The Resting State FMRI Study Of Generalized Anxiety Disorder

Backgrounds and objective:Generalized AGeneralized anxiety disorder(GAD) is a major type of anxiety disorders. There have been several task-based studies on it. However, there are only very few GAD studies using resting state methods, which can be helpful in unveiling neural substrates of GAD as well as anxiety disorder in general. We used 24 subjects with GAD and 24 healthy controls and conducted a resting state study. We first explored brain regions with abnormal regional homogeneity(ReHo) and found that right thalamusof GAD patients had significantly lower ReHo than controls, and the ReHo value was negatively correlated to Hamilton Anxiety Rating Scale(HAMA) score. In addition, the amygdala is the core area ofpatient with anxiety disorder,so we used the right thalamus andleft Amygdalar Subregion as seed regions to perform functional connectivity(FC) analysis.Thisstudy is to explore whether there are aberrant functional connectivity or dysfunction of theneural networks in GAD,and further to investigate theclinicalsignificance of functional connectivity by focusing on their association with symptomseverity in GAD patients.Methods:Totally 24 GAD patients and 24 healthy controls matched at gender, age and education level were examinedusing rs-fMRI.HAMA Scale and Self-Rating Anxiety Scale(SAS)were used to assessed the symptom severity of GAD patients. Brain imaging was carried outon a 3T Siemens Trio Tim MR scanner, The fMRI data were processed by SPM8, DPARSF and REST soft based on MATLAB2011 b. Results were displayed using REST soft.First,two-sample t-test was carried out to investigate the differences of the ReHo value between the patients and healthy controls,The statistical threshold was set at p<0.05, the minimum cluster size was set to 10 voxels. Subsequently,to investigate whether the ReHo of significant regions was correlated with SAS and HAMA scores of the patients, twocorrelational analyses were alsoconducted.Second,two-sample t-test was carried out to investigate the differences of the functional connectivity between the patients and healthy controls for each ROI, The statistical threshold was set at p<0.05, FDR voxel-wise corrected, the minimum cluster size was set to 20 voxels. Subsequently, the group differences of functional connectivity in GAD patients were correlated with the SAS and HAMA scores using Pearsoncorrelation analysis.Results:1. ReHo Results:Compared with the healthy controls, decreased ReHo was found in GAD patients in theright middle occipital gyrus, right thalamus, right fusiform gyrus, left middle frontal gyrus. Compared with the healthy controls, increased ReHo was found in GAD patients in the right precuneus, right inferior frontal gyrus, left superior frontal gyrus, left middle frontal gyrus, right precentral gyrus.2. Functional connectivity results:Compared with the healthy controls,(1) when the seed was located in the right thalamus, patients with GAD showed decreased functional connectivity mainly inbilateral anterior cingulate cortex(ACC), bilateral cerebellum, bilateral thalamus, bilateral putamen, bilateral caudate, left amygdala, left hippocampus, left globus pallidus, the right medial prefrontal cortex(mPFC), right posterior cingulate cortex(PCC).(2) when the seed was located in the leftCMA, patients with GAD showed decreased functional connectivity mainly inbilateral thalamus,left putamen,left globus pallidus,left hippocampus,and bilateralmiddlecingulate cortex.(3) when the seed was located in the left LBA, patients with GAD showedincreased functional connectivity mainly inmedial prefrontal cortex.(4) when the seed was located in the left SFA, patients with GAD showed increased functional connectivity mainly in medial prefrontal cortex,and decreased functional connectivity mainly in corpus callosum,andposterior cingulate cortex.3. Pearson correlation analysis showed that the ReHo values of the right thalamus in GAD patients were significantly negatively correlated withHAMAscores(r=-0.637, p=0.001),the strength of functional connectivitybetween the right thalamus and ACC has positively correlated with HAMA scores in GAD patients.( r = 0.498, p<0.05)Conclusion:1. In the present study,We first explored brain regions with abnormal regional homogeneity(ReHo) and found that right thalamus of GAD patients had significantly lower ReHo than controls, This suggests that thalamus might be a key region related to anxiety. The correlational analysis results also showed that the ReHo is negatively correlated to HAMA score, which is an indication of the severity of GAD symptoms. This corroborates the lowered ReHo in patients compared to controls, and thus suggests that the ReHo of thalamus doesn’t only differ between GAD patients and healthy controls, but can also predict severity of anxiety symptoms.2. In our functional connectivity analysis,we found that theabnormal functional connectivity betweenAmygdalar Subregion,right thalamus and frontal regions, amygdala, basal ganglia and several other regions for GAD patients. These results suggest that, except for the frontal-basal ganglia-thalamic circuit, the amygdala-frontal circuit may also be an important neural substrate of generalized anxiety.Besides, the right thalamus-ACC connectivity is positively correlated to HAMA score.indicating that the intensity of resting state functional connectivity between the right thalamus-ACC may be an imaging indicators for assessment of the symptom severity of GAD patients.