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Peer-reviewedCC BY-NC-ND 4.0BMC Psychiatry

Hypoconnected state characterized in first-episode schizophrenia: topological abnormalities and clinical correlations

  1. 1Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029 China
  2. 2Department of Psychiatry, Nanjing Brain Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210029 China

Abstract

Background: Disrupted connectivity among cerebral networks is a key feature of schizophrenia (SZ). Dynamic functional connectivity (dFC) analysis, which captures the time-varying properties of brain networks, has emerged as a pivotal approach for investigating functional abnormalities in SZ. However, the topological properties of patients across different connectivity states remain poorly understood.

Methods: We recruited 50 patients with acute, first-episode, treatment-naive SZ and 43 healthy controls (HCs). A sliding-window approach was employed to examine dFC states in patients relative to HCs. Functional networks under different states were constructed based on the Dosenbach 160 atlas. Graph theory analyses were performed to calculate topological metrics (global and nodal properties), and correlations between abnormal metrics and clinical scales were analyzed within patient group.

Results: Patients stayed more frequently and persistently in a hypoconnected state. In this state, patients demonstrated widespread nodal topological impairments in the default mode network, cingulo-opercular network, and sensorimotor network. Conversely, the hyperconnected state was characterized by a lower clustering coefficient and a shorter shortest path length, and higher network efficiency in patients compared to HCs. Furthermore, aberrant nodal clustering coefficients in hypoconnected state correlated with psychotic symptoms and cognitive deficits.

Conclusion: Individuals with SZ exhibit distinct topological abnormalities across different network states. The hypoconnected state, in particular, may serve as a critical window into the pathophysiological mechanisms of the disease.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12888-026-08489-w.

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BibTeX
@article{hou2026hypoconnected,
  title = {{Hypoconnected state characterized in first-episode schizophrenia: topological abnormalities and clinical correlations}},
  author = {Lingzhi Hou and Yinyu Peng and Haiyan Tang and Chuyuan Zhang and Chongyang Han and Peiyu Cao and Shuzhan Gao and Xijia Xu},
  journal = {BMC Psychiatry},
  year = {2026},
  month = aug,
  doi = {10.1186/s12888-026-08489-w},
  url = {https://doi.org/10.1186/s12888-026-08489-w},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Hypoconnected state characterized in first-episode schizophrenia: topological abnormalities and clinical correlations
AU  - Lingzhi Hou
AU  - Yinyu Peng
AU  - Haiyan Tang
AU  - Chuyuan Zhang
AU  - Chongyang Han
AU  - Peiyu Cao
AU  - Shuzhan Gao
AU  - Xijia Xu
PY  - 2026
DA  - 2026/08/08
JO  - BMC Psychiatry
DO  - 10.1186/s12888-026-08489-w
UR  - https://doi.org/10.1186/s12888-026-08489-w
AB  - Background: Disrupted connectivity among cerebral networks is a key feature of schizophrenia (SZ). Dynamic functional connectivity (dFC) analysis, which captures the time-varying properties of brain networks, has emerged as a pivotal approach for investigating functional abnormalities in SZ. However, the topological properties of patients across different connectivity states remain poorly understood.  Methods: We recruited 50 patients with acute, first-episode, treatment-naive SZ and 43 healthy controls (HCs). A sliding-window approach was employed to examine dFC states in patients relative to HCs. Functional networks under different states were constructed based on the Dosenbach 160 atlas. Graph theory analyses were performed to calculate topological metrics (global and nodal properties), and correlations between abnormal metrics and clinical scales were analyzed within patient group.  Results: Patients stayed more frequently and persistently in a hypoconnected state. In this state, patients demonstrated widespread nodal topological impairments in the default mode network, cingulo-opercular network, and sensorimotor network. Conversely, the hyperconnected state was characterized by a lower clustering coefficient and a shorter shortest path length, and higher network efficiency in patients compared to HCs. Furthermore, aberrant nodal clustering coefficients in hypoconnected state correlated with psychotic symptoms and cognitive deficits.  Conclusion: Individuals with SZ exhibit distinct topological abnormalities across different network states. The hypoconnected state, in particular, may serve as a critical window into the pathophysiological mechanisms of the disease.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12888-026-08489-w.
SN  - 1471-244X
ER  -