Resting-state hyper- and hypo-connectivity in early schizophrenia: which tip of the iceberg should we focus on?

In this study, we explore the intricate landscape of brain connectivity in the early stages of schizophrenia, focusing on the patterns of hyper- and hypoconnectivity. Despite existing literature’s support for altered functional connectivity (FC) in schizophrenia, inconsistencies and controversies persist regarding specific dysconnections.

Leveraging a large sample of 100 first-episode schizophrenia patients (42 females/58 males) and 90 healthy controls (50 females/40 males), we compare the functional connectivity (FC) across 90 brain regions of the Automated Anatomical Labeling atlas. We inspected the effects of medication and examined the association between FC changes and duration of illness as well as symptom severity of the disorder. Our approach also includes a comparative analysis of two denoising strategies for functional magnetic resonance imaging data.

In the group of patients, 247 region pairs exhibited greater FC, while 134 region pairs showed reduced FC compared to healthy controls. We found a significant correlation between patients’ FC and symptom severity, and antipsychotic medication. However, when a more moderate denoising scheme was used, the results became significantly skewed towards hypoconnectivity in patients. Moreover, there was no relationship between FC and medication or symptom severity in the case of the moderate denoising scheme.

Altogether, we found an overall balanced picture of both hyper- and hypoconnectivity in patients with schizophrenia compared to the healthy controls and unraveled a link between FC in patients and the severity of symptoms and medication. Notably, the balanced picture of FC gets significantly disrupted when less stringent data denoising is applied.