The Relationship Between White Matter Volume And Cognitive Function In First-episode Childhood And Adolescence-onset Schizophrenic Patients With Auditory Verbal Hallucinations

BackgroundSchizophrenia(SZ)is a kind of common chronic severe psychosis.It often shows different symptom groups in clinic,including auditory verbal hallucinations,delusion and cognitive dysfunction.The etiology and pathogenesis of this disease are still unclear.Studies have shown that the pathogenesis of SZ may be related to neurodevelopmental abnormalities,and the changes of white matter(WM)development track are closely related to schizophrenia.Childhood and adolescent-onest schizophrenia(CAOS)began before the age of 18.Compared with adult patients,the clinical symptoms of children and adolescence-onest with schizophrenia are more typical,hallucinations are more common,and cognitive function and social function are damaged more seriously.Auditory verbal hallucinations(AVH)is a major perceptual disorder in schizophrenic patients.Self injury and wounding behaviors under the control of command auditory hallucinations bring serious harm to patients,families and society.At present,researches on auditory hallucinations are mostly found in adults,and there are few studies on children and adolescence-onest with schizophrenia.Whether patients with auditory hallucinations have changes in white matter volume at the early stage of illness is still uncertain,and whether the degree of cognitive function changes is the same,and the relationship between white matter volume and cognitive function is still unclear.Therefore,this study takes children and adolescence-onest with schizophrenia as the research objects to explore the potential imaging markers of auditory hallucinations and the potential neuroimaging basis of cognitive function changes.Objectives1.To analyze the changes of WMV in the first-episode children with schizophrenia.2.To analyze the relationship among the severity of AVH and WMV and cognitive function in the first-episode children with schizophrenia.Methods1.Participants: Eighty-four first-episode CAOS were selected as the case group,and and 35 healthy children were included as the control group(HCs).,whose gender,age,ethnicity and education levels were matched with the case group.2.Assessment of cognitive function and clinical symptoms: the cognitive function of all subjects was assessed by the Chinese version of measurement and treatment research to improve cognition in schizophrenia consensus cognitive battery(MCCB)and Stroop color words test.The severity of psychiatric symptoms in all patients was evaluated using the Positive and Negative Syndrome Scale(PANSS),and The CAOS patients were divided into three groups according to the auditory verbal hallucinations(AVH)assessment of positive symptoms scale(SAPS): non-AVHs(0,1),mild to moderate AVHs(2,3)and severe AVHs(4,5).3.Image data processing and analysis: in the MATLAB 2013b(the math works,Inc.,Natick,Massachusetts)platform,using spm8(statistical parametric mapping,http://www.fil.ion.ucl.ac.uk/spm)Vbm8(voxel based morphology dbm.neuro.uni-Jena.De / VBM /)and rest(rs-f MRI data analysis toolkit,http:// www.restfmri.net)Software package.The process of analysis includes format reconstruction,spatial standardization,image segmentation,brain volume calculation,smoothing and so on.Finally,the WMV is analyzed statistically after smoothing.4.Statistical analysis: rest software was used to analyze the brain regions that differed between the case group and the HCs,and the white matter volume values were calculated.The threshold level was set as P<0.05,and Alphasim was corrected.Pearson correlation/Spearman correlation was used to analyze the correlation between the volume of white matter in different brain regions and the score of PANSS scale,AVH score and cognitive function score,α=0.05,double-tailed test.Results1.Comparison of the WMV and cognitive function between case group and control group(1)Comparison of WMV between the two groups: compared with the HCs,the WMV in the left anterior cerebellar gyrus,left superior temporal gyrus,left cingulate gyrus,corpus callosum and left middle frontal gyrus of the case group was significantly decreased(P<0.05,Alphasim correction).(2)Comparison of cognitive function between the two groups: the score of connection test in the case group was higher than that in the HCs;the scores of symbol coding,HVLTR,BVMT-R,word fluency,digit span,maze and Stroop Color-word test in the case group were lower than those in the HCs(P<0.01).2.Comparison of white matter volume and cognitive function between different severity auditory hallucination groups(1)The WMV differences among the three groups were mainly located in the left superior temporal gyrus,right superior temporal gyrus and left inferior frontal gyrus(P<0.05,alphasim correction).Compared with non-AVH,The WMV of left superior temporal lobe was decreased in mild to moderate AVH;compared with non-AVHs,the WMV of left superior temporal lobe was increased in severe AVH;compared with mild to moderate AVH,the WMV of left superior temporal gyrus was increased in severe AVH(P<0.05,alphasim correction).(2)There was no significant difference in the scores of cognitive function among the three groups(P>0.05).3.Correlation analysis between the volume of WM in different brain regions and PANSS scalePearson correlation analysis showed that the white matter volume of the left anterior cerebellar lobe was negatively correlated with the positive symptom score(r=-0.34,P<0.05),and the left superior temporal lobe was negatively correlated with the negative symptom score(r=-0.24,P<0.05).4.Correlation analysis between the volume of white matter and auditory hallucination score in different severity groupsSpearman correlation analysis showed that white matter volume of right superior temporal lobe was positively correlated with auditory hallucination score(rs=0.26,P=0.02).5.Correlation analysis between white matter volume and cognitive function in different severity auditory hallucination groupsPearson correlation analysis showed that The WMV in the right superior temporal lobe was positively correlated with Stroop word and Stroop color score in the non AVHs(r=0.55,0.45,P=0.01,0.04),the WMV in the left superior frontal lobe was negatively correlated with Stroop Color score in the mild and moderate AVHs(r=-0.34,P=0.04),the WMV in the right superior temporal lobe was negatively correlated with Stroop Color score in the severe AVHs(r=-0.44,P=0.04).Conclusions1.Compared with the HCs,we found decreased WMV in multiple brain regions in CAOS.The occurrence of AVH may be related to the decrease of temporal lobe volume,and the occurrence of severe AVH is related to the compensatory increase of temporal lobe volume.2.First-episode schizophrenics have extensive cognitive dysfunction,and cognitive dysfunction may be related to abnormal changes in brain white matter volume.