Association between gut microbiota and anxiety disorders: a bidirectional two-sample mendelian randomization study.

BACKGROUND: There are many articles reporting that the component of intestinal microbiota implies a link to anxiety disorders (AD), and the brain-gut axis is also a hot topic in current research. However, the specific relevance between gut microbiota and AD is uncertain. We aimed to investigate causal relationship between gut microbiota and AD by using bidirectional Mendelian randomization (MR). METHODS: Genetic instrumental variable (IV) for the gut microbiota were obtained from a genome-wide association study (GWAS) involving 18,340 participants. Summary data for AD were derived from the GWAS and included 158,565 cases and 300,995 controls. We applied the inverse variance weighted (IVW) method as the main analysis. Cochran's Q values was computed to evaluate the heterogeneity among IVs. Sensitivity analyses including intercept of MR-Egger method and MR-PRESSO analysis were used to test the horizontal pleiotropy. RESULT: We discovered 9 potential connections between bacterial traits on genus level and AD. Utilizing the IVW method, we identified 5 bacterial genera that exhibited a direct correlation with the risk of AD: genus Eubacteriumbrachygroup, genus Coprococcus3, genus Enterorhabdus, genus Oxalobacter, genus Ruminiclostridium6. Additionally, we found 4 bacterial genera that exhibited a negative association with AD: genus Blautia, genus Butyricicoccus, genus Erysipelotrichaceae-UCG003 and genus Parasutterella. The associations were confirmed by the sensitivity analyses. CONCLUSION: Our study found a causal relation between parts of the gut microbiota and AD. Further randomized controlled trials are crucial to elucidate the positive effects of probiotics on AD and their particular protection systems.

Cortical hypoperfusion in patients with idiopathic rapid eye movement sleep behavior disorder detected with arterial spin-labeled perfusion MRI.

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is an important risk factor for α-synucleinopathy. OBJECTIVE: We investigated alterations in the cerebral blood flow (CBF) based on arterial spin-labeled (ASL) imaging in patients with iRBD to determine brain perfusion changes associated with the disorder. METHODS: Fifteen patients with iRBD and twenty age-gender-matched healthy controls were enrolled. Cortical perfusions were compared between the two groups after the ASL data was co-registered to the high-resolution T1-weighted images. RESULTS: No significant differences were detected between the groups in regard to age, gender, education, or UPDRS-III score. The iRBD group showed a lower MMSE score than the healthy controls (27.07 ± 2.25 vs. 28.55 ± 1.23, p < 0.05). Compared with the healthy controls, the iRBD group showed significantly decreased CBF values in the right inferior frontal gyrus, right middle frontal gyrus, and right insula (p < 0.05 corrected). CONCLUSION: The cortical hypoperfusion areas in patients with iRBD were similar to the patterns in patients with α -synucleinopathies. ASL perfusion MRI is a potential approach to find biomarkers in preclinical stages of α -synucleinopathies.

Abnormal Anterior Cingulate N-Acetylaspartate and Executive Functioning in Treatment-Resistant Depression After rTMS Therapy.

BACKGROUND: Cognitive impairment is a key feature of treatment-resistant depression (TRD) and can be related to the anterior cingulate cortex (ACC) function. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. However, no studies to date have investigated the association between neurobiochemical changes within the anterior cingulate and executive dysfunction measured in TRD being treated with rTMS. METHODS: Thirty-two young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study [active (n=18) vs. sham (n=14)]. ACC metabolism was investigated before and after high-frequency (15 Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy (1H-MRS). The results were compared with 28 age- and gender-matched healthy controls. Executive functioning was measured with the Wisconsin Card Sorting Test (WCST) among 34 subjects with TRD and 28 healthy subjects. RESULTS: Significant reductions in N-acetylaspartate (NAA) and choline-containing Compound levels in the left ACC were found in subjects with TRD pre-rTMS when compared with healthy controls. After successful treatment, NAA levels increased significantly in the left ACC of subjects and were not different from those of age-matched controls. In the WCST, more perseverative errors and fewer correct numbers were observed in TRD subjects at baseline. Improvements in both perseverative errors and correct numbers occurred after active rTMS. In addition, improvement of perseverative errors was positively correlated with enhancement of NAA levels in the left ACC in the active rTMS group. CONCLUSIONS: Our results suggest that the NAA concentration in the left ACC is associated with an improvement in cognitive functioning among subjects with TRD response to active rTMS.

Acute Augmented Effect of Virtual Reality (VR)-Integrated Relaxation and Mindfulness Exercising on Anxiety and Insomnia Symptoms: A Retrospective Analysis of 103 Anxiety Disorder Patients With Prominent Insomnia.

BACKGROUND: Anxiety disorder is one of the most common mental disorders and often accompanied with sleep disturbance which can in turn exacerbate anxiety symptoms, creating a vicious cycle. In addition to psychopharmacological therapy, the effectiveness of psychotherapy as cognitive behavioral therapy (CBT) for treating anxiety disorders and insomnia has been well documented and widely accepted, but it is labor-intensive and costly. However, virtual reality (VR)-integrated CBT may improve this condition but needs more evidences to support its extensive application in routine clinical practice. OBJECTIVES: This explorative study was aimed to conduct a retrospective analysis to evaluate the acute (2 weeks) augmented effect of VR-integrated relaxation and mindfulness exercising in improving anxiety and insomnia symptoms for patients who were diagnosed with anxiety disorders and concurrently with prominent insomnia symptoms and admitted to the Department of Psychiatry, The Affiliated Guangdong Second Provincial General Hospital of Jinan University during January 2021 to June 2021. METHODS: All patients who were admitted to the department of psychiatry during January 1, 2021 to June 30, 2021 were screened with inclusion criteria and exclusion criteria, and the sociodemographic and clinical data of those included patients were collected from the electronic medical record system of the hospital using a self-designed case report form (CRF). Subjects who were administrated with medication alone were designated as conventional group, and those receiving treatment of medication combined with VR-integrated CBT (VR relaxation and mindfulness exercising) as VR group. The baseline and 2-week posttreatment data were compared between the two groups. RESULTS: In total, there were 103 patients (70 female, 68%) included in the study. Among all, 68 (66.02%) were designated as the "VR group," and 35 (33.98%) as the "conventional group." The majority of patients (67%) were diagnosed with generalized anxiety disorder (GAD). Twenty-three (22.3%) patients had a comorbid diagnosis with primary insomnia, and insomnia was just one of the accompanying symptoms with anxiety for the rest 80 subjects. No statistically significant differences were found between VR and conventional groups in all baseline sociodemographic and clinical characteristics except for occupation. There were statistically significant differences for the remission rates of anxiety symptoms or insomnia symptoms and reduction of Hamilton Anxiety Rating Scale or Insomnia Severity Index total scores between conventional and VR groups. Greater remission rates or score reductions were found in VR group than in conventional group either for anxiety or for insomnia. Robust differences still existed when controlled for the variable "occupation." CONCLUSIONS: Two-week augmented VR-integrated relaxation and mindfulness exercising is acutely beneficial for relieving both anxiety and insomnia symptoms and worth being recommended for routine clinical practice. Further prospective and randomized study compared to traditional CBT to explore its acute and long-term effect on anxiety and insomnia is needed.

m6A/m1A/m5C-Associated Methylation Alterations and Immune Profile in MDD.

Major depressive disorder (MDD) is a prevalent psychiatric condition often accompanied by severe impairments in cognitive and functional capacities. This research was conducted to identify RNA modification-related gene signatures and associated functional pathways in MDD. Differentially expressed RNA modification-related genes in MDD were first identified. And a random forest model was developed and distinct RNA modification patterns were discerned based on signature genes. Then, comprehensive analyses of RNA modification-associated genes in MDD were performed, including functional analyses and immune cell infiltration. The study identified 29 differentially expressed RNA modification-related genes in MDD and two distinct RNA modification patterns. TRMT112, MBD3, NUDT21, and IGF2BP1 of the risk signature were detected. Functional analyses confirmed the involvement of RNA modification in pathways like phosphatidylinositol 3-kinase signaling and nucleotide oligomerization domain (NOD)-like receptor signaling in MDD. NUDT21 displayed a strong positive correlation with type 2 T helper cells, while IGF2BP1 negatively correlated with activated CD8 T cells, central memory CD4 T cells, and natural killer T cells. In summary, further research into the roles of NUDT21 and IGF2BP1 would be valuable for understanding MDD prognosis. The identified RNA modification-related gene signatures and pathways provide insights into MDD molecular etiology and potential diagnostic biomarkers.

Electrophysiological Changes on Laryngeal Motor Neuropathways Cause Voice Disorders for Postradiotherapy Patients with Nasopharyngeal Carcinoma.

OBJECTIVE: This study explored electrophysiological changes in the laryngeal motor neuropathway and determined whether lesions in the laryngeal motor cortex (LMC) and its descending tract contribute to voice deterioration and peripheral nerve palsy in patients with nasopharyngeal carcinoma (NPC) postradiotherapy (RT). STUDY DESIGNS: Prospective cohort study. METHODS: Twenty-two patients with NPC at 2 to 4years post-RT (8 female and 14 male), 22 patients with NPC at 8 to 10years post-RT (8 female and 14 male), and 22 healthy individuals (9 female and 13 male) were selected to test their magnetic evoked potentials (MEP), motor nerve conduction, and voice quality using transcranial magnetic stimulation, laryngeal electromyography, and the XION DiVAS acoustic analysis software. Three groups were matched according to approximate age. Multiple comparisons were performed among the three groups. RESULTS: The voice quality of post-RT patients with NPC deteriorated compared to that of healthy individuals. Bilateral LMC and their corticonuclear tracts to the bilateral ambiguous nuclei of post-RT patients with NPC were impaired according to multigroup comparisons of MEP amplitudes, latencies, and resting motor thresholds. The vagus and recurrent laryngeal nerves (RLN) of post-RT patients with NPC were impaired according to multigroup comparisons of the amplitude and latencies of the compound muscle action potential and latencies of f-waves. CONCLUSIONS: The voice quality of patients with NPC deteriorated after RT. The pathogenesis of post-RT voice deterioration may involve radiation-induced injuries to the vagus, RLN, and bilateral LMC. Furthermore, radiation-induced injuries to the bilateral LMC may contribute to vagus and RLN palsies. These findings support the use of transcranial approaches to treating voice disorders and peripheral nerve palsies in post-RT patients with NPC. TRIAL REGISTRATION: ChiCTR2100054425; Electrophysiological Study of Vocal-Fold Mobility Disorders After Radiotherapy for NPC Patients via Magnetic Evoked Potential and Their Correlation with Voice Quality Assessment; https://www.chictr.org.cn/bin/project/edit?pid=144429.

Sleep problems in adolescents with depression: Role of childhood trauma, alexithymia, rumination, and self-esteem.

BACKGROUND: While sleep problems are common in adolescents with depression, the exact prevalence has not been reported. Although previous studies have shown that childhood trauma, alexithymia, rumination, and self-esteem are related to sleep problems, the interactions between these factors remain unclear. METHODS: This study, conducted from March 1, 2021 to January 20, 2022, employed a cross-sectional design. The participants were 2192 adolescents with depression with a mean age of 15 years. The Chinese version of the Pittsburgh Sleep Quality Index, Childhood Trauma Questionnaire, Toronto Alexithymia Scale-20, Ruminative Response Scale, and Rosenberg Self-Esteem Scale were used to measure sleep problems, childhood trauma, alexithymia, rumination, and self-esteem, respectively. We used PROCESS 3.3 for SPSS to determine the chain mediating effect of alexithymia and rumination and the moderating effect of self-esteem in the relationship between childhood trauma and sleep problems. RESULTS: Up to 70.71 % of adolescents with depression had sleep problems. Furthermore, alexithymia and rumination played a chain mediation role in the relationship between childhood trauma and sleep problems. Finally, self-esteem moderated the relationships between alexithymia and sleep problems and rumination and sleep problems. LIMITATIONS: Owing to the study design, we cannot derive causal relationships between variables. Further, the self-reported data may have been influenced by subjective participant factors. CONCLUSIONS: This study reveals potential ways of how childhood trauma influences sleep problems in adolescents with depression. These findings suggest that interventions targeting alexithymia, rumination, and self-esteem in adolescents with depression may be effective in reducing their sleep problems.

A psychological investigation of coronavirus disease 2019 (COVID-19) patients in mobile cabin hospitals in Wuhan.

BACKGROUND: This study investigated the depression, anxiety, and insomnia levels of coronavirus disease 2019 (COVID-19) patients admitted to two mobile cabin hospitals in Jianghan District (Wuhan, China). METHODS: Thirty COVID-19 (eight mild type and twenty-two common type) patients were evaluated using the Patient Health Questionnaire-9, the Generalized Anxiety Disorder 7 Questionnaire, the Insomnia Severity Index, and a semi-structured interview. RESULTS: All 30 patients reported varying degrees of anxiety, depression, and insomnia. The levels of depression and anxiety in mild type COVID-19 patients were significantly lower than those in common type COVID-19 patients. Significant improvements in depression (P<0.001) and anxiety (P<0.001) levels were found in the COVID-19 patients at the second evaluation compared with the baseline (admittance to hospital). More than 80% patients agreed that medical security, support from other patients, and a better living environment were the main reasons for improvements to their adverse psychological states. CONCLUSIONS: Varying degrees of anxiety, depression, and insomnia frequently occur in patients with COVID-19. Standard treatment protocols and patient-centered care in the mobile cabin hospitals in this study provided the chance for COVID-19 patients to successfully improve their mental health during the outbreak of the pandemic.

Longitudinal surveys of prevalence rates and use patterns of illicit drugs at selected high-prevalence areas in China from 1993 to 2000.

AIMS: To identify the prevalence, patterns and trends of illicit drug use in the general population of selected high-prevalence areas in China between 1993 and 2000. DESIGN, SETTING AND PARTICIPANTS: Cluster sampling was employed and the Epidemiological Inventory for Illicit Drug Use (EIIDU) used as survey instrument. In 1993, 1996 and 2000, 56 792, 67 319 and 53 747 individuals aged 15 or above in community were interviewed, respectively, at the three time-points. MEASUREMENTS: Demographics and drug-related data were collected and the prevalence patterns of illicit drug are described. FINDINGS: The life-time prevalences of illicit drug use in the three consecutive surveys in 1993, 1996 and 2000 were 1.08, 1.60 and 1.52%, respectively, and the 1-year prevalence rates were 0.91, 1.17 and 1.17%, respectively. Heroin was the first choice for drug use (51.8% in 1993, 83.4% in 1993 and 95.9% in 2000). The two most frequent routes of drug administration were inhalation (89.2% in 1993, 60.1% in 1996 and 93.5% in 2000) and intravenous injection (27.2% in 1993, 31.0% in 1996 and 25.7% in 2000). CONCLUSION: At least for the time being, illicit drug use may have plateaued in these selected high-prevalence areas.

Association of CYP2D6 and CYP1A2 gene polymorphism with tardive dyskinesia in Chinese schizophrenic patients.

AIM: To investigate the possible association of the CYP2D6 gene C100T polymorphism and the CYP1A2 gene C163A polymorphism with tardive dyskinesia (TD) in Chinese patients with schizophrenia. METHODS: The recruited schizophrenic patients were assessed with the Abnormal Involuntary Movement Scale (AIMS), and divided into groups with TD (n=91) and without TD (n=91) according to the AIMS score. Polymorphisms of the CYP2D6 and CYP1A2 genes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). RESULTS: No allele frequencies deviated from Hardy-Weinberg equilibrium. No significant differences in genotypes frequencies of the CYP2D6 C100T polymorphism were observed between patients with TD and without TD (Chi2=4.078, P>0.05), but patients with TD had a significant excess of the T allele compared with those without TD (Chi2=4.28, P<0.05). Moreover, the frequency of the CYP1A2 C allele in patients with TD was significantly higher than that in those without TD (Chi2=6.38, P<0.05). An association between TD and the CYP2D6 100T and CYP1A2 163C alleles was observed. Additionally, there were no differences in the mean AIMS scores among different genotypes in TD patients as a group or in smokers. The results of logistic regression analysis demonstrated that mean age and duration of illness were risk factors for TD, but not sex, cumulative exposure to neuroleptic drugs in years, CYP2D6 or CYP1A2 genotype. CONCLUSION: The C100T polymorphism of the CYP2D6 gene and the C163A polymorphism of the CYP1A2 gene may be associated with neuroleptic drug-induced tardive dyskinesia in Chinese patients with schizophrenia. However, genetic factors have a weaker association with susceptibility to TD compared with mean age and duration of illness.