A Prospective Study On Alteration Of Structural And Functional Networks Of Major Depressive Disorder With Anhedonia

Objective:Compared with major depressive disorder（MDD）patients with mild anhedonia（MDD-MA）,those who with severe anhedonia（MDD-SA）tend to experience a severer clinical condition and have a worse prognosis.The underlying biological mechanism of anhedonia in MDD remains largely unknown.The present study aims to explore the changes of clinical symptoms of each MDD group and the differences between the two MDD groups before after the antidepressant treatment,and structural and resting-state functional node characteristics of the brain in MDD-SA before and during antidepressant treatment course.Methods:In this case control study,ninety participants with current MDD and 20 health controls（HCs）were recruited.All patients received antidepressant medical treatment.24-item Hamilton Depression Scale(HAMD-₂₄)and Snaith–Hamilton Pleasure Scale（SHAPS）were used to assess the severity of depression and anhedonia at three timepoint including baseline,the second month end and the sixth month end.Structural and functional magnetic resonance images of the brain of all the MDD patients were collected at baseline and the end of 6^thmonth（for HC,only at baseline）.Top 25%of the MDD patients on SHAPS scores were used as MDD-SA group（n=20）,while the bottom 25%were used as MDD-MA group（n=18）.Therefore,38 MDD patients and 20 HCs were finally included in the present study.Graph theory was adopted to analyze structural and functional nodal characteristic including betweenness（b_i）,degree（k_i）and efficiency（e_i）.Statistical methods include analysis of variance,t-test and correlation analysis.Results:Clinical characteristics:1)No significant difference was identified in HAMD-₂₄score between the two MDD groups at baseline and the end of 2^ndmonth.At the end of 6^thmonth,the MDD-SA group reported significantly higher HAMD-₂₄score than the MDD-MA group（t=2.199,P<0.05）.The deduction rate of MDD-SA group at the end of2^ndand 6^thmonth were 54.40%and 74.22%),of MDD-MA group were66.25%and 89.97%.The deduction rate of MDD-SA group has the tendency of significantly lower than the MDD-MA group at the end of 6^thmonth（t=-1.972,P=0.056）.The recovery rate of MDD-SA group（13/20）was significantly lower than that of MDD-MA group at the end of 6^thmonth（18/18）（χ²=7.723,P<0.01）.2)The SHAPS score of MDD-SA group was significantly higher than that of MDD-MA group at baseline,the end of 2^ndand 6^thmonth（t=36.990,11.135,5.194;P<0.001）.Compared with baseline,the SHAPS scores of MDD-SA groups were significantly lower at the end of 2^ndand 6^thmonth（t=-7.174,-16.356;P<0.001）,the SHAPS scores of MDD-MA group were significantly lower at the end of 6^thmonth（t=-5.497,P<0.001）.The deduction rate of MDD-SA group at the end of 2^ndand 6^thmonth were significantly higher than that of MDD-MA group respectively（t=5.259,12.090;P<0.001）.3)Correlation:The SHAPS scores at baseline could predict the deduction of HAMD-₂₄scores at the 6^th-month-end（B=-0.255,P<0.05）.Structural nodal properties:1)At baseline,significant differences were showed among MDD-SA,MDD-MA and HC groups in 7 brain regions including right medial superior frontal gyrus（RMSFG）（F=3.330～6.012,P<0.05）.（1）The increases in k_iand e_iof the RMSFG were similar between MDD-SA and the MDD-MA groups（MDD-SA/MDD-MA vs.HC,t=2.186～2.723,P<0.05;MDD-SA vs.MDD-MA,P>0.05）.（2）The unique change in the MDD-SA group is the significant increase in k_iand b_iin the left inferior temporal gyrus（LITG）and in e_iof the right angular gyrus（RANG）（MDD-SA vs.HC,t=2.209～2.912,P<0.05;MDD-MA vs.HC,P>0.05;MDD-SA vs.MDD-MA,t=2.303～4.210,P<0.05）.（3）The unique change in the MDD-MA group is the significant increase in b_iof the left middle occipital gyrus（LMOG）（MDD-MA vs.HC,t=2.417,P<0.05;MDD-SA vs.HC,P>0.05;MDD-SA vs.MDD-MA,t=-2.681,P<0.05）.2)At the 6^th-month-end,the k_iand e_iof the RMSFG has no significant differences compared with themselves at baseline.The k_iand e_iwas still significantly higher than HC（MDD-SA/MDD-MA vs.HC,t=2.166～3.050,P<0.05;MDD-SA vs.MDD-MA,P>0.05）.（2）The k_iof the LITG significantly decreased in the MDD-SA group（t=-2.434,P<0.05）,no significantly change in b_i,but both significantly higher than HC（MDD-SA/MDD-MA vs.HC,t=2.044,2.624;P<0.05）.（3）The b_iof LMOG in the MDD-MA group had the tendency of significantly decrease at the end of 6^thmonth（t=-1.996,P=0.062）.3)correlation,the b_iof the LITG and the e_iof the RANG were positively correlated with SHAPS scores（B=1.769,0.001;P<0.05）.Functional nodal properties:1)Differences:Repeated measures two-factor ANCOVA showed significant main effects of group on the e_iand k_iof left superior frontal gyrus（LSFG）（F=9.490,7.650;P<0.01）,and on the e_iand k_iof left medial orbital-frontal gyrus（LMOFG）（F=9.124,7.508;P<0.01）.Compared with the MDD-MA group,the significantly higher e_iand k_iof the LSFG（F=0.023,1.556;P<0.05）,and the significantly higher e_iand k_iof the LMOFG were demonstrated in the MDD-SA group（F=0.023,1.340;P<0.05）at baseline.2)Correlation:Higher SHAPS scores could result in higher values of e_iand k_iof LSFG（B=0.001,0.089;P<0.05）,and higher e_iof LMOFG（B=0.001,P<0.05）at baseline;higher SHAPS scores could result in higher values of e_iof LSFG at the end of 6months treatment（B=0.001,P<0.05）.Conclusions:1.Compared with MDD-MA patients,the MDD-SA patients had a poor treatment response.Anhedonia predicts a bad prognosis of MDD patients.2.The structural nodal properties of higher degree and betweenness in the LITG was associated with anhedonia,higher betweenness in the LITG might be the neuroimaging marker of MDD-SA.3.The functional nodal properties of higher efficiency in the RANG might be associated with anhedonia.4.The functional nodal properties of higher efficiency in the LSFG might be associated with anhedonia.5.The enhancement betweenness in the LMOG might associated with MDD-MA.