Table_2_A systems biology approach for discovering the cellular and molecular aspects of psychogenic non-epileptic seizure.XLSX

ObjectivesPsychogenic non-epileptic seizure (PNES) is the most common non-epileptic disorder in patients referring to epilepsy centers. Contrary to common beliefs about the disease’s harmlessness, the death rate of PNES patients is similar to drug-resistant epilepsy. Meanwhile, the molecular pathomechanism of PNES is unknown with very limited related research. Thus, the aim of this in silico study was to find different proteins and hormones associated with PNES via a systems biology approach.
MethodsDifferent bioinformatics databases and literature review were used to find proteins associated with PNES. The protein-hormone interaction network of PNES was constructed to discover its most influential compartments. The pathways associated with PNES pathomechanism were found by enrichment analysis of the identified proteins. Besides, the relationship between PNES-related molecules and psychiatric diseases was discovered, and the brain regions that could express altered levels of blood proteins were discovered.
ResultsEight genes and three hormones were found associated with PNES through the review process. Proopiomelanocortin (POMC), neuropeptide Y (NPY), cortisol, norepinephrine, and brain-derived neurotrophic factor (BDNF) were identified to have a high impact on the disease pathogenesis network. Moreover, activation of Janus kinase-signaling transducer and activator of transcription (JAK–STAT) and JAK, as well as signaling of growth hormone receptor, phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT), and neurotrophin were found associated with PNES molecular mechanism. Several psychiatric diseases such as depression, schizophrenia, and alcohol-related disorders were shown to be associated with PNES predominantly through signaling molecules.
SignificanceThis study was the first to gather the biochemicals associated with PNES. Multiple components and pathways and several psychiatric diseases associated with PNES, and some brain regions that could be altered during PNES were suggested, which should be confirmed in further studies. Altogether, these findings could be used in future molecular research on PNES patients.

研究目的：心因性非癫痫性发作（Psychogenic non-epileptic seizure, PNES）是转诊至癫痫中心的患者中最常见的非癫痫性疾病。与大众对该疾病良性无害的认知相悖，PNES患者的死亡率与耐药性癫痫相当。与此同时，PNES的分子发病机制尚不明确，相关研究亦极为匮乏。因此，本项计算生物学研究的目的在于通过系统生物学方法，筛选与PNES相关的各类蛋白质与激素。
研究方法：本研究通过检索多类生物信息学数据库并结合文献综述，筛选与PNES相关的蛋白质；随后构建PNES的蛋白质-激素相互作用网络，以识别其中的核心调控模块；通过对筛选得到的蛋白质进行富集分析，明确与PNES发病机制相关的信号通路。此外，本研究还揭示了PNES相关分子与精神疾病之间的关联，并确定了可出现血液蛋白水平异常表达的脑区。
研究结果：经文献综述与数据库检索，本研究共筛选得到8个基因与3种与PNES相关的激素。阿黑皮素原（Proopiomelanocortin, POMC）、神经肽Y（Neuropeptide Y, NPY）、皮质醇、去甲肾上腺素以及脑源性神经营养因子（Brain-derived neurotrophic factor, BDNF）被证实对PNES的发病网络具有显著调控作用。此外，本研究发现贾纳斯激酶-信号转导与转录激活因子（Janus kinase-signaling transducer and activator of transcription, JAK-STAT）通路及贾纳斯激酶的激活，以及生长激素受体、磷脂酰肌醇3-激酶/蛋白激酶B（Phosphatidylinositol 3-kinase /Protein kinase B, PI3K/AKT）和神经营养素的信号转导均与PNES的分子机制相关。多项精神疾病，如抑郁症、精神分裂症及酒精相关障碍，均主要通过信号分子与PNES产生关联。
研究意义：本研究为首个系统性汇总PNES相关生物化学物质的研究。本研究明确了多个与PNES相关的分子组分、信号通路及精神疾病，并提出了PNES发病过程中可能出现异常的脑区，上述结论尚需后续研究进一步验证。综上，本研究结果可为未来针对PNES患者的分子生物学研究提供参考依据。