Effects Of Venlafaxine For The Brain Plasticity Of Patients With Generalized Anxiety Disorder:A Magnetic Resonance Imaging Study

Objective:Generalized anxiety disorder(GAD)is a common type of anxiety disorders.This study was to observe the neuro-pathological characteristics in GAD and the changes of brain function in patients with GAD before and after the 24-week drug therapy,explore the effects of drug therapy on neural plasticity in patients with GAD.Methods:1.Participants were recruited from Shanghai Psychotherapy and Psychological Counseling Center.In the same period,healthy control(HC)were recruited in surrounding communities and websites.Gender,age and education level were matched with the patient group.2.Assessments of the clinical symptoms,interoceptive index and side effects were performed at baseline and week 2,week 4,week 8,week 12 and week 24 after the start of intervention.The baseline,week 8 and week 24 were also collected MRI data from the subjects.3.Assessments were evaluate by Hamilton Anxiety Scale(HAMA)and Hamilton Depression Scale 17(HAMD17),7-item Generalized Anxiety Disorder Scale(GAD-7),Patient Health Questionnaire-9(PHQ-9),Clinical Global Impression-severity of illness(CGI-s),mental tracking paradigm(MTP)and body perception questionnaire(BPQ).Using the Siemens 3.0 T magnetic resonance imaging(MRI)scanner to collect the MRI data.4.All data were analyzed using the SPSS version 17.0.The MRI data were preprocessed and analyzed using following software including FSL,C-PAC,gRAICAR and ANTs.According to the data distribution and research purposes,independent or paired-samples t test,chi-square test,non-parametric test,analysis of variance(ANOVA)or covariance(ANCOVA),analysis of variance of repeated measures,correlation analysis were performed.P < 0.05 was defined as the threshold of statistic analysis.Results:Part 1.The study of exploring the neuro-pathological characteristics in generalized anxiety disorder1.51 patients with GAD and 49 HCs were enrolled to the study.The clinical symptoms and interoceptive levels are statistically significant difference between the two groups.2.Compared with HCs,the GAD group showed deactivation in right lingual gyrus,left superior parietal gyrus and right middle temporal gyrus under interoceptive task;the group by task interactive effects showed the altered activation in the cerebellum,left fusiform gyrus and right lingual gyrus.3.Using the automated subgroup detection program,gRAICAR,to detect subgroups in the baseline cross-sectional data.The results suggested that the visual network was differentiated between the group of patients with GAD and the HC group.Fractional amplitude low frequency fluctuation(fALFF)was applied as effect index,compared with HCs,the GAD group showed deactivation in the bilateral lingual gyrus,bilateral middle occipital gyrus and left postcentral gyrus.Using regional homogeneity(ReHo)as effect indexes,found GAD group showed reduced homogeneity in the right thalamus,the right middle occipital gyrus,the right lingual gyrus and right postcentral gyrus compared with HCs;Increased homogeneity in the lefy angular gyrus were found comparing the GAD group with HC group.The increased functional connectivity between the right anterior insular and the right precentral cortex was found when compared GAD group with HC group.4.Through the analysis of the physiological and physiological interaction of the insular,it was found that under different tasks,the insular connected to different brain regions.Under interoceptive task,compared with HCs,the GAD showed increased connectivity from the anterior insulat to the left medial prefrontal cortex,right superior frontal gyrus,the left precentral gyrus and the cerebellum;Compared with the HC group,the posterior part of the insular showed enhanced connect to the right hippocampus extended to the right amygdala in GAD group.Part 2.The study of exploring the the changes of brain function in patients with generalized anxiety disorder before and after the 24-week drug therapy5.31 patients with GAD,28 HCs were enrolled.In baseline,the clinical symptoms and interoceptive levels are statistically significant difference between the two groups.6.By comparing the difference between the baseline and the week 24 follow-up data,the time by task by group interactive effects indicated the differences in the right inferior temporal gyrus,bilateral middle temporal,and bilateral precuneus were statistically significant.7.Compared week 8 with baseline found that the time by group interactive effects were showed in right precentral gyrus and postcentral gyrus.The functional connectivity between the right anterior insular and the right putamen were changed by the time when compared GAD group with HC group.8.Under the interoception task,the connectivity between the right anterior insular and the right angular gyrus were changed by the time when compared GAD group with HC group.Under the exteroception task,the connectivity between the right posterior insular and the right lingual gyrus,the bilateral superior temporal gyrus,the left middle temporal,the left paracentral lobule were changed by the time when compared GAD group with HC group.Conclusions:1.Drug therapy can improve the activation of the right lingual gyrus,the left superior parietal gyrus and right middle temporal gyrus in the patients with GAD,which can reduce the symptoms of anxiety.2.The enhanced connectivity between anterior insular and cognitive control cortex consist in the interoceptive neural pathway in patients with generalized anxiety disorder.The exteroceptive neural pathway was enhanced between posterior insular and the "memory pivot" and "fear pivot".