Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury DOI:10.1038/s41398-023-02313-9
TRACK-TBI prospective level 1 trauma-center cohort with European-ancestry mild traumatic brain injury participants, PTSD symptom outcome at 6 months, and PTSD polygenic-risk-score analysis.
Homo sapiens n=714
Conditions: mild traumatic brain injury probable post-traumatic stress disorder
Findings
Higher PTSD polygenic risk predicted probable PTSD 6 months after mild traumatic brain injury.
Show evidence (1 reference)
DOI:10.1038/s41398-023-02313-9 SUPPORT Human Clinical
"One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury."
The cohort captured a clinically relevant PTSD outcome after traumatic injury.
DOI:10.1038/s41398-023-02313-9
Show evidence (1 reference)
DOI:10.1038/s41398-023-02313-9 SUPPORT Human Clinical
"We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients."
The publication describes a reusable cohort for post-trauma PTSD genetic risk modeling.
Posttraumatic stress disorder (PTSD) prevalence: an umbrella review DOI:10.1017/S0033291724002319
Umbrella-review dataset synthesizing 59 reviews of PTSD prevalence across trauma-exposed contexts, diagnostic instruments, and trauma-event types.
Homo sapiens
Conditions: post-traumatic stress disorder trauma exposure
Findings
PTSD prevalence estimates were heterogeneous but pooled at approximately 24% across included reviews.
Show evidence (1 reference)
DOI:10.1017/S0033291724002319 SUPPORT Human Clinical
"Overall PTSD prevalence was 23.95% (95% confidence interval 95% CI 20.74-27.15), with no publication bias or significant small-study effects, but a high level of heterogeneity between meta-analyses."
Captures the principal prevalence finding and heterogeneity caveat.
DOI:10.1017/S0033291724002319
Show evidence (1 reference)
DOI:10.1017/S0033291724002319 SUPPORT Human Clinical
"Fifty-nine reviews met the criteria of this umbrella review."
The publication documents the evidence base for a synthesized PTSD prevalence dataset.
🔬

Clinical Trials

4
NCT06947538 NOT_APPLICABLE RECRUITING
SMART stepped-care trial testing adaptive sequences of digital and brief trauma- or skills-focused interventions for PTSD treatment access, engagement, and effectiveness in routine care.
Target Phenotypes: Anxiety Intrusive re-experiencing
Show evidence (1 reference)
"The adaptive intervention sequences a digital mental health intervention (DMHI) and brief trauma- and skills-focused treatments for PTSD."
ClinicalTrials.gov record supports stepped-care intervention testing for PTSD symptoms.
NCT04044534 PHASE_II RECRUITING
Phase 2 clinical trial evaluating intranasal insulin for reducing PTSD symptoms.
Target Phenotypes: Anxiety
Show evidence (1 reference)
"To evaluate if intranasal insulin is effective in reducing PTSD symptoms."
ClinicalTrials.gov summary states the intervention target.
NCT05517304 NOT_APPLICABLE RECRUITING
Trial of transcutaneous cervical vagal nerve stimulation versus sham stimulation in veterans with PTSD, including brain imaging, physiology, and PTSD symptom outcomes.
Target Phenotypes: Anxiety
Show evidence (1 reference)
"This study effects the effects of transcutaneous cervical vagal nerve stimulation (tcVNS) or a sham control on brain, physiology, and PTSD symptoms in Veterans with posttraumatic stress disorder (PTSD)."
ClinicalTrials.gov summary supports neuromodulation testing with symptom and physiologic outcomes.
NCT05729789 NOT_APPLICABLE RECRUITING
Pilot study of online group written exposure therapy for PTSD, compared with group cognitive processing therapy outcomes.
Target Phenotypes: Intrusive re-experiencing
Show evidence (1 reference)
"The goal of this clinical trial is to test if Written Exposure Therapy (WET) works well in a group setting in patients with post-traumatic stress disorder (PTSD)."
ClinicalTrials.gov summary documents a PTSD psychotherapy trial.
{ }

Source YAML

click to show
name: Post-Traumatic Stress Disorder
creation_date: "2026-04-24T20:56:38Z"
updated_date: "2026-04-27T15:25:26Z"
category: Psychiatric
description: >-
  Post-traumatic stress disorder is a trauma- and stressor-related psychiatric
  disorder characterized by intrusive recollections, avoidance, negative mood
  or cognition changes, and hyperarousal after traumatic exposure.
disease_term:
  preferred_term: post-traumatic stress disorder
  term:
    id: MONDO:0005146
    label: post-traumatic stress disorder
parents:
- Mental Health Disorder
prevalence:
- population: trauma-exposed populations across PTSD prevalence reviews
  percentage: 23.95
  notes: >-
    Umbrella-review pooled PTSD prevalence across eligible reviews; estimates
    vary widely by population, trauma context, and measurement approach.
  evidence:
  - reference: DOI:10.1017/S0033291724002319
    reference_title: "Posttraumatic stress disorder (PTSD) prevalence: an umbrella review"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Overall PTSD prevalence was 23.95% (95% confidence interval 95% CI
      20.74-27.15), with no publication bias or significant small-study effects,
      but a high level of heterogeneity between meta-analyses.
    explanation: >-
      Umbrella-review evidence supports PTSD as a common outcome in
      trauma-exposed contexts while emphasizing heterogeneity.
- population: civilians residing in armed conflict-affected regions
  percentage: 23.70
  notes: >-
    Meta-analysis estimate for PTSD symptoms among war-afflicted civilians.
  evidence:
  - reference: DOI:10.1136/gpsych-2023-101438
    reference_title: "Prevalence of post-traumatic stress disorder and depressive symptoms among civilians residing in armed conflict-affected regions: a systematic review and meta-analysis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We estimated a prevalence of 23.70% (95% CI 19.50% to 28.40%) for PTSD
      symptoms and 25.60% (95% CI 20.70% to 31.10%) for depressive features
      among war-afflicted civilians.
    explanation: >-
      Conflict-exposed civilian populations have a high pooled PTSD-symptom
      burden.
pathophysiology:
- name: Traumatic Stress Exposure
  description: >-
    Exposure to psychologically threatening or horrific traumatic events is the
    initiating environmental context required for PTSD.
  biological_processes:
  - preferred_term: response to stress
    term:
      id: GO:0006950
      label: response to stress
    modifier: ABNORMAL
  downstream:
  - target: Polygenic Susceptibility to PTSD after Trauma
    description: >-
      Trauma exposure is required, while inherited liability modifies who
      develops persistent PTSD symptoms after exposure.
    evidence:
    - reference: DOI:10.1038/s41398-023-02313-9
      reference_title: Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Many patients with mild traumatic brain injury (mTBI) are at risk for
        mental health problems such as posttraumatic stress disorder (PTSD).
      explanation: >-
        TRACK-TBI frames PTSD risk in a post-trauma cohort and tests genetic
        susceptibility in that context.
  - target: HPA-Axis Regulation Alteration
    description: >-
      Traumatic stress activates stress-response pathways that can become
      persistently dysregulated in PTSD.
    evidence:
    - reference: PMID:30790632
      reference_title: "HPA axis regulation in posttraumatic stress disorder: A meta-analysis focusing on potential moderators."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Posttraumatic stress disorder (PTSD) is often associated with
        alterations in the hypothalamic-pituitary-adrenal (HPA) axis.
      explanation: >-
        Meta-analysis supports HPA-axis involvement after PTSD develops.
  evidence:
  - reference: DOI:10.1192/bja.2024.27
    reference_title: "Assessment and diagnosis of post-traumatic stress disorders (PTSDs) for medico-legal and other clinical purposes: DSM-5-TR PTSD, ICD-11 PTSD and ICD-11 complex PTSD"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Given ongoing debate, the article proposes that trauma exposure is best
      defined in future iterations of the DSM and ICD as exposure to one or more
      psychologically threatening or horrific experiences that are overwhelming.
    explanation: >-
      The diagnostic review supports traumatic exposure as the initiating
      context for PTSD assessment.
- name: Polygenic Susceptibility to PTSD after Trauma
  description: >-
    Common-variant genetic liability increases the probability of probable PTSD
    after traumatic injury, but does not by itself cause PTSD without a trauma
    context. PTSD genetic liability overlaps with genetic risk for other
    neurodegenerative conditions including REM sleep behavior disorder, suggesting
    shared genetic mechanisms underlying trauma response and neurodegenerative
    risk.
  downstream:
  - target: Epigenetic Stress-Response Regulation
    description: >-
      Genetic and environmental susceptibility are represented as upstream of
      molecular regulation systems involved in stress responses.
  evidence:
  - reference: DOI:10.1038/s41398-023-02313-9
    reference_title: Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We used data from individuals of European ancestry with mTBI enrolled in
      TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma
      center patients.
    explanation: >-
      Prospective trauma-center cohort data support inherited liability as a
      post-trauma PTSD risk modifier.
  - reference: DOI:10.1038/s41398-023-02313-9
    reference_title: Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly
      four times higher (aOR = 3.71, 95% CI 1.80–7.65) than in the lowest
      PTSD-PRS quintile.
    explanation: >-
      A PTSD polygenic risk score predicted probable PTSD after mild traumatic
      brain injury.
  - reference: PMID:42168223
    reference_title: Genetic associations between post-traumatic stress disorder and REM-sleep behavior disorder.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      While not supporting a causal relationship, genetic analyses revealed a
      significant association between PTSD and iRBD, consistent with the
      exploratory imaging substudy. These findings suggest that individuals
      genetically at risk for PTSD may also be at higher risk for iRBD.
    explanation: >-
      Genome-wide genetic analyses support shared genetic predisposition between
      PTSD and isolated REM sleep behavior disorder, with implications for
      understanding both psychiatric and neurodegenerative disease mechanisms.
- name: Epigenetic Stress-Response Regulation
  description: >-
    Trauma and other environmental stressors are associated with epigenetic
    mechanisms affecting HPA-axis, neurotrophic, neurotransmitter, and immune
    systems relevant to PTSD.
  biological_processes:
  - preferred_term: chromatin organization
    term:
      id: GO:0006325
      label: chromatin organization
    modifier: ABNORMAL
  downstream:
  - target: HPA-Axis Regulation Alteration
    description: >-
      Epigenetic changes in HPA-axis-related genes are modeled upstream of
      altered endocrine stress regulation.
  - target: Neuroimmune Activation
    description: >-
      Epigenetic changes in immune-function genes are modeled upstream of
      altered inflammatory signaling.
  evidence:
  - reference: DOI:10.1159/000541822
    reference_title: "Epigenetic Alterations in Post-Traumatic Stress Disorder: Comprehensive Review of Molecular Markers"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Studies show that environmental stressors can induce various epigenetic
      changes that shape the PTSD phenotype.
    explanation: >-
      Review evidence supports environmentally induced epigenetic regulation as
      a PTSD susceptibility and phenotype mechanism.
  - reference: DOI:10.1159/000541822
    reference_title: "Epigenetic Alterations in Post-Traumatic Stress Disorder: Comprehensive Review of Molecular Markers"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This review investigated gene methylation changes in association with
      PTSD, including those related to the hypothalamic-pituitary-adrenal axis,
      brain-derived neurotrophic factor, neurotransmitters, and immune system
      functioning, as well as the role of histones and regulatory noncoding
      RNAs.
    explanation: >-
      The reviewed molecular systems map directly to HPA, neurotransmission,
      and immune pathophysiology nodes.
- name: HPA-Axis Regulation Alteration
  description: >-
    PTSD is associated with altered hypothalamic-pituitary-adrenal axis
    regulation, including lower morning and 24-hour cortisol in meta-analysis,
    though moderator patterns are inconsistent.
  biological_processes:
  - preferred_term: response to stress
    term:
      id: GO:0006950
      label: response to stress
    modifier: ABNORMAL
  locations:
  - preferred_term: hypothalamus
    term:
      id: UBERON:0001898
      label: hypothalamus
  - preferred_term: pituitary gland
    term:
      id: UBERON:0000007
      label: pituitary gland
  - preferred_term: adrenal gland
    term:
      id: UBERON:0002369
      label: adrenal gland
  downstream:
  - target: Neuroimmune Activation
    description: >-
      Stress-hormone regulation interacts with inflammatory signaling in PTSD
      models and clinical studies.
    evidence:
    - reference: PMID:31991875
      reference_title: "Inflammation in Post-Traumatic Stress Disorder (PTSD): A Review of Potential Correlates of PTSD with a Neurological Perspective."
      supports: PARTIAL
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        these alterations may further reinforce the related clinical symptoms
        of PTSD such as sustained fear and anxiety.
      explanation: >-
        The review links glucocorticoid signaling, HPA-axis function, immune
        function, and PTSD symptoms, but presents a proposed pathway rather than
        a single definitive causal experiment.
  - target: Threat-Circuit and Fear-Extinction Dysregulation
    description: >-
      Stress-axis dysregulation affects limbic and prefrontal systems that
      regulate fear, anxiety, and memory.
    evidence:
    - reference: PMID:35927237
      reference_title: The role of the immune system in posttraumatic stress disorder.
      supports: PARTIAL
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Importantly, inflammation can influence neural circuits and
        neurotransmitter signaling in regions of the brain relevant to fear,
        anxiety, and emotion regulation.
      explanation: >-
        This supports downstream circuit effects through immune signaling;
        stress-axis involvement is part of the broader PTSD biology.
  evidence:
  - reference: PMID:30790632
    reference_title: "HPA axis regulation in posttraumatic stress disorder: A meta-analysis focusing on potential moderators."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Morning and 24 h cortisol were significantly lower in PTSD than in
      controls (g = -0.21; 95% CI: -0.42-(-0.01); g = -0.31; CI:
      -0.60-(-0.03)).
    explanation: >-
      Meta-analysis supports lower cortisol measures in PTSD compared with
      controls.
- name: Neuroimmune Activation
  description: >-
    PTSD is associated with peripheral inflammatory markers and immune-system
    changes that may affect brain circuits involved in fear, anxiety, and
    emotion regulation.
  cell_types:
  - preferred_term: microglial cell
    term:
      id: CL:0000129
      label: microglial cell
  - preferred_term: astrocyte
    term:
      id: CL:0000127
      label: astrocyte
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  - preferred_term: cytokine production
    term:
      id: GO:0001816
      label: cytokine production
    modifier: INCREASED
  - preferred_term: cytokine-mediated signaling pathway
    term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    modifier: ABNORMAL
  locations:
  - preferred_term: amygdala
    term:
      id: UBERON:0001876
      label: amygdala
  - preferred_term: hippocampal formation
    term:
      id: UBERON:0002421
      label: hippocampal formation
  - preferred_term: prefrontal cortex
    term:
      id: UBERON:0000451
      label: prefrontal cortex
  downstream:
  - target: Threat-Circuit and Fear-Extinction Dysregulation
    description: >-
      Inflammatory markers are associated with structural and functional
      alterations in amygdala, hippocampus, and frontal cortex.
    evidence:
    - reference: PMID:31991875
      reference_title: "Inflammation in Post-Traumatic Stress Disorder (PTSD): A Review of Potential Correlates of PTSD with a Neurological Perspective."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        neuroimaging-based studies demonstrated that altered inflammatory
        markers are associated with structural and functional alterations in
        brain regions that are responsible for the regulation of stress and
        emotion, including the amygdala, hippocampus, and frontal cortex.
      explanation: >-
        This directly links inflammatory markers with PTSD-relevant
        stress/emotion brain circuitry.
  evidence:
  - reference: PMID:35927237
    reference_title: The role of the immune system in posttraumatic stress disorder.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      some individuals with PTSD also exhibit elevated concentrations of
      inflammatory markers, including C-reactive protein, interleukin-6, and
      tumor necrosis factor-α.
    explanation: >-
      Review evidence supports inflammatory-marker elevation in a subset of
      individuals with PTSD.
  - reference: PMID:31991875
    reference_title: "Inflammation in Post-Traumatic Stress Disorder (PTSD): A Review of Potential Correlates of PTSD with a Neurological Perspective."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Major findings included elevated levels of serum proinflammatory cytokines
      in individuals with PTSD across various trauma types, as compared with
      those without PTSD.
    explanation: >-
      Structured review evidence supports increased proinflammatory cytokines
      across trauma contexts.
- name: Threat-Circuit and Fear-Extinction Dysregulation
  description: >-
    Altered amygdala, hippocampal, and prefrontal cortical function affects
    threat detection, emotional regulation, fear reactivity, and traumatic
    memory processing.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: learning
    term:
      id: GO:0007612
      label: learning
    modifier: ABNORMAL
  - preferred_term: memory
    term:
      id: GO:0007613
      label: memory
    modifier: ABNORMAL
  - preferred_term: modulation of chemical synaptic transmission
    term:
      id: GO:0050804
      label: modulation of chemical synaptic transmission
    modifier: ABNORMAL
  locations:
  - preferred_term: amygdala
    term:
      id: UBERON:0001876
      label: amygdala
  - preferred_term: hippocampal formation
    term:
      id: UBERON:0002421
      label: hippocampal formation
  - preferred_term: prefrontal cortex
    term:
      id: UBERON:0000451
      label: prefrontal cortex
  downstream:
  - target: Intrusive Re-experiencing
    description: >-
      Abnormal threat and memory circuitry contributes to intrusive traumatic
      recollections and flashbacks.
    evidence:
    - reference: PMID:31991875
      reference_title: "Inflammation in Post-Traumatic Stress Disorder (PTSD): A Review of Potential Correlates of PTSD with a Neurological Perspective."
      supports: PARTIAL
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Dysfunction in the regions of the prefrontal cortex, amygdala, and
        hippocampus are then responsible for functions of executive control,
        emotional lability, fear reactivity, and retrieval of traumatic memories
        as demonstrated in PTSD.
      explanation: >-
        The review links dysfunction in these regions to traumatic-memory
        retrieval and fear reactivity.
  - target: Hyperarousal and Anxiety
    description: >-
      Altered threat circuitry contributes to persistent threat perception,
      hyperarousal, and anxiety.
  evidence:
  - reference: PMID:31991875
    reference_title: "Inflammation in Post-Traumatic Stress Disorder (PTSD): A Review of Potential Correlates of PTSD with a Neurological Perspective."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      particular brain regions may be identifiable as neural correlates of PTSD,
      including the prefrontal cortex, hippocampus, and amygdala of the brain.
    explanation: >-
      Review evidence supports amygdala-hippocampal-prefrontal circuitry as a
      PTSD-relevant neurobiological substrate.
phenotypes:
- name: Intrusive Re-experiencing
  category: Behavioral
  description: >-
    Recurrent intrusive traumatic memories, flashbacks, and nightmares.
  phenotype_term:
    preferred_term: Intrusive re-experiencing
  diagnostic: true
  evidence:
  - reference: DOI:10.1159/000541822
    reference_title: "Epigenetic Alterations in Post-Traumatic Stress Disorder: Comprehensive Review of Molecular Markers"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      PTSD is characterized by nightmares, flashbacks and avoidance of stressors.
    explanation: >-
      Review abstract supports nightmares and flashbacks as PTSD symptom
      features.
- name: Avoidance of Trauma Reminders
  category: Behavioral
  description: >-
    Avoidance of trauma-related internal experiences or external reminders.
  phenotype_term:
    preferred_term: Avoidance of trauma reminders
  diagnostic: true
  evidence:
  - reference: DOI:10.1159/000541822
    reference_title: "Epigenetic Alterations in Post-Traumatic Stress Disorder: Comprehensive Review of Molecular Markers"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      PTSD is characterized by nightmares, flashbacks and avoidance of stressors.
    explanation: >-
      The abstract identifies avoidance as a core PTSD symptom feature.
- name: Hyperarousal and Anxiety
  category: Behavioral
  description: >-
    Persistent threat perception, heightened arousal, fearfulness, and anxiety.
  phenotype_term:
    preferred_term: Anxiety
    term:
      id: HP:0000739
      label: Anxiety
  diagnostic: true
  evidence:
  - reference: DOI:10.1192/bja.2024.27
    reference_title: "Assessment and diagnosis of post-traumatic stress disorders (PTSDs) for medico-legal and other clinical purposes: DSM-5-TR PTSD, ICD-11 PTSD and ICD-11 complex PTSD"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the clinical presentation of PTSDs; psychological models of PTSDs; how to
      approach assessment and differential diagnosis
    explanation: >-
      The diagnostic review supports clinical presentation and assessment of
      PTSD symptom clusters, including arousal and threat-related symptoms.
- name: Depressive Symptoms
  category: Behavioral
  description: >-
    Depressive symptoms can co-occur with PTSD and complicate assessment,
    functioning, and outcomes.
  phenotype_term:
    preferred_term: Depression
    term:
      id: HP:0000716
      label: Depression
  evidence:
  - reference: DOI:10.1136/gpsych-2023-101438
    reference_title: "Prevalence of post-traumatic stress disorder and depressive symptoms among civilians residing in armed conflict-affected regions: a systematic review and meta-analysis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We estimated a prevalence of 23.70% (95% CI 19.50% to 28.40%) for PTSD
      symptoms and 25.60% (95% CI 20.70% to 31.10%) for depressive features
      among war-afflicted civilians.
    explanation: >-
      Meta-analysis supports frequent depressive features in a high-risk PTSD
      context.
diagnosis:
- name: Clinician-administered PTSD assessment
  presence: >-
    PTSD diagnosis is established by clinical assessment using diagnostic
    criteria and validated clinician-administered interviews, with screening
    questionnaires used as aids rather than stand-alone diagnostics.
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: MAXO:0000487
      label: clinical assessment
  evidence:
  - reference: DOI:10.1192/bja.2024.27
    reference_title: "Assessment and diagnosis of post-traumatic stress disorders (PTSDs) for medico-legal and other clinical purposes: DSM-5-TR PTSD, ICD-11 PTSD and ICD-11 complex PTSD"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      This article provides an overview and critique of key topics, literature
      and principles to inform comprehensive and meticulous assessment of PTSDs.
    explanation: >-
      Diagnostic review supports comprehensive clinical assessment for PTSD.
  - reference: DOI:10.1002/jts.23013
    reference_title: "A clinician's guide to the 2023 VA/DoD Clinical Practice Guideline for Management of Posttraumatic Stress Disorder and Acute Stress Disorder"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The CPG recommendations are accompanied by a clinical algorithm, which
      incorporates principles of evidence-based practice, shared
      decision-making, and functional and contextual assessments of goals and
      outcomes.
    explanation: >-
      Guideline summary supports structured clinical algorithms and contextual
      functional assessment.
- name: Biomarker and neuroimaging research is not diagnostic
  presence: >-
    Inflammatory, endocrine, imaging, and genetic markers support mechanistic
    research but are not established as stand-alone diagnostic tests.
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: MAXO:0000487
      label: clinical assessment
  evidence:
  - reference: PMID:31991875
    reference_title: "Inflammation in Post-Traumatic Stress Disorder (PTSD): A Review of Potential Correlates of PTSD with a Neurological Perspective."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Future studies that utilize both central and peripheral inflammatory
      markers are warranted to elucidate the underlying neurological pathway of
      the pathophysiology of PTSD.
    explanation: >-
      The review frames biomarkers as needing further study for mechanisms,
      not as current diagnostic replacements.
differential_diagnoses:
- name: Acute stress disorder
  description: >-
    Acute stress disorder is considered when trauma-related symptoms occur in
    the immediate post-trauma period before persistence thresholds for PTSD are
    met.
  disease_term:
    preferred_term: acute stress disorder
    term:
      id: MONDO:0003763
      label: acute stress disorder
  evidence:
  - reference: DOI:10.1002/jts.23013
    reference_title: "A clinician's guide to the 2023 VA/DoD Clinical Practice Guideline for Management of Posttraumatic Stress Disorder and Acute Stress Disorder"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The 2023 Department of Veterans Affairs /Department of Defense Clinical
      Practice Guideline for Management of Posttraumatic Stress Disorder and
      Acute Stress Disorder is described herein.
    explanation: >-
      The guideline covers PTSD and acute stress disorder together, supporting
      the distinction in post-trauma assessment.
- name: Adjustment disorder
  description: >-
    Adjustment disorder can follow stressors and cause distress or impairment,
    but does not require the full PTSD trauma and symptom-cluster profile.
  disease_term:
    preferred_term: adjustment disorder
    term:
      id: MONDO:0003265
      label: adjustment disorder
  evidence:
  - reference: DOI:10.1192/bja.2024.27
    reference_title: "Assessment and diagnosis of post-traumatic stress disorders (PTSDs) for medico-legal and other clinical purposes: DSM-5-TR PTSD, ICD-11 PTSD and ICD-11 complex PTSD"
    supports: PARTIAL
    evidence_source: OTHER
    snippet: >-
      A range of topics relevant to assessment are discussed, including: the
      complex relationship between trauma and PTSDs; DSM-5-TR PTSD and ICD-11
      PTSD and complex PTSD diagnoses and the similarities and differences
      between them; the clinical presentation of PTSDs; psychological models of
      PTSDs; how to approach assessment and differential diagnosis
    explanation: >-
      The abstract supports differential-diagnosis assessment, but does not
      specifically name adjustment disorder.
- name: Major depressive disorder
  description: >-
    Depressive symptoms frequently co-occur in trauma-exposed populations and
    can overlap with PTSD negative mood and cognition symptoms.
  disease_term:
    preferred_term: major depressive disorder
    term:
      id: MONDO:0002009
      label: major depressive disorder
  evidence:
  - reference: DOI:10.1136/gpsych-2023-101438
    reference_title: "Prevalence of post-traumatic stress disorder and depressive symptoms among civilians residing in armed conflict-affected regions: a systematic review and meta-analysis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This meta-analysis aims to estimate the prevalence of post-traumatic
      stress disorder (PTSD) and depressive symptoms among civilians residing in
      armed conflict-affected regions.
    explanation: >-
      The meta-analysis supports close assessment of depressive symptoms in
      PTSD-prone trauma contexts.
- name: Substance use disorder
  description: >-
    Substance use disorder commonly co-occurs with PTSD and can complicate
    symptom attribution, treatment planning, and outcomes.
  disease_term:
    preferred_term: substance-related disorder
    term:
      id: MONDO:0002494
      label: substance-related disorder
  evidence:
  - reference: DOI:10.1002/jts.23049
    reference_title: "State of the Science: Treatment of comorbid posttraumatic stress disorder and substance use disorders"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs)
      co-occur at high rates, with research showing that up to nearly 60% of
      individuals with PTSD also suffer from an alcohol and/or drug use disorder.
    explanation: >-
      Co-occurrence at high rates supports assessment for SUD during PTSD
      differential and comorbidity evaluation.
treatments:
- name: Trauma-focused psychotherapy
  description: >-
    First-line trauma-focused psychotherapies for PTSD include exposure therapy
    such as prolonged exposure, cognitive processing therapy, trauma-focused
    cognitive behavioral therapy, EMDR, and narrative exposure therapy.
  treatment_term:
    preferred_term: cognitive behavior therapy
    term:
      id: MAXO:0000883
      label: cognitive behavior therapy
  target_phenotypes:
  - preferred_term: Intrusive re-experiencing
  - preferred_term: Avoidance of trauma reminders
  - preferred_term: Anxiety
    term:
      id: HP:0000739
      label: Anxiety
  evidence:
  - reference: PMID:26574151
    reference_title: "Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Evidence supports efficacy of exposure therapy (high SOE) including the
      manualized version Prolonged Exposure (PE); cognitive therapy (CT),
      cognitive processing therapy (CPT), cognitive behavioral therapy
      (CBT)-mixed therapies (moderate SOE); eye movement desensitization and
      reprocessing (EMDR) and narrative exposure therapy (low-moderate SOE).
    explanation: >-
      Systematic review evidence supports trauma-focused psychotherapy options
      including PE, CPT, CBT-based therapies, EMDR, and narrative exposure
      therapy for adults with PTSD.
  - reference: PMID:35044471
    reference_title: "Comparison of Prolonged Exposure vs Cognitive Processing Therapy for Treatment of Posttraumatic Stress Disorder Among US Veterans: A Randomized Clinical Trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This randomized clinical trial found that although PE was statistically
      more effective than CPT, the difference was not clinically significant,
      and improvements in PTSD were meaningful in both treatment groups.
    explanation: >-
      A large randomized trial supports both prolonged exposure and cognitive
      processing therapy as effective PTSD psychotherapies.
- name: Serotonergic antidepressant pharmacotherapy
  description: >-
    SSRI and SNRI pharmacotherapy can be used for PTSD symptom reduction,
    including sertraline, paroxetine, and venlafaxine.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: sertraline
      term:
        id: CHEBI:9123
        label: sertraline
    - preferred_term: paroxetine
      term:
        id: CHEBI:7936
        label: paroxetine
    - preferred_term: venlafaxine
      term:
        id: CHEBI:9943
        label: venlafaxine
  target_phenotypes:
  - preferred_term: Anxiety
    term:
      id: HP:0000739
      label: Anxiety
  evidence:
  - reference: PMID:34992738
    reference_title: "Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      For individual monotherapy agents compared to placebo in two or more
      studies, we found small statistically significant evidence for the
      antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the
      antipsychotic quetiapine.
    explanation: >-
      Systematic review and meta-analysis evidence supports several
      antidepressant monotherapies for reducing PTSD symptom severity,
      including paroxetine, sertraline, and venlafaxine.
clinical_trials:
- name: NCT06947538
  phase: NOT_APPLICABLE
  status: RECRUITING
  description: >-
    SMART stepped-care trial testing adaptive sequences of digital and brief
    trauma- or skills-focused interventions for PTSD treatment access,
    engagement, and effectiveness in routine care.
  target_phenotypes:
  - preferred_term: Anxiety
    term:
      id: HP:0000739
      label: Anxiety
  - preferred_term: Intrusive re-experiencing
  evidence:
  - reference: clinicaltrials:NCT06947538
    reference_title: "Adaptive Interventions to Improve Posttraumatic Stress Disorder (PTSD) Treatment Access, Engagement, and Effectiveness in Routine Care"
    supports: SUPPORT
    snippet: >-
      The adaptive intervention sequences a digital mental health intervention
      (DMHI) and brief trauma- and skills-focused treatments for PTSD.
    explanation: >-
      ClinicalTrials.gov record supports stepped-care intervention testing for
      PTSD symptoms.
- name: NCT04044534
  phase: PHASE_II
  status: RECRUITING
  description: >-
    Phase 2 clinical trial evaluating intranasal insulin for reducing PTSD
    symptoms.
  target_phenotypes:
  - preferred_term: Anxiety
    term:
      id: HP:0000739
      label: Anxiety
  evidence:
  - reference: clinicaltrials:NCT04044534
    reference_title: Intranasal Insulin for Treating Posttraumatic Stress Disorder
    supports: SUPPORT
    snippet: >-
      To evaluate if intranasal insulin is effective in reducing PTSD symptoms.
    explanation: >-
      ClinicalTrials.gov summary states the intervention target.
- name: NCT05517304
  phase: NOT_APPLICABLE
  status: RECRUITING
  description: >-
    Trial of transcutaneous cervical vagal nerve stimulation versus sham
    stimulation in veterans with PTSD, including brain imaging, physiology, and
    PTSD symptom outcomes.
  target_phenotypes:
  - preferred_term: Anxiety
    term:
      id: HP:0000739
      label: Anxiety
  evidence:
  - reference: clinicaltrials:NCT05517304
    reference_title: Transcutaneous Vagal Nerve Stimulation in Veterans With Posttraumatic Stress Disorder
    supports: SUPPORT
    snippet: >-
      This study effects the effects of transcutaneous cervical vagal nerve
      stimulation (tcVNS) or a sham control on brain, physiology, and PTSD
      symptoms in Veterans with posttraumatic stress disorder (PTSD).
    explanation: >-
      ClinicalTrials.gov summary supports neuromodulation testing with symptom
      and physiologic outcomes.
- name: NCT05729789
  phase: NOT_APPLICABLE
  status: RECRUITING
  description: >-
    Pilot study of online group written exposure therapy for PTSD, compared
    with group cognitive processing therapy outcomes.
  target_phenotypes:
  - preferred_term: Intrusive re-experiencing
  evidence:
  - reference: clinicaltrials:NCT05729789
    reference_title: "Investigating Group Written Exposure Therapy for Posttraumatic Stress Disorder: A Pilot Study"
    supports: SUPPORT
    snippet: >-
      The goal of this clinical trial is to test if Written Exposure Therapy
      (WET) works well in a group setting in patients with post-traumatic stress
      disorder (PTSD).
    explanation: >-
      ClinicalTrials.gov summary documents a PTSD psychotherapy trial.
datasets:
- accession: DOI:10.1038/s41398-023-02313-9
  title: Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury
  description: >-
    TRACK-TBI prospective level 1 trauma-center cohort with European-ancestry
    mild traumatic brain injury participants, PTSD symptom outcome at 6 months,
    and PTSD polygenic-risk-score analysis.
  organism:
    preferred_term: Homo sapiens
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  sample_count: 714
  conditions:
  - mild traumatic brain injury
  - probable post-traumatic stress disorder
  publication: DOI:10.1038/s41398-023-02313-9
  evidence:
  - reference: DOI:10.1038/s41398-023-02313-9
    reference_title: Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We used data from individuals of European ancestry with mTBI enrolled in
      TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma
      center patients.
    explanation: >-
      The publication describes a reusable cohort for post-trauma PTSD genetic
      risk modeling.
  findings:
  - statement: Higher PTSD polygenic risk predicted probable PTSD 6 months after mild traumatic brain injury.
    evidence:
    - reference: DOI:10.1038/s41398-023-02313-9
      reference_title: Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5
        score ≥33) at 6 months post-injury.
      explanation: >-
        The cohort captured a clinically relevant PTSD outcome after traumatic
        injury.
- accession: DOI:10.1017/S0033291724002319
  title: "Posttraumatic stress disorder (PTSD) prevalence: an umbrella review"
  description: >-
    Umbrella-review dataset synthesizing 59 reviews of PTSD prevalence across
    trauma-exposed contexts, diagnostic instruments, and trauma-event types.
  organism:
    preferred_term: Homo sapiens
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  conditions:
  - post-traumatic stress disorder
  - trauma exposure
  publication: DOI:10.1017/S0033291724002319
  evidence:
  - reference: DOI:10.1017/S0033291724002319
    reference_title: "Posttraumatic stress disorder (PTSD) prevalence: an umbrella review"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Fifty-nine reviews met the criteria of this umbrella review.
    explanation: >-
      The publication documents the evidence base for a synthesized PTSD
      prevalence dataset.
  findings:
  - statement: PTSD prevalence estimates were heterogeneous but pooled at approximately 24% across included reviews.
    evidence:
    - reference: DOI:10.1017/S0033291724002319
      reference_title: "Posttraumatic stress disorder (PTSD) prevalence: an umbrella review"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Overall PTSD prevalence was 23.95% (95% confidence interval 95% CI
        20.74-27.15), with no publication bias or significant small-study
        effects, but a high level of heterogeneity between meta-analyses.
      explanation: >-
        Captures the principal prevalence finding and heterogeneity caveat.
notes: >-
  This curation keeps the pathophysiology granular: trauma exposure,
  polygenic susceptibility, epigenetic regulation, HPA-axis regulation,
  neuroimmune activation, and threat-circuit dysregulation are separate nodes
  connected by downstream edges.
📚

References & Deep Research

Deep Research

1
Falcon
Disease Characteristics Research Template
Edison Scientific Literature 65 citations 2026-04-24T17:20:27.727817

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

  • Disease Name: Post-Traumatic Stress Disorder
  • MONDO ID: (if available)
  • Category: Psychiatric

Research Objectives

Please provide a comprehensive research report on Post-Traumatic Stress Disorder covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.


1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

  • What is the disease? Provide a concise overview.
  • What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
  • What are the common synonyms and alternative names?
  • Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

  • Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
  • Risk Factors:

    Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

  • Genetic risk factors (causal variants, susceptibility loci, modifier genes)
  • Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
  • Protective Factors:

    Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

  • Genetic protective factors (protective variants, modifier alleles)
  • Environmental protective factors (diet, lifestyle, exposures that reduce risk)
  • Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

    Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

  • Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

    Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

  • Pathogenic Variants:
  • Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
  • Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
  • Variant type/class (missense, frameshift, nonsense, splice-site, structural)
  • Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
  • Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
  • Functional consequences (loss of function, gain of function, dominant negative)
  • Modifier Genes: Genes that modify disease severity or expression
  • Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

    Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

  • Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

    Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

  • Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

    Search first: CDC databases, WHO, PubMed, NHANES

  • Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

    Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

  • Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

    Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

  • Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

    Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

  • Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

    Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

  • Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

    Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

  • Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

    Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

  • Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

    Search first: PubMed, Gene Ontology, Reactome

  • Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

    Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

  • Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Molecular Profiling (if available):
  • Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
  • Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
  • Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
  • Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
  • Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
  • Advanced Technologies (if applicable):
  • Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
  • Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
  • Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
  • Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

  • Organ Level:
  • Primary organs directly affected
  • Secondary organ involvement (complications, secondary effects)
  • Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

    Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

  • Tissue and Cell Level:
  • Specific tissue types affected (epithelial, connective, muscle, nervous)
  • Specific cell populations targeted (with Cell Ontology terms)

    Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

  • Subcellular Level:
  • Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

    Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

  • Localization:
  • Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
  • Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

  • Onset:
  • Typical age of onset (congenital, pediatric, adult, geriatric)
  • Onset pattern (acute, subacute, chronic, insidious)

    Search first: OMIM, Orphanet, HPO, PubMed

  • Progression:
  • Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
  • Progression rate (rapid, slow, variable)
  • Disease course pattern (episodic, relapsing-remitting, progressive, stable)
  • Disease duration (self-limited, chronic lifelong)

    Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

  • Patterns:
  • Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
  • Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

  • Epidemiology:
  • Prevalence (cases per 100,000 at given time)
  • Incidence (new cases per 100,000 per year)

    Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

  • For Genetic Etiology:
  • Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
  • Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
  • Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
  • Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
  • Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
  • Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
  • Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
  • Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
  • Population Demographics:
  • Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
  • Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
  • Geographic distribution of specific variants
  • Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
  • Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

  • Clinical Tests:
  • Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
  • Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
  • Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
  • Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
  • Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
  • Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
  • Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
  • Genetic Testing:

    Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

  • Overview of recommended genetic testing approach
  • Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
  • Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
  • Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
  • Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
  • Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
  • Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
  • FISH > Search first: ClinVar, cytogenetics databases, PubMed
  • Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
  • Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
  • Omics-Based Diagnostics (if applicable):
  • RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
  • Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
  • Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
  • Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
  • Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
  • Clinical Criteria:
  • Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
  • Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
  • Screening:
  • Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

  • Survival and Mortality:
  • Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
  • Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
  • Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
  • Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
  • Morbidity and Function:
  • Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
  • Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
  • Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
  • Disease Course:
  • Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
  • Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
  • Prediction:
  • Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
  • Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

  • Pharmacotherapy:
  • Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
  • Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
  • Advanced Therapeutics:
  • Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
  • Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
  • RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
  • Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
  • Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
  • Surgical and Interventional:
  • Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
  • Supportive and Rehabilitative:
  • Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
  • Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
  • Experimental:
  • Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
  • Treatment Outcomes:
  • Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
  • Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
  • Treatment Strategy:
  • Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
  • Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
  • Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

  • Prevention Levels:
  • Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
  • Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
  • Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
  • Immunization: Vaccine strategies (if applicable)

    Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

  • Screening and Early Detection:
  • Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
  • Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
  • Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
  • Behavioral Interventions: Lifestyle modifications to reduce risk

    Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

  • Counseling: Genetic counseling (risk assessment, family planning guidance)

    Search first: NSGC resources, ACMG guidelines, GeneReviews

  • Public Health:
  • Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
  • Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
  • Prophylaxis: Preventive medications or procedures

    Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

  • Taxonomy: Species affected (with NCBI Taxon identifiers)

    Search first: NCBI Taxonomy

  • Breed: Specific breeds affected (with VBO identifiers if applicable)

    Search first: VBO (Vertebrate Breed Ontology)

  • Gene: Orthologous genes in other species (with NCBI Gene IDs)

    Search first: NCBI Gene

  • Natural Disease:
  • Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
  • Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
  • Comparative Biology:
  • Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
  • Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
  • Transmission (if applicable):
  • Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
  • Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

  • Model Types:
  • Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
  • Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
  • Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
  • Genetic Models:
  • Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
  • Model Characteristics:
  • Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
  • Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
  • Applications:
  • Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
  • Resources:
  • Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic and clinical claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes from abstracts where possible to support key statements
  • Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Post-Traumatic Stress Disorder (PTSD): Comprehensive Disease Characteristics Research Report (Psychiatric)

Executive summary (current understanding; 2023–2024 emphasis)

Post-traumatic stress disorder (PTSD) is a trauma- and stressor-related psychiatric disorder characterized by persistent re-experiencing of a traumatic event, avoidance of reminders, and alterations in threat detection/arousal and mood/cognition that cause functional impairment. Contemporary research and guidelines emphasize (i) heterogeneity across diagnostic frameworks (DSM-5-TR vs ICD-11), (ii) strong evidence for trauma-focused psychotherapies as first-line treatment, (iii) robust epidemiologic burden in conflict and displacement settings, and (iv) emerging but not-yet-clinically-validated biological markers implicating HPA-axis dysregulation and neuroimmune activation. (bisson2024posttraumaticstressdisorder pages 1-2, schincariol2024posttraumaticstressdisorder pages 2-3, lang2024acliniciansguide pages 5-5, lawrence2024posttraumaticstress pages 5-5)

A compact, citation-rich snapshot suitable for knowledge-base ingestion is provided in the embedded table below.

Category Key points Key citations
Identifiers/Definitions Disease: Post-traumatic stress disorder (PTSD), a trauma- and stressor-related mental disorder that may develop after exposure to exceptionally threatening/horrifying events. DSM-5-TR vs ICD-11: DSM-5-TR requires qualifying trauma exposure and 4 symptom clusters—intrusion, avoidance, negative alterations in cognition/mood, and arousal/reactivity—with duration >1 month and functional impairment; ICD-11 defines 3 core clusters—re-experiencing, avoidance, and persistent sense of current threat—with symptoms lasting several weeks and impairment. ICD-11 additionally distinguishes PTSD and complex PTSD (CPTSD) as sibling diagnoses. Recent population work found DSM-5 and ICD-11 prevalence can be similar overall but identify only partially overlapping cases (κ=0.62). URLs: https://doi.org/10.1192/bja.2024.27 (Aug 2024); https://doi.org/10.1136/bmj.h6161 (Nov 2024); https://doi.org/10.1017/S2045796025100164 (Aug 2025). Siddaway 2024, BJPsych Advances, doi:10.1192/bja.2024.27; Bisson et al. 2024, BMJ, doi:10.1136/bmj.h6161; Pettrich et al. 2025, Epidemiol Psychiatr Sci, doi:10.1017/S2045796025100164 (siddaway2024assessmentanddiagnosis pages 1-2, siddaway2024assessmentanddiagnosis pages 3-4, bisson2024posttraumaticstressdisorder pages 1-2, pettrich2025theprevalenceof pages 1-2)
Epidemiology General burden: Umbrella review of 59 reviews found pooled PTSD prevalence 23.95% (95% CI 20.74–27.15), with wide heterogeneity across trauma contexts; lifetime global prevalence cited around 5.6%. General adult estimates: BMJ review reports point prevalence about 3% and lifetime prevalence 1.9%–8.8%. Context-specific: armed-conflict civilians 23.70% (95% CI 19.50–28.40%); displaced people in Africa 55.64% (95% CI 42.76–68.41%); internally displaced persons in Africa 51% (95% CI 38–64); Ethiopian war-affected communities 48.4% (95% CI 37.1–59.8%). German general population: trauma exposure 47.2%; probable PTSD 4.7% by both DSM-5 and ICD-11 algorithms. URLs: https://doi.org/10.1017/S0033291724002319 (Sep 2024); https://doi.org/10.1136/gpsych-2023-101438 (Jun 2024); https://doi.org/10.3389/fpsyt.2024.1336665 (Mar 2024); https://doi.org/10.1371/journal.pone.0300894 (Apr 2024); https://doi.org/10.3389/fpsyt.2024.1399013 (May 2024). Schincariol et al. 2024, Psychol Med, doi:10.1017/S0033291724002319; Ahmed et al. 2024, Gen Psychiatry, doi:10.1136/gpsych-2023-101438; Andualem et al. 2024, Front Psychiatry, doi:10.3389/fpsyt.2024.1336665; Tesfaye et al. 2024, PLoS One, doi:10.1371/journal.pone.0300894; Tinsae et al. 2024, Front Psychiatry, doi:10.3389/fpsyt.2024.1399013; Pettrich et al. 2025, doi:10.1017/S2045796025100164 (schincariol2024posttraumaticstressdisorder pages 1-2, ahmed2024prevalenceofposttraumatic pages 1-2, andualem2024prevalenceofposttraumatic pages 1-2, tesfaye2024posttraumaticstressdisorder pages 1-2, tinsae2024posttraumaticstressdisorder pages 1-2, pettrich2025theprevalenceof pages 1-2)
Risk factors Sex: female sex repeatedly increases risk—OR 2.2 (95% CI 1.2–4.3) in Ethiopian war-affected communities; pooled OR 1.99 (95% CI 1.65–2.32) in African IDPs. Trauma severity/cumulative trauma: witnessing murder of a loved one OR 3.0; close family member killed/seriously injured OR 3.1; moderate/high perceived threat to life OR 3.4. In IDPs, dose-response for traumatic events: 4–7 events OR 2.09, 8–11 events OR 3.15, 12–16 events OR 5.37. Social/contextual: poor social support OR 4.4; no longer married OR 1.93; unemployment OR 1.92; repeated displacement OR 2.13; illness without medical care OR 1.92. Comorbidity: depression OR 2.97 in IDPs; depression symptoms OR 2.8 and anxiety symptoms OR 3.4 in Ethiopian war-affected communities. Interpersonal trauma is noted to produce more severe/lasting PTSD than many non-intentional events. Tinsae et al. 2024, Front Psychiatry, doi:10.3389/fpsyt.2024.1399013; Tesfaye et al. 2024, PLoS One, doi:10.1371/journal.pone.0300894; Schincariol et al. 2024, doi:10.1017/S0033291724002319 (tinsae2024posttraumaticstressdisorder pages 1-2, tinsae2024posttraumaticstressdisorder pages 10-11, tesfaye2024posttraumaticstressdisorder pages 15-16, tesfaye2024posttraumaticstressdisorder pages 1-2, schincariol2024posttraumaticstressdisorder pages 2-3)
Diagnostics Diagnostic approach: validated clinician-administered interviews should be used to establish diagnosis; screening tools should not be used alone to diagnose PTSD. Structured interviews: CAPS-5, CAPS-CA-5, PSSI-5. Self-report measures: PCL-5, PDS-5. ICD-11 PTSD/CPTSD tools: International Trauma Questionnaire (ITQ), ITQ-CA; International Trauma Interview validation also cited. Assessment caveats: PCL-5-based prevalence depends strongly on cut-off; one general-population study found cut-off methods aligned more with DSM-5 than ICD-11. PCL-5 lacks depersonalization/derealization items, so DSM-5 dissociative subtype may be missed. Questionnaires are faster but more bias-prone; interviews are more comprehensive but time-consuming. URLs: https://doi.org/10.1002/jts.23013 (Jan 2024); https://doi.org/10.1192/bja.2024.27 (Aug 2024); https://doi.org/10.1002/cpp.3012 (May 2024). Lang et al. 2024, J Trauma Stress, doi:10.1002/jts.23013; Siddaway 2024, doi:10.1192/bja.2024.27; Sarr et al. 2024, Clin Psychol Psychother, doi:10.1002/cpp.3012; Pettrich et al. 2025, doi:10.1017/S2045796025100164 (lang2024acliniciansguide pages 4-4, siddaway2024assessmentanddiagnosis pages 10-11, sarr2024asystematicreview pages 35-35, pettrich2025theprevalenceof pages 6-7, pettrich2025theprevalenceof pages 1-2)
Treatment 2023 VA/DoD first-line (“strong for”): trauma-focused psychotherapies CPT, EMDR, PE; first-line medications paroxetine, sertraline, venlafaxine. Trauma-focused psychotherapy is preferred first-line because meta-analyses show larger and more persistent improvement. Other options: Ehlers’ cognitive therapy, present-centered therapy, written exposure therapy (WET), and mindfulness-based stress reduction have weaker/supportive roles; prazosin is suggested against for overall PTSD but suggested for nightmares. Strong against: benzodiazepines and cannabis/cannabis derivatives. Guideline also suggests against invasive interventions such as ECT and vagus nerve stimulation for routine PTSD treatment because of limited efficacy evidence/harms. Some brief treatment formats in implementation/research: trauma-focused treatments often 8–16 sessions; WET can be 5 sessions. URLs: https://doi.org/10.1002/jts.23013 (Jan 2024); Figure summary from guideline article page 22. Lang et al. 2024, J Trauma Stress, doi:10.1002/jts.23013; Koven 2024, Eur J Med Health Res, doi:10.59324/ejmhr.2024.2(5).01; BMJ review 2024, doi:10.1136/bmj.h6161 (lang2024acliniciansguide pages 5-5, koven2024ptsdtreatmentliterature pages 1-2, koven2024ptsdtreatmentliterature pages 2-3, lang2024acliniciansguide media 0f51705c, geter2024posttraumaticstress pages 41-47)
Mechanisms Core pathophysiology: dysregulation of stress systems links limbic threat circuitry to endocrine and immune abnormalities. Canonical HPA cascade: amygdala/limbic input → hypothalamic CRH → pituitary ACTH → adrenal cortisol. Reviews report low cortisol / hypocortisolism, enhanced glucocorticoid receptor sensitivity, and stronger negative feedback in many PTSD cohorts. Inflammation/immune: elevated IL-6, TNF-α, IL-1β, chemokine changes, interferon-related gene expression, and reduced anti-inflammatory/regulatory cytokines. Neuroimmune mechanisms: microglia, astrocytes, mast cells, NLRP3-related signaling, COX-2/PGE2 pathways, endothelial-brain microvasculature signaling. Affected circuits/regions: amygdala, hippocampus, prefrontal cortex, PVN; consequences include impaired fear extinction, altered memory/emotion regulation, and possible neurodegenerative/somatic disease links. Epigenetics/genetics: FKBP5 and glucocorticoid signaling are repeatedly implicated; epigenetic reviews also highlight NR3C1, BDNF, and SLC6A4-related alterations. URLs: https://doi.org/10.1016/j.bbih.2024.100849 (Nov 2024); https://doi.org/10.1007/s11481-023-10064-z (Apr 2023); https://doi.org/10.1159/000541822 (Nov 2024). Lawrence & Scofield 2024, Brain Behav Immun Health, doi:10.1016/j.bbih.2024.100849; Govindula et al. 2023, J Neuroimmune Pharmacol, doi:10.1007/s11481-023-10064-z; Golubeva et al. 2024, Complex Psychiatry, doi:10.1159/000541822 (lawrence2024posttraumaticstress pages 5-5, lawrence2024posttraumaticstress pages 1-2, lawrence2024posttraumaticstress pages 2-4, govindula2023emphasizingthecrosstalk pages 1-2)
Trials Representative active/recent trials from ClinicalTrials.gov: STEPPS (NCT06947538; recruiting; Boston Medical Center; posted Apr 27 2025) tests a SMART stepped-care model using webSTAIR, coaching, Brief STAIR, and WET; nonresponse defined as <15-point decrease on PCL-5. Intranasal insulin for PTSD (NCT04044534; phase 2; recruiting; VA Connecticut; posted Aug 5 2019, updated Sep 16 2025) tests 40 IU twice daily with CAPS-5 outcome and amygdala hyperactivation rationale. tcVNS in Veterans with PTSD (NCT05517304; recruiting; VA ORD; posted Aug 26 2022, updated Mar 3 2026) evaluates PTSD symptoms, PET-measured insula activation, and IL-6. Group WET (NCT05729789; recruiting; St. Joseph’s Healthcare Hamilton; posted Feb 15 2023, updated Apr 17 2024) evaluates 6-session online group WET, hypothesizing low dropout (<10%) and symptom reduction. URLs: https://clinicaltrials.gov/study/NCT06947538 ; https://clinicaltrials.gov/study/NCT04044534 ; https://clinicaltrials.gov/study/NCT05517304 ; https://clinicaltrials.gov/study/NCT05729789 ClinicalTrials.gov records: NCT06947538; NCT04044534; NCT05517304; NCT05729789 (NCT06947538 chunk 1, NCT04044534 chunk 1, NCT05517304 chunk 1, NCT05729789 chunk 1)

Table: This table compiles high-yield PTSD facts for a knowledge base entry, including diagnostic frameworks, epidemiology, risk factors, diagnostics, treatment recommendations, mechanisms, and active clinical trials. It is designed to provide a compact but citation-rich snapshot anchored to the gathered evidence.


1. Disease information

1.1 Concise overview

PTSD is defined in authoritative clinical reviews as “a mental disorder that may develop after exposure to exceptionally threatening or horrifying events.” (BMJ, Nov 2024, DOI: https://doi.org/10.1136/bmj.h6161). (bisson2024posttraumaticstressdisorder pages 1-2)

1.2 Key identifiers (available from evidence)

  • MeSH (ClinicalTrials.gov browse term): Stress Disorders, Post-Traumatic (MeSH ID: D013313), visible in ClinicalTrials.gov-derived trial metadata. (NCT04044534 chunk 1)
  • MONDO / ICD-10 / ICD-11 code strings: Not retrieved in the currently available evidence; should be added from ICD-11 and MONDO resources directly.

1.3 Common synonyms / alternative names

  • Post-traumatic stress disorder; Posttraumatic stress disorder; PTSD. (bisson2024posttraumaticstressdisorder pages 1-2, schincariol2024posttraumaticstressdisorder pages 2-3)

1.4 Provenance of information

This report integrates aggregated disease-level sources: clinical guidelines/summaries, umbrella/systematic reviews and meta-analyses, and clinical trial registry records; it does not derive from individual EHR case reports (though some evidence relates to EHR/biobank approaches in the broader retrieved corpus). (lang2024acliniciansguide pages 5-5, schincariol2024posttraumaticstressdisorder pages 1-2, NCT06947538 chunk 1)


2. Etiology

2.1 Primary causal factors

PTSD requires exposure to a traumatic stressor (Criterion A–type exposure in DSM-5-TR; “extremely threatening or horrific event(s)” in ICD-11). (bisson2024posttraumaticstressdisorder pages 1-2, siddaway2024assessmentanddiagnosis pages 3-4)

2.2 Risk factors (quantitative, recent)

Conflict/displacement settings show particularly high pooled prevalence and strong associations with social/clinical risk factors. - War-affected Ethiopian communities (meta-analysis; May 2024; Frontiers in Psychiatry): pooled prevalence 48.4% (95% CI 37.1–59.8) with risk factors including female sex (OR 2.2), poor social support (OR 4.4), depression symptoms (OR 2.8), anxiety symptoms (OR 3.4), and threat/severity indicators (e.g., perceived threat to life OR 3.4). (https://doi.org/10.3389/fpsyt.2024.1399013). (tinsae2024posttraumaticstressdisorder pages 1-2) - Internally displaced persons (IDPs) in Africa (systematic review/meta-analysis; Apr 2024; PLOS ONE): pooled PTSD prevalence 51% (95% CI 38–64) and dose–response with number of traumatic events (e.g., 12–16 events OR 5.37). Other pooled risk factors include female sex (OR 1.99), depression (OR 2.97), repeated displacement (OR 2.13), and illness without medical care (OR 1.92). (https://doi.org/10.1371/journal.pone.0300894). (tesfaye2024posttraumaticstressdisorder pages 1-2) - Displaced people in Africa (Mar 2024; Frontiers in Psychiatry): pooled PTSD prevalence 55.64% (95% CI 42.76–68.41%); associated factors included female sex, unemployment, and depression. (https://doi.org/10.3389/fpsyt.2024.1336665). (andualem2024prevalenceofposttraumatic pages 1-2)

2.3 Protective factors

Direct quantitative protective-factor synthesis was limited in retrieved evidence. However, poor social support was strongly associated with PTSD in war-affected communities (OR 4.4), implying that strong social support is plausibly protective in those contexts. (tinsae2024posttraumaticstressdisorder pages 1-2)

2.4 Gene–environment interactions and polygenic risk (2023 evidence)

PTSD risk is partly genetically influenced and interacts with traumatic exposures. - In a prospective cohort of mild traumatic brain injury (TRACK-TBI; Translational Psychiatry; Jan 2023; DOI: https://doi.org/10.1038/s41398-023-02313-9), probable PTSD at 6 months occurred in 16.3% (116/714; PCL-5 ≥33). A PTSD polygenic risk score (PRS) significantly predicted PTSD: top PRS quintile vs lowest aOR 3.71 (95% CI 1.80–7.65), and adding PRS improved discrimination (AUC 0.687→0.733). Authors interpret PRS as potentially actionable for enhanced follow-up/early intervention, pending prospective validation. (stein2023polygenicriskfor pages 3-5)


3. Phenotypes

3.1 Core symptom domains (DSM-5-TR vs ICD-11)

DSM-5-TR groups symptoms into four clusters: intrusion; avoidance; negative alterations in cognitions and mood; and alterations in arousal and reactivity, with persistence >1 month and functional impairment. (schincariol2024posttraumaticstressdisorder pages 2-3, bisson2024posttraumaticstressdisorder pages 1-2)

ICD-11 defines PTSD with three core clusters: re-experiencing in the present; avoidance; and a persistent perception of heightened current threat, with symptoms lasting several weeks and causing distress/impairment; ICD-11 additionally recognizes complex PTSD (CPTSD) as a sibling diagnosis. (schincariol2024posttraumaticstressdisorder pages 2-3, siddaway2024assessmentanddiagnosis pages 3-4)

3.2 Suggested HPO mappings (examples)

(These are ontology suggestions; exact mapping should be verified against HPO.) - Intrusive memories/flashbacks → Recurrent intrusive memories; Flashback (HPO suggestion). - Nightmares → Nightmares (HPO suggestion). - Avoidance → Avoidant behavior (HPO suggestion). - Hypervigilance / exaggerated startle → Hypervigilance; Increased startle response (HPO suggestion). - Sleep disturbance/insomnia (not core ICD-11 but common DSM-5-TR symptom content) → Insomnia (HPO suggestion). (schincariol2024posttraumaticstressdisorder pages 2-3, bisson2024posttraumaticstressdisorder pages 1-2)

3.3 Comorbidities and functional impacts

  • PTSD and substance use disorders (SUDs) “co-occur at high rates,” with estimates “up to nearly 60%” comorbidity for alcohol and/or drug use disorder in PTSD populations (Journal of Traumatic Stress; Jun 2024; DOI: https://doi.org/10.1002/jts.23049). (back2024stateofthe pages 3-4)
  • PTSD has clinically relevant associations with physical illness (e.g., cardiovascular/metabolic/autoimmune/neurocognitive risk) in HPA-axis focused reviews; these are mechanistically linked to stress physiology and immune alterations. (lawrence2024posttraumaticstress pages 1-2)

4. Genetic / molecular information

4.1 Causal genes

No monogenic causal genes were supported in the retrieved evidence; PTSD is treated as a polygenic and multifactorial disorder with environmental necessity (trauma exposure). (barr2025multivariategenomewideassociation pages 1-4, stein2023polygenicriskfor pages 3-5)

4.2 Polygenic architecture (quantitative statements available)

A recent multivariate GWAS preprint summarizing background evidence reports twin-based heritability around 30–40% and SNP-based variance explained roughly 5–9% for PTSD (interpret cautiously as preprint/background). (barr2025multivariategenomewideassociation pages 1-4)

4.3 Epigenetic information (2024 review)

A 2024 epigenetics review emphasizes that environmental stressors can induce epigenetic changes relevant to PTSD, focusing on DNA methylation/chromatin regulation/noncoding RNA and highlighting gene systems related to HPA-axis regulation, neurotrophins, neurotransmission, and immune function. (Complex Psychiatry; Nov 2024; DOI: https://doi.org/10.1159/000541822). (hu2025thecentralrole pages 3-5)

4.4 Key limitation

The retrieved 2023–2024 corpus did not include a primary, large PTSD GWAS locus paper with a complete locus list; thus, locus-level curation is incomplete in this report.


5. Environmental information

5.1 Environmental factors and exposures

  • Conflict/war exposure and displacement are associated with markedly elevated PTSD prevalence (e.g., 23.70% among civilians in conflict-affected regions; 51–55% among displaced/IDP populations in Africa). (ahmed2024prevalenceofposttraumatic pages 1-2, tesfaye2024posttraumaticstressdisorder pages 1-2)

5.2 Lifestyle factors

Specific lifestyle exposures (diet, exercise) were not directly quantified in retrieved evidence; substance use is addressed under comorbidity and treatment evidence. (back2024stateofthe pages 3-4)

5.3 Infectious agents

Not applicable as a primary cause in the evidence retrieved.


6. Mechanism / pathophysiology

6.1 Causal chain (trigger → biology → symptoms)

A consistent contemporary mechanistic model is: 1) Trauma exposure initiates stress responses and threat-learning processes (diagnostic prerequisite). (bisson2024posttraumaticstressdisorder pages 1-2) 2) Stress-system dysregulation: the limbic system (including amygdala) influences hypothalamic CRH release → pituitary ACTH → adrenal cortisol; PTSD is often associated with low cortisol and heightened glucocorticoid receptor sensitivity and enhanced negative feedback. (Brain, Behavior, & Immunity–Health; Nov 2024; DOI: https://doi.org/10.1016/j.bbih.2024.100849). (lawrence2024posttraumaticstress pages 5-5) 3) Neuroimmune activation: elevated pro-inflammatory cytokines (e.g., IL-6, TNF-α, IL-1β) and reduced regulatory cytokines occur alongside stress physiology; immune signaling can influence brain function through endothelial/microglial/astrocytic mechanisms. (lawrence2024posttraumaticstress pages 5-5, govindula2023emphasizingthecrosstalk pages 1-2) 4) Circuit-level manifestations: altered function in hippocampus/amygdala/prefrontal cortex contributes to dysregulated fear extinction, emotional processing, memory re-experiencing, hypervigilance, and impaired executive control. (lawrence2024posttraumaticstress pages 5-5)

6.2 Molecular pathways / suggested GO terms (examples)

(These are ontology suggestions; verify in GO for exact labels.) - HPA axis signaling / glucocorticoid response: “response to glucocorticoid”; “regulation of hormone secretion”. (lawrence2024posttraumaticstress pages 5-5) - Inflammatory signaling: “cytokine-mediated signaling pathway”; “inflammatory response”; “interferon signaling”. (lawrence2024posttraumaticstress pages 5-5, govindula2023emphasizingthecrosstalk pages 1-2) - COX-2/PGE2 axis: “prostaglandin biosynthetic process”; “cyclooxygenase pathway” (suggested). (govindula2023emphasizingthecrosstalk pages 1-2)

6.3 Cell types / suggested CL terms (examples)

  • Microglia (CL suggestion); Astrocytes (CL suggestion); Mast cells (CL suggestion) are explicitly implicated in neuroinflammatory mechanisms in PTSD-focused HPA/immune reviews. (lawrence2024posttraumaticstress pages 5-5)

7. Anatomical structures affected (UBERON suggestions)

Primary neuroanatomical structures repeatedly implicated include: - Amygdala (UBERON suggestion) (lawrence2024posttraumaticstress pages 5-5) - Hippocampus (UBERON suggestion) (lawrence2024posttraumaticstress pages 5-5) - Prefrontal cortex (UBERON suggestion) (lawrence2024posttraumaticstress pages 5-5) - Hypothalamic paraventricular nucleus (PVN) (UBERON suggestion) (govindula2023emphasizingthecrosstalk pages 1-2)

An example of ongoing mechanistically motivated neuromodulation research targets insula activation via imaging outcomes (see tcVNS trial). (NCT05517304 chunk 1)


8. Temporal development

8.1 Onset and duration thresholds

  • DSM-5-TR: symptoms persist >1 month. (schincariol2024posttraumaticstressdisorder pages 2-3)
  • ICD-11: symptoms persist “several weeks.” (schincariol2024posttraumaticstressdisorder pages 2-3)

8.2 Course, chronicity, and recurrence

A 2024 umbrella review reports that World Mental Health Surveys estimate 25–40% recover within 12 months (many within 6 months), while meta-analyses suggest nearly 50% may develop chronic PTSD if untreated. (schincariol2024posttraumaticstressdisorder pages 2-3)

A 2024 systematic review on PTSD recurrence concludes terminology/definitions are inconsistent and meta-analysis was not possible, indicating uncertainty around recurrence prevalence and predictors. (schincariol2024posttraumaticstressdisorder pages 2-3)


9. Inheritance and population

9.1 Epidemiology (recent quantitative estimates)

  • Umbrella review of PTSD prevalence (Psychological Medicine; Sep 2024; DOI: https://doi.org/10.1017/S0033291724002319): pooled prevalence 23.95% (95% CI 20.74–27.15) across trauma-exposed contexts/reviews, with substantial heterogeneity. (schincariol2024posttraumaticstressdisorder pages 1-2)
  • Conflict-affected civilians (General Psychiatry; Jun 2024; DOI: https://doi.org/10.1136/gpsych-2023-101438): pooled prevalence 23.70% (95% CI 19.50–28.40). (ahmed2024prevalenceofposttraumatic pages 1-2)
  • German general population survey (Epidemiology and Psychiatric Sciences; Aug 2025; DOI: https://doi.org/10.1017/S2045796025100164): 47.2% reported ≥1 lifetime traumatic event; probable PTSD 4.7% under both DSM-5 and ICD-11 screening algorithms. (pettrich2025theprevalenceof pages 1-2)

9.2 Sex ratio

Pooled evidence in African displacement/war-affected meta-analyses shows higher risk for women (e.g., OR 1.99 in IDPs; OR 2.2 in Ethiopian war-affected communities). (tesfaye2024posttraumaticstressdisorder pages 1-2, tinsae2024posttraumaticstressdisorder pages 1-2)

9.3 Genetic architecture

Polygenic risk contributes to susceptibility (see PRS evidence), but no Mendelian inheritance pattern is supported. (stein2023polygenicriskfor pages 3-5)


10. Diagnostics

10.1 Clinical criteria (DSM-5-TR; ICD-11)

  • DSM-5-TR requires qualifying exposure and 4 symptom clusters with >1 month duration and functional impairment. (schincariol2024posttraumaticstressdisorder pages 2-3, bisson2024posttraumaticstressdisorder pages 1-2)
  • ICD-11 emphasizes 3 core symptom clusters and includes CPTSD as a related diagnosis. (schincariol2024posttraumaticstressdisorder pages 2-3)

10.2 Validated assessments (with implementation caveats)

  • The 2023 VA/DoD clinician guide emphasizes that diagnosis should be established with validated clinician-administered interviews such as CAPS-5 or the PTSD Symptom Scale–Interview (PSS-I) and that screening tools should not be used alone to establish a diagnosis (Journal of Traumatic Stress; Jan 2024; DOI: https://doi.org/10.1002/jts.23013). (lang2024acliniciansguide pages 4-4)
  • Structured interviews and self-report instruments include CAPS-5/CAPS-CA-5/PSSI-5 and self-report measures such as PDS-5, with ICD-11-aligned measures including ITQ and ITQ-CA for PTSD/CPTSD. (siddaway2024assessmentanddiagnosis pages 10-11)
  • Population screening work shows cut-off selection on PCL-5 markedly affects prevalence estimates and that DSM-5 vs ICD-11 algorithms can identify partially distinct cases despite similar overall prevalence. (pettrich2025theprevalenceof pages 4-5)

10.3 Biomarkers and imaging

No validated, scalable diagnostic biomarkers were established in the evidence. Reviews highlight cortisol-axis markers and inflammatory cytokines (e.g., IL-6, TNF-α) as biologically plausible but heterogeneous across studies and sensitive to sampling and comorbidity. (lawrence2024posttraumaticstress pages 2-4, lawrence2024posttraumaticstress pages 5-5)


11. Outcome / prognosis

Quantitative prognosis evidence in the retrieved corpus is limited; the umbrella review-derived course estimates suggest substantial early recovery for a subset (25–40% within 12 months) but substantial chronicity risk if untreated (~50%). (schincariol2024posttraumaticstressdisorder pages 2-3)


12. Treatment

12.1 First-line treatments (authoritative guideline synthesis; 2023 VA/DoD)

A clinician’s guide to the 2023 VA/DoD Clinical Practice Guideline (Journal of Traumatic Stress; Jan 2024; DOI: https://doi.org/10.1002/jts.23013) emphasizes trauma-focused psychotherapies as first-line and recommends starting with one of three recommended trauma-focused treatments when feasible, using shared decision-making. (lang2024acliniciansguide pages 5-5)

From the guideline summary figure, “strong for” interventions include: - Psychotherapies: Cognitive Processing Therapy (CPT), Eye Movement Desensitization and Reprocessing (EMDR), Prolonged Exposure (PE). (lang2024acliniciansguide media 0f51705c) - Medications: paroxetine, sertraline, venlafaxine. (lang2024acliniciansguide media 0f51705c)

“Strong against” includes benzodiazepines and cannabis/cannabis derivatives. (lang2024acliniciansguide media 0f51705c, lang2024acliniciansguide pages 5-5)

12.2 Other psychotherapies and adjuncts

The guideline also suggests additional psychotherapies (e.g., Written Exposure Therapy; Present-Centered Therapy; Ehlers’ cognitive therapy) and mind–body approaches such as mindfulness-based stress reduction. (lang2024acliniciansguide pages 5-5)

12.3 Pharmacotherapy nuances

The guideline suggests against prazosin for overall PTSD treatment but suggests prazosin for PTSD-related nightmares. (lang2024acliniciansguide pages 5-5)

12.4 Comorbid PTSD and substance use disorders (SUD)

A 2024 state-of-the-science review reports that rigorously conducted trials support individual, manualized, trauma-focused treatments for PTSD/SUD, and that patients do not need to be abstinent to benefit. It highlights COPE (integrating Prolonged Exposure with CBT for SUD) as the most studied integrated treatment, with evidence for reductions in PTSD symptoms and substance use and improved remission outcomes, delivered in-person and via telehealth. (Journal of Traumatic Stress; Jun 2024; DOI: https://doi.org/10.1002/jts.23049). (back2024stateofthe pages 3-4)

12.5 Suggested MAXO terms (examples)

(Verify exact MAXO IDs in downstream curation.) - Trauma-focused psychotherapy; prolonged exposure therapy; cognitive processing therapy; EMDR; SSRI administration; SNRI administration; prazosin administration for nightmares; shared decision-making in care planning. (lang2024acliniciansguide media 0f51705c, lang2024acliniciansguide pages 5-5)


13. Prevention

13.1 Evidence status

The VA/DoD clinician guide states that no pharmacological interventions had sufficient evidence to recommend for prevention of PTSD or acute stress disorder. (lang2024acliniciansguide pages 5-5)

13.2 Emerging early-intervention / stepped-care implementation research

A SMART stepped-care trial (STEPPS; NCT06947538; first posted Apr 27 2025; recruiting) aims to improve PTSD treatment access/engagement via a sequence of a digital intervention (webSTAIR), coaching, and brief clinician-administered treatments (Brief STAIR, WET), reflecting real-world implementation priorities in routine care. (ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT06947538). (NCT06947538 chunk 1)


14. Other species / natural disease

PTSD is a human psychiatric diagnosis; however, mechanistic evidence relies heavily on preclinical stress models.

Preclinical support for inflammation-linked mechanisms: A 2024 review cites rodent evidence that PTSD-like symptoms were reduced after chronic inflammation treatment with ibuprofen, supporting a causal role for inflammation in symptom expression (preclinical). (lawrence2024posttraumaticstress pages 5-5)


15. Model organisms

Detailed model-organism cataloging was not retrieved; available evidence supports that animal stress paradigms are used to interrogate inflammatory mediators (e.g., COX-2/PGE2 signaling and cytokines) and HPA-axis dysregulation in PTSD-like phenotypes. (govindula2023emphasizingthecrosstalk pages 1-2)


Recent developments and real-world applications (2023–2024 emphasis)

1) Guideline evolution and implementation focus: The 2023 VA/DoD guideline (described in 2024) centers trauma-focused psychotherapy first-line, shared decision-making, and cautions against benzodiazepines/cannabis; this directly influences real-world care systems (e.g., VA and civilian implementation projects) and informs stepped-care/digital delivery research. (lang2024acliniciansguide pages 5-5, lang2024acliniciansguide media 0f51705c, NCT06947538 chunk 1)

2) High-burden humanitarian contexts: 2024 meta-analyses quantify PTSD prevalence in armed conflict and displacement, supporting prioritization of scalable, culturally sensitive services in LMIC and conflict settings. (ahmed2024prevalenceofposttraumatic pages 1-2, tesfaye2024posttraumaticstressdisorder pages 1-2, andualem2024prevalenceofposttraumatic pages 1-2)

3) Precision mental health directions: 2023 evidence indicates polygenic risk scores can stratify risk for PTSD after a defined trauma exposure (mTBI), suggesting an emerging path toward targeted follow-up and early intervention trials. (stein2023polygenicriskfor pages 3-5)


Limitations of this evidence synthesis (important for knowledge-base use)

  • ICD-10/ICD-11 code strings and MONDO ID were not retrieved in the evidence state and should be added from the official classification/ontology sources.
  • Locus-level details from the most recent large PTSD GWAS (2023–2024) were not available in retrieved full texts; genetic findings here therefore emphasize PRS and general heritability rather than comprehensive locus enumeration.
  • Differential diagnosis content and some phenotype frequency estimates beyond prevalence (e.g., symptom-level frequencies) were limited in the retrieved evidence.

Key URLs (selected)

  • VA/DoD clinician guide summary (Jan 2024): https://doi.org/10.1002/jts.23013 (lang2024acliniciansguide pages 5-5)
  • BMJ clinical review (Nov 2024): https://doi.org/10.1136/bmj.h6161 (bisson2024posttraumaticstressdisorder pages 1-2)
  • PTSD prevalence umbrella review (Sep 2024): https://doi.org/10.1017/S0033291724002319 (schincariol2024posttraumaticstressdisorder pages 1-2)
  • Conflict-affected civilians meta-analysis (Jun 2024): https://doi.org/10.1136/gpsych-2023-101438 (ahmed2024prevalenceofposttraumatic pages 1-2)
  • IDPs in Africa meta-analysis (Apr 2024): https://doi.org/10.1371/journal.pone.0300894 (tesfaye2024posttraumaticstressdisorder pages 1-2)
  • HPA-axis dysregulation review (Nov 2024): https://doi.org/10.1016/j.bbih.2024.100849 (lawrence2024posttraumaticstress pages 5-5)
  • Stepped-care trial STEPPS: https://clinicaltrials.gov/study/NCT06947538 (NCT06947538 chunk 1)

References

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