Linking individual variability in functional brain connectivity to polygenic risk in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a highly heterogeneous disease, which brings great difficulties to clinical diagnosis and therapy. Its mechanism is still unknown. Prior neuroimaging studies mainly focused on mean differences between patients and healthy controls (HC), largely ignoring individual differences between patients. METHODS: This study included 112 MDD patients and 93 HC subjects. Resting-state functional MRI data were obtained to examine the patterns of individual variability of brain functional connectivity (IVFC). The genetic risk of pathways including dopamine, 5-hydroxytryptamine (5-HT), norepinephrine (NE), hypothalamic-pituitary-adrenal (HPA) axis, and synaptic plasticity was assessed by multilocus genetic profile scores (MGPS), respectively. RESULTS: The IVFC pattern of the MDD group was similar but higher than that in HCs. The inter-network functional connectivity in the default mode network contributed to altered IVFC in MDD. 5-HT, NE, and HPA pathway genes affected IVFC in MDD patients. The age of onset, duration, severity, and treatment response, were correlated with IVFC. IVFC in the left ventromedial prefrontal cortex had a mediating effect between MGPS of the 5-HT pathway and baseline depression severity. LIMITATIONS: Environmental factors and differences in locations of functional areas across individuals were not taken into account. CONCLUSIONS: This study found MDD patients had significantly different inter-individual functional connectivity variations than healthy people, and genetic risk might affect clinical manifestations through brain function heterogeneity.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Meta-analysis of the efficacy of Xuebijing combined with hemoperfusion in treating paraquat poisoning.

BACKGROUND: Paraquat (PQ) is a herbicide that is highly toxic to humans and animals. Xuebijing can regulate immune and inflammatory mediators. Blood purification is a conventional treatment for paraquat poisoning. Therefore, this study aimed to investigate the clinical effect of Xuebijing combined with hemoperfusion on acute paraquat poisoning (APQ). METHODS: The PubMed, Cochrane Library, EMbase, CNKI, CBM, and Wanfang databases were searched by computer for randomized controlled trials (RCT) of Xuebijing combined with hemoperfusion in the treatment of APQ. The search time was from the establishment of database to April 2020. The documents were screened and extracted according to the inclusion and exclusion criteria. Meta-analysis and Revman 5.3 were used to evaluate the quality. RESULTS: The metanalysis included 10 studies, totaling 636 patients. Results showed that the 7-day survival rate of Xuebijing combined with hemoperfusion group was higher than that of the control group [hazard ratio (HR) =1.17, 95% confidence interval (CI): (1.04, 1.32), P<0.008], while 14-day survival rate was higher [HR =1.52, 95% CI: (1.13, 2.06), P<0.006], alanine aminotransferase (ALT) was lower [mean difference (MD) =-32.5, 95% CI: (-52.24, -12.76), P=0.001], creatinine was lower [MD =-60.73, 95% CI: (-103.42, -18.04), P<0.005], oxygen partial pressure (PaO2) was higher [MD =6.21, 95% CI: (1.78, 10.64), P=0.006], and C-reactive protein (CRP) was lower [MD =-6.15, 95% CI: (-7.14, -5.16), P<0.00001]. However, there was no statistical difference in oxygen saturation (SpO2) and carbon dioxide PaO2 between the two groups. CONCLUSIONS: Xuebijing combined with hemoperfusion and conventional treatment can improve the 7-day and 14-day survival rate, oxygenation level, liver and kidney function, and inflammatory response of paraquat poisoning (PQ) patients.

Voice recognition and altered connectivity in schizophrenic patients with auditory hallucinations.

Auditory verbal hallucination (AVH) is a pathological hallmark of schizophrenia; however, their neural basis is unclear. Voice identity is an important phenomenological feature of AVHs. Certain voice identity recognition deficits are specific to schizophrenic patients with AVHs. We tested our hypothesis that among schizophrenia patients with hallucination, dysfunctional voice identity recognition is associated with poor functional integration in the neural networks involved in the evaluation of voice identity. Using functional magnetic resonance imaging (fMRI) during a voice recognition task, we examined the modulation of neural network connectivity in 26 schizophrenic patients with or without AVHs, and 13 healthy controls. Our results showed that the schizophrenic patients with AVHs had altered frontotemporal connectivity compared to the schizophrenic patients without AVHs and healthy controls. The latter two groups did not show any differences in functional connectivity. In addition, the strength of frontotemporal connectivity was correlated with the accuracy of voice recognition. These findings provide preliminary evidence that impaired functional integration may contribute to the faulty appraisal of voice identity in schizophrenic patients with AVHs.