Increased short-range and long-range functional connectivity in first-episode, medication-naive schizophrenia at rest

Schizophrenia is conceived as a disconnection syndrome and anatomical distance may affect functional connectivity (FC) in schizophrenia patients. However, whether and how anatomical distance affects FC remains unclear in first-episode, medication-naive schizophrenia at rest.

Forty-nine schizophrenia patients and 50 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging scanning. Regional FC strength was computed for each voxel in the brain, which was further divided into short-range and long-range FC strength.

The patients exhibited increased short-range positive FC strength in the left superior medial frontal gyrus, and increased long-range positive FC strength in the right angular gyrus and bilateral posterior cingulate cortex (PCC)/precuneus compared with the controls. Further seed-based FC analysis showed that the left superior medial frontal gyrus had increased short-range FC with the right inferior frontal gyrus, while the right angular gyrus and bilateral PCC/precuneus had increased long-range FC with the prefrontal gyrus. No significant correlation was observed between abnormal FC strength and clinical variables in the patient group.

The findings reveal a pattern of increased anatomical distance affecting FC in the patients, with the results of increased short-range positive FC strength in the anterior default-mode network (DMN) and increased long-range positive FC strength in the posterior DMN in schizophrenia, and highlight the importance of the DMN in the neurobiology of schizophrenia.