Chacko Thomas P, Toole J Tory, Morris Matthew C, Page Jeffrey, Forsten Robert D, Barrett John P, Reinhard Matthew J, Brewster Ryan C, Costanzo Michelle E, Broderick Gordon
Center for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, United States.
War Related Illness and Injury Study Center (WRIISC), Department of Veterans Affairs, Washington, DC, United States.
Front Psychiatry. 2023 Oct 27;14:1180929. doi: 10.3389/fpsyt.2023.1180929. eCollection 2023.
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.
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 = 6 subjects.
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.
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.
2016年，在古巴哈瓦那任职的外交人员开始报告可听到的感官现象，同时伴有与脑损伤相符的复杂且持续的神经症状。这些异常健康事件（AHI）及其后续症状的病因仍然不明。本报告通过构建已发表的生物行为途径网络模型，并利用已发表文献中的现有数据评估此类途径的失调如何解释这些受试者的功能丧失，来研究假定的暴露-症状病理。鉴于其表现与轻度创伤性脑损伤（mTBI）相似，我们将后者作为一种临床相关手段，以评估在哈瓦那综合征中观察到的神经心理学特征是否至少部分可由神经传递、神经炎症或两者的失调来解释。
对9000多篇出版物进行自动文本挖掘，生成了一个网络，该网络由273个已记录的调节相互作用组成，将29种神经化学标记与来自简易情绪调查、创伤后应激障碍检查表和额叶系统行为量表的9种神经心理学结构联系起来。对通过该网络的信息流进行分析，得出了一组调节规则，这些规则与已知机制途径的偏差在6%以内，与6名受试者的神经心理学特征相符。
联合满足已记录途径和观察到的症状特征的神经化学标记的预测表达显示，在脑源性神经营养因子（BDNF）、胶质细胞源性神经营养因子（GDNF）、胰岛素样生长因子1（IGF1）和谷氨酸表达降低的情况下，白细胞介素-1β（IL-1B）、白细胞介素-10（IL-10）、神经生长因子（NGF）和去甲肾上腺素水平显著升高（错误发现率<5%）。促肾上腺皮质激素释放激素（CRH）和白细胞介素-6（IL-6）的升高在所有受试者中也得到了一致预测。此外，神经调节动力学模拟显示，受试者似乎并未“陷入”持续性疾病，而是似乎处于缓慢的恢复轨迹。
对驻哈瓦那外交官所测神经心理学症状的这种计算分析表明，这些AHI症状可能部分由与mTBI相关的已知神经免疫和神经传递调节机制的破坏所支持。
