Thetreatment Of Cognitive Symptoms And The Relationship Between Cognitive Symptoms And Gray Matter Volume Of First Episode Antipsychotic-na(i|¨)ve Schizophrenia

Part1The Cognitive Effects and Clinical Effects of Novel Antipsychotic Drugs and Their Relationship on First Episode Antipsychotic-naive SchizophreniaObjective:To invesitigate six-month cognitive effects and effects of clinical effects of olanzapine, risperidone and aripiprazole and the relationship of the both effects on first episode antipsychotic-naive schizophrenia.Methods:This study is a randomized, open-label clinical drug trial. Study subjects included one hundred patients who met DSM-Ⅳ study criteria and60cases of healthy volunteers whose age, sex and years of education were similar to the patients’ as the normal control group. The patients were randomizedly divided into olanzapine group (32cases, dosage range0.5-20mg), risperidone group (34cases, dosage range1-4mg) and aripiprazole group(34cases, dosage range5-20mg). A battery of cognitive tests and Positive and Negative Syndrome Scale were used to assess cogition and psychotic symptoms at baseline and after treatment six months respectively. The normal control group was only performed cognitive tests at baseline. Six cognitive tests were used to assess five cognitive domains. Hopkins Verbal Learning Test-Revised was used to assess verbal learning and memory; Brief Visuospatial domain scores, including processing speed (t (26)=-2.11, P=0.045) and selective attention (t (26)=-3.30, P=0.003). Risperidone improved all five cognitive domains, including verbal learning (t (22)=-2.25, P=0.035), processing speed (t (22)=-4.05, P=0.001), visual learning (t (22)=-4.59, P<0.001), selective attention (t (22)=-4.42, P<0.001) and working memory (t (22)=-2.70, P=0.013). Aripiprazole improved visual learning (t (23)=-2.48, P=0.021) and working memory (t (23)=-2.61, P=0.016). Although group-by-time main effects revealed that there were significant differences on mean z-score changes of cognitive composite scores(P =0.034) for the three antipsychotics after six months of treatment, differences disappeared between treatment groups after Bonferroni multiple comparisons correction. Pearson correlations did not Memory Test—Revised was used to assess visual learning and memory; Spatial span subtest was used to assess nonverbal working memory; animal naming and digit symbol coding were used to assess processing speed; Stroop Color and Word Test was used to assess selective attention. All data of the patients who completed6-month trial were input SPSS15.0(Statistical Package for the Social Sciences) in order to make further statistical analysis.Results:(1) Irrespective of medication type, the patients showed significant improvements in cognitive composite score and the four cognitive domain scores (z scores), including processing speed, working memory, selective attention and visual learning over time. Paired t tests showed that the cognitive composite scores of all three treatment medications increased over time [olanzapine, t (26)=-2.12, P=0.044); risperidone (t (22)=-5.48, P<0.001) and aripiprazole t (23)=-3.43, P=0.002)]. A paired t test showed that olanzapine improved2of the5domain scores, including processing speed (t (26)=-2.11, P=0.045) and selective attention (t (26)=-3.30, P=0.003). Risperidone improved all five cognitive domains, including verbal learning (t (22)=-2.25, P=0.035), processing speed (t (22)=-4.05, P=0.001), visual learning (t (22)=-4.59, P<0.001), selective attention (t (22)=-4.42, P<0.001) and working memory (t (22)=-2.70, P=0.013). Aripiprazole improved visual learning (t (23)=-2.48, P=0.021) and working memory (t (23)=-2.61, P=0.016). Although group-by-time main effects revealed that there were significant differences on mean z-score changes of cognitive composite scores (P=0.034) for the three antipsychotics after six months of treatment, differences disappeared between treatment groups after Bonferroni multiple comparisons correction.(2) Pearson correlations did not show a relationship between the z change scores of the cognitive composite score and individual cognitive domains and the treatment-related change scores in the clinical PANSS positive and negative score for the entire sample (P>0.134) after6-month follow-up. For each group, the Pearson correlations showed no correlation between change in cognitive performances and change in negative symptoms scores (P>0.11). For risperidone group, the relationship between the performance of processing speed change and PANSS positive symptoms change showed siginificantly positive correlation(r=0.438, P=0.037). For risperidone group, the relationship between the performance of processing speed change and PANSS positive symptoms change showed siginificantly negative correlation (r=-0.41,P=0.033).(3) At baseline and after treatment6months, compared with the normal control group, the independent sample t test showed that the test indicators points of HVLT-R,VF,DSC, Stroop Color and Word Test of three groups all had significant differences(all P<0.01)Conclusion:(1) To antipsychotic-naive first-episode schizophrenia, the three novel antipsychotic drugs may improve individual cognitive domains, but may have similar effects on global cognition.(2) To antipsychotic-naive first-episode schizophrenia, after6months treatment, their cognitive performances are still worse than that of the normal control group, cognitive impairment may be the core symptoms of schizophrenia. Six figures,9tables and73references. Part2The Relationship between Cognitive Symptoms and Gray Matter Volume of First Episode Antipsychotic-naive SchizophreniaObjective:To explore the relationship between cerebral gray matter volume and cognitive symptoms of first episode antipsychotic-naive schizophrenia.Methods:This study is a case control design. Fourty-five patients with antipsychotic-naive first-episode schizophrenia and thirty-nine age-sex matched healthy control subjects were performed cognitive assessment and Magnatic Resonance Imaging scan respectively. The cognitive tests included Hopkins Verbal Learning Test-Revised (HVLT-R), Brief Visuospatial Memory Test—Revised (BVMT-R), Verbal Fluency Test (VF, animal naming) and Spatial Span Subtest (SSS). Three-dimensional structural magnetic resonance imaging was used to collect raw data of all study subjects. These data were used voxel-based morphometry (VBM) to investigate differences in gray matter volumes of the two groups. Other data were input SPSS15.0soft in order to make further stastical analysis.Results:(1) Two Independent Sample t test were used to compare the performances of HVLT-R, BVMT-R, SSS and VF of the two grous. Compared with healthy control group, the performances of the four cognitive tests were all lower than that of the former, exsiting significant differences, and specifically, HVLT-R (t=4.24, P<0.001), BVMT-R(t=5.57,P<0.001), SSS (t=2.56, P<0.012) and VF (t=5.73, P<0.001).(2) Compared with healthy control group, the patient group had lower gray matter volume in left insula, right hippocampus, right and left middle temporal gyrus, left temporal pole, left superior temporal gyrus, right anterior cingulate, fusiform, left inferior temporal gyrus, left inferior frontal gyrus, left middle occipital gyrus, angular gyrus, right insula and left hippocampus. Extracting the brain regions which were bigger than50voxels as region of interest including left and right insula, left and right anterior cingulate, left and right hippocampus, right parahippocampal gyrus, right amygdala, left inferior occipital gyrus, left superior temporal gyrus, left temporal pole-sup, left middle temporal gyrus and left inferior temporal gyrus. The volumes of all braion regions mentioned above of two groups exsited significant differences (all P<0.001).(3) Cognitive performances and gray matter volumes extracted mentioned above were used to make correlation analysis. The results showed that the performances of HVLT-R and SSS existed positive correlation with gray matter volume of left anterior cingulate gyrus (r=0.39, P=0.01; r=0.39, P=0.01) and right anterior cingulate gyrus (r=0.34,P=0.03;r=0.39,P=0.01) and right insula (r=0.32,P=0.036; r=0.38, P=0.012) respectively.Conclusion:(1) Antipsychotic-naive first-episode schizophrenic patients have showed extensively lower gray matter volume, including frontal lobe, temporal lobe, occipital lobe, amygdala and cingulate gyrus. Furthermore, cognitive dysfunction has also emerged. Both may have correlation.(2) Anterior cingulate gyrus and insula may be the pathologic basis of cognitive impairment of first-episode schizophrenia. Seven figures,4tables and46references.