| Background There are no work about repetitive transcranial magnetic stimulation (rTMS) on schizophrenia patientsin the bilateral prefrontal white matter metabolism change, and the effect of rTMS on the cognitive function in patients with schizophrenia show inconsistent results.Objectives (1) Studying the effects of rTMS on the bilateral prefrontal white matter of the patients with schizophrenia, to study the possible mechanism of the rTMS in neurobiological.(2) Studying the effects of rTMS on cognitive function of the patients with schizophrenia, to provide clinical therapeutic basement about schizophrenia.Methods A total of71hospitalized schizophrenics fulfilled the criteria for schizophrenia according to the International Classification of Diseases, revision10(ICD-10). The patients of schizophrenia were required not using antipsychotic drugs and other drugs which effect the neurotransmitter acetylcholine at least7days. The patients were randomly divided into study group and case-control group. The study group (n=36) accepted lOHz rTMS really stimulation combined with risperidone tablets, and the case-control group (n=35) received lOHz rTMS sham stimulation treatment with risperidone tablets. Recruiting33healthy volunteers as normal-control group. All patients were examined at bilateral prefrontal white matter nerve biochemecial metabolites for NAA, Cho, Cr by Proton Magnetic Resonance Spectroscopy (’H-MRS), and evaluate the cognitive function of patients with the Event Related Potential P300(P300) and Wisconsin Card Sorting Test (WCST) and evaluate the mental symptoms with PANSS at before rTMS treatment, after2weeks and after4weeks. The research indicators of P300included amplitude and latency of P3and NP3; and the study indicators of WCST included the completion of the classification numbers (Cc), correct responses numbers (Re), the percentage of conceptualization level response (Rf%), the error response numbers (Re), perseverative responses number (Rp), sustained numbers of error (Rpe) and the numbers of required response to complete the first category (Rf). The healthy volunteers were test once by ’H-MRS, P300and WCST. Using SPSS16.0for general descriptive statistics, repeated measures analysis of variance, Independent-Sample Test, Pesrson correlation analysis, et al statistical analysis.Results1. rTMS in combination with risperidone on the influence of the profrontal lobe1H-MRS target of schizophrenics.(1)Before treatment, two and four weekends after treatment, NAA/Cr values in the left prefrontal white matter were significant differences among3groups (F=4.529,3.735,3.334, P all<0.05). Before treatment and after two weeks treatment, the study group and the case-control group lower than the normal-control group about NAA/Cr values in the left prefrontal white matter(P<0.05), the difference was no significantly differences between the study group and the case-control group(P>0.05). After four weeks treatment, between the study group and the normal-control group about NAA/Cr values in the left prefrontal white matter, the difference was no significantly differences(P>0.05), the case-control group lower than the normal group (P<0.05), the study group higher than the case-control group(,P<0.05).(2) Compared with before treatment, there was no obviously change about NAA/Cr calues in the left prefrontal white matter of the study group after two weeks(P>0.05), After four weeks, the NAA/Cr calues in the left prefrontal white matter increased(P<0.05); the NAA/Cr calues in the left prefrontal white matter of the case-control group no obviously change after two and four weeks(P>0.05).2. rTMS in combination with risperidone on the influence the indexes of the cognitive function of schizophrenics.(1) Before treatment, two and four weekends after treatment, the indexes of P300and WCST were significant differences among the3groups (P<0.05or0.01). Before treatment and after two weeks treatment, the latency of P3and NP3, Re, Rp, Rpe, Rf, both the study group and case-control group, higher than the normal control group, the amplitude of P3and NP3, Cc, Re, Rf%lower than the normal-control group, the difference was significantly differences(P<0.05or0.01); the indexes of P300and WCST on the study group and case-control group was no significantly differences(P>0.05). After four weeks treatment, compared with the normal-control group, the latency and amplitude of P3and NP3, Cc, Re, Rp, Rpe, Rf in the study group have no significant difference (P>0.05), the Rf%of the study group lower than the normal-control group, the Re of the study group higher than the normal-control group, the difference was significantly differences(P <0.05); The latency of P3and NP3, Re, Rf in the case-control group higher than the normal-control group, but the amplitude of P3and NP3, Cc, Re, Rf%lower than the normal-control group, the difference was significant difference (P<0.05or0.01), The latency of P3, NP3in the study group lower than the case-control group, but the amplitude of P3and NP3, Cc, Re, Rf%higher than the case-control group (P<0.05).(2)Compare with before treatment, the P300and WCST in the study group and normal-control group were no obviously change after two weeks(P>0.05); After four weeks, the latency of P3and NP3, Re, Rp, Rpe, Rf were shorten, and the amplitude of P3and NP3, Cc, Re, Rf%were increased(P<0.05or0.01). After4weeks treatment, The latency and amplitude of P3, NP3in the case-control group was no obviously change(P>0.05), Cc, Re, Rf%were increased, Re, Rp, Rpe, Rf were reduced(P<0.01).3. Metabolism of patients with schizophrenia prefrontal physical and cognitive function correlation analysis of indicators. Before treatment, the NAA/Cr values in the left prefrontal white matter of the study group and the case-control group showed a significant positive correlation with Cc, Re, Rf%, P3and NP3amplitude (r, Fz:0.301/0.299, Cz:0.236/0.234,0.265,0.271and0.259, P<0.05), and the NAA/Cr values showed a significant negative correlation with Re, Rp, Rpe, Rf, P3and NP3latency (r, Fz:-0.246/-0.267, Cz:-0.235/-0.238,-0.285,-0.274,-0.251and-0.275, P<0.05). After four weeks treatment, the NAA/Cr value changes in the left prefrontal white matter of the study group were significantly positive correlated with Cc,(Fz site)P3and NP3amplitude changes (r=0.378,0.373and0.341, P<0.05), and the NAA/Cr value changes showed a significant negative correlation with Rpe, Rf,(Fz site)P3and NP3latency changes (r=-0.364,-0.351,-0.342and-0.352, P<0.05).4. rTMS combination with risperidone on the influence of efficacy and safety of patients with schizophrenia.(1) Before treatment, the total points of PANS S and each factor points, between the study group and the case-control groups, were no significant difference (P>0.05). After two and four weeks, the total points of PANSS, negtive syndrome score and general psychopathology score of study groups lower than the control-case group (P<0.05or0.01), while the two positive syndrome scores were no significantly differences(P>0.05).(2) Compared with before treatment, the total points of PANSS, negtive syndrome score and general psychopathology score of study groups were decreased after two weeks treatment (P<0.05or P<0.01), the total points of PANSS and each factor points of case-control group were no obviously changed after two weeks treatment (P>0.05). The total points of PANSS and each factor points were decreased after four weeks treatment (P <0.05or P<0.01).The ratio of headache incidence of study group is higher than control-case group(χ2=4.390, P<0.05). The drug related adverse effects rate compare between the two groups has no statistical significance(χ2=2.80, P>0.05).Conclusions1. There have correlation between the low expression of the left prefrontal NAA of patients with schizophrenia and the generation of cognitive dysfunction;10Hz rTMS combined with risperidone can improve the abnormal metabolic of the left prefrontal NAA of patients with schizophrenia, and they may be repair the brain neuron function.2.10Hz rTMS combined with risperidone is helpful to enhance the brain excitability and the speed of information processing and disposal of the patients with schizophrenia, and to improve their memory, attention and executive function of the patients with schizophrenia obviously.3.10Hz rTMS combined with risperidone is better helpful to improve the negative symptoms of schizophrenics, also improve the positive symptoms of schizophrenics, and it is earlier effect, higher security. |
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