Cerebrospinal fluid proteomic signatures are associated with symptom severity of first-episode psychosis.
Cerebrospinal fluid proteomic signatures are associated with symptom severity of first-episode psychosis.
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DOI：
10.1016/j.jpsychires.2024.02.002
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发表时间：
2024-02
影响因子：
4.8
通讯作者：
Humza Haroon;Ada M.-C. Ho;Vinod K. Gupta;Surendra Dasari;Carl M. Sellgren;S. Cervenka;G. Engberg;Feride Eren;Sophie Erhardt;J. Sung;Doo-Sup Choi
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作者：
Humza Haroon;Ada M.-C. Ho;Vinod K. Gupta;Surendra Dasari;Carl M. Sellgren;S. Cervenka;G. Engberg;Feride Eren;Sophie Erhardt;J. Sung;Doo-Sup Choi
除了它们在临床环境中的诊断、监测或预后效用之外，分子生物标志物可能有助于理解精神疾病（包括精神分裂症）的病理生理学。使用非靶向代谢组学，我们最近确定了八个脑脊液（CSF）代谢物独特的首发精神病（FEP）的主题相比，健康对照（HC）。在这项研究中，我们试图研究与FEP相关的CSF蛋白质组特征。我们采用16重串联质谱标签（TMT）质谱（MS）检查15个诊断为FEP的个体和15个年龄和性别匹配的健康对照（HC）的CSF样本中的相对蛋白质丰度。多元线性回归模型（MLRM）鉴定了FEP和HC之间16种差异丰富的CSF蛋白，p < 0.01。其中，两种最重要的CSF蛋白是胶原α-2（IV）链（COL 4A 2：标准平均差[SMD] =-1.12，p = 1.64 × 10−4）和神经源性神经营养因子（NDNF：SMD =-1.03，p = 4.52 × 10−4），与HC相比，这两种蛋白在FEP受试者中均下调。我们还鉴定了几种与FEP受试者的病理生理学和症状特征及严重程度相关的潜在CSF蛋白，包括COL 4A 2、NDNF、hornerin（HRNR）、contactin-6（CNTN 6）、电压依赖性钙通道亚基α-2/δ-3（CACNA 2D 3）、原肌球蛋白α-3链（TPM 3和TPM 4）。此外，几种蛋白质特征与认知表现有关。虽然结果需要重复，但我们的探索性研究表明，CSF蛋白特征可用于增加对精神病病理生理学的理解。
Apart from their diagnostic, monitoring, or prognostic utility in clinical settings, molecular biomarkers may be instrumental in understanding the pathophysiology of psychiatric disorders, including schizophrenia. Using untargeted metabolomics, we recently identified eight cerebrospinal fluid (CSF) metabolites unique to first-episode psychosis (FEP) subjects compared to healthy controls (HC). In this study, we sought to investigate the CSF proteomic signatures associated with FEP. We employed 16-plex tandem mass tag (TMT) mass spectrometry (MS) to examine the relative protein abundance in CSF samples of 15 individuals diagnosed with FEP and 15 age-and-sex-matched healthy controls (HC). Multiple linear regression model (MLRM) identified 16 differentially abundant CSF proteins between FEP and HC atp< 0.01. Among them, the two most significant CSF proteins were collagen alpha-2 (IV) chain (COL4A2: standard mean difference [SMD] = −1.12,p= 1.64 × 10−4) and neuron-derived neurotrophic factor (NDNF: SMD = −1.03,p= 4.52 × 10−4) both of which were down-regulated in FEP subjects compared to HC. We also identified several potential CSF proteins associated with the pathophysiology and the symptom profile and severity in FEP subjects, including COL4A2, NDNF, hornerin (HRNR), contactin-6 (CNTN6), voltage-dependent calcium channel subunit alpha-2/delta-3 (CACNA2D3), tropomyosin alpha-3 chain (TPM3 and TPM4). Moreover, several protein signatures were associated with cognitive performance. Although the results need replication, our exploratory study suggests that CSF protein signatures can be used to increase the understanding of the pathophysiology of psychosis.