A regulatory pathway model of neuropsychological disruption in Havana syndrome
IntroductionIn 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....
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1180929/full |
| _version_ | 1797646904051367936 |
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| author | Thomas P. Chacko J. Tory Toole Matthew C. Morris Jeffrey Page Robert D. Forsten John P. Barrett John P. Barrett Matthew J. Reinhard Matthew J. Reinhard Ryan C. Brewster Michelle E. Costanzo Michelle E. Costanzo Michelle E. Costanzo Gordon Broderick Gordon Broderick |
| author_facet | Thomas P. Chacko J. Tory Toole Matthew C. Morris Jeffrey Page Robert D. Forsten John P. Barrett John P. Barrett Matthew J. Reinhard Matthew J. Reinhard Ryan C. Brewster Michelle E. Costanzo Michelle E. Costanzo Michelle E. Costanzo Gordon Broderick Gordon Broderick |
| author_sort | Thomas P. Chacko |
| collection | DOAJ |
| description | IntroductionIn 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.MethodAutomated 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.ResultsPredicted 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.DiscussionThis 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. |
| first_indexed | 2024-03-11T15:09:34Z |
| format | Article |
| id | doaj.art-2fc1da81a36f4437a6624aaecfecb611 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-03-11T15:09:34Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-2fc1da81a36f4437a6624aaecfecb6112023-10-29T16:52:46ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402023-10-011410.3389/fpsyt.2023.11809291180929A regulatory pathway model of neuropsychological disruption in Havana syndromeThomas P. Chacko0J. Tory Toole1Matthew C. Morris2Jeffrey Page3Robert D. Forsten4John P. Barrett5John P. Barrett6Matthew J. Reinhard7Matthew J. Reinhard8Ryan C. Brewster9Michelle E. Costanzo10Michelle E. Costanzo11Michelle E. Costanzo12Gordon Broderick13Gordon Broderick14Center for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, United StatesCenter for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, United StatesCenter for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, United StatesCenter for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, United StatesWar Related Illness and Injury Study Center (WRIISC), Department of Veterans Affairs, Washington, DC, United StatesWar Related Illness and Injury Study Center (WRIISC), Department of Veterans Affairs, Washington, DC, United StatesDepartment of Preventive Medicine and Biostatistics, Uniformed Services University, Bethesda, MD, United StatesWar Related Illness and Injury Study Center (WRIISC), Department of Veterans Affairs, Washington, DC, United StatesComplex Exposures Threats Center, Department of Veterans Affairs, Washington, DC, United StatesWar Related Illness and Injury Study Center (WRIISC), Department of Veterans Affairs, Washington, DC, United StatesWar Related Illness and Injury Study Center (WRIISC), Department of Veterans Affairs, Washington, DC, United StatesComplex Exposures Threats Center, Department of Veterans Affairs, Washington, DC, United StatesDepartment of Medicine, Uniformed Services University, Bethesda, MD, United StatesCenter for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, United StatesComplex Exposures Threats Center, Department of Veterans Affairs, Washington, DC, United StatesIntroductionIn 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.MethodAutomated 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.ResultsPredicted 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.DiscussionThis 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.https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1180929/fullneuropsychologyneuroimmunologyneurotransmissionmild traumatic brain injurycomputational modelregulatory pathways |
| spellingShingle | Thomas P. Chacko J. Tory Toole Matthew C. Morris Jeffrey Page Robert D. Forsten John P. Barrett John P. Barrett Matthew J. Reinhard Matthew J. Reinhard Ryan C. Brewster Michelle E. Costanzo Michelle E. Costanzo Michelle E. Costanzo Gordon Broderick Gordon Broderick A regulatory pathway model of neuropsychological disruption in Havana syndrome Frontiers in Psychiatry neuropsychology neuroimmunology neurotransmission mild traumatic brain injury computational model regulatory pathways |
| title | A regulatory pathway model of neuropsychological disruption in Havana syndrome |
| title_full | A regulatory pathway model of neuropsychological disruption in Havana syndrome |
| title_fullStr | A regulatory pathway model of neuropsychological disruption in Havana syndrome |
| title_full_unstemmed | A regulatory pathway model of neuropsychological disruption in Havana syndrome |
| title_short | A regulatory pathway model of neuropsychological disruption in Havana syndrome |
| title_sort | regulatory pathway model of neuropsychological disruption in havana syndrome |
| topic | neuropsychology neuroimmunology neurotransmission mild traumatic brain injury computational model regulatory pathways |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1180929/full |
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