1、www.pku6h. cn 司天梅 2013-06-30Schizophrenia is a complex and severe brain disorder; showing positive, negative and cognitive symptoms;It typically emerges around adolescence, with males, on average, showing an earlier age at onset than females.Environment risk factors such as prenatal stress, obstetri
2、c complications, malnutrition and viral infection may increase the susceptibility of schizophrenia later in life. schizophrenia is a neurodegenerative disease associated with frequent relapses. Developmental Stage describes the stage of life during which the various events and phenomena occur; Clini
3、cal Signs and Symptoms refers to the mental and behavioral manifestations of the illness; Stage of Illness describes all premorbid and morbid phases of the illness; Pathologic Process refers the hypothesized pathogenic and pathophysiologic mechanisms that underlie and are causal to the clinical mani
4、festations of the disorder; Developmental Process and Events indicates the neurobiologic maturational processes and environmental events that may unmask or destabilize the neural circuits made vulnerable by etiologic and pathogenic factors.www.pku6h. cn 司天梅 2013-06-30围出生期神经元增生神经元迁移树突生长和分枝出生后：中间神经元的成
5、熟、谷氨酸能突触修剪、中脑皮层多巴胺能投射、髓鞘化www.pku6h. cn 司天梅 2013-06-30In the healthy control group, brain surface contraction occurred mainly along the dorsal prefrontal surface.The majority of other surface regions showed either considerably less surface contraction or surfaceexpansion of a very small magnitude ( 0
6、.05mm per year; Figure 1, column 1). In the FESZ group,surface contraction also occurred in the dorsal prefrontal regions, but at a much greater magnitude.The pre- and postcentral gyri and parietal regions also showed surface contraction in the patient group,in contrast to the mixed pattern of more
7、subtle contraction and expansion in the healthy controls(Figure 1, column 2). The absolute differences I mean surface contraction between the two groupswere isolated to the dorsal surfaces of the frontal and parietal lobes (Figure 1, column 3). As a whole,the FESZ patients and the healthy controls s
8、howed very similar spatial patterns of brain surface contraction,with those of the former exaggerated in magnitude.www.pku6h. cn 司天梅 2013-06-30Which antipsychotic drug should be preferred for the treatment of schizophrenia?This is a multiple-treatments meta-analysis, comparative efficacy and tolerab
9、ility of 15 antipsychotic drugs in schizophrenia.This meta-analysis included 212 RCTs trials, between October, 1955, and September, 2012, and nearly 45 thousand participants to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. The mean duration of illness was 124 ye
10、ars (SD 66) and the mean age of trial participants was 384 years (SD 69).www.pku6h. cn 司天梅 2013-06-30Forest plot for efficacy of antipsychotics drugs compared with placeboTreatments are ranked according to their surface under the cumulative ranking (SUCRA) values (appendix p 98).SMD=standardised mea
11、n difference. CrI=credible interval.They defined the standardised mean difference of 02 is small, 05 medium, and 08 large.All drugs were superior to placebo (range of mean effect sizes 033 to 088; and clozapine was significantly more effective than all the other drugs. After clozapine, amisulpride,
12、olanzapine, and risperidone were significantly more effective than the ot er drugs apart from paliperidone and zotepine. These effect sizes were small (range 011 to 033.www.pku6h. cn 司天梅 2013-06-30Apart from haloperidol, ziprasidone, and lurasidone,all drugs produced more weight gain than placebo.Ol
13、anzapine produced significantly more weight gain than most other drugs. Clozapine, iloperidone, chlorpromazine, sertindole, quetiapine, risperidone, and paliperidone produced significantly more weight gain than haloperidol,ziprasidone, lurasidone, aripiprazole, amisulpride, and asenapine. Standardis
14、ed mean differences for these comparisons ranged from 018 to 057, very large. www.pku6h. cn 司天梅 2013-06-30Clozapine, sertindole, olanzapine, quetiapine, aripiprazole, iloperidone, amisulpride, and asenapine did notcause significantly more extrapyramidal side-eff ects than placebo. Zotepine, chlorpro
15、mazine, lurasidone, risperidone, and paliperidone were among the least well tolerated drugs, because theyproduced significantly more extrapyramidal side-effects than several others in the analysis.www.pku6h. cn 司天梅 2013-06-30Aripiprazole, quetiapine, asenapine, chlorpromazine, and iloperidone did no
16、t cause significantly increased prolactin concentrations compared with placebo. Paliperidone and risperidone were associated with significantly more prolactin increase than all other drugs including haloperidol, and haloperidol wasassociated with significantly more than the rest apart from chlorprom
17、azine and sertindole. Clozapine and zotepine could not be included in the analysis,because the one direct comparison between them was not linked with any other drug in the network (standardised mean diff erence 123,95% CrI 18 to 064, in favour of clozapine; n=52).44 Nousable data were available for
18、amisulpride.www.pku6h. cn 司天梅 2013-06-30Lurasidone, aripiprazole, paliperidone, and asenapine were not associated with significant QTc prolongation compared with placebo. The standardisedmean diff erences of the other drugs compared with placebo ranged from marginal (011, haloperidol) to large(090, sertindole). www.pku6h. cn 司天梅 2013-06-30Amisulpride, paliperidone, sertindole, and iloperidone were not signifi cantly more sedating than placebo.
