The Relationship Between Cognitive Function And Hippocampal Subfields’ Volume Of First-episode Schizophrenia Patients

Objective: The purpose of this study was to analyze the relationship between the volume of the hippocampus’ subfields and the cognitive dysfunction of patients with first-episode schizophrenia(FES),the latter including neurocognition(NC)and facial emotional cognition(FEC),and to explore the possible biological basis of cognitive dysfunction of SCZ.Methods: In this study,41 patients with FES who met The Diagnostic criteria of DSMIV(The Diagnostic and Statistical Manual of Mental Disorders,the Fourth Edition)schizophrenia and who have never been medicated were recruited as subjects.At the same time,27 healthy controls(HC)matched with age,sex,and educational background of patients with FES were recruited.Demographic information of all subjects was collected respectively,and the Positive and Negative Syndrome Scale(PANSS)was used to evaluate the severity of clinical symptoms in the FES group,and NC and FEC functional level tests were conducted on subjects of two groups.The Digit Span Test(DST),the Semantic Similarity Test(SST),the Stroop Color-Word Test(SCWT),the Auditory Word Learning Test(AVLT),the Trail Making Test(TMT),the Controlled Oral Word Association Test(COWAT),the Clock Drawing Test,CDT)and the Wisconsin Card Sorting Test(WCST)are used to evaluate NC function levels,counting the correct number of tests and answer times.The FEC functional level was tested by facial emotion classification task,the results of subjects’ recognition and selection were counted,and the curve fitting formula of logical function was applied to calculate the corresponding shift point and slope of the fitting curve.High-resolution magnetic resonance images of T1 and T2 were collected within 3 days of recruitment.Free Surfer 6.0 was used to divide the subfields of the hippocampus in the FES group and HC group,and the volume of each subfield of the hippocampus were measured.SPSS Statistics 22.0 software was used to conduct statistical analysis on demography data,NC results,the shift point and slope of FEC,as well as the volume of each hippocampal subfields by independent sample t-test.The results were expressed as mean ± standard deviation.The sex ratio was statistically analyzed by the chi-square test.Pearson correlation analysis was conducted for NC results and the shift point and slope of FEC,hippocampal subfields’ volume,and PANSS scores of FES patients.All results above were statistically different at P < 0.05.Results:(1)The scores of DST,SST,SCWT,AVLT,TMT,COWAT and WSCT in the FES group were significantly lower than those in the HC group,and there was no statistical difference in the correct number of CDT and SCWT card A between the two groups.Compared with HC group,the shift point and slope of facial emotion classification test in FES group were significantly higher than HC group.(2)The total volume and subfields’ volume of the hippocampus in FES group were lower than those in HC group.There were statistically significant differences in total volume,CA(cornu ammonis)1,presubiculum,parasubiculum,and HATA(hippocampal amygdala transition area)subfields’ volume of the left hippocampus as well as total volume,subiculum,CA1,presubiculum,parasubiculum,ML(molecular layer),HATA volume in the right hippocampus between the two groups.(3)In FES group,total volume of left hippocampus(r=0.287,P=0.018),total volume of right hippocampus(r=0.349,P=0.004),left CA1(r=0.259,P=0.033),HATA(r=0.267,P =0.027),right subiculum(r=0.300,P =0.013),CA1(r=0.333,P =0.006),presubiculum(r=0.272,P =0.025),ML(r=0.309,P =0.010),HATA(r=0.243,P =0.046)volume were significantly positively correlated with DST scores.The left hippocampus CA1(r=0.252,P =0.038),HATA(r=0.274,P =0.024),the total volume of the right hippocampus(r=0.286,P =0.018),CA1(r=0.335,P =0.005),the presubiculum(r=0.257,P =0.034),ML(r=0.266,P =0.029),and HATA(r=0.298,P =0.014)volume were significantly positively correlated with SST scores,and the volume of right CA1(r=-0.245,P =0.044)was significantly negatively correlated with SCWT card A time.The volume of right HATA(r=-0.272,P =0.025)was negatively correlated with SCWT card B time,and the volume of right presubiculum(r=0.277,P =0.022)was positively correlated with the first AVLT scores.There was a significant positive correlation between the volume of right parasubiculum and the second AVLT score(r=0.244,P =0.045).The total volume of the left hippocampus(r=-0.255,P =0.036),the total volume of the right hippocampus(r=-0.272,P =0.025),the volume of the left CA1(r=-0.252,P =0.038),the left presubiculum(r=-0.370,P =0.002),the left parasubiculum(r=-0.379,P=0.001),the volume of right CA1(r=-0.290,P =0.016),presubiculum(r=-0.380,P =0.001),parasubiculum(r=-0.357,P =0.040),ML(r=-0.250,P =0.040)were significantly negatively correlated with TMT-A time.There were significant negative correlations between volume of left HATA(r=-0.245,P =0.044),right CA1(r=-0.258,P =0.034),presubiculum(r=-0.296,P =0.033),parasubiculum(r=-0.258,P =0.033),HATA(r=-0.269,P =0.045)and TMT-B time.The volume of right hippocampus(r=0.244,P=0.045),left parasubiculum(r=0.266,P =0.028),left HATA(r=0.253,P =0.037),right subiculum(r=0.347,P =0.004),right presubiculum(r=0.337,P =0.006),right parasubiculum(r=0.332,P =0.006)and right HATA(r=0.269,P =0.026)were significantly positively correlated with COWAT scores.(4)There was a significant negative correlation between the volume of right HATA and FEC slope(r=-0.296,P =0.04)in FES group.(5)In the FES group,there was a significant negative correlation between the volume of left subiculum and the negative factor scores(r=-0.317,P =0.044).The total volume of right hippocampus(r=-0.402,P =0.009),the volume of right CA1(r=-0.407,P =0.008)and right ML(r=-0.416,P =0.007)were negatively correlated with the scores of disorganized factor.There was a significant negative correlation between the volume of left presubiculum(r=-0.317,P =0.044),left parasubiculum(r=-0.512,P =0.001)and the depressed factor scores.(6)The FEC slope in FES group was significantly negatively correlated with PANSS total scores(r=-0.327,P =0.037),negative factor scores(r=-0.442,P =0.004)and depression factor scores(r=-0.310,P =0.049).Conclusions: The decrease in the hippocampal subfield volume in the FES group was associated with the decrease in NC and FEC functional levels,as well as with the severity of clinical symptoms.These results suggest that changes in volume of hippocampal subfields are involved in the early course of SCZ,and they may play a corresponding or opposite role in the progression of SCZ.It might be the structural basis of cognitive impairment of SCZ.