| Background:Alterations of brain function have been implicated in the pathophysiology of schizophrenia. On clinical treatment, antipsychotic drugs can ameliorate the symptoms in schizophrenia. However, it is still unclear about the mechanism that how the drug play its role to change the brain function.The aim of our study is to investigate the effect of Palmitate Paliperidone Injection(which is known as dopamine receptor antagonist) on brain function, to understand its treatment effect by examining alterations of regional homogeneity (ReHo) of brain resting state functional magnetic resonance imaging in patients with schizophrenia before and after treatment with Palmitate Paliperidone, and to analysis the relevance of ReHo and symptoms in patients. On basis of these, to explore the mechanism of antipsychotic drugs in brain functional level.Methods:17 schizophrenia patients diagnosed with DSM-Ⅳ (Diagnostic and Statistical Manual of Mental Disorder, forth edition) and 17 gender- and age-matched healthy controls were included in this study. All participants were arranged to undergo magnetic resonance imaging (MRI) scan session (patients with schizophrenia were scanned twice at baseline and the end of 3rd month respectively, healthy controls were scanned once), and PANSS、 PSP were collected from all patients at baseline and the end of 3rd month. All resting state functional magnetic resonance imaging (rs-fMRI) data of 17 patients and 17 healthy controls were processed automatically by using the software DPARSF running on MATLAB 2012a. Regional homogeneity (ReHo) images of resting state functional magnetic resonance imaging were obtained after the normalization, segmentation, detrend, filter and smoothing steps. Compared the two sets ReHo images of patients group, which were collected at baseline and the end of 3rd month by pair-samples t-test, and compared the ReHo images of healthy control group and patients group by two-sample t-test respectively to detect regions where group differences exit pertaining to the ReHo images. Then two correlation analyses were performed:the ReHo images at baseline were correlated with the psychopathology ratings (which involved PANSS and PSP) at baseline, ReHo values in regions where changes were calculated before and after treatment with Palmitate Paliperidone were correlated with psychopathology ratings (which involved PANSS and PSP) changes before and after the 13 weeks treatment.Results:1. Compared with the scales score of patients at the end of 3rd month and baseline, there were statistically significant differences in the total score, the negative symptoms score, the positive symptoms score, the delusion score, the hallucination score of PANSS, and PSP score (P<0.05), and the reduction rate of PANSS was 38.97%±25.06%.2. The incidence of adverse reaction was 70.59%, of which the incidence of extrapyramidal reaction was 64.71%, the incidence of heartbeat tachycardia was 17.65%, incidence of insomnia was 11.76%, the incidence of menstrual disorder in female patients was 66.67%, and all patients can tolerate these adverse reaction.3. Compared with the healthy control group, the ReHo images of the patients at baseline, ReHo increased in the following brain regions:left parietal lobe, bilateral dorsal prefrontal cortex, precuneus, angular gyrus and left cerebellum posterior lobe, and decreased in these regions:bilateral postcentral gyrus, lingual gyrus, right occipital lobe, right temporal lobe, right ventral prefrontal cortex; the ReHo images of the patients at the end of 3rd month, ReHo increased in the following brain regions:left inferior parietal lobule, dorsal prefrontal cortex, ventral lateral prefrontal cortex, precuneus, angular gyrus, left posterior cingulate gyrus, left cerebellum posterior lobe and decreased in these regions:postcentral gyrus, inferior temporal gyrus, lingual gyrus, right occipital lobe, right inferior parietal lobule, the ventromedial prefrontal cortex (orbitofrontal).4. Compared with patients’ ReHo images at the end of 3rd month and baseline, ReHo of left posterior cingulate gyrus, right medial frontal gyrus, right insula-right frontal lobe, and left inferior parietal lobule increaseed; ReHo of left middle temporal gyrus, right inferior temporal gyrus, midbrain decreased.5. About patients group, the correlation analysis between ReHo values at baseline and psychopathology ratings (which involved PANSS and PSP) at baseline suggested that:1) PANSS scores were positively correlated with the ReHo values of right lingual gyrus, right cerebellum posterior lobe, and negatively correlated with the ReHo values of left cerebellum anterior lobe;2)PANSS positive symptoms scores were positively correlated with the ReHo values of left superior temporal gyrus, left hippocampus gyrus, left precentral gyrus, and negatively correlated with the ReHo values of left superior occipital gyrus; 3) PANSS negtive symptoms scores were negatively correlated with the ReHo values of the left insula, right inferior temporal gyrus; 4) PANSS delusion symptom scores were positively correlated with the ReHo values of left middle frontal gyrus, right middle temporal gyrus, and negatively correlated with the ReHo values of left superior occipital gyrus; 5) PANSS hallucination symptom scores were positively correlated with the ReHo values of right inferior frontal gyrus, and negatively correlated with the ReHo values of right lingual gyrus and left superior occipital gyrus; 6) PSP scores were negatively correlated with the ReHo value of left parahippocampal gyrus and right superior occipital gyrus.6. About patients group, the correlation analysis between ReHo values changes and psychopathology ratings changes before and after the 13 weeks treatment with Palmitate Paliperidone suggested that:1) the ReHo values changes of Right middle frontal gyrus, left inferior parietal lobe, left cerebellum posterior lobe were positively correlated with the PANSS reduction rate, the ReHo values changes of left temporal pole-middle temporal and left lingual gyrus were negatively correlated with the PANSS reduction rate; 2) the ReHo values changes of left superior temporal gyrus (BA41), left supramarginal gyrus, left precentral gyrus(BA6), right superior frontal gyrus (BA6) were positively correlated with the improvement of positive symptoms; 3) the ReHo values changes of left inferior temporal gyrus (BA19), right superior frontal gyrus, right middle frontal gyrus (dorsolateral and ventrolateral prefrontal cortex) were positively correlated with the improvement of negative symptoms, the ReHo values changes of left orbital frontal gyrus was negatively correlated with the negative symptom improvement;4)the ReHo value change of left cerebellum posterior lobe was positively correlated with the improvement of delusion; 5) the ReHo values changes of left fusiform gyrus-parahippocampal gyrus, right superior frontal gyrus (BA6) were positively correlated with the improvement of hallucination;6) the ReHo values changes of left middle temporal gyrus (BA19), right middle frontal gyrus, right inferior frontal gyrus (dorsolateral prefrontal cortex) were positively correlated with the improvement of PSP, the ReHo values changes of left orbital frontal gyrus was negatively related with the improvement of PSP.Conclusion:1. Palmitate Parliperidone for schizophreniais efficacious,itis able to improve the positive symptoms, negative sympotoms and promote the recovery of social function of patients with schizophrenia; and its treatment is tolerable.2. Compared with ReHo images of the healthy control group and the patients group at baseline and the end of 3rd month, there were many brain regions with abnormal activities in frontal gyrus, temporal gyrus, parietal lobe, occipital lobe and insula, which suggest that the abnormity of brain function in patients with schizophrenia is extensive.3. Compared with patients’ ReHo images at the end of 3rd month and baseline, ReHo of right medial frontal gyrus, right insula-right frontal gyrus, left posterior cingulate gyrus, and left inferior parietal lobule increaseed; ReHo of left middle temporal gyrus, right inferior temporal gyrus, midbrain decreased; which reflets Pamitate Paliperidone has an effect on the brain function of patients with schizophrenia, and the effect may mediate by dopamine(DA).4. There were correlation between the psychotic symptoms, social dysfunction and the ReHo values of part of frontal gyrus, temporal gyrus, occipital lobe, midbrain-limbic system and bilateral cerebellum at baseline, and the changes of ReHo values of part of frontal gyrus, temporal gyrus, parietal lobe, occipital lobe, midbrain-limbic system and bilateral cerebellumin rs-fMRI were related with the improvement of different sympotoms, which indicate that, influencing the function of these brain regions, Palmitate Paliperidone achieves its treatment effect in schizophrenia. However, it is not one-to-one correspondence between the correlation between ReHo values and psychopathology ratings at baseline and the correlation between ReHo values changes and psychopathology ratings changes before and after the 13 weeks treatment with Palmitate Paliperidone, which may reflect that there is overall brain function abnormity but not some brain regions abnormity independently in Schizophrenia. |
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