Comparative Analysis Of Gray Matter Volume Abnormalities Between First-episode,drug-na(?)ve Patients In Schizophrenia And Its Ultra High-risk Population

Background：Schizophrenia is a severe mental illness, which shows mainly hallucinations,delusions and social withdrawal and apathy in clinical，with impaired cognitivefunction. And schizophrenia is a huge loss to the people, because the disease results incognitive impairment in patients with early stage,and continuing into their oldage,even need expensive treatment and rehabilitation costs. Therefore, earlyintervention for schizophrenia has a certain significance. But as the effectiveness ofsocial risk criteria for mental illness still have considerable controversy，especially itsfalse positive problem. There is an urgent need to address neurobiology basis whichcan predict transformation of schizophrenia. And the better solution to this problemis comparing and analyzing brain structures of schizophrenia in different stages. Tostudy brain morphology of schizophrenia in different stages including prodromalstage，first episode and normal stage in Han Chinese,we compared UHR individualsand antipsychotic-na ve,first episode schizophrenia patients, along with healthynormal control volunteers from the community, who were matched in terms ofgender，age，and years of formal education. We hypothesized using a voxel-basedmorphometry(VBM)-cross-sectional design to investigate gray matter abnormalities atthe different stages of the disease to show some brain regions structure abnormal changes, so that people would further understand the neurodevelopmental hypothesisabout schizophrenia.Objective：1. To clear change of gray matter volume in prodromal and early stage ofschizophrenia in Han Chinese population.2. To explore starting regions of gray matter in early stage of schizophrenia.3. To explore neurodevelopmental theory of schizophrenia from radiological point ofview.4. Methods:1. The establishment of the research object: Total income of35casesstudied,including15UHR subjects were recruited from all regions in China；10firstepisode schizophrenia of Han Chinese were recruited from the community and10healthy volunteers.2.Imaging acquisition:MRI was performed on a3.0-T Philips scanner(Philips MedicalSystems). A high-resolution T1-weighted sequence using a three-demensionalmagnetization prepared rapid acquisition gradient echo sequence(3D-MPRAGE) wasused. Images of the whole brain were acquired in a sagittal orientation,yielding188slices with a thickness of1mm.3. MRI data processing：For preprocessing of structural MRI data, we used VBMtoolbox(VBM5) with the Statistical Parametric Mapping5software package.Then,Modulated GM images were smoothed with a full width at half maximum(FWHM)~12mm isotropic Gaussian kernel, which was for reducing the individual differenceof brain anatomy and to increase the signal to noise ratio.4. Statistical analysis：a. Group differences in demographic were assessed using ANOVA and Chi-squaredtest.b. Comparisons among Voxel-based groups were performed using SPM5. The spatialcoordinates obtained from the SPM5-results were converted to standard wereconverted to standard Talairach-brain coordinates and then entered into TalairachDaemon Client. We defined an overall threshold of significance of p ＜.001(uncorrected) and selected a spatial extent threshold of10contiguous voxel.Results:1. Comparison of gray matter、white matter、Cerebrospinal fluid and the totalintracranial volume among three groups, results showed no significant difference.2. The brain area of the right lobule crus in cerebellum where the UHR subjects hadless regional GM volume than the healthy controls （cluster size of31voxel;coordinates:-87-4719）.However, we found the brain area of the leftdorsolateral superior frontal gyrus（cluster size of98voxel; coordinates：-27657）,where the UHR populations showed significantly greater GM volumecompared to normal controls3. Brain areas where first-episode schizophrenia patients had less regional GMvolume than the UHR subjects.Significant decrease were found near the lefthippocampus (cluster size of1273voxel;coordinates:-17-6-23) and the rightsuperior temporal gyrus(cluster size of61voxel; coordinates:5614-11).4. Brain areas where the first episode schizophrenic patients had less regional GMvolume than the healthy subjects. Significant decreases were found near the lobulebilaterally in cerebellum hemisphere,the right superior temporal gyrus and thelobule of vermis. Besides, We found a cluster around the right postcentral gyruswhere increased GM volume in the first-episode schizophrenic patients weresignificant compared to the healthy subjects.Conclusion：1. Brain structure of schizophrenic showed multiple brain gray matterabnormalities,which has existed before clinical symptoms appear.2. There has found no clear synchronicity between disease progression ofschizophrenia and gray matter defect.3. We should be according to the development trajectory change of executivefunction and the potential and dynamic change of the neural mechanism to explain neurodevelopment hypothesis of schizophrenia.