No abstract

Background: Generalized anxiety disorder (GAD) is a common affective disorder characterized by comprehensive anxiety with dysregulation of brain activity which can be reflected by functional magnetic resonance imaging (f-MRI). We aimed to examine abnormal aberrant amplitude low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) in GAD and evaluate their ability to predict treatment remission. Methods: Using resting-state fMRI (Rs-fMRI), we examined ALFF and ReHo in 30 GAD patients and 30 healthy control (HC) participants. Using on DEPASF4.3 Advanced Edition, voxel-based two-sample t-test analysis was performed on the ALFF and ReHo maps to compare GAD to HC groups, and to compare remitters (n=9) and non-remitters (n=21). Pearson's correlation analysis was used to explore the relationship between baseline Hamilton Anxiety Rating Scale (HAM-A) scores/illness duration and mean ALFF/ReHo values. The severity of GAD symptoms was rated with HAM-A. Remission was defined as HAM-A ≤7 by week 8. Results: Compared to the HC group, GAD patients showed lower ALFF in the right postcentral and right precentral gyrus; lower ReHo in the right precentral, right postcentral, and left precentral gyrus; and higher ReHo in the left posterior cingulate cortex. ALFF values for left postcentral gyrus was negatively correlated with baseline HAM-A, while that of the middle frontal gyrus was positively correlated with baseline HAM-A scores. ReHo value of the left postcentral gyrus was negatively correlated with baseline HAM-A, while that of the right middle frontal gyrus was positively correlated with baseline HAM-A scores. ALFF of the right frontal_superior_orbital and right frontal-medial-orbital cortex was positively correlated with illness duration. ReHo of the left supplementary motor area cortex was negatively correlated with illness duration.Remitters showed higher ALFF in the left hippocampus and higher ReHo value in the right postcentral cortex compared to nonremitters.Conclusions: These results suggest that altered regional brain activity and local synchronization may be related to the pathophysiology of GAD and have certain value in predicting remission in treatment.

IntroductionS100 calcium-binding protein B (S100B) is a neurotrophic factor that regulates neuronal growth and plasticity by activating astrocytes and microglia through the production of cytokines involved in Generalized Anxiety Disorder (GAD). However, few studies have combined S100B and cytokines to explore their role as neuro-inflammatory biomarkers in GAD.MethodsSerum S100B and cytokines (IL-1β, IL-2, IL-4, and IL-10) of 108 untreated GAD cases and 123 healthy controls (HC) were determined by enzyme-linked immunosorbent assay (ELISA), while Hamilton Anxiety Rating Scale (HAMA) scores and Hamilton Depression Rating Scale (HAMD) scores were measured to evaluate anxiety and depression severity. This was used to help physicians identify persons having GAD. Machine learning techniques were applied for feature ordering of cytokines and S100B and the classification of persons with GAD and HC.ResultsThe serum S100B, IL-1β, and IL-2 levels of GAD cases were significantly lower than HC (P < 0.001), and the IL-4 level in persons with GAD was significantly higher than HC (P < 0.001). At the same time, IL-10 had no significant difference between the two groups (P = 0.215). The feature ranking distinguishing GAD from HC using machine learning ranked the features in the following order: IL-2, IL-1β, IL-4, S100B, and IL-10. The accuracy of S100B combined with IL-1β, IL-2, IL-4, and IL-10 in distinguishing persons with GAD from HC was 94.47 ± 2.06% using an integrated back propagation neural network based on a bagging algorithm (BPNN-Bagging).ConclusionThe serum S-100B, IL-1β, and IL-2 levels in persons with GAD were down-regulated while IL-4 was up-regulated. The combination of S100B and cytokines had a good diagnosis value in determining GAD with an accuracy of 94.47%. Machine learning was a very effective method to study neuro-inflammatory biomarkers interacting with each other and mediated by plenty of factors.

No abstract

Background: Generalized anxiety disorder (GAD) is partly attibuted to the dysregulation of nueroinflammation which can be mediated by adiponectin. We conducted this study was to explore the characteristics of peripheral adiponectin and its role in predicting treatment outcome in patients with generalized anxiety disorder (GAD) treated by escitalopram or venlafaxine. Methods: A total of 70 untreated GAD inpatients who met the diagnosis criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) were enrolled and randomly selected for treatment with escitalopram (n=36) or venlafaxine (n=34) for 8 weeks. The serum adiponectin level of GAD and healthy controls (HCs) was measured by enzyme-linked immunosorbent assay (ELISA) before treatment. Hamilton Anxiety Rating Scale (HAM-A) assessment was conducted at baseline and at 1, 2, 4, and 8 weeks after treatment respectively. Serum adiponectin levels were compared between GAD patients and HCs, as well as between remission and nonremission cases; the correlation between baseline adiponectin level and HAM-A reduction rate were also analyzed. Results: The serum adiponectin levels were higher in GAD patients compared to HCs (t=2.304; P=0.023), the serum adiponectin levels were higher in remission cases compared to nonremission cases (t=2.255, P=0.027), and the receiver operating characteristic (ROC) area in predicting treatment remission was 0.652±0.066 (P=0.029). The correlation between baseline adiponectin level and HAM-A reduction rate of GAD cases treated with escitalopram and venlafaxine in the endpoint was 0.362 (P=0.030) and −0.026 (P=0.883), respectively, and the ROC area of baseline adiponectin level in predicting treatment remission was 0.72±0.086 (P=0.024) and 0.473±0.102 (P=0.469), respectively.Conclusions: Peripheral adiponectin is upregulated in GAD, and it seems higher baseline adiponectin level predicts a better treatment remission treated by escitalopram but not with venlafaxine, which suggests adiponectin maybe a potential key biomarker in Chinese GAD.