Muscle Strength And Neuroimaging Studies On Suicide Risk In Non-elderly Patients With Major Depressive Disorder

Part 1 Study on the association between suicide risk and sarcopenia among non-elderly patients with major depressive disorderObjective:Sarcopenia is a skeletal muscle disorder.Recent studies have shown an association between muscle health and suicide.However,there have been no previous studies on the relationship between suicide risk severity and sarcopenia in major depressive disorder(MDD).This study aimed to explore the association between suicide risk severity and sarcopenia in non-elderly Chinese inpatients with MDD.Methods:The first-episode drug-naive MDD inpatients aged 20-59 years with the 24-item Hamilton Rating Scale for Depression(HAMD-24)scores of>20 were included,who were then classified into low,intermediate,high and very high suicide risk groups according to the Nurses’ Global Assessment of Suicide Risk(NGASR).The HAMD-24,the Hamilton Rating Scale for Anxiety(HAMA)and the SARC-F questionnaire were used to assess depression severity,anxiety severity and sarcopenia,respectively.The plasma levels of cortisol and adrenocorticotropic hormone(ACTH)were measured.Results:A total of 192 MDD inpatients(122 females,70 males;aged 39.3±11.7 years)were included,with 12.5%meeting criteria for sarcopenia.There were significant differences in gender,HAMD score and prevalence of sarcopenia among the suicide risk groups.Adjusted ordinal regression analysis showed that sarcopenia was significantly associated with more severe suicide risk(OR=2.39,95%CI 1.02-5.58,P=0.044)independent of depression severity.Conclusion:This study revealed that sarcopenia was significantly associated with higher suicide risk in non-elderly Chinese MDD inpatients after adjustment for depression severity.Intervention of sarcopenia might be effective in reducing the risk of suicide in non-elderly MDD patients.Part 2 Changes in grey matter volume and its association with muscle strength by suicide risk severity in non-elderly patients with major depressive disorderObjective:The first part of our study found the association between muscle health and suicide,and previous study found the alteration of grey matter volume in MDD patients with suicide attempt or ideation.The second part of our study aimed to explore alterations in grey matter volume(GMV)and muscle strength index between different suicide risk severity groups in first-episode drug-naive MDD patients,and the mediation effect of muscle strength index in the relationship between suicide risk severity and GMV.Methods:This was a cross-sectional study targeting first-episode drug-naive MDD inpatients aged 18-59 years with the 24-item Hamilton Rating Scale for Depression(HAMD-24)scores of>20 and moderate physical activity according to IPAQ-SF(International physical activity questionnaire-short form)at the psychiatric department from May 2019 to January 2020.The patients were then classified into low and mid-to-high suicide risk groups according to the Nurses’ Global Assessment of Suicide Risk(NGASR).The NGASR,HAMD,HAMA were used to assess suicide risk severity,depression severity and anxiety severity,respectively.Handgrip strength and appendicular muscle strength were measured and then adjusted by body weight to get the muscle strength indexes.All patients underwent 3D structural MRI scan and the voxel-based morphometry(VBM)approach was employed to analyzed the images.Results:A total of 92 MDD inpatients were included,with 40 patients(15 males,aged 29.4±10.2 years)in the low suicide risk group and 52 patients(15 males,aged 27.4±9.1 years)in the mid-to-high suicide risk group.There were no significant differences in age,sex,education years,body weight and BMI between the groups.Compared with the low-risk group,patients in the mid-to-high risk group showed significant reduced GMV in the right superior frontal gyrus(P<0.05,FWE correction).Partial correlation analysis showed that the NGASR score was negatively associated with the GMV in the right superior frontal gyrus(SFG)(r=-0.477,P<0.001),handgrip index(HGi)and appendicular muscle strength index(AMSi)was positively associated with the GMV in the right SFG(r=0.317,P=0.015;r=0.260,P=0.049),the HGi and the AMSi was negatively associated with NGASR score(r=-0.481,P<0.001;r=-0.539,P<0.001).Mediation analysis showed that HGi and AMSi both partially mediated the negative correlation between the GMV in the right SFG and suicide risk score,which accounting for 26.6%and 25.8%of the total effect,respectively.Conclusion:This study revealed that higher suicide risk was significantly associated with reduced GMV in the right SFG in non-elderly MDD patients.The muscle strength index might mediate the correlation between the GMV of right SFG and suicide risk,which indicated that the muscle strength might be involved in the neural mechanism of the increased suicide risk caused by brain remodeling,and increasing muscle strength index might improve brain remodeling and be effective in reducing the risk of suicide in non-elderly MDD patients.Part 3 Changes in white matter integrity and its association with muscle strength by suicide risk severity in non-elderly patients with major depressive disorderObjective:The first part of our study found the association between muscle health and suicide,and the second part of our study confirmed the mediation effect of muscle strength index in suicide-related alteration of grey matter volume in MDD patients.The third part of our study aimed to explore alterations in white matter integrity and muscle strength index between different suicide risk severity groups in first-episode drug-naive MDD patients,and the associations among suicide risk severity,white matter integrity and muscle strength index.Methods:This was a cross-sectional study targeting first-episode drug-naive MDD inpatients aged 18-59 years with the HAMD-24 scores of>20 and moderate physical activity according to IPAQ-SF(International physical activity questionnaire-short form)at the psychiatric department from May 2019 to January 2020.The patients were then classified into low and mid-to-high suicide risk groups according to the Nurses’ Global Assessment of Suicide Risk(NGASR).The NGASR,HAMD and HAMA were used to assess suicide risk severity,depression severity and anxiety severity,respectively.Handgrip strength and appendicular muscle strength were measured and then adjusted by body weight to get the muscle strength indexes.DTI(diffusion tensor imaging)data were collected and analyzed by TBSS(tract-based spatial statistics,TBSS)of FSL(FMRIB software library).Results:A total of 82 MDD inpatients were included,with 40 patients(10 males)in the low suicide risk group and 42 patients(10 males)in the mid-to-high suicide risk group.There were no significant differences in age,sex,education years,body weight and BMI between the groups.Compared with the low-risk group,patients in the mid-to-high risk group showed significant increased HAMD score and muscle strength indexes.The significant different white matter regions in FA values after FWE correction were left superior longitudinal fasciculus(SLF)and left forceps minor(FM).Partial correlation analysis showed that among all the MDD patients,the NGASR score was positively associated with the FA value of left SLF and FM(r=0.402,P=0.002;r=0.331,P=0.011),and negatively with the RD value of left SLF and FM(r=-0.351,P=0.006;r=-0.257,P=0.049).The handgrip index(HGi)was negatively associated with the FA value of left SLF(r=-0.259,P=0.048).Moderation effect analysis showed that HGi moderated the relationship between suicide risk severity and the white matter integrity of left SLF.Conclusion:This study revealed that those with higher suicide risk might have abnormal white matter integrity in the left SLF and FM.The HGi might be involved in the relationship between white matter integrity of left SLF and suicide risk in non-elderly MDD patients.