Emotion reactivity-related brain network analysis in generalized anxiety disorder: a task fMRI study.

BACKGROUND: Generalized anxiety disorder (GAD) is closely associated with emotional dysregulation. Patients with GAD tend to overreact to emotional stimuli and are impaired in emotional regulation. Using emotional regulation task, studies have found hypo-activation in prefrontal cortex (PFC) of GAD patients and concluded with inadequate top-down control. However, results remain inconsistent concerning PFC and limbic area's reactivity to emotional stimuli. What's more, only a few studies aim to identify how limbic area interacts with PFC in GAD patients. The current study aims to identify the difference in PFC-limbic circuitry response to emotional stimuli between GAD patients and healthy controls (HCs) from the perspective of brain network. Through brain network analysis, it revealed the connectivity between limbic area and PFC, and moreover, the orientation of connectivity, all of which gave a better test of inadequate top-down control hypothesis. METHODS: During fMRI scanning, participants were required to complete an emotional face identification task (fearful, neutral, happy facial expression). 30 participants (16 GAD patients, 14 HCs) were included in the formal analysis. A Bayesian-network based method was used to identify the brain network consisting of several pre-hypothesized regions of interest (ROIs) under each condition (negative, positive, neutral). In total, six graphs were obtained. Each of them represented the brain network that was common to the group under corresponding condition. RESULTS: Results revealed that GAD patients showed more bottom-up connection but less top-down connection regardless of condition, relative to HCs. Also, the insula was more connected but the amygdala was less connected regardless of condition, relative to HCs. the results also revealed a very different brain network response between GAD patients and HCs even under neutral condition. CONCLUSIONS: More bottom-up connection but less top-down connection may indicate that GAD patients are insufficient in top-down control, in keeping with inadequate top-down control hypothesis. The more connected insula may indicate GAD patients' abnormality in interoception processing. Relative to HCs, distinct brain network response pattern in GAD patients under neutral condition suggests GAD patients' abnormality in distinguishing safety from threat and intolerance of uncertainty.

The mediating role of transmembrane protein 132D methylation in predicting the occurrence of panic disorder in physical abuse.

Objective: Genome Wide Association study (GWAS) has revealed that the transmembrane protein 132D (TMEM132D) is a gene of sensitive for panic disorder (PD). As the main type of childhood trauma experience, childhood abuse has become a public health issue attracting much attention at home and abroad, and has been proved to be a risk factor for the onset of PD. However, how it affects the occurrence and development of panic disorder has not yet been revealed. We examined the relationship between TMEM132D methylation, childhood abuse and symptoms based on this finding. Materials and methods: Thirty-two patients with PD and 22 healthy controls (HCs) were recruited after age, gender, and the education level were matched. The DNA methylation levels of CpG sites across the genome were examined with genomic DNA samples (PD, N = 32, controls, N = 22) extracted from subjects' elbow venous blood. A mediation model was used to explore the relationship between the methylation degree of different CpG sites and childhood maltreatment and clinical symptoms. Results: We found that the PD group had significantly lower methylation at CpG1, CpG2, CpG3, CpG4, CpG5, CpG6, CpG7, CpG8, CpG11, CpG14, and CpG18 than did the HCs (p < 0.05). The CpG2 (r = 0.5953, p = 0.0117) site in the priming region of TEME132D gene were positively associated with PDSS score. The CpG2 (r = 0.4889, p = 0.046) site in the priming region of TEME132D gene were positively associated with physical abuse. Furthermore, path analyses showed that the methylation of CpG2 of TMEM132D played a fully mediating role in the relationship between physical abuse and PD symptom severity (95. Conclusion: Childhood abuse experiences, especially physical abuse, are significantly related to PD. The methylation of CpG2 of TMEM132D was shown to have a fully mediating effect between panic disorder and physical abuse. The interaction between TMEM132D methylation and physical abuse can predict panic disorder.

The alteration of cognitive function networks in remitted patients with major depressive disorder: an independent component analysis.

INTRODUCTION: Dysfunctional connectivity of resting-state functional networks has been observed in patients with major depressive disorder (MDD), particularly in cognitive function networks including the central executive network (CEN), default mode network (DMN) and salience network (SN). Findings from studies examining how aberrant functional connectivity (FC) changed after antidepressant treatment, however, have been inconsistent. Thus, the purpose of the present study was to explore potential mechanisms of altered cognitive function networks during resting-state between remitted major depressive disorder (rMDD) patients and healthy controls (HCs) and furthermore, the relationship between dysfunctional connectivity patterns in rMDD and clinical symptoms. METHODOLOGY: In this study, 19 HCs and 19 rMDD patients were recruited for resting-state functional magnetic resonance imaging (fMRI) scanning. FC was evaluated with independent component analysis for CEN, DMN and SN. Two sample t tests were conducted to compare differences between rMDD and HCs. A Pearson correlation analysis was also performed to examine the relationship between connectivity of networks and cognitive function scores and clinical symptoms. RESULTS: Compared to healthy controls, remitted patients showed lower connectivity in CEN, mostly in the superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior parietal lobule (IPL) and part of the supramarginal gyrus (SMG). Conversely, the bilateral insula, part of the SMG (a key node of the CEN) and dorsal anterior cingulate cortex (dACC) of the DMN showed higher connectivity in rMDD patients. Pearson correlation results demonstrated that connectivity of the right IPL in CEN was positively correlated with cognitive function scores, and connectivity of the left insula was negatively correlated with BDI scores. CONCLUSIONS: Though rMDD patients reached the standard of clinal remission, unique impairments of FC in cognitive function networks remained. Aberrant FC between cognitive function networks responsible for executive control was observed in rMDD and may be associated with residual clinical symptoms.

Identifying generalized anxiety disorder using resting state habenular circuitry.

Studies identify the habenula as a key subcortical component in anxiety, with a role in predicting error coding within the evaluative system. However, no clinical reports of generalized anxiety disorder (GAD) describe resting state functional connectivity of habenular circuits. We hypothesized that resting-state functional connectivities of habenula would show differences in neuroanatomical correlates of the evaluative system (prefrontal cortex, habenula) of patients with GAD. We obtained 22 patients with GAD and 21 HCs, matched for gender, age, and years of education. Resting-state functional connectivity of the habenula was assessed using a seed-based template imposed on whole brain MRI, which provided an objective and semi-automated segmentation algorithm in MNI space. Patients with GAD demonstrated enhanced connectivities in the bilateral premotor cortex, right ventrolateral prefrontal cortex, medial frontal cortex, as well as the left orbitofrontal cortex, and reduced connectivities in the left posterior cingulate cortex, and right pulvinar. Moreover, striking differences of abnormal connectivities between groups were observed via analysis of receiver operating characteristic curves (ROC) of statistically significant. These results including ROC curves suggest the potential importance of the habenula in evaluating and deciding to personally relevant reward-related information.