Abstract
Convergent evidence has suggested a significant effect of antipsychotic exposure on brain structure and function in patients with schizophrenia, yet the characteristics of favorable treatment outcome remains largely unknown. In this work, we aimed to examine how large-scale brain networks are modulated by antipsychotic treatment, and whether the longitudinal changes could track the improvements of psychopathologic scores. Thirty-four patients with first-episode drug-naïve schizophrenia and 28 matched healthy controls were recruited at baseline from Shanghai Mental Health Center. After 8 weeks of antipsychotic treatment, 24 patients were re-scanned. Through a systematical dynamic functional connectivity (dFC) analysis, we investigated the schizophrenia-related intrinsic alterations of dFC at baseline, followed by a longitudinal study to examine the influence of antipsychotic treatment on these abnormalities by comparing patients at baseline and follow-up. A structural connectivity (SC) association analysis was further carried out to investigate longitudinal anatomical changes that underpin the alterations of dFC. We found a significant symptomatic improvement-related increase in the occurrence of a dFC state characterized by stronger inter-network integration. Furthermore, symptom reduction was correlated with increased FC variability in a unique connectomic signature, particularly in the connections within the default mode network and between the auditory, cognitive control, and cerebellar network to other networks. Additionally, we observed that the SC between the superior frontal gyrus and medial prefrontal cortex was decreased after treatment, suggesting a relaxation of normal constraints on dFC. Taken together, these findings provide new evidence to extend the dysconnectivity hypothesis in schizophrenia from static to dynamic brain network. Moreover, our identified neuroimaging markers tied to the neurobiology of schizophrenia could be used as potential indicators in predicting the treatment outcome of antipsychotics.
Highlights
Schizophrenia is a severe mental illness characterized by complex clinical symptoms, including hallucinations, delusions, and cognitive deficits[1]
In this study, we performed a systematical dynamic functional connectivity (FC) (dFC) analysis to investigate how antipsychotic medication modifies largescale brain networks in firstepisode drug-naïve (FEDN) schizophrenia and how these alterations relate to changes in symptoms
The longitudinal changes of dFC state occurrence and FC variability emerged as key indicators of symptomatic improvement in schizophrenia
Summary
Schizophrenia is a severe mental illness characterized by complex clinical symptoms, including hallucinations, delusions, and cognitive deficits[1]. Other similar studies have suggested that antipsychotic medications could significantly affect the FC, but altered connectivity was not associated with the relief of psychotic symptoms[9,10,11,12,13] The inconsistency of these findings may be partially due to an assumption that the functional couplings between brain regions are static, ignoring the time-varying properties of FC. Only one study, to the best of our knowledge, has attempted to examine the effects of antipsychotic exposure on dFC properties of schizophrenia and showed treatment effects of risperidone on dFC in insular in firstepisode drug-naïve (FEDN) schizophrenia[28] It is still largely unknown how antipsychotic treatment might modify dynamic patterns in large-scale brain networks and whether these changes are related to symptomatic improvement longitudinally
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