Hongru Zhu

Anatomical deficits in adult posttraumatic stress disorder: A meta-analysis of voxel-based morphometry studies

Evidence from previous anatomical studies indicate that widespread brain regions are involved in the pathogenesis of posttraumatic stress disorder (PTSD). The aim of the present study was to quantitatively integrate the literature on structural abnormalities seen on individuals with PTSD. Twenty voxel-based analysis studies were analysed through a comprehensive series of meta-analyses. Compared with healthy controls, PTSD patients showed a significant reduction in grey matter (GM) in the left anterior cingulate gyrus (ACC) at the whole-brain level. Several brain regions, including the left ACC, the left insula and the right parahippocampal gyrus were significantly smaller in individuals with PTSD than in trauma-exposed healthy subjects. Furthermore, the clinician-administered PTSD scale scores were negatively correlated with GM in the left ACC and positively correlated with GM in the left insula. In addition, PTSD patients who experienced accidental or non-accidental trauma had anatomical changes in different brain regions. These results suggest that the smaller ACC and insular cortex within the limbic-prefrontal circuit contribute to the pathogenesis of PTSD. Moreover, the PTSD patients with different types of trauma may have different cerebral deficits.

Alterations in Low-Level Perceptual Networks Related to Clinical Severity in PTSD after an Earthquake: A Resting-State fMRI Study

Background Several task-based functional MRI (fMRI) studies have highlighted abnormal activation in specific regions involving the low-level perceptual (auditory, visual, and somato-motor) network in posttraumatic stress disorder (PTSD) patients. However, little is known about whether the functional connectivity of the low-level perceptual and higher-order cognitive (attention, central-execution, and default-mode) networks change in medication-naïve PTSD patients during the resting state. Methods We investigated the resting state networks (RSNs) using independent component analysis (ICA) in 18 chronic Wenchuan earthquake-related PTSD patients versus 20 healthy survivors (HSs). Results Compared to the HSs, PTSD patients displayed both increased and decreased functional connectivity within the salience network (SN), central executive network (CEN), default mode network (DMN), somato-motor network (SMN), auditory network (AN), and visual network (VN). Furthermore, strengthened connectivity involving the inferior temporal gyrus (ITG) and supplementary motor area (SMA) was negatively correlated with clinical severity in PTSD patients. Limitations Given the absence of a healthy control group that never experienced the earthquake, our results cannot be used to compare alterations between the PTSD patients, physically healthy trauma survivors, and healthy controls. In addition, the breathing and heart rates were not monitored in our small sample size of subjects. In future studies, specific task paradigms should be used to reveal perceptual impairments. Conclusions These findings suggest that PTSD patients have widespread deficits in both the low-level perceptual and higher-order cognitive networks. Decreased connectivity within the low-level perceptual networks was related to clinical symptoms, which may be associated with traumatic reminders causing attentional bias to negative emotion in response to threatening stimuli and resulting in emotional dysregulation.

Altered spontaneous neuronal activity of visual cortex and medial anterior cingulate cortex in treatment-naïve posttraumatic stress disorder

BACKGROUND Although no more traumatic stimuli exists, a variety of symptoms are persisting in chronic Posttraumatic Stress Disorder (PTSD) patients. It is therefore necessary to explore the spontaneous brain activity of treatment-naïve PTSD patients during resting-state. METHOD Seventeen treatment-naïve PTSD patients and twenty traumatized controls were recruited and underwent a resting functional magnetic resonance imaging (Rs-fMRI) scan. The differences of regional brain spontaneous activity between the participants with and without PTSD were measured by Amplitude of Low-frequency fluctuation (ALFF). The relationship between the altered brain measurements and the symptoms of PTSD were analyzed. RESULT Compared to traumatized controls, the PTSD group showed significantly altered ALFF in many emotion-related brain regions, such as the medial anterior cingulate cortex (MACC), dorsolateral prefrontal cortex (DLPFC), insular (IC), middle temporal gyrus (MTG), and ventral posterior cingulate cortex (VPCC). Interestingly this is the first report of a hyperactive visual cortex (V1/V2) during resting-state in treatment-naïve PTSD patients. There were significant positive correlations between ALFF values in the bilateral visual cortex and re-experiencing or avoidance in PTSD. Negative correlation was observed between ALFF values in MACC and avoidance. CONCLUSION This study suggested that the visual cortex and the MACC may be involved in the characteristic symptoms of chronic PTSD, such as re-experiencing and avoidance. Future studies that focus on these areas of the brain are required, as alteration of these areas may act as a biomarker and could be targeted in future treatments for PTSD.

Altered spontaneous neuronal activity in chronic posttraumatic stress disorder patients before and after a 12-week paroxetine treatment.

BACKGROUND Abnormal functional brain activity has been revealed in patients with Posttraumatic Stress Disorder (PTSD) in recent years, while the recovery neuromechanism of PTSD has not yet been elucidated. The aim of this study was to investigate the altered spontaneous brain activity in treatment-naïve chronic PTSD patients before and after 12 weeks׳ treatment with paroxetine. METHODS Twenty-one earthquake-related PTSD patients and seventeen traumatized controls underwent a resting functional magnetic resonance imaging (Rs-fMRI) scan at baseline. Amplitude of low-frequency fluctuation (ALFF) was calculated and compared between PTSD patients and controls. Then, the PTSD group completed 12 weeks of treatment with paroxetine, and Rs-fMRI was repeated to compare with the baseline. Lastly, correlation analyses of ALFF values within altered brain areas were conducted. RESULTS Hyperactive function of visual cortex was observed in PTSD patients before and after treatment. After treatment, significantly increased ALFF values were observed in the left orbitofrontal cortex (OFC), while decreased ALFF values were found in the precuneus. Interestingly, a negative correlation between the mean ALFF values of OFC and those of precuneus and visual cortex was only observed in controls, but not in PTSD patients pre- or post-treatment. LIMITATIONS A corresponding control condition was absent in this study. CONCLUSION The findings showed that manipulating regional spontaneous activity of precuneus and OFC could be a potential prognostic indicator of PTSD. However, hyperactive function of visual cortex and disrupted connections between OFC, precuneus and visual cortex did not reverse after treatment, which could be a potential target for further treatment.

Altered Topological Properties of Brain Networks in Social Anxiety Disorder: A Resting-state Functional MRI Study

Recent studies involving connectome analysis including graph theory have yielded potential biomarkers for mental disorders. In this study, we aimed to investigate the differences of resting-state network between patients with social anxiety disorder (SAD) and healthy controls (HCs), as well as to distinguish between individual subjects using topological properties. In total, 42 SAD patients and the same number of HCs underwent resting functional MRI, and the topological organization of the whole-brain functional network was calculated using graph theory. Compared with the controls, the patients showed a decrease in 49 positive connections. In the topological analysis, the patients showed an increase in the area under the curve (AUC) of the global shortest path length of the network (Lp) and a decrease in the AUC of the global clustering coefficient of the network (Cp). Furthermore, the AUCs of Lp and Cp were used to effectively discriminate the individual SAD patients from the HCs with high accuracy. This study revealed that the neural networks of the SAD patients showed changes in topological characteristics, and these changes were prominent not only in both groups but also at the individual level. This study provides a new perspective for the identification of patients with SAD.

Gray Matter Abnormalities in Non-comorbid Medication-naive Patients with Major Depressive Disorder or Social Anxiety Disorder

Background An overlap of clinical symptoms between major depressive disorder (MDD) and social anxiety disorder (SAD) suggests that the two disorders exhibit similar brain mechanisms. However, few studies have directly compared the brain structures of the two disorders. The aim of this study was to assess the gray matter volume (GMV) and cortical thickness alterations between non-comorbid medication-naive MDD patients and SAD patients. Methods High-resolution T1-weighted images were acquired from 37 non-comorbid MDD patients, 24 non-comorbid SAD patients and 41 healthy controls (HCs). Voxel-based morphometry analysis of the GMV (corrected with a false discovery rate of p < 0.001) and vertex-based analysis of cortical thickness (corrected with a clusterwise probability of p < 0.001) were performed, and group differences were compared by ANOVA followed by post hoc tests. Outcomes Relative to the HCs, both the MDD patients and SAD patients showed the following results: GMV reductions in the bilateral orbital frontal cortex (OFC), putamen, and thalamus; cortical thickening in the bilateral medial prefrontal cortex, posterior dorsolateral prefrontal cortex, insular cortex, left temporal pole, and right superior parietal cortex; and cortical thinning in the left lateral OFC and bilateral rostral middle frontal cortex. In addition, MDD patients specifically showed a greater thickness in the left fusiform gyrus and right lateral occipital cortex and a thinner thickness in the bilateral lingual and left cuneus. SAD patients specifically showed a thinner cortical thickness in the right precentral cortex. Interpretation Our results indicate that MDD and SAD share common patterns of gray matter abnormalities in the orbitofrontal-striatal-thalamic circuit, salience network and dorsal attention network. These consistent structural differences in the two patient groups may contribute to the broad spectrum of emotional, cognitive and behavioral disturbances observed in MDD patients and SAD patients. In addition, we found disorder-specific involvement of the visual processing regions in MDD and the precentral cortex in SAD. These findings provide new evidence regarding the shared and specific neuropathological mechanisms that underlie MDD and SAD.

Multimodal MRI-Based Classification of Trauma Survivors with and without Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder. It can be difficult to discern the symptoms of PTSD and obtain an accurate diagnosis. Different magnetic resonance imaging (MRI) modalities focus on different aspects, which may provide complementary information for PTSD discrimination. However, none of the published studies assessed the diagnostic potential of multimodal MRI in identifying individuals with and without PTSD. In the current study, we investigated whether the complementary information conveyed by multimodal MRI scans could be combined to improve PTSD classification performance. Structural and resting-state functional MRI (rs-fMRI) scans were conducted on 17 PTSD patients, 20 trauma-exposed controls without PTSD (TEC) and 20 non-traumatized healthy controls (HC). Gray matter volume (GMV), amplitude of low-frequency fluctuations (ALFF), and regional homogeneity were extracted as classification features, and in order to integrate the information of structural and functional MRI data, the extracted features were combined by a multi-kernel combination strategy. Then a support vector machine (SVM) classifier was trained to distinguish the subjects at individual level. The performance of the classifier was evaluated using the leave-one-out cross-validation (LOOCV) method. In the pairwise comparison of PTSD, TEC, and HC groups, classification accuracies obtained by the proposed approach were 2.70, 2.50, and 2.71% higher than the best single feature way, with the accuracies of 89.19, 90.00, and 67.57% for PTSD vs. HC, TEC vs. HC, and PTSD vs. TEC respectively. The proposed approach could improve PTSD identification at individual level. Additionally, it provides preliminary support to develop the multimodal MRI method as a clinical diagnostic aid.

Altered regional and integrated resting-state brain activity in general social anxiety disorder patients before and after group cognitive behavior therapy

We aimed to investigate the recovery neuromechanism underlying the treatment efficacy in generalized social anxiety disorder (GSAD). We recruited fifteen patients with GSAD and nineteen healthy control (HC) participants, all of whom underwent a baseline resting-state fMRI scan. The GSAD patients underwent an additional fMRI scan after group cognitive behavior therapy (GCBT). Amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) measures were used to examine altered regional and integrated spontaneous brain activity in group comparisons. After GCBT, ALFF of the right precuneus decreased. At baseline, the GSAD group showed higher ALFF in the left precuneus and the left middle temporal gyrus (MTG) and lower ALFF in the lingual gyrus compared with the HC group. The DC of the left precuneus and the MTG were attenuated and the right putamen increased in the post-treatment group. The changes in DC in the precuneus were positively correlated with changes in clinical symptom. The abnormal ALFF of the precuneus, MTG and lingual gyrus may be the neural underpinning of GSAD, whereas the neural response to symptom remission after GCBT was achieved by a rebalance within the default mode network.

Characteristics of objective daytime sleep among individuals with earthquake-related posttraumatic stress disorder: A pilot community-based polysomnographic and multiple sleep latency test study.

Little is known about the objective sleep characteristics of patients with posttraumatic stress disorder (PTSD). The present study examines the association between PTSD symptom severity and objective daytime sleep characteristics measured using the Multiple Sleep Latency Test (MSLT) in therapy-naïve patients with earthquake-related PTSD. A total of 23 PTSD patients and 13 trauma-exposed non-PTSD (TEN-PTSD) subjects completed one-night in-lab polysomnography (PSG) followed by a standard MSLT. 8 of the 23 PTSD patients received paroxetine treatment. Compared to the TEN-PTSD subjects, no significant nighttime sleep disturbances were detected by PSG in the subjects with PTSD; however, a shorter mean MSLT value was found in the subjects with PTSD. After adjustment for age, sex, and body mass index, PTSD symptoms, particularly hyperarousal, were found to be independently associated with a shorter MSLT value. Further, the mean MSLT value increased significantly after therapy in PTSD subjects. A shorter MSLT value may be a reliable index of the medical severity of PTSD, while an improvement in MSLT values might also be a reliable marker for evaluating therapeutic efficacy in PTSD patients.