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Dynamic functional connectivity and its anatomical substrate reveal treatment outcome in first-episode drug-naive schizophrenia.

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.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC8115129 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectiveThe pathogenesis of schizophrenia (SCH) is related to the dysfunction of monoamine neurotransmitters, and the habenula participates in regulating the synthesis and release of dopamine. We examined the static functional connectivity (sFC) and dynamic functional connectivity (dFC) of habenula in first-episode schizophrenia patients using resting state functional magnetic resonance imaging (rs-fMRI) in this study.MethodsA total of 198 first-Episode, drug-Naïve schizophrenia patients and 199 healthy controls (HC) underwent rs-fMRI examinations. The sFC and dFC analysis with habenula as seed was performed to produce a whole-brain diagram initially, which subsequently were compared between SCH and HC groups. Finally, the correlation analysis of sFC and dFC values with the Positive and Negative Symptom Scale (PANSS) were performed.ResultsCompared with the HC groups, the left habenula showed increased sFC with the bilateral middle temporal gyrus, bilateral superior temporal gyrus, and right temporal pole in the SCH group, and the right habenula exhibited increased sFC with the left middle temporal gyrus, left superior temporal gyrus, and left angular gyrus. Additionally, compared with the HC group, the left habenula showed decreased dFC with the bilateral cuneus gyrus and bilateral calcarine gyrus in the SCH group. The PANSS negative sub-scores were positively correlated with the sFC values of the bilateral habenula with the bilateral middle temporal gyrus, superior temporal gyrus and angular gyrus. The PANSS general sub-scores were positively correlated with the sFC values of the right habenula with the left middle temporal gyrus and left superior temporal gyrus. The hallucination scores of PANSS were negatively correlated with the sFC values of the left habenula with the bilateral cuneus gyrus and bilateral calcarine gyrus; The anxiety scores of PANSS were positively correlated with the dFC values of the left habenula with the right temporal pole.ConclusionThis study provides evidence that the habenula of the first-episode schizophrenia patients presented abnormal static functional connectivity with temporal lobe and angular gyrus, and additionally showed weakened stability of functional connectivity in occipital lobe. This abnormality is closely related to the symptoms of hallucination and anxiety in schizophrenia, which may indicate that the habenula involved in the pathophysiology of schizophrenia by affecting the dopamine pathway.

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Dynamic functional connectivity and its anatomical substrate reveal treatment outcome in first-episode drug-naive schizophrenia.

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