Identifying causal associations between women's reproductive traits and risk of schizophrenia: a multivariate validated two-sample Mendelian randomization analysis.

BACKGROUND: A significant association between women's reproductive traits and the risk of schizophrenia (SCZ) has been discovered, but the causalities remain unclear. We designed a two-sample univariate Mendelian randomization (MR) study using female-specific SNPs collected from a large-scale genome-wide association study as a genetic tool to explore the causal effect of female reproductive traits on the risk of SCZ, and conducted a multivariate MR study to re-validate the above findings. METHODS: From extensive genome-wide association studies (GWAS) of people with European ancestry (n = 176,881 to 418,758 individuals), summary-level data on five female reproductive variables were extracted. Summary-level information on SCZ was taken from a GWAS meta-analysis involving 320,404 people with European ancestry. The inverse variance weighting estimations for both univariable MR (UVMR) and multivariable MR (MVMR) were presented as the primary results. MR-Egger, weighted median, simple mode, and weighted mode regression methods for UVMR, and MVMR-Egger, MVMR-Lasso, and MVMR-median methods for MVMR were used for sensitivity analyses. RESULTS: The UVMR produced compelling proof for a connection between genetically predicted later age at first sexual intercourse (AFS) (OR, 0.632; 95% CI, 0.512-0.777; P < 0.01) and decreased SCZ risk. Pleiotropy analysis of the AFS-SCZ association confirmed the robustness of the MR results (P > 0.05). Consistent, substantial causal effects of AFS (OR, 0.592; 95%CI, 0.407-0.862; P < 0.01) on the risk of SCZ were demonstrated after adjusting for body mass index, years of schooling, and smoking initiation using MVMR. CONCLUSIONS: Our findings provide convincing evidence that early AFS is a risk factor for SCZ. SCZ risk may be decreased by raising awareness of reproductive healthcare for women.

Panic disorder aging characteristics: The role of telomerase reverse transcriptase gene and brain function.

Panic disorder (PD) causes serious functional damage and disability and accelerates the process of individual aging. The pathological basis of PD is the same as that of age-related diseases, which is proposed as a new viewpoint in recent years. Memory decline and social functional impairment are common manifestations of accelerated aging in PD. The function of telomerase reverse transcriptase (TERT) and telomere length (TL) is abnormal in patients with aging and PD. However, the molecular mechanism behind remains unclear. The purpose of this study was to explore the relationship between TERT gene expression (including DNA methylation) and the changes in PD aging characteristics (memory and social function). By TERT gene knockout mice, we found that loss of TERT attenuated the acquisition of recent fear memory during contextual fear conditioning. This study reported that a significantly lower methylation level of human TERT (hTERT) gene was detected in PD patients compared with healthy control and particularly decreased CpG methylation in the promoter region of hTERT was associated with the clinical characteristics in PD. Regional homogeneity (ReHo) analysis showed that the methylation of hTERT (cg1295648) influenced social function of PD patients through moderating the function of the left postcentral gyrus (PCG). This indicates that the hTERT gene may play an important role in the pathological basis of PD aging and may become a biological marker for evaluating PD aging. These findings provide multidimensional evidence for the underlying genetic and pathological mechanisms of PD.

The design of a novel arthroscopy shaver.

Cases of arthroscopic surgery have increased over the past two decades, and arthroscopic shaver systems have become a commonly used orthopedic tool. Nevertheless, most shavers generally have problems such as the cutting edge is not sharp enough and easy to wear. This paper aims to discuss the structural characteristics of BJKMC's (Bojin◊ Kinetic Medical) novel arthroscopic shaver, the double serrated blade. The product's design and verification process are outlined. BJKMC's articular arthroscopy shaver has a "tube in a tube" structure, comprising a stainless steel outer sleeve and a rotating hollow inner tube. The outer sleeve and inner tube have corresponding suction and cutting windows, and there are serrated teeth on the inner and outer casing. To verify the design rationality, it was compared to Dyonics◊'s equivalent product, the Incisor◊ Plus Blade. The appearance, cutting tool hardness, metal pipe roughness, cutting tool wall thickness, tooth profile, and angle, overall structure, and the key dimensions were examined and compared. Compared with Dyonics◊'s Incisor◊ Plus Blade, BJKMC's Double Serrated Blade had a smoother working surface, harder and thinner blade head. Therefore, BJKMC's product may have satisfactory performance when it comes to surgery.

Glutamic Acid Decarboxylase 1 Gene Methylation and Panic Disorder Severity: Making the Connection by Brain Gray Matter Volume.

Objective: This study aimed to test the hypothesis that the relationship between glutamic acid decarboxylase (GAD) 1 gene methylation and severity of clinical symptoms of panic disorder (PD) is mediated by the effect of GAD1 gene methylation on gray matter volume (GMV) and the effect of GMV on PD. Methods: Panic disorder (n = 24) patients were recruited consecutively from the Affiliated Brain Hospital of Nanjing Medical University through outpatient and public advertising, eligible healthy controls (HCs) (n = 22) were recruited from public advertising. We compared GMV and GAD1 gene methylation in PD and HCs to estimate the differences, and on the basis of the relationship between gray matter volumes and GAD1 gene methylation in PD patients was evaluated, the role of GMV as a mediator of GAD1 gene methylation and PD clinical symptoms was analyzed. Results: Panic disorder patients had significantly lower methylation in the GAD1 promoter region on Cytosine-phosphate-guanine (CPG) 7 than HCs (t = 2.380, p = 0.021). Pearson correlation analysis found a significant negative association between cg171674146 (cg12) site and clinical severity (n = 24, r = -0.456, p = 0.025). Compared to HCs, patients with PD had decreased gray matter volumes in several brain regions, which were also associated with PD severity. Left postcentral gyrus (PoCG) GMV mediated the association between cg12 methylation and PD severity, and there was a significant mediation effect of right angular gyrus (ANG) gray matter volumes on the relationship between cg12 methylation and PD severity. Limitation: No direct results can be derived for methylation patterns in different brain regions; the study is cross-sectional; relatively small size.

Neural Effects of Cognitive Behavioral Therapy in Psychiatric Disorders: A Systematic Review and Activation Likelihood Estimation Meta-Analysis.

Background: Cognitive behavioral therapy (CBT) is a first-line psychotherapeutic treatment that has been recommended for psychiatric disorders. Prior neuroimaging studies have provided preliminary evidence suggesting that CBT can have an impact on the activity of brain regions and functional integration between regions. However, the results are far from conclusive. The present article aimed to detect characteristic changes in brain activation following CBT across psychiatric disorders. Method: Web of Science, Cochrane Library, Scopus, and PubMed databases were searched to identify whole-brain functional neuroimaging studies of CBT through 4 August 2021. To be included in the meta-analysis, studies were required to examine functional activation changes between pre-and post-CBT. The included studies were then divided into subgroups according to different task paradigms. Then, an activation likelihood estimation algorithm (ALE) was performed in the different meta-analyses to identify whether brain regions showed consistent effects. Finally, brain regions identified from the meta-analysis were categorized into eight functional networks according to the spatial correlation values between independent components and the template. Results: In total, 13 studies met inclusion criteria. Three different meta-analyses were performed separately for total tasks, emotion tasks, and cognition tasks. In the total task ALE meta-analysis, the left precuneus was found to have decreased activation. For the cognition task ALE meta-analysis, left anterior cingulate (ACC) and left middle frontal gyrus (MFG) were found to have decreased activation following CBT. However, the emotion task ALE meta-analysis did not find any specific brain regions showing consistent effects. A review of included studies revealed default mode network (DMN), executive control network (ECN), and salience network (SN) were the most relevant among the eight functional networks. Conclusion: The results revealed that the altered activation in the prefrontal cortex and precuneus were key regions related to the effects of CBT. Therefore, CBT may modulate the neural circuitry of emotion regulation. This finding provides recommendations for the rapidly developing literature.

A meta-analysis on neural changes of cognitive training for mental disorders in executive function tasks: increase or decrease brain activation?

BACKGROUND: Cognitive impairment is often found in patients with psychiatric disorders, and cognitive training (CT) has been shown to help these patients. To better understand the mechanisms of CT, many neuroimaging studies have investigated the neural changes associated with it. However, the results of those studies have been inconsistent, making it difficult to draw conclusions from the literature. Therefore, the objective of this meta-analysis was to identify consistent patterns in the literature of neural changes associated with CT for psychiatric disorders. METHODS: We searched for cognitive training imaging studies in PubMed, Cochrane library, Scopus, and ProQuest electronic databases. We conducted an activation likelihood estimation (ALE) for coordinate-based meta-analysis of neuroimaging studies, conduct behavioral analysis of brain regions identified by ALE analysis, conduct behavioral analysis of brain regions identified by ALE analysis, and then created a functional meta-analytic connectivity model (fMACM) of the resulting regions. RESULTS: Results showed that CT studies consistently reported increased activation in the left inferior frontal gyrus (IFG) and decreased activation in the left precuneus and cuneus from pre- to post- CT. CONCLUSION: CT improves cognitive function by supporting language and memory function, and reducing neuronal resources associated with basic visual processing.

Altered spontaneous neural activity in frontal and visual regions in patients with acrophobia.

BACKGROUND: Acrophobia is a prevalent type of specific phobia, which frequently leads to functional impairments and occupational limitations. However, the neural pathology of acrophobia is still largely unknown. METHODS: 26 acrophobic patients and 30 healthy controls were enrolled in this study. All participants underwent a resting-state fMRI scan. Severity of symptoms was evaluated using self-report and behavioral measures. The regional homogeneity (ReHo) and seed-based functional connectivity (FC) were then examined. RESULTS: Compared to controls, acrophobic patients demonstrated higher ReHo in the right fusiform gyrus and lower ReHo in the bilateral superior frontal gyrus. Lower FC of right fusiform gyrus-bilateral caudate, right fusiform gyrus-right parahippocampal gyrus, and left medial superior frontal gyrus-left cuneus was also found in the acrophobia group. Additionally, there were negative correlations between behavior avoidance scores and FC of right fusiform gyrus- right parahippocampal gyrus (r = -0.42, p = 0.04) and between scores of the 7-item generalized anxiety disorder scale and FC of left medial superior frontal gyrus- left cuneus (r = -0.40, p = 0.049) in the acrophobia group. LIMITATIONS: Owing to the cross-sectional design, it was unclear whether the functional abnormalities found in the acrophobic patients were related to state or trait effects. CONCLUSIONS: Preliminary results indicated that acrophobic patients revealed abnormal brain function in orbitofrontal cortex, medial prefrontal cortex, and visual regions. These abnormalities may be helpful in understanding the possible neurobiological mechanism of acrophobia and may serve as potential intervention and prevention targets.

Symptom provocation in obsessive-compulsive disorder: A voxel-based meta-analysis and meta-analytic connectivity modeling.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous psychiatric illness with a complex array of symptoms and potentially distinct neural underpinnings. We employed meta-analysis and connectivity modeling of symptom dimensions to delineate the circuit mechanisms of OCD. METHODS: With the activation likelihood estimation (ALE) algorithm we performed meta-analysis of whole-brain functional magnetic resonance imaging (fMRI) studies of symptom provocation. We contrasted all OCD patients and controls in a primary analysis and divided the studies according to clinical symptoms in secondary meta-analyses. Finally, we employed meta-analytic connectivity modeling analyses (MACMs) to examine co-activation patterns of the brain regions revealed in the primary meta-analysis. RESULTS: A total of 14 experiments from 12 eligible studies with a total of 238 OCD patients (124 men) and 219 healthy controls (120 men) were included in the primary analysis. OCD patients showed higher activation in the right caudate body/putamen/insula and lower activation in the left orbitofrontal cortex (OFC), left inferior frontal gyrus (IFG), left caudate body/middle cingulate cortex (MCC), right middle temporal gyrus (MTG), middle occipital gyrus (MOG) and right lateral occipital gyrus (LOG). MACMs revealed significant co-activation between left IFG and left caudate body/MCC, left MOG and right LOG, right LOG and MTG. In the secondary meta-analyses, the washing subgroup showed higher activation in the right OFC, bilateral ACC, left MOG and right caudate body. CONCLUSION: OCD patients showed elevated dorsal striatal activation during symptom provocation. In contrast, the washing subgroup engaged higher activation in frontal, temporal and posterior cortical structures as well as right caudate body. Broadly consistent with the proposition of cortico-striatal-thalamic-cortical circuit dysfunction, these findings highlight potentially distinct neural circuits that may underlie the symptoms and potentially etiological subtypes of OCD.

Nitric Oxide Synthase Type 1 Methylation Is Associated With White Matter Microstructure in the Corpus Callosum and Greater Panic Disorder Severity Among Panic Disorder Patients.

Objectives: Methylation of the neuronal nitric oxide synthase (NOS1/nNOS) gene has recently been identified as a promising biomarker of psychiatric disorders. NOS1 plays an essential role in neurite outgrowth and may thus affect the microstructure development of white matter (WM) in the corpus callosum (CC), which is known to be altered in panic disorder (PD). We examined the relationship between NOS1 methylation, WM tracts in the CC, and symptoms based on this finding. Methods: Thirty-two patients with PD and 22 healthy controls (HCs) were recruited after age, gender, and the education level were matched. The cell type used was whole-blood DNA, and DNA methylation of NOS1 was measured at 20 CpG sites in the promoter region. Although 25 patients with PD were assessed with the Panic Disorder Severity Scale (PDSS), diffusion tensor imaging (DTI) scans were only collected from 16 participants with PD. Results: We observed that the PD group showed lower methylation than did the HCs group and positive correlations between the symptom severity of PD and methylation at CpG4 and CpG9. In addition, CpG9 methylation was significantly correlated with the fractional anisotropy (FA) and mean diffusivity (MD) values of the CC and its major components (the genu and the splenium) in the PD group. Furthermore, path analyses showed that CpG9 methylation offers a mediating effect for the association between the MD values of the genu of the CC and PD symptom severity (95% CI = -1.731 to -0.034). Conclusions: The results suggest that CpG9 methylation leads to atypical development of the genu of the CC, resulting in higher PD symptom severity, adding support for the methylation of NOS1 as a future prognostic indicator of PD.