Influence of More Than 5 Years of Continuous Exposure to Antipsychotics on Cerebral Functional Connectivity of Chronic Schizophrenia

Abstract

Objective: To explore the effect of long-term antipsychotics use on the strength of functional connectivity (FC) in the brains of patients with chronic schizophrenia. Method: We collected resting-state functional magnetic resonance imaging from 15 patients with continuously treated chronic schizophrenia (TCS), 19 patients with minimally TCS (MTCS), and 20 healthy controls (HCs). Then, we evaluated and compared the whole-brain FC strength (FCS; including full-range, short-range, and long-range FCS) among patients with TCS, MTCS, and HCs. Results: Patients with TCS and MTCS showed reduced full-/short-range FC compared with the HCs. No significant differences in the whole-brain FCS (including full-range, short-range, and long-range FCS) or clinical characteristics were identified between patients with TCS and MTCS. Additionally, the FCS in the right fusiform gyrus, right inferior temporal gyrus, and right inferior occipital gyrus negatively correlated with the duration of illness and positively correlated with onset age across all patients with chronic schizophrenia. Conclusions: Regardless of the long-term use of antipsychotics, patients with chronic schizophrenia show decreased FC compared with healthy individuals. For some patients with chronic schizophrenia, the influence of long-term and minimal/short-term antipsychotic exposure on resting-state FC was similar. The decreased full- and short-range FCS in the right fusiform gyrus, right inferior temporal gyrus, and right inferior occipital gyrus may be an ongoing pathological process that is not altered by antipsychotic interventions in patients with chronic schizophrenia. Large-sample, long-term follow-up studies are still needed for further exploration.

Abnormal network homogeneity of default-mode network and its relationships with clinical symptoms in antipsychotic-naïve first-diagnosis schizophrenia

“…The difference in results may be associated with the heterogeneity of patients with schizophrenia. Nevertheless, research comprising functional or structural MRI using different analyses, such as global-brain FC ( Zhao et al, 2022 ), the dynamic amplitude of low-frequency fluctuation ( Wang et al, 2021 ), full- and short-range strength of FC ( Miao et al, 2020 ), and Trace ( Lee et al, 2016 ), have observed aberrant ITG in patients with schizophrenia, which is associated with psychotic ( Lee et al, 2016 ) and cognitive symptoms ( Lee et al, 2016 ) and might predict the response to an antipsychotic drug after 8 weeks ( Zhu et al, 2018 ). Previous studies also showed that both patients with schizophrenia and their unaffected siblings shared similar alterations in the ITG ( Liu H. et al, 2012 ; Zhu et al, 2018 ), and the neural activity of ITG was regulated by regulating by the Disrupted-in-Schizophrenia-1 gene ( Gou et al, 2018 ), suggesting that the ITG might be a potential biomarker of endophenotype for schizophrenia.…”

“… Zhu et al (2020) stated that the right ITG might show unique abnormalities in patients with schizophrenia compared with those with bipolar disorder and attention-deficit/hyperactivity disorder. Moreover, Miao et al (2020) showed that the functional impairment in this region might be an ongoing pathological process in schizophrenia patients, and it is barely affected by antipsychotic drugs. Above all, to a certain extent, our results provided diverse findings regarding ITG and novel insights into exploring symptomatic and cognitive-related mechanisms in patients with schizophrenia.…”

Transcriptional signatures of the whole-brain voxel-wise resting-state functional network centrality alterations in schizophrenia

“…The search strategy identified 459 studies, and 21 of them met our inclusion criteria 10 – 16 , 52 – 65 , comprising a total of 1057 patients with schizophrenia (mean age: 26.1) and 1186 healthy controls (mean age: 27.5). Four of the included studies divided patients with schizophrenia into two subgroups according to clinical characteristics 52 , 53 , 55 , 61 , and thus the two sets of data were obtained from each study. The diagnostic criteria employed in the literature included in our study were predominantly based on widely recognized and accepted classifications, including the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD).…”