| Objective:Depressive disorders are a general term for a group of disorders characterized by depressed mood or state of mind,with complex and diverse clinical manifestations,mainly including three dimensions:affective symptoms,cognitive symptoms,and somatic symptoms.Functional somatization symptoms are more prevalent in children and adolescents,and the co-morbidity between functional somatization symptoms and adolescent depressive disorder is high clinically,and both co-morbidities have significant negative effects on the treatment and prognosis of adolescent depressive disorder.It has been found that cellular inflammatory response and brain neural circuits play an important role in the occurrence and development of depressive disorder and somatization symptoms,and the two may partially overlap,but the specific mechanism of action is unclear.There are few studies on functional somatization symptoms and depressive disorders,and they are mostly focused on clinical features and psychological factors,while biological studies are lacking.In this study,we investigated the neuroimmune characteristics and correlation of depressive disorder with functional somatization symptoms in adolescents using cranial MRI,emotional memory and inflammatory factor tests.Methods:According to the Diagnostic and Statistical Manual of Mental Disorders,5th edition(DSM-5)diagnostic criteria for major depressive episode,adolescent patients with depressive disorder(FSS:adolescent depression with somatization symptoms group;non-FSS:without somatization group)and healthy controls(HC group),with the healthy control group coming from adolescent students recruited during the same period with demographic information matching the MDD group.In Experiment 1,clinical symptoms were assessed by Hamilton Depression Inventory(HAMD17),Children’s Somatization Inventory(CSI),Toronto alexithymia scale(TAS),and Childhood Trauma Questionnaire(CTQ),followed by brain imaging using resting-state magnetic resonance(rs-MRI)and analyzed by brain gray matter volume(GMV)and amplitude of low frequency fluctuations(ALFF),respectively The brain structure and functional differences of the subjects were analyzed and correlated with clinical symptoms.In Experiment 2,emotional memory tests were used to assess the characteristics of memory bias in depressed adolescents with somatization symptoms,and the brain imaging basis of memory bias was investigated.In Experiment 3,serum cellular immune factors were tested using the "microplate electrochemiluminescence immunoassay" method(MSD electrochemiluminescence analyzer)to investigate the differences between subjects and to analyze the correlation between clinical symptoms and serum cellular immune factors,the correlation between brain gray matter volume(GMV),low frequency fluctuation amplitude(ALFF)and cellular immune factor was investigated in the group with somatization depression.Results:Experiment 1:(1)The three groups of subjects differed in clinical scale scores,the FSS and non-FSS had greater total scores on the Hamilton Depression Scale(HAMD17),the Children’s Somatization Inventory(CSI),the Toronto alexithymia scale(TAS),and the Childhood Trauma Questionnaire score(CTQ)than the normal control group,and when compared between the two depression subgroups,the FSS had greater HAMD,CSI,and TAS than non-FSS(P<0.05),and the FSS scores were positively correlated with HAMD(r=0.464),CTQ(r=0.427)and TAS(r=0.378),respectively(P<0.05).(2)There were significant differences in gray matter volume(GMV),low frequency amplitude(ALFF)of right superior occipital gyrus and right inferior temporal gyrus among the three groups(F=29.394,F=21.715;F=33.642,P<0.05).The GMV of the supplementary motor brain area in FSS and non-FSS depression group was higher than that in normal control group,and non-FSS group was higher than that in FSS group(P<0.05).There was a negative correlation between the GMV of the right supplementary motor area and the total score of CSI in FSS group(r=-0.376,P<0.05).The low frequency amplitudes(ALFF)of the right superior occipital gyrus and right inferior temporal gyrus in FSS group were higher than those in non-FSS group and normal control group,respectively(P<0.05).The ALFF values of right superior occipital gyrus and right inferior temporal gyrus were negatively correlated with the total score of Functional Somalization Scale(CSI)in FSS depression group(r=0.483,P<0.05;r=0.423,P<0.05).(3)Correlation analysis was performed between gray matter volume(GMV)and clinical symptom scale(CSI,CTQ,TAS)scores in the group with FSS depression,and CSI scores were positively correlated with gray matter volume in the middle occipital gyrus(pr=0.665,P<0.05),and TAS scores were positively correlated with gray matter volume in the caudate nucleus(Caudate)(pr=0.551,P<0.05);with FSS depression group low frequency amplitude(ALLF)was correlated with clinical symptom scale(FSS,CTQ,TAS)scores,CTQ scores were positively correlated with supplementary motor area ALLF(pr=0.577,P<0.05)and TAS scores were positively correlated with middle temporal gyrus ALLF(pr=0.413,P<0.05;pr=0.551,P<0.05).Experiment 2:(1)Three groups were tested for emotional memory,the positive picture score of the depressed group with FSS was lower than that of the normal group without FSS(5.44±1.23VS.6.32±1.31,P<0.05;5.44±1.23 VS.7.07±0.91,P<0.05),the neutral image score of FSS group was lower than that of normal group(4.51±1.33 vs.5.80±0.93,P<0.05).The recognition rate of negative pictures in FFS group was higher than that in non-FSS group(48.33±23.55VS36.93±18.79,P<0.05),and the recognition rate of negative pictures in FSS group was higher than that in neutral group(48.33±23.55VS33.72±23.57,P<0.05).(2)Positive picture score was negatively correlated with adolescent depression severity(HAMD)and somatization symptom severity(CSI)score(r=-0.221,P<0.05;r=-0.291,P<0.05),and negative picture recognition accuracy was positively correlated with CSI score(r=0.249,P<0.05).(3)The difference between the three groups in the occipital gyrus and inferior temporal gyrus was negatively correlated with the negative picture score(r=-0.292,P<0.05;r=-0.304,P<0.05);The inferior temporal gyrus was positively correlated with the recognition rate of negative images(r=0.312,P<0.05).In group analysis,the recognition rate of negative images was positively correlated with the ALFF of left and right middle occipital gyrus in FSS group(pr=0.644,P<0.05;pr=0.573,P<0.05).Experiment 3:(1)There were statistically significant differences in the levels of cellular inflammatory factors(IL-1b,IL-6,IL-23,TNF-α)between the three groups;there were statistically significant differences in the levels of IL-1b and TNF-α factors between the accompanying FSS group and the non-FSS group and the healthy control group,respectively(z=12.646,P<0.05;z=28.981,P<0.05),and there were no statistically significant differences in the distribution of IL-6 factors between the non-FSS group and the healthy control group(z=14.686,P<0.05).There was no statistically significant difference between the FSS group and the healthy control group(P>0.05);there was a statistically significant difference between the FSS group and the healthy control group in the distribution of IL-6 factor(z=14.686,P<0.05);there was a statistically significant difference between the three groups in the distribution of IL-23 factor(z=24.064,P<0.05);there was no statistically significant difference between the three groups in IL-4 and IL-6 factors There was no statistically significant difference between the three groups for IL-4 and IL-6 factors(P>0.05);when the correlation analysis was performed between the cytosolic inflammatory factors and the total scores of HAMD 17 and CSI in the adolescent depression group,the HAMD score was positively correlated with the concentration of IL-23 factors(r=0.216,P<0.05),and the CSI score was positively correlated with the concentration of IL-4 and IL-23 factors(r=0.259,P<0.05;r=0.226,P<0.05).(2)The correlation between cellular inflammatory factors and TAS score and factor score in the two depression subgroups was analyzed respectively,the results showed that TNF-α in the non-FSS group was negatively correlated with the TAS scale factor of ability to recognize and differentiate emotions from somatic feelings(r=-0.270,P<0.05);the levels of IL-23 and TNF-α in the group with FSS were positively correlated with the TAS scale factor of ability to describe emotions(r=0.365,P<0.05;r=0.390,P<0.05).There was a positive correlation between IL-1b factor level and extroverted thinking factor score(r=-0.350,P<0.05),and the rest of immune factors were not significantly correlated with the related scale score(P>0.05).(3)The serum inflammatory factors were correlated with the total CTQ score and factor scores of subjects in the two depression subgroups,respectively,and the levels of IL-1b,IL-4,IL-6,IL-23,and TNF-α factors in the FSS group were positively correlated with the CTQ emotional neglect factor score(r=0.455;r=0.350;r=0.320;r=0.485;r=0.481;P<0.05),TNF-α factor level was positively correlated with CTQ somatic neglect factor score(r=0.314,P<0.05);IL-23 factor level in non-FSS group was positively correlated with CTQ scale somatic neglect factor score(r=0.282,P<0.05),and the rest of immune factors were not significantly correlated with the related scale score(P>0.05).(4)The different brain regions of the three groups in experiment 1 were taken as the brain regions of interest,and the correlation analysis was conducted with the cellular inflammatory factors of the subjects.The results showed that GMV in the supplementary exercise region was negatively correlated with IL-1b and TNF-α serum inflammatory factors(r=-0.374,P<0.05;r=-0.384,P<0.05),ALFF of occipital gyrus was positively correlated with IL-2,IL-6 and IL-23 factors(r=0.328;r=0.468;r=0.376,P<0.05),ALFF of inferior temporal gyrus was positively correlated with IL-6 factor(r=0.354,P<0.05).The correlation analysis of serum inflammatory factors with GMV and ALFF in FSS group showed that IL-6 was negatively correlated with GMV of left left rectus gyri(pr=-0.361,P<0.05),and IL-23 was negatively correlated with caudate nucleus gyri(pr=-0.665,P<0.05).TNF was negatively correlated with the left fusiform gyrus(pr=-0.573,P<0.05).There was no significant correlation between brain function(ALLF)and cellular inflammatory factors(P>0.05).Conclusion:The severity of somatization and depressive symptoms,narrative disorder and early life trauma were positively correlated in adolescents with depressive disorder;there were differences in gray matter volume of right supplementary motor area,low frequency amplitude of right superior occipital gyrus and right inferior temporal gyrus in patients with and without somatization symptoms,and it was related to the severity of somatization symptoms;somatization symptoms are related to emotional memory bias in adolescents depressive disorders,and the superior occipital gyrus,inferior temporal gyrus and middle occipital gyrus may be related brain regions;somatization symptoms,alexithymia and childhood trauma were correlated with different serum inflammatory factors,and GMV and ALFF were correlated with inflammatory factors in some brain regions of the depressed group with somatization symptom. |
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