The Remodeling Of Brain Networks In Patients With Schizophrenia By Antipsychotic Drugs

Schizophrenia,as a type of serious mental disorders with unknown etiology,characterizes by significant abnormalities in cognition,emotion and behavior domains.These dysfunctions always lead to obvious social impairment in patients.The disconnection of brain is considered as a potential mechanism of schizophrenia.With the development of brain imaging technology and the introduction of complex networks' theory,brain structural and functional connectivity is regarded as the hotspot in schizophrenia at present.A large number of studies have illustrated the abnormalities of structural and functional networks in schizophrenia,which is also considered as a main endophenotype of schizophrenia.The treatment of antipsychotic drugs is the most effective tool to control the illness.The common antipsychotic drugs focus on the dopamine receptor,which is observed in the basal ganglia.Therefore,based on the neuroimaging approaches and clinical treatment information,this thesis will investigate the structural and functional connectivity of basal ganglia and global brain,as well as the effects the antipsychotic drugs on these features.The work of this paper are as follows:1.For the local structure feature,the structural alteration of basal ganglia in schizophrenia was discussed.Comparing the local diffusion parameter including fractional anisotropy(FA)and mean diffusivity(MD)in healthy controls,patients with schizophrenia illustrated abnormal diffusion parameters in basal ganglia and thalamus.In detail,reduced FA values in eight regions of interest(ROIs),and increased MD values in seven ROIs except the left globus pallidus were observed in schizophrenia patients.Furthermore,the increased FA was associated with the positive symptom subscale score negatively.The grey matter volume of the six ROIs in the patient group was obvious decreased,while the volume was increased in the bilateral putamen.These findings implicated the heterogeneity of the basal ganglia structure in schizophrenia.The specific alteration in the different nuclei,which was related with the clinical symptom,might provide the evidence to identify the target of the treatment.2.For the local functional connectivity(FC),the change of FC of basal ganglia was investigated in patients with schizophrenia.This chapter compared the basal ganglia FC in schizophrenia patients with the healthy control group,and found that the FC of bilateral caudate nucleus was enhanced in schizophrenia patients.Patients demonstrated the increased FC between bilateral caudate nucleus and superior frontal gyrus,but the decreased FC between bilateral caudate nucleus and cerebellar cortex.In addition,the FC between the right caudate nucleus and the supplementary motor area and the cingulate cortex was decreased in patients.Further analysis revealed that the duration of the disease was positively correlated with changes in the FC between the right caudate nucleus and the superior frontal gyrus,suggesting a progressive process of schizophrenia.Because the caudate plays a role to filter the input information,the abnormality related to the caudate might reflect the foundation the delusion,which is a key positive symptom in schizophrenia.3.For the FC in global brain level,the degree centrality(DC),a voxel-level key feature in whole-brain network,was evaluated.In this chapter,schizophrenia patients showed the altered DC compared with healthy controls.In detail,it was found that in schizophrenia patients illustrated the decreased local DC in the primary sensory cortex,but increased DC in high-level cognitive cortex.The decreased DC in right middle occipital gyrus was negative related to the illness duration.In addition,the DC in the left lingual gyrus was related to the positive symptom,and the negative symptom score was associated with the DC in the bilateral dorsal lateral prefrontal cortex,supper frontal gyrus,postcentral gyrus and cuneus in schizophrenia.These differences of network features can reflect the distributed changes of node importance in patients with schizophrenia,and the different symptom might associate with the abnormality in different regions.The findings would contribute to the pointed treatment for the specifical symptom in a given patients.4.This chapter was to investigate the remodeling effect of antipsychotic drugs on the brain basal ganglia network in patients with schizophrenia.The independent component analysis(ICA)and FC analysis for fMRI data was used to investigate the effect of antipsychotic drugs on basal ganglia network.By comparing the FC of basal ganglia in patients with schizophrenia before and after 6 months of in the use of antipsychotic drugs,this study had found that the FCs between bilateral caudate nucleus and bilateral middle frontal gyrus,was reduced after treatment.In addition,the FCs between bilateral thalamus and the left side of the caudate nucleus and cerebellar cortex,the FCs between left thalamus and right caudate nucleus as well as the FCs between auditory network and sensorimotor network were obviously reduced after treatment.According to the findings in previous chapter,the antipsychotic drugs could reduce the abnormal increased FC between bilateral caudate nuclei in patients with schizophrenia,suggesting that some specific networks might response to antipsychotic drugs to improve the symptom of schizophrenia.5.To explore the remodeling effect of antipsychotic drugs on the whole-brain network of patients with schizophrenia,this chapter investigated the effects of risperidone and clozapine on the FC of whole-brain network in patients with schizophrenia using the DC and support vector regression model.By comparing the brain functional imaging of schizophrenia patients with two antipsychotic drugs with different mechanisms,it was found that the brain regions with the significant differences in DC values of schizophrenia treated with risperidone and clozapine were located in the middle temporal gyrus.In addition,support vector regression model identifies some key brain regions,including thalamus,insula and primary sensomotor cortex,to reflect the effects of antipsychotic drugs.Especially,the DC value in these regions had a good predictive effect on negative symptoms in clozapine group.In summary,the finding from this thesis supported that the specific alteration in basal ganglia and their functional network,and the whole-brain network was related to the schizophrenia.Some alteration showed the association with the illness duration and/or clinical symptom.Treatment by antipsychotic drugs would cause to the improvement of FC in some regions and networks,and then release the psychotic symptoms.However,the alteration of brain network was individual for schizophrenia subjects.More detailed investigation and more experiments would be performed to confirm and extend the understanding schizophrenia in the future.