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Macroscale thalamic functional organization disturbances and underlying core cytoarchitecture in early-onset schizophrenia

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Fan,  Yun-Shuang
School of Life Science & Technology, University of Electronic Science and Technology of China, Chengdu, China;
Otto Hahn Group Cognitive Neurogenetics, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Bayrak,  Seyma       
Otto Hahn Group Cognitive Neurogenetics, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Wan,  Bin
Otto Hahn Group Cognitive Neurogenetics, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Institute of Neuroscience and Medicine, Research Center Jülich, Germany;
International Max Planck Research School on Neuroscience of Communication: Function, Structure, and Plasticity, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Valk,  Sofie L.       
Otto Hahn Group Cognitive Neurogenetics, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Institute of Neuroscience and Medicine, Research Center Jülich, Germany;

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Citation

Fan, Y.-S., Xu, Y., Bayrak, S., Shine, J. M., Wan, B., Li, H., et al. (2023). Macroscale thalamic functional organization disturbances and underlying core cytoarchitecture in early-onset schizophrenia. Schizophrenia Bulletin, 49(5), 1375-1386. doi:10.1093/schbul/sbad048.


Cite as: https://hdl.handle.net/21.11116/0000-000D-09C1-F
Abstract
Background and hypothesis: Schizophrenia is a polygenetic mental disorder with heterogeneous positive and negative symptom constellations, and is associated with abnormal cortical connectivity. The thalamus has a coordinative role in cortical function and is key to the development of the cerebral cortex. Conversely, altered functional organization of the thalamus might relate to overarching cortical disruptions in schizophrenia, anchored in development.

Study design: Here, we contrasted resting-state fMRI in 86 antipsychotic-naive first-episode early-onset schizophrenia (EOS) patients and 91 typically developing controls to study whether macroscale thalamic organization is altered in EOS. Employing dimensional reduction techniques on thalamocortical functional connectome (FC), we derived lateral-medial and anterior-posterior thalamic functional axes.

Study results: We observed increased segregation of macroscale thalamic functional organization in EOS patients, which was related to altered thalamocortical interactions both in unimodal and transmodal networks. Using an ex vivo approximation of core-matrix cell distribution, we found that core cells particularly underlie the macroscale abnormalities in EOS patients. Moreover, the disruptions were associated with schizophrenia-related gene expression maps. Behavioral and disorder decoding analyses indicated that the macroscale hierarchy disturbances might perturb both perceptual and abstract cognitive functions and contribute to negative syndromes in patients.

Conclusions: These findings provide mechanistic evidence for disrupted thalamocortical system in schizophrenia, suggesting a unitary pathophysiological framework.