| BackgroundSchizophrenia is a severe form of mental illness that has unknown etiology and poor prognosis.The pathogenesis of schizophrenia is not yet clear.More and more studies have shown that neurodevelopmental disorder is closely related to the pathogenesis of schizophrenia.Some scholar think that neurodevelopmental disorder is one of the important pathophysiology mechanisms of schizophrenia.Childhood and adolescence onset schizophrenia are defined as onset of psychosis before age 18.Compared with adult onset of patients,childhood and adolescence onset schizophrenia are more closely related to neurodevelopmental abnormalities,clinical symptoms is less atypical,cognitive impairment is more apparent,treatment and prognosis are wore.There are many studies have found that schizophrenia has abnormal brain structure and function,cognitive dysfunction at home and abroad.At the same time,they found that cognitive dysfunction is related to the abnormal changes of brain structure and function.Our previous research found that brain shrinkage,ventricle enlargement and cognitive dysfunction appeared in the children with schizophrenia.There are few reports on the brain function and the relationship between the brain function and cognitive function of childhood and adolescence schizophrenia,so we carried out a research into this subject.Objectives1.To investigate the characteristics of cognitive function in childhood and adolescence-onset schizophrenia.2.To analyze the resting state of brain function in childhood and adolescence-onset schizophrenia.3.To explore the relationship between the cognitive function and resting state brain function in childhood and adolescence-onset schizophrenia.Methods1.50 childhood and adolescence-onset schizophrenia(patients group)were chosen as the research group and 33 healthy children with age and sex matched(healthy group) were chosen as the control group.2.The cognitive function was estimated with MATRICS Consensus Cognitive Battery (MCCB)which included Trail Making Test A(TMA),Symbol Coding,Hopkins Verbal Learning Test-Revised(HVLT-R),Brief Visuospatial Memory Test-revised(BVMT-R),STROOP color,Verbal Fluency Test(VF),Digital Span test and Maze Test in all study controls.3.Using functional magnetic resonance imaging(fMRI)3.0 system to check the whole brain resting state fMRI of all the subjects.DPARSF software was used to analyze the imaging date of preprocessing.All study controls were studied using Resting-State fMRI Data Analysis Toolkit(REST)software to obtain the areas of the brain where the ALFF changes were statistically significant.4.The ALFF of the blood oxygenation level dependent resting-state functional Magnetic Resonance Imaging(BOLD-fMRI)signal for each participant was calculated.Groups of ALFF values were correlated with their cognitive function scores to find the areas of the brain where are positively correlated with cognitive function scores.5.Selecting the areas of the brain where the ALFF values are positively correlated with cognitive function scores as seeds point to find the areas of the whole brain where are statistically significant connection with seed point.Results1.The comparison of cognitive function in the childhood and adolescence schizophrenia group and the healthy control group of children and adolescentsCompared with the controls,the patients showed significant differences in TMA(63.74±36.58 vs 38.73±13.35,t=4.41,P<0.01),Symbol Coding(37.64±12.93 vs56.85±9.57,t=-7.31,P<0.01),HVLT-R(19.40±6.07 vs 26.85±3.92,t=-6.79,P<0.01),BVMT-R(18.60±8.14 vs 30.58±2.76,t=-9.60,P<0.01),Words(63.72±16.04 vs92.00±16.39,t=-7.80,P<0.01),Color(42.24±11.75 vs 64.03±13.95,t=-7.67,P<0.01),Color Words(24.86±8.77 vs 35.42±8.03,t=-5.55,P<0.01),VF(14.32±3.90 vs 19.85±4.12,t=-6.18,P<0.01),Digital Span test(43.98±14.52 vs 78.03±18.08,t=-9.48,P<0.01),and Maze Test(11.32±5.31 vs 19.82±4.25,t=-8.07,P<0.01).Compared to the control group,all the tests scores were lower except for TMA,the differences were statistically significant(P<0.05).2.The results of ALFF have been showed in the children and adolescents with schizophrenia group and the healthy control group of children and adolescentsCompared to the controls,Childhood and adolescence-onset schizophrenia showed significantly decreased ALFF in the left medial frontal and temporal lobe while in the area of left frontal lobe,left caudate,right fusiform gyrus,right frontal lobe and right caudate were increased(P<0.05,corrected by Alphasim).3.The correlation analyses between the value of ALFF and cognitive function in the children and adolescents with schizophrenia and healthy controls(1)The correlation between the cognitive function and the value of ALFF in the children and adolescents with early-onset schizophrenia.Pearson correlation analysis showed that BVMT-R scores were positively correlated with the value of ALFF in the left medial frontal gyrus(r=0.41);Digital Span test scores were negatively correlated with the value of ALFF in the right caudate(r=-0.30);Maze Test scores were negatively correlated with the value of ALFF in the Left caudate(r=-0.28);the test of multiple correlation coefficient were statistically significant(P<0.05).(2)The correlation between the cognitive function and the value of ALFF in thehealthy controls.Pearson correlation analysis showed that HVLT-R scores and color scores were positively correlated with the value of ALFF in the left frontal lobe(r=0.37,0.38);Symbol Coding and color words scores were negatively correlated with the value of ALFF in the right caudate(r=-5.48,-0.40);the test of multiple correlation coefficient were statistically significant(P<0.05).4.The results of functional connectivity have been showed between the children and adolescents with schizophrenia group and the healthy control group of children and adolescentsSelecting the brain areas where correlated with cognitive function as seeds point to analysis the resting state dysfunctional connection of the whole brain regions.When the right caudate was used as seed,compared to healthy controls,reduced connectivities were observed in the left cerebellum,left cerebellum anterior lobe,left superior temporal gyrus,cuneus lobe,cingulate gyrus,right frontal lobe,right middle temporal gyrus,right postcentral gyrus,right precunes and right middle frontal gyrus;When the left frontal lobe was used as seed,compared to healthy controls,reduced connectivities were observed in the left lingual gyrus,right temporal lobe,right inferior parietal lobe and right postcentral gyrus;When the left caudate was used as seed,compared to healthy controls,reduced connectivities were observed in the left inferior parietal lobe,left middle temporal gyrus,right occipital lobe and right parietal;When the left medial frontal gyrus was used as seed,compared to healthy controls,reduced connectivities were observed in the left inferior temporal gyrus,left fusiform gyrus,left middle temporal gyrus,orbitofrontal cortex lobe,posterior cingulate,right fusiform gyrus and right medial frontal gyrus(p< 0.05,corrected by FDR).Conclusions1.There were cognitive impairment in the speed of proceeding,working memory,verbal learning,visual learning,anti-interference ability,attention and reasoning in the children and adolescents with early-onset schizophrenia.2.There are some abnormal spontaneous neural activity of the brain regions in children and adolscents with early-onset schizophrenia,which includes frontal lobe,caudate,left temporal lobe and other brain areas.3.The ALFF value changes of some brain regions were closely to the cognitive function in in childhood and adolescence schizophrenia,which prompt cognitive dysfunction may be associated with abnormal spontaneous neuronal activity.4.There are some abnormal functional connectivity of the brain regions in children and adolscents with early-onset schizophrenia.These abnormalities may be providing a basis for studying the brain function of schizophrenia. |
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