Fryar-Williams Stephanie, Tucker Graeme, Clements Peter, Strobel Jörg
Youth in Mind Research Institute, Unley, SA 5061, Australia.
Department of Medical Specialities, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5000, Australia.
Int J Mol Sci. 2024 Dec 12;25(24):13348. doi: 10.3390/ijms252413348.
The ( C677T gene polymorphism is associated with neurological disorders and schizophrenia. Patients diagnosed with schizophrenia and schizoaffective disorder and controls ( 134) had data collected for risk factors, molecular and neuro-sensory variables, symptoms, and functional outcomes. Promising gene variant-related predictive biomarkers were identified for diagnosis by Receiver Operating Characteristics and for illness duration by linear regression. These were then analyzed using Spearman's correlation in relation to the duration of illness. Significant correlations were ranked by strength and plotted on graphs for each C677T variant. Homozygous 677 TT carriers displayed a mid-illness switch to depression, with suicidality and a late-phase shift from lower to higher methylation, with activated psychosis symptoms. 677 CC variant carriers displayed significant premorbid correlates for family history, developmental disorder, learning disorder, and head injury. These findings align with those of low methylation, oxidative stress, multiple neuro-sensory processing deficits, and disability outcomes. Heterozygous 677 CT carriers displayed multiple shifts in mood and methylation with multiple adverse outcomes. The graphically presented ranked biomarker correlates for illness duration allow a perspective of psychosis development across gene variants, with the potential for phase of illness monitoring and new therapeutic insights to prevent or delay psychosis and its adverse outcomes.
（C677T基因多态性与神经疾病和精神分裂症有关。对被诊断为精神分裂症和分裂情感性障碍的患者以及对照组（134人）收集了风险因素、分子和神经感觉变量、症状及功能结果的数据。通过受试者工作特征曲线确定了有前景的与基因变异相关的预测生物标志物用于诊断，并通过线性回归确定用于疾病持续时间的生物标志物。然后使用斯皮尔曼相关性分析这些生物标志物与疾病持续时间的关系。根据强度对显著相关性进行排序，并针对每个C677T变异绘制图表。纯合子677 TT携带者在疾病中期转向抑郁，伴有自杀倾向，在后期从低甲基化转变为高甲基化，伴有精神病性症状激活。677 CC变异携带者在病前与家族史、发育障碍、学习障碍和头部损伤有显著相关性。这些发现与低甲基化、氧化应激、多种神经感觉处理缺陷及残疾结果的发现一致。杂合子677 CT携带者在情绪和甲基化方面有多次转变，伴有多种不良后果。以图表形式呈现的按疾病持续时间排序的生物标志物相关性，能够从基因变异角度了解精神病的发展情况，具有监测疾病阶段以及获得预防或延缓精神病及其不良后果的新治疗见解的潜力。
