A regulatory pathway model of neuropsychological disruption in Havana syndrome
Abstract
A regulatory pathway model of neuropsychological disruption in Havana syndrome Chacko TP, Toole JT, Morris MC, Page J, Forsten RD, Barrett JP, Reinhard MJ, Brewster RC, Costanzo ME, Broderick G. A regulatory pathway model of neuropsychological disruption in Havana syndrome. Front Psychiatry. 2023 Oct 27;14:1180929. doi: 10.3389/fpsyt.2023.1180929. Abstract Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. The etiology of these Anomalous Health Incidents (AHI) and subsequent symptoms remains unknown. This report investigates putative exposure-symptom pathology by assembling a network model of published bio- behavioral pathways and assessing how dysregulation of such pathways might explain loss of function in these subjects using data available in the published literature. Given similarities in presentation with mild traumatic brain injury (mTBI), we used the latter as a clinically relevant means of evaluating if the neuropsychological profiles observed in Havana Syndrome Havana Syndrome might be explained at least in part by a dysregulation of neurotransmission, neuro-inflammation, or both. Method: Automated text-mining of >9,000 publications produced a network consisting of 273 documented regulatory interactions linking 29 neuro-chemical markers with 9 neuropsychological constructs from the Brief Mood Survey, PTSD Checklist, and the Frontal Systems Behavior Scale. Analysis of information flow through this network produced a set of regulatory rules reconciling to within a 6% departure known mechanistic pathways with neuropsychological profiles in N = 6 subjects. Results: Predicted expression of neuro-chemical markers that jointly satisfy documented pathways and observed symptom profiles display characteristically elevated IL-1B, IL-10, NGF, and norepinephrine levels in the context of depressed BDNF, GDNF, IGF1, and glutamate expression (FDR < 5%). Elevations in CRH and IL-6 were also predicted unanimously across all subjects. Furthermore, simulations of neurological regulatory dynamics reveal subjects do not appear to be “locked in” persistent illness but rather appear to be engaged in a slow recovery trajectory. Discussion: This computational analysis of measured neuropsychological symptoms in Havana-based diplomats proposes that these AHI symptoms may be supported in part by disruption of known neuroimmune and neurotransmission regulatory mechanisms also associated with mTBI. Open access paper: frontiersin.org
AI evidence extraction
Main findings
Using automated text-mining of >9,000 publications, the authors built a regulatory network linking neurochemical markers to neuropsychological constructs and derived regulatory rules that reconciled known mechanistic pathways with observed symptom profiles in N=6 subjects within a reported 6% departure. The model predicted elevated IL-1B, IL-10, NGF, and norepinephrine with depressed BDNF, GDNF, IGF1, and glutamate (FDR < 5%), and unanimously predicted elevations in CRH and IL-6 across subjects. Simulations suggested subjects were not "locked in" persistent illness but were on a slow recovery trajectory.
Outcomes measured
- Neuropsychological symptom profiles (Brief Mood Survey, PTSD Checklist, Frontal Systems Behavior Scale)
- Predicted neurochemical marker expression patterns (e.g., IL-1B, IL-10, NGF, norepinephrine, BDNF, GDNF, IGF1, glutamate, CRH, IL-6)
- Modeled recovery trajectory (simulated regulatory dynamics)
Limitations
- Etiology/exposure source is described as unknown; no specific EMF/RF exposure characterization is provided in the abstract
- Very small sample size (N=6)
- Computational/network modeling based on published literature and symptom measures; predicted biomarkers are not described as directly measured in subjects in the abstract
- Findings are framed as putative/mechanistic support and may not establish causation
View raw extracted JSON
{
"publication_year": 2023,
"study_type": "other",
"exposure": {
"band": null,
"source": null,
"frequency_mhz": null,
"sar_wkg": null,
"duration": null
},
"population": "Diplomatic personnel serving in Havana, Cuba (Havana syndrome / Anomalous Health Incidents subjects)",
"sample_size": 6,
"outcomes": [
"Neuropsychological symptom profiles (Brief Mood Survey, PTSD Checklist, Frontal Systems Behavior Scale)",
"Predicted neurochemical marker expression patterns (e.g., IL-1B, IL-10, NGF, norepinephrine, BDNF, GDNF, IGF1, glutamate, CRH, IL-6)",
"Modeled recovery trajectory (simulated regulatory dynamics)"
],
"main_findings": "Using automated text-mining of >9,000 publications, the authors built a regulatory network linking neurochemical markers to neuropsychological constructs and derived regulatory rules that reconciled known mechanistic pathways with observed symptom profiles in N=6 subjects within a reported 6% departure. The model predicted elevated IL-1B, IL-10, NGF, and norepinephrine with depressed BDNF, GDNF, IGF1, and glutamate (FDR < 5%), and unanimously predicted elevations in CRH and IL-6 across subjects. Simulations suggested subjects were not \"locked in\" persistent illness but were on a slow recovery trajectory.",
"effect_direction": "unclear",
"limitations": [
"Etiology/exposure source is described as unknown; no specific EMF/RF exposure characterization is provided in the abstract",
"Very small sample size (N=6)",
"Computational/network modeling based on published literature and symptom measures; predicted biomarkers are not described as directly measured in subjects in the abstract",
"Findings are framed as putative/mechanistic support and may not establish causation"
],
"evidence_strength": "low",
"confidence": 0.7399999999999999911182158029987476766109466552734375,
"peer_reviewed_likely": "yes",
"stance": "neutral",
"stance_confidence": 0.66000000000000003108624468950438313186168670654296875,
"summary": "This paper reports a computational regulatory pathway model intended to explain neuropsychological disruption reported in Havana syndrome/Anomalous Health Incidents, with etiology stated as unknown. Automated text-mining of >9,000 publications was used to build a network linking neurochemical markers to neuropsychological constructs, and the model was applied to symptom data from six subjects. The analysis predicted a pattern of neuroimmune and neurotransmission dysregulation and simulated a slow recovery trajectory.",
"key_points": [
"The study addresses Havana syndrome/AHI symptoms in diplomats and notes the etiology remains unknown.",
"Automated text-mining of >9,000 publications generated a network of 273 regulatory interactions linking 29 neurochemical markers to 9 neuropsychological constructs.",
"Neuropsychological constructs were derived from the Brief Mood Survey, PTSD Checklist, and Frontal Systems Behavior Scale.",
"Regulatory rules from the network were reported to match observed symptom profiles in N=6 subjects within a 6% departure.",
"The model predicted elevated IL-1B, IL-10, NGF, and norepinephrine with depressed BDNF, GDNF, IGF1, and glutamate (FDR < 5%).",
"Elevations in CRH and IL-6 were predicted unanimously across all subjects.",
"Simulations suggested subjects were not in a fixed persistent-illness state but in a slow recovery trajectory.",
"The discussion proposes symptoms may be supported in part by neuroimmune and neurotransmission dysregulation mechanisms also associated with mild traumatic brain injury."
],
"categories": [
"Havana Syndrome",
"Neuropsychology",
"Neuroinflammation",
"Computational Modeling"
],
"tags": [
"Havana Syndrome",
"Anomalous Health Incidents",
"Diplomats",
"Regulatory Network Model",
"Text Mining",
"Neuroinflammation",
"Neurotransmission",
"Cytokines",
"Interleukins",
"BDNF",
"IL-6",
"CRH",
"Mild Traumatic Brain Injury",
"PTSD Checklist",
"Frontal Systems Behavior Scale"
],
"keywords": [
"Havana syndrome",
"Anomalous Health Incidents",
"neuropsychological disruption",
"regulatory pathway model",
"text-mining",
"network model",
"neuroimmune",
"neurotransmission",
"mTBI",
"IL-1B",
"IL-10",
"NGF"
],
"suggested_hubs": [],
"social": {
"tweet": "Front Psychiatry (2023): Computational text-mining/network model links Havana syndrome symptom profiles (N=6) to predicted neuroimmune/neurotransmission dysregulation (e.g., IL-6, CRH) and suggests a slow recovery trajectory; etiology remains unknown.",
"facebook": "A Frontiers in Psychiatry (2023) paper uses automated text-mining of >9,000 publications to build a regulatory network model connecting neurochemical markers to neuropsychological constructs in Havana syndrome/AHI. Applied to symptom data from six subjects, the model predicts neuroimmune and neurotransmission dysregulation and simulates a slow recovery trajectory; the etiology is described as unknown.",
"linkedin": "Frontiers in Psychiatry (2023) presents a computational regulatory pathway model for neuropsychological disruption in Havana syndrome/AHI. Using text-mining of >9,000 publications, the authors built a network linking neurochemical markers to neuropsychological constructs and applied it to symptom profiles in N=6 subjects, predicting neuroimmune/neurotransmission dysregulation and a slow recovery trajectory; etiology remains unknown."
}
}
AI can be wrong. Always verify against the paper.
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