| Objectives1． Using MRI investigate the changes of brain cortical thickness in drug na vefirst episode schizophrenia patients, study the imageology in schizophrenia,to provide some new clues to further elucidate the pathogenesis and clinictreatment of this disease.2． Study the levels of folate, homocysteine(Hcy) and brain-derivedneurotrophic factor (BDNF) in drug na ve first episode schizophreniapatients, investigate whether they involved in the pathogenesis ofschizophrenia.3． Study cortical thickness associations with serum levels of folate, Hcy andBDNF biomarker in drug na ve first episode schizophrenia patients andhealthy control subjects, to further explore the correlation between theimaging and the biological mechanisms in drug na ve first episodeschizophrenia patients.Methods1.45experimenters which came from the First Affiliated Hospital ofZhengzhou University, and28healthy individuals which inhabit inzhengzhou were enrolled in the study according to the standard set. Allpatients enrolled were assessed by Positive and Negative Symptoms Scale(PANSS). Matrics Consensus Cognitive Battery(MCCB) was used toevalute the cognitive function.2. All subjects collected venous blood early in the second morning on an emptystomach and without medication. Serum folate level was measured usingthe electrochemical luminescence method and Hcy level was measuredusing Enzymatic Cycling Assay. Serum levels of BDNF were measured using enzyme-linked immunosorbent assay (ELISA).3. All subjects enrolled were scanned by Three-dimensional MagneticResonance Imaging (3D-MRI) on the first day. Scan to keep subjects restingstate: quiet lie on your back, eyes closed, a foam pad fixed head with MRImachine matching, earplugs isolated noise. All the scanned image data weregathered by the first pretreatment.4. Freesurfer was used to parcellate cortical regions. Cortical thickness wascomputed by finding the shortest distance between a given point on theestimated pial surface and the gray-white matter boundary and vice versaand averaging these two values[1].5. Assessment methods: The PANSS score includes positive symptoms,negative symptoms and general pathology. Matrics Consensus CognitiveBattery(MCCB) was used to evalute the cognitive function. Which includeTMT, HVLT, BVMT, Stroop color word test, Continuous performance tast.All of the patients in group into the detailed interrogation and graded byscoring criteria, It was carried out by one clinical psychiatrist who hadattended a training session for the proper use of PANSS to ensure thereliability of the ratings.6. The data were analyzed using SPSS20.0. The values were presented as themeans±SD. Normality of the distribution was checked using theKolmogorov-Smirnov one-sample test. The two study groups werecompared for continuous variables by an independent t-test. For discretevariables, two study groups were compared by chi-square test. Used ageneral linear model controlling to estimate differences in cortical thicknessbetween the groups. Monte Carlo simulations were performed in order toidentify significant contiguous clusters of significant vertex-wise groupdifferences (p<0.01). The correlation between surum folic and Hcy levelswith negative symptoms and cognitive function and the correlation betweencortical thickness and surum folic and Hcy, BDNF levels using Pearson’scorrelation analysis. Two-tailed p<0.05were considered significant. Results1. There was no significant difference in the two groups in age, education,gender and smoking history (p>0.05).2. These clusters comprised two in the left hemisphere, insula and superiortemporal areas, and five in the right hemisphere, supramarginal, inferiorparietal, superior frontal, lateral occipital, and rostral middle frontal areas.Among them, almost all clusters showed reduced cortical thickness, whileonly lateral occipital area showed increased cortical thickness in firstepisode schizophrenia patients as compared to healthy control subjects(p’s<0.01).3. Serum levels of folate was significantly decreased (p<0.001), serum levels ofHCY was significantly increased (p=0.006), and serum levels of BDNF wassignificantly decreased (p=0.001) in first episode schizophrenia patients ascompared to healthy control subjects. Serum folate level in schizophreniagroup had negative correlation with negative symptoms (r=-0.25), and Hcylevel had negative correlation with cognitive function scores(r=-0.38,r=-0.33, r=-0.30, r=-0.30).4. Pearson correlation showed that among the7cortical areas that showinggroup differences, only left insula cluster averaged cortical thickness wassignificantly positively correlated with serum levels of BDNF in healthycontrol subjects (r=0.396, p=0.037), while not in first episode schizophreniapatients (r=0.035, p=0.819). Cortical thickness had no correlated withserum levels of and HCY in first episode schizophrenia patients and healthycontrol subjects(p>0.05).Conclusion1. Cortical thinning is present in first episode schizophrenia patients inwidespread regions, indicating neurodevelopmental disorder at the onset ofschizophrenia, this further support the hypothesis of primaryneurodevelopment disorder affecting the normal cerebral cortex development in schizophrenia[2-4].2. Serum folate level was decreased, HCY level was elevated and BDNF levelwas decreased in first episode schizophrenia patients. Insula corticalthickness is positively correlated with BDNF level whith prompt that leftinsula might be the major target cortical region for neurodevelopmental orneurotrophic factors. |
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