Background Negative symptoms in schizophrenia (SZ), such as apathy and diminished expression, have limited treatments and significantly impact daily life. Our study focuses on the functional division of the striatum: limbic—motivation and reward, associative—cognition, and sensorimotor—sensory and motor processing, aiming to identify potential biomarkers for negative symptoms. Study Design This longitudinal, 2-center resting-state-fMRI (rsfMRI) study examines striatal seeds-to-whole-brain functional connectivity. We examined connectivity aberrations in patients with schizophrenia (PwSZ), focusing on stable group differences across 2-time points using intra-class-correlation and associated these with negative symptoms and measures of cognition. Additionally, in PwSZ, we used negative symptoms to predict striatal connectivity aberrations at the baseline and used the striatal aberration to predict symptoms 9 months later. Study Results A total of 143 participants (77 PwSZ, 66 controls) from 2 centers (Berlin/Geneva) participated. We found sensorimotor-striatum and associative-striatum hypoconnectivity. We identified 4 stable hypoconnectivity findings over 3 months, revealing striatal-fronto-parietal-cerebellar hypoconnectivity in PwSZ. From those findings, we found hypoconnectivity in the bilateral associative striatum with the bilateral paracingulate-gyrus and the anterior cingulate cortex in PwSZ. Additionally, hypoconnectivity between the associative striatum and the superior frontal gyrus was associated with lower cognition scores in PwSZ, and weaker sensorimotor striatum connectivity with the superior parietal lobule correlated negatively with diminished expression and could predict symptom severity 9 months later. Conclusions Importantly, patterns of weaker sensorimotor striatum and superior parietal lobule connectivity fulfilled the biomarker criteria: clinical significance, reflecting underlying pathophysiology, and stability across time and centers.

中文翻译：

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患有阴性症状的精神分裂症患者的纹状体功能连接低下，纵向发现

背景精神分裂症（SZ）的阴性症状，例如冷漠和表达减弱，治疗方法有限，并且严重影响日常生活。我们的研究重点是纹状体的功能划分：边缘系统——动机和奖励、联想——认知、感觉运动——感觉和运动处理，旨在识别阴性症状的潜在生物标志物。研究设计 这项纵向、2 中心静息态功能磁共振成像 (rsfMRI) 研究检查了纹状体种子与全脑的功能连接。我们检查了精神分裂症 (PwSZ) 患者的连通性畸变，重点使用类内相关性在两个时间点上稳定的组间差异，并将这些差异与阴性症状和认知测量相关联。此外，在 PwSZ 中，我们使用阴性症状来预测基线时的纹状体连接畸变，并使用纹状体畸变来预测 9 个月后的症状。研究结果 来自 2 个中心（柏林/日内瓦）的总共 143 名参与者（77 名 PwSZ，66 名对照组）参与了研究。我们发现感觉运动纹状体和联想纹状体连接性低下。我们在 3 个月内发现了 4 个稳定的低连接性发现，揭示了 PwSZ 中的纹状体-额叶-顶叶-小脑低连接性。从这些发现中，我们发现 PwSZ 中双侧关联纹状体与双侧副扣带回和前扣带皮层的连接性低下。此外，联合纹状体和额上回之间的连接不足与 PwSZ 中较低的认知评分相关，而感觉运动纹状体与顶上小叶的连接较弱与表达减少呈负相关，并且可以预测 9 个月后症状的严重程度。结论 重要的是，感觉运动纹状体和顶上小叶连接较弱的模式满足生物标志物标准：临床意义、反映潜在的病理生理学以及跨时间和中心的稳定性。