He Xiao-Yan, Wei An-Pei, Huang Zhuo-Hui, Wang Fei, Guo Li Li, Hou Cai-Lan
The Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu, China.
School of Humanities and Management Science, Wannan Medical College, Wuhu, Anhui, China.
Front Psychiatry. 2025 May 8;16:1581756. doi: 10.3389/fpsyt.2025.1581756. eCollection 2025.
Cognitive impairment represents a core feature of schizophrenia spectrum disorders, predating psychosis onset and persisting throughout illness progression. This cross-sectional study systematically evaluates neurocognitive functioning across five critical populations: multi-episode chronic schizophrenia (MECS), first-episode psychosis (FEP), clinical high-risk (CHR) individuals, first-degree relatives (FDR), and healthy controls (HC).
A comprehensive neuropsychological battery was administered to 366 participants: 40 MECS, 94 FEP, 54 CHR, 80 FDR, and 98 HC. Assessments included: Processing speed: Trail Making Test-A (TMT-A), Digit Symbol Coding Test (DST). Attention: Continuous Performance Test (CPT). Verbal memory: Hopkins Verbal Learning Test-Revised (HVLT-R).Visual memory: Brief Visuospatial Memory Test-Revised (BVMT-R). Executive function: Stroop Color and Word Test (SCWT). Group differences were analyzed using Analysis of Covariance (covariates: age, education) with Bonferroni correction, supplemented by multinomial logistic regression.
A stepwise gradient of impairment emerged across the schizophrenia spectrum (HC > FDR > CHR > FEP > MECS), with significant between-group differences (<0.001) persisting after covariate adjustment. Key findings revealed: 1. MECS demonstrated cognitive deficits, showing significantly poorer verbal memory (HVLT-R:d=0.65:<0.001) and executive function (Stroop words:d=0.56, p=0.003,Stroop color:d=0.60, =0.006,Stroop words color:d=0.46, =0.03) performance than FEP.2. CHR exhibited intermediate impairment: - Outperformed FEP in processing speed (TMT-A: d=0.45, p=0.009, DST: d=065, p=0.001), attention (CPT: d=0.42, =0.03), and executive function (Stroop words color: d=0.39, =0.03). - Underperformed FDR across all domains except visual memory (BVMT-R: d=0.16, =0.92).3. FDR showed subtle but consistent deficits relative to HC (all tests <0.05), with largest effects in visual memory (BVMT-R: d=0.99, <0.001).
These findings support a stratified continuum of cognitive impairment across schizophrenia progression. While chronic patients manifest generalized deficits, at-risk populations demonstrate distinct profiles: FDR display subclinical vulnerabilities, whereas CHR show intermediate impairment exceeding familial risk but preceding acute psychosis. The differential trajectory of verbal memory and executive function deficits from FEP to MECS suggests progressive deterioration in higher-order cognitive domains. These gradient patterns may inform stage-specific cognitive interventions across the schizophrenia spectrum.
认知障碍是精神分裂症谱系障碍的核心特征，在精神病发作之前就已出现，并在疾病进展过程中持续存在。这项横断面研究系统地评估了五个关键人群的神经认知功能：多发作慢性精神分裂症（MECS）、首发精神病（FEP）、临床高危（CHR）个体、一级亲属（FDR）和健康对照（HC）。
对366名参与者进行了全面的神经心理测试：40名MECS、94名FEP、54名CHR、80名FDR和98名HC。评估包括：处理速度：连线测验A（TMT-A）、数字符号编码测验（DST）。注意力：连续性能测验（CPT）。言语记忆：霍普金斯言语学习测验修订版（HVLT-R）。视觉记忆：简短视觉空间记忆测验修订版（BVMT-R）。执行功能：斯特鲁普颜色和文字测验（SCWT）。使用协方差分析（协变量：年龄、教育程度）并进行邦费罗尼校正分析组间差异，并辅以多项逻辑回归。
在精神分裂症谱系中出现了逐步的损伤梯度（HC>FDR>CHR>FEP>MECS），协变量调整后组间仍存在显著差异（<0.001）。主要发现显示：1. MECS表现出认知缺陷，其言语记忆（HVLT-R：d=0.65，<0.001）和执行功能（斯特鲁普文字：d=0.56，p=0.003；斯特鲁普颜色：d=0.60，=0.006；斯特鲁普文字颜色：d=0.46，=0.03）的表现明显比FEP差。2. CHR表现出中度损伤：- 在处理速度（TMT-A：d=0.45，p=0.009；DST：d=0.65，p=0.001）、注意力（CPT：d=0.42，=0.03）和执行功能（斯特鲁普文字颜色：d=0.39，=0.03）方面优于FEP。- 除视觉记忆（BVMT-R：d=0.16，=0.92）外，在所有领域的表现均不如FDR。3. FDR相对于HC表现出细微但一致的缺陷（所有测试<0.05），在视觉记忆方面影响最大（BVMT-R：d=0.99，<0.001）。
这些发现支持了精神分裂症进展过程中认知障碍的分层连续体。虽然慢性患者表现出普遍的缺陷，但高危人群表现出不同的特征：FDR表现出亚临床易损性，而CHR表现出中度损伤，超过家族风险但早于急性精神病。从FEP到MECS言语记忆和执行功能缺陷的不同轨迹表明高阶认知领域的逐渐恶化。这些梯度模式可能为精神分裂症谱系中特定阶段的认知干预提供信息。
