Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China.
Schizophr Bull. 2024 Jul 27;50(4):827-838. doi: 10.1093/schbul/sbae026.
Cortical thickness (CT) alterations, mismatch negativity (MMN) reductions, and cognitive deficits are robust findings in first-episode psychosis (FEP). However, most studies focused on medicated patients, leaving gaps in our understanding of the interrelationships between CT, MMN, neurocognition, and psychosocial functioning in unmedicated FEP. This study aimed to employ multiple mediation analysis to investigate potential pathways among these variables in unmedicated drug-naïve FEP.
We enrolled 28 drug-naïve FEP and 34 age and sex-matched healthy controls. Clinical symptoms, neurocognition, psychosocial functioning, auditory duration MMN, and T1 structural magnetic resonance imaging data were collected. We measured CT in the superior temporal gyrus (STG), a primary MMN-generating region.
We found a significant negative correlation between MMN amplitude and bilateral CT of STG (CT_STG) in FEP (left: r = -.709, P < .001; right: r = -.612, P = .008). Multiple mediation models revealed that a thinner left STG cortex affected functioning through both direct (24.66%) and indirect effects (75.34%). In contrast, the effects of the right CT_STG on functioning were mainly mediated through MMN and neurocognitive pathways.
Bilateral CT_STG showed significant association with MMN, and MMN plays a mediating role between CT and cognition. Both MMN alone and its interaction with cognition mediated the effects of structural alterations on psychosocial function. The decline in overall function in FEP may stem from decreased CT_STG, leading to subsequent MMN deficits and neurocognitive dysfunction. These findings underline the crucial role of MMN in elucidating how subtle structural alterations can impact neurocognition and psychosocial function in FEP.
皮质厚度（CT）改变、失匹配负波（MMN）减少和认知缺陷是首发精神病（FEP）的可靠发现。然而，大多数研究都集中在用药患者身上，这使得我们对未用药 FEP 中 CT、MMN、神经认知和社会心理功能之间的相互关系的理解存在空白。本研究旨在采用多元中介分析来研究未经药物治疗的 FEP 中这些变量之间的潜在途径。
我们招募了 28 名未经药物治疗的 FEP 和 34 名年龄和性别匹配的健康对照者。收集了临床症状、神经认知、社会心理功能、听觉持续 MMN 和 T1 结构磁共振成像数据。我们测量了初级 MMN 生成区域——颞上回（STG）的 CT。
我们发现 FEP 中 MMN 幅度与双侧 STG 的 CT（CT_STG）呈显著负相关（左侧：r=-0.709，P<0.001；右侧：r=-0.612，P=0.008）。多元中介模型显示，左侧 STG 皮质变薄通过直接（24.66%）和间接（75.34%）途径影响功能。相比之下，右侧 CT_STG 对功能的影响主要通过 MMN 和神经认知途径。
双侧 CT_STG 与 MMN 有显著关联，MMN 在 CT 和认知之间起着中介作用。MMN 本身及其与认知的相互作用，介导了结构改变对社会心理功能的影响。FEP 中整体功能的下降可能源于 CT_STG 的减少，进而导致随后的 MMN 缺陷和神经认知功能障碍。这些发现强调了 MMN 在阐明细微结构改变如何影响 FEP 中的神经认知和社会心理功能方面的关键作用。
