The Analysis Of Clinical Characters And Mri Study On Brain Functional And Structural Changes In Patients With Treatment-resistant Schizophrenia And Their Relatives

Object The aim of this study was to explore the clinical characters of patients with treatment-resistant schizophrenia(TRS), and to explore the brain function in resting state, white matter integrity and characteristies of gray matter density in patients with TRS and their relatives, by using the regional homogeneity (ReHo) approach, diffusion tensor imaging (DTI) techniques and three dimension MRI (3D).Methods 139 patients with TRS,66 patients with non-TRS (meeting the CCMD-III and DSM-IV diagnosis critietia of schizophrenia), 118 non-psychotic first-degree relatives of TRS,100 healthy volunteers were assessed using the Positive and Negative Syndrome Scale(PANSS), digital span and digital symbol tests, PANSS sorces were requested≥60 in patients. The patients with TRS, their non-psychotic siblings, and age, gender and education-matched healthy controls were underwent a resting-state fMRI scan and diffusion tensor imaging scan. By using a regional homogeneity (ReHo) approach in analyzing functional magnetic resonance imaging (fMRI) datasets in order to detect whether the abnormal brain activity exists in resting state of patients with TRS and their non-psychotic siblings. Fractional anisotropy (FA) was measured in patients with TRS, their non-psychotic siblings and healthy controls with an automated voxel-based method of analysis. And gray matter was analyzed with a voxel-based morphometry method in patients with TRS, their non-psychotic siblings and healthy controls.Results 32 patients with TRS,32 non-psychotic siblings and 44 healthy controls finished MRI scan. Some data were excluded because of head movement. Data could be analyzed finally including 24 patients with TRS (12 females and 12 males),26 non-psychotic siblings(14 females and 12 males), and 39 healthy controls(21 females and 18 males) in fMRI part, and 26 patients with TRS (13 females and 13 males),26 non-psychotic siblings(14 females and 12 males), and 39 healthy controls(21 females and 18 males) in DTI part, and 27 patients with TRS (14 females and 13 males),28 non-psychotic siblings(15 females and 13 males), and 39 healthy controls(21 females and 18 males) in 3D part.1. clinical characters:there was predominance in the male gender and introvert in premorbid personality in patients with TRS. the patients with TRS were significant poor social function, less education, earlier age at first onset(p=0.001), longer duration of illness (p=0.000), longer duration of untreated psychosis(p=0.000), higher number of hospitalizations (p=0.000) than those of the patients with non-TRS. The patients with TRS show insidious onset, persistent course of illness, and predominance of mixed type. There was significant difference in negative scale of PANSS scores between TRS group and non-TRS group(p=0.002). depressive symptoms is common in TRS. Medication was predominance in treatment of TRS, and therapeutic alliance is common, but treatment compliance is poor. The patients with TRS and relatives were significantly less digital span and digital symbol test scores than those of the healthy controls, the digital span and digital symbol test results were significantly negative correlation with course of disease, DUP and negative scale of PANSS scores, and significantly positive correlation with education and age of onset(p<0.05) in patiets with TRS.2. ReHo analysis:Compared with control subjects, patients with TRS showed alter ReHo of blood oxygen level dependent (BOLD) signal in resting brain, the encephalic regions of decreased ReHo were found in left superior frontal gyrus, cingulate gyrus and posterior cingutate. No increased ReHo region was found. Compared with non-psychotic siblings, the region of decreased ReHo were found in left superior frontal gyrus, precentral gyrus, and the increased ReHo region in right cuneus, lingual lobe and bilateral postcentral gyrus. Compared with control subjects, non-psychotic siblings showed decreased ReHo in left cuneus, no increased ReHo encephalic region was found.3. DTI analysis:Compared with healthy controls, patients with TRS exhibited significantly decreased fractional anisotropy (FA) values in bilateral callosum, right inferior frontal gyrus, left anterior cingutate, posterior cingutate and right middle temporal gyrus, And significantly increased FA values in left fusiform gyrus, precuneus, cingulate gyrus, middle cingulate gyrus, declive and tuber of cerebellum posterior lobe, and right thalami, cerebellar tonsil. Compared with non-psychotic siblings, significantly decreased FA values in bilateral anterior cingutate, left callosum and right middle temporal gyrus. no regions with significantly increased FA in patients was found. Compared with healthy controls, non-psychotic siblings exhibited significantly decreased FA values in left inferior parietal lobule, cingulum and right cuneus, And significantly increased FA values in bilateral cerebellar tonsil, right middle temporal gyrus and left inferior semi-lunar lobule, there was significant negative correlation between the FA values in callosum (x=-10, y=14, z=22; Z=4.14, cluster=72) of patients with TRS and scores of negtive psychotic symptoms (r=-0.454,p=0.020), course of disease (r=-0.421,p=0.032), and significantly positive correlation with education (r=-0.443,p=0.024).4.3D analysis:Compared with healthy controls, patients with TRS showed significantly decreased gray matter density in left medial frontal gyrus, precuneus, insula, right hippocampal gyrus, middle frontal gyrus, superior frontal gyrus, precentral gyrus, postcentral gyrus, inferior temporal gyrus, cuneus, and bilateral inferior parietal lobule. And significantly increased gray matter density in bilateral lateral globus pallidus. Compared with non-psychotic siblings, significantly decreased gray matter density in left medial frontal gyrus, inferior frontal gyrus, right precentral gyrus, middle temporal gyrus, middle frontal gyrus, superior frontal gyrus, cuneus, hippocampal gyrus, and bilateral postcentral gyrus. no regions with significantly increased gray matter density in patients was found. Compared with healthy controls, non-psychotic siblings exhibited significantly decreased gray matter density in left medial frontal gyrus, inferior parietal lobule, right insula, superior parietal lobule, no regions with significantly increased gray matter density in non-psychotic siblings group was found.Conclusions 1. The patients with TRS have special clinical characters, that reflect different etiopathogenisis in biological and social psychological aspect, the cognitive function of patients with TRS and their relatives was impairment.2. Abnormal brain activity of patients with TRS and their non-psychotic siblings might exist in resting state. The abnormal brain activity in right cuneate lobe in non-psychotic siblings may be potential substructure of illness.3. The patients with TRS and their non-psychotic siblings showed decreased fractional anisotropy and gray matter density in callosum, frontal lobe, parietal lobe, temporal lobe and occipital lobe, that may increase the risk of schizophrenia episode, and may be substructure of psychiatric symptom and cognitive function impairment.