Efficacy Observation And Multimodal Magnetic Resonance Imaging Studies Of Danhu Ningshen Prescription In The Treatment Of Generalized Anxiety Disorder

Study 1 Clinical study of Danhu Ningshen Prescription in the treatment of generalized anxiety disorder(Yin deficiency and internal heat syndrome)OBJECTIVE:To observe the clinical efficacy of the traditional Chinese medicine Danhu Ningshen Prescription in the treatment of generalized anxiety disorder(GAD)and to evaluate the safety of the clinical use of Danhu Ningshen Prescription.METHODS:Between June 2022 and March 2023,100 patients with generalized anxiety disorder(GAD)who met the criteria of nadir were recruited from the Guang’anmen Hospital geriatric department,and were divided into 50 cases in the traditional Chinese medicine group and 50 cases in the western medicine group using a randomization method.The patients’ anxiety status was evaluated by the HAMA(Hamilton Anxiety Scale,HAMA)scale,the TCM symptom score scale,and the GAD-7(Generalized Anxiety Disorder-7 Scale,GAD-7),and the anxiety status was evaluated by the Hamilton’s Depression Scale(HAMD)for depression was excluded.In the Chinese medicine group,the patients were given 1 dose of Danhu Ningshen Prescription soup once a day,once in the morning and once in the evening;in the Western medicine group,the patients were given 2 tablets of bupropion hydrochloride twice a day(5 mg/tablet).The treatment course was 6 weeks,and the changes of each scale score were observed at baseline and at the end of 3 and 6 weeks of treatment in both groups.RESULTS:1.There was no statistical difference between the Chinese and Western medicine groups in the comparison of HAMA scale,TCM symptom score scale,GAD-7 scale and HAMD scale at baseline level(P>0.05);compared with baseline,the scores of HAMA scale,TCM symptom score scale and GAD-7 scale decreased significantly in the Chinese and Western medicine groups at the end of 6 weeks of treatment compared with baseline,with statistically significant differences(P<0.01).2.The total effective rate of HAMA scale reduction was 86.0%in the Chinese medicine group and 84.0%in the western medicine group;there was no statistical difference between the Chinese medicine and western medicine groups(P>0.05);the subscales of HAMA scale "insomnia" "autonomic nervous system symptoms "There was a statistical difference between the two groups(p<0.05);3.The total effective rate of reduction in the Chinese medicine symptom score scale was 88.0%in the Chinese medicine group and 84.0%in the western medicine group,and there was a statistical difference between the two groups(p<0.05);in the two groups,at the end of 3 weeks There was a statistical difference between the two groups in the reduction rate of "restlessness" at the end of 3 weeks(p<0.05),but there was no statistical difference at the end of 6 weeks;there was a statistical difference between the two groups in the reduction rate of "difficulty sleeping" and "gender-related symptoms" at the end of 6 weeks.There was a statistical difference between the two groups in the rate of "difficulty in sleeping" and "gender-related symptoms" at the end of 6 weeks(P<0.05),but there was no statistical difference between the Chinese and Western medicine groups in other subsets.CONCLUSIONS:1.Danhu Ningshen Prescription can effectively reduce the HAMA scale score,TCM symptom score and GAD-7 score of GAD patients,and effectively improve the clinical symptoms of GAD patients.2.Danhu Ningshen Prescription has anxiolytic effect comparable to that of buspirone hydrochloride.The total clinical efficiency of Danhu Ningshen Prescription in treating generalized anxiety disorder is 86%,and Danhu Ningshen Prescription is superior to buspirone hydrochloride in improving patients’ TCM symptoms,with less clinical side effects and better safety.Study 2 Multimodal magnetic resonance study of generalized anxiety disorder and the intervention mechanism of Danhu Ningshen PrescriptionOBJECTIVE:Multimodal magnetic resonance imaging techniques include:Resting state functional MRI(rs-fMR)and Diffusion kurtosis imaging(DKI)technology based on Voxel-based analysis(VBA),To explore the changes of brain function and structure in patients with generalized anxiety disorder,and to explore the neuroimaging mechanism of Danhuningshen prescription in the treatment of generalized anxiety disorder.METHODS:1.Subject recruitment:From the subjects recruited in the clinical study part,20 cases in the disease group were randomly selected,of which the disease group was subdivided into 10 cases each in the Chinese and Western medicine groups.Age-,sex-,and education-matched normal subjects were recruited in 20 cases as a healthy control group.Multimodal MRI data were collected at baseline and at the end of 6 weeks of treatment for the Chinese and Western medicine treatment groups,respectively,and only one MRI data was collected for the healthy control group.The healthy control group received HAMA scale,GAD-7 scale,and HAMD scale screening to exclude generalized anxiety disorder and depression.2.Data acquisition:A Magneton Skyra 3.0T MRI scanner and a 20-channel phased-array head orthogonal coil were used to perform head scans,followed by conventional head localization scans,cross-sectional T1WI and T2WI serial scans to exclude organic lesions of the central nervous system;then blood oxygen-dependent imaging BOLD scans and DKI image acquisition were performed,with a total scan time of 19 min14s.3.Data preprocessing:The SPM12(Statistical Parametric Mapping)toolkit based on matlab(version 2013b)was used;resting-state functional magnetism was performed using amplitude of low-frequency fluctuation(ALFF)and local coherence(ReH).regional homogeneity(ReHo)methods were used as research tools;the DKI part was calculated by DKE software to obtain individual mean kurtosis(MK),axial kurtosis(AK),radial kurtosis(RK),kurtosis fractional anisotropy(KFA)values and other relevant scalar indicators.4.Data statistics:using VBA method,SPM was applied to anova test for mALFF,fmALFF.szReHo,KFA,MK,AK,RK image data of normal and disease groups,covariates gender and age were added,mask was selected as AAL 116 binary mask.significance threshold was selected as Voxele_P<0.001,cluster_P<0.05,FWE corrected;two-sample t-test for mALFF,fmALFF,szReHo,KFA,MK,AK,RK in normal and disease groups;finally,mALFF,fmALFF,szReHo,KFA,MK,AK,RK in Chinese and Western medicine groups before and after treatment paired t-test without adding covariates.RESULTS:1.Differential brain regions between normal and disease groups:compared to the normal group,patients in the GAD group had lower mALFF and szReHo values in the Angular_L;higher mALFF values in the Temporal_Pole_Mid_R,Cerebelum_Crus1_L,Occipital_Mid_L.Rectus_R and Postcentral_L;lower KFA values in the Fusiform_L,Inferior fronto-occipital fasciculus L and Inferior longitudinal fasciculus L;inferior parietal lobule L,Superior longitudinal fasciculus L and Superior longitudinal fasciculus(temporal part)L;increased AK values in the Prefrontal lobe L,Caudate_L,Putamen_L,Anterior thalamic radiation L,Anterior limb of internal capsule L,Superior longitudinal fasciculus L,Body of corpus callosum,Superior fronto-occipital fasciculus L,External capsule L and Superior corona radiata L;increased RK values in corpus callosum,Cingulum(cingulate gyrus)R,right prefrontal lobe,Genu of corpus callosum,Forceps major,Splenium of corpus callosum and Cingulum(cingulate gyrus).2.Differences in brain regions before and after treatment in the Chinese medicine group:after treatment with Chinese medicine,the mALFF values of the patient’s left superior cerebellum decreased and the mALFF values of the Parietal_Inf_L increased;the mfALFF values of the Parietal_Inf_L and Frontal_Mid_R;the szReHo values of the Frontal_Mid_Orb increased;the KFA values of the left prefrontal lobe,the Caudate_L,the white matter bundle including the Anterior thalamic radiation L,Body of corpus callosum,Superior corona radiata L,et al,decreased;MK values increased in the right caudate nucleus head,white matter bundles including the Anterior thalamic radiation R,Anterior limb of internal capsule R.and Posterior limb of internal capsule R;AK values increased in the Cingulum_Mid_L,Precuneus_L,and Insula_L,white matter bundles including the bilateral Superior longitudinal fasciculus,Anterior thalamic radiation L,and the bilateral Cingulum(cingulate gyrus);the right thalamus,white matter bundles including Anterior thalamic radiation R,Anterior limb of internal capsule R,and Posterior limb of internal capsule R elevated RK values.3.Difference brain areas before and after treatment in the western drug group:after treatment in the western drug group:patients had elevated mALFF values in the Parietal_Sup_L and Precentral_R;elevated mfALFF values in the Frontal_Mid_R;no significant difference brain areas in szReHo values;patients had decreased KFA values in the Frontal_Sup_Medial_L,the Rectus_L,Frontal_Mid_Orb_L,the Anterior thalamic radiation L,Cingulum(cingulate gyrus)L,Forceps major,etc.;patients had decreased MK values in Frontal_Sup_L and Inferior longitudinal fasciculus R;patients had decreased AK values in the Body of corpus callosum,Caudate_L,Postcentral_L,Forceps major,Anterior thalamic radiation R,Inferior longitudinal fasciculus L and Corticospinal tract L;the RK values of the Frontal_Mid_L,supplementary motor area,Caudate_L,Anterior thalamic radiation L,Forceps major,Inferior fronto-occipital fasciculus L and External capsule L were reduced.4.Results of correlation analysis:KFA values of the Parietal_Inf_L were significantly correlated with HAMA scale scores(P<0.05,t=-0.581),and they were negatively correlated;KFA values of the the Fusiform_L were significantly correlated with HAMA scale scores(P<0.05,t=-0.475),and they were negatively correlated;AK values of the Caudate_L were negatively correlated with HAMA scale scores The AK value of the left caudate nucleus was significantly correlated with the HAMA scale score(P<0.05,t=-0.528),and the two were negatively correlated.CONCLUSIONS:1.There are functional and structural abnormalities in several brain regions of GAD,mainly including the left parietal inferior angular gyrus,left fusiform gyrus,left caudate nucleus and limbic system.2.Structural parameters of some brain regions in GAD patients are correlated with scores on the HAMA scale.Brain regions such as the left parietal inferior angular gyrus,left fusiform gyrus and left caudate nucleus may be used as reference indicators for clinical diagnosis or screening of GAD.3.The Chinese medicine Dan Huuningxin can regulate the abnormal activation of brain regions in patients with GAD,improve the function of left inferior parietal angular gyrus,orbitofrontal middle frontal gyrus,left upper cerebellum,and improve the structural integrity of left prefrontal lobe and left caudate nucleus to realize the anti-anxiety effect.