Lányi Orsolya, Zahemszky Daniel, Wenning Alexander Schulze, Engh Marie Anne, Molnár Zsolt, Horváth András Attila, Hegyi Péter, Csukly Gábor
Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary; Center for Translational Medicine, Semmelweis University, Budapest, Hungary.
Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Jun 9. doi: 10.1016/j.bpsc.2025.05.017.
Cerebello-thalamo-cortical (CTC) network dysfunctions are well documented in schizophrenia spectrum disorders (SSDs) and preclinical states. However, small samples and methodological heterogeneity often limit individual neuroimaging studies. To overcome these challenges, we conducted a coordinate-based meta-analysis to characterize CTC alterations across illness stages and examine associations with symptom dimensions.
Our meta-analysis was preregistered and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the recommendations of the Cochrane Handbook. A systematic search was conducted in 3 databases in September 2023. Included articles used seed-based resting-state functional magnetic resonance imaging in patients with SSDs, patients with first-episode psychosis, participants at clinical high risk for psychosis, and healthy control participants. Seeds were defined in the thalamus and the cerebellum. Two coordinate-based meta-analytic methods, activation likelihood estimation and seed-based d mapping, were used. Risk of bias was evaluated per the Organization for Human Brain Mapping recommendations.
In SSDs thalamic hypoconnectivity was found in the prefrontal cortex, limbic lobe, thalamus, and cerebellum, whereas hyperconnectivity was observed in the somatomotor and visual association areas (29 studies, 2768 patients). Dysconnectivity was linked to disease progression and symptoms. Cerebellar analysis indicated hypoconnectivity in the prefrontal cortex, cerebellum, and thalamus, with hyperconnectivity in the motor cortex, somatosensory cortex, and orbitofrontal cortex (19 studies, 1159 patients). Cerebellar clusters did not survive multiple comparison correction.
Our findings provide robust meta-analytic evidence of CTC dysconnectivity in SSDs, suggesting that this network captures a core neurobiological feature of psychotic disorders. Consistent patterns of altered CTC connectivity underscore the importance of future clinical investigations of this network as a potential target for therapeutic interventions.
小脑-丘脑-皮质（CTC）网络功能障碍在精神分裂症谱系障碍（SSD）及临床前状态中已有充分记录。然而，样本量小和方法学异质性常常限制了个体神经影像学研究。为克服这些挑战，我们进行了一项基于坐标的荟萃分析，以描述疾病各阶段CTC的改变，并检验其与症状维度的关联。
我们的荟萃分析预先进行了注册，并遵循系统评价和荟萃分析的首选报告项目（PRISMA）指南以及Cochrane手册的建议。2023年9月在3个数据库中进行了系统检索。纳入的文章使用基于种子的静息态功能磁共振成像，研究对象包括SSD患者、首发精神病患者、临床高危精神病参与者以及健康对照参与者。种子点定义在丘脑和小脑中。使用了两种基于坐标的荟萃分析方法，即激活可能性估计和基于种子的d映射。根据人类脑图谱组织的建议评估偏倚风险。
在SSD中，发现丘脑与前额叶皮质、边缘叶、丘脑和小脑之间存在低连接性，而在躯体运动和视觉联合区域观察到高连接性（29项研究，2768例患者）。连接性异常与疾病进展和症状相关。小脑分析表明，前额叶皮质、小脑和丘脑存在低连接性，而运动皮质、躯体感觉皮质和眶额叶皮质存在高连接性（19项研究，1159例患者）。小脑簇在多重比较校正后未通过检验。
我们的研究结果为SSD中CTC连接性异常提供了有力的荟萃分析证据，表明该网络捕捉到了精神障碍的核心神经生物学特征。CTC连接性改变的一致模式强调了未来将该网络作为治疗干预潜在靶点进行临床研究的重要性。
