Risperidone Effects On Insular Subdivisions And Dopaminergic Pathways In Schizophrenia

Schizophrenia is a chronic,severe psychiatric disorder that its clinical features are cognition,emotion,thought and behavior impairment.It is presented with positive symptoms(delusions and hallucinations)and negative symptoms(particularly impaired motivation,reduction in spontaneous speech,and social withdrawal).Since the pathology of schizophrenia is complex,the cause of this disorder remains unknown.And the treatments,especially pharmacological treatments,are still a major issue in the study of schizophrenia.Patients with schizophrenia are widely reported for abnormal brain connections.Recently,the blood oxygen level dependent-functional magnetic resonance imaging(BOLD-fMRI)technology provides an effective measure for the research of brain connections in mental disease.In current study,we employed fMRI technology to analyze the brain connections in schizophrenia.Furthermore,we also utilized functional connectivity and effective connectivity technology to study the effect of medicine on the brain connections of the patients,and explored the pathophysiology of schizophrenia.The main context includes the following two parts:1.A whole-brain dynamic functional connectivity analysis was conducted based on six regions of interest for the bilateral insular subdivisions,and we focus on if and how antipsychotic medications change the dynamic functional connectivity of insular subdivisions after 8 weeks of treatment.Our results showed that prior treatment,treatment na?ve first-episode schizophrenia patients(FESP)showed decrease dynamic functional connectivity between insular subdivisions and the bilateral supplementary motor area,bilateral central precuneus,bilateral middle temporal gyrus,left superior temporal gyrus.After treatment,these patients exhibited increase dynamic functional connectivity between insular subdivisions and bilateral supplementary motor area,right postcentral gyrus,bilateral middle temporal gyrus,left superior temporal gyrus and right fusiform gyrus,then the dynamic functional connectivity in right posterior precuneus and right inferior parietal lobule was decrease.Furthermore,greater improvement of dynamic functional connectivity between left dorsal anterior insula and the supplementary motor area correlated with more reduction in positive symptoms.These results suggested that,comparing with the healthy controls,the patients with schizophrenia exhibited abnormal patterns of fluctuating connectivity of insular subdivision circuits,and risperidone monotherapy modified these connections.These findings would provide new insight into the neuropathology and pharmacological treatments of schizophrenia.2.A Granger causality analysis was employed to investigate if and how the 8 weeks' risperidone treatment influences the causal connectivity of dopaminergic pathways in FESP.Our results showed that compared with the healthy controls,the FESP exhibited decrease excitatory effect from the ventral tegmental area to the left middle frontal gyrus and the left inferior frontal gyrus.After treatment,the patients exhibited increase excitatory effect from ventral tegmental area to the left inferior frontal gyrus.And the patients showed increase inhibitory effect from the bilateral substantia nigra to the bilateral precuneus,bilateral posterior cingulate gyrus,left inferior parietal lobule,left superior parietal lobule,left superior frontal gyrus,left middle frontal gyrus and right occipital lobe when compared with the controls.After treatment,the patients showed decrease inhibitory effect from the bilateral substantia nigra to the bilateral precuneus,left cingulate gyrus and right superior frontal gyrus.These results indicate that the abnormal effective connectivity of dopaminergic pathways in schizophrenia,and the risperidone monotherapy may restore these connections,which would provide more-specific targets for the treatment of schizophrenic.Taken together,our study found that the insular subdivisions-related circuits and the dopaminergic pathways were abnormal in the patients with schizophrenia,and these abnormities may be potential biomarkers for schizophrenia.Furthermore,we also found that risperidone monotherapy could influence these circuits,which may offer important evidence for the pharmacotherapy of schizophrenia.