Integrated Cognitive Training For Cognitive Function Of Patients With Schizophrenia

Objective: This study aimed to establish a three-stage integrated cognitive training,and to verify its feasibility through pilot experiment.A randomized controlled clinical trial was carried out to preliminary validate the effect of the integrated cognitive training on cognitive function of schizophrenia,and its possible neural mechanismsas.We aimed to explore the relationship between the COMT gene polymorphism and the cognitive function and brain structure in schizophrenia patients and healthy people.Methods: Part.1 Through summarizing the theoriess and methds of cognitive training both at home and abroad,we established a three-stage integrated cognitive training.The schizophrenia outpatients were recruited in Shanghai Mental Health Center,a pilot study was conducted to verify the feasibility of the integrate cognitive training.The randomized,blinded assessment and parallel control design(registration number: Chi CTR-IOR-15006678)was used to validate the effect of integrated cognitive training on cognitive function in schizophrenia patients.In piolt study,after the training,the patients were asked to assess its interestingness and practicability,as well as the difficulty and the training time of the metacognitive training,to verify the feasibility of integrated cognitive training.In the RCT,the schizophrenia inpatients who met the inclusion criterias were randomly divided into the integrated cognitive training group and the health education control group,according to block randomization.the integrated training group received the integrated cognitive training and the control group received the routine treatment.Cognitive functional assessment,clinical symptom assessment,and magnetic resonance imaging were performed at baseline,immediately after the intervention,and six months after the intervention respectively.The DC and f ALFF were used to assess the effect of integrated cognitive training on important nodes in the brain network and the effect on brain spontaneity.Statistical methods used two-sample t test,paired t test,chi-square test,repeated measures analysis of variance,correlation analysis,multiple stepwise linear regression analysis.Part.2This section included 56 first-episode and drug-na?ve schizophrenics and 56 sex age-matched normal subjects.Subjects were assessed for cognitive function,assessment of patient clinical symptoms,single gene sequencing of COMT(rs4680),and f MRI scans.This section divides COMT(rs4680)into Met-carrying genotypes(Met / Met and Val / Met)and Val / Val homozygote genotypes.The f MRI data was subjected to preprocessing(format conversion,time correction,head motion correction,removal of covariates,filtering,normalization,smoothing,etc.),and measurement and statistical analysis of degree centroid(DC).The f MRI statistic utilized the method of Alpha Sim multiple comparison and correction,and the cognitive and symptom analyzes were analyzed using SPSS.Results: Part.1 1.A total of 910 schizophrenia patients were screened,117 schizophrenic patients met the inclusion criteria and were enrolled successfully.According to the principle of intentionality analysis,a total of 113 subjects were included in the data analysis.There was no statistical difference between the two groups in demographic datas and baseline cognitive function,clinical symptoms between the two groups.2.In immediatly assessment,compared with the control group,the intergrated cognitive training group was significantly improved in the domain of speed of processing,while the control group was significantly lower than baseline in the efficacy index.In half-yearly follow-up assessment,compared with the control group,the intergrated cognitive training group was significantly improved in the domains of verbal learning,visual learning and social cognition,while the control group was significantly improved in the subgroups of the positive and negative symptom scalesthe positive symptom scale total score,the general psychopathological scale total score and the total scale.An ANOVA for repeated measurement showed that,in the assessment of cognitive function,the clinical symptoms and social function indexes,the interaction effect of time × intervention were not statistically significant.3.The 3 × 2(time × group)ANOVA results using the DC indicator showed that,the interaction effect between time and group was significant at the left lingual gyrus(Cluster = 34,F = 8.83,p = 0.000,MNI coordinates:-6,-81,-3).The 3 × 2(time × group)ANOVA results using the f ALFF indicator showed that,the time-group interactions(p> 0.05)were not significant at any brain areas.With comparison of DC values of different groups at different time points showed that,at 6 months of follow-up,the DC value in the integrated cognitive training group decreased and the DC value in the control group increased.At six months of follow-up compared with baseline,there was a negative correlation in the added value between of left lingual DC and verbal learning(r =-0.570,p = 0.027)in cognitive training group.4.Analysising of the factors influenced the integrating cognitive training showed that,there was a significant correlation between age,the baseline verbal learning ability and the cognitive improvment;patients with poor baseline scores in the fluency test and Hopkins verbal learning test benefited more from the integrated cognitive training.Part.2 The scores of the first-episode schizophrenia patients in all cognitive domains were lower than normal subjects.Compared with normal subjects,the DC in patients with first-episode schizophrenia increased in the medial prefrontal lobe,while at the top-occipital junction the value reduced.In the first-episode schizophrenia group,DC in medial prefrontal lobes increased in patients with Met-carrying genotype compared to patients with Val / Val homozygote genotype.In normal subjects,Met-carrying genotype subjects were tested for DC elevation in the left hippocampus and left amygdala compared to subjects with Val / Val homozygote genotype.Conclusions: Part.1 1.It is feasible to integrated cognitive training for schizophrenia patients,but its efficacy was week.2.Age,onset age and baseline verbal learning ability are related with the intervention effect.The baseline ability of verbal learning could predict the effect of the integrated cognitive training.3.Integrated cognitive training affects the importance of nodes in the lingual gyrus,and the changes in the importance of the lingual gyrus nodes are negatively correlated with changes in vocabulary learning ability.Part.2 In FES,the cognitive impairment was accociated with the FC of the m PFC,the COMT genotype affected the relationship between cognition function and the FC of m PFC.In healthy people,the COMT genotype may influence the cognitive function through left hippocampus.