Distinctively different human neurobiological responses after trauma exposure and implications for posttraumatic stress disorder subtyping.

Trauma elicits various adaptive and maladaptive responses among all exposed people. There may be distinctively different patterns of adaptation/maladaptation or types according to neurobiological predisposition. The present study aims to dissect the heterogeneity of posttraumatic conditions in order to identify clinically meaningful subtypes in recently traumatized individuals and evaluate their neurobiological correlates and long-term prognosis. We implemented a data-driven classification approach in both discovery (n = 480) and replication (n = 220) datasets of trauma-exposed and trauma-unexposed individuals based on the clinical data across a wide range of assessments. Subtype-specific patterns of functional connectivity in higher-order cortical networks, longitudinal clinical outcomes, and changes in functional connectivity were also evaluated. We identified four distinct and replicable subtypes for trauma-exposed individuals according to posttraumatic stress symptoms. Each subtype was distinct in clinical characteristics, brain functional organization, and long-term trajectories for posttraumatic symptoms. These findings help enhance current understanding of mechanisms underlying the human-specific heterogeneous responses to trauma. Furthermore, this study contributes data towards the development of improved interventions, including targeting of subtype-specific characteristics, for trauma-exposed individuals and those with PTSD.

Identifying unique subgroups in suicide risks among psychiatric outpatients.

BACKGROUND: The presence of psychiatric disorders is widely recognized as one of the primary risk factors for suicide. A significant proportion of individuals receiving outpatient psychiatric treatment exhibit varying degrees of suicidal behaviors, which may range from mild suicidal ideations to overt suicide attempts. This study aims to elucidate the transdiagnostic symptom dimensions and associated suicidal features among psychiatric outpatients. METHODS: The study enrolled patients who attended the psychiatry outpatient clinic at a tertiary hospital in South Korea (n = 1, 849, age range = 18-81; 61% women). A data-driven classification methodology was employed, incorporating a broad spectrum of clinical symptoms, to delineate distinctive subgroups among psychiatric outpatients exhibiting suicidality (n = 1189). A reference group of patients without suicidality (n = 660) was included for comparative purposes to ascertain cluster-specific sociodemographic, suicide-related, and psychiatric characteristics. RESULTS: Psychiatric outpatients with suicidality (n = 1189) were subdivided into three distinctive clusters: the low-suicide risk cluster (Cluster 1), the high-suicide risk externalizing cluster (Cluster 2), and the high-suicide risk internalizing cluster (Cluster 3). Relative to the reference group (n = 660), each cluster exhibited distinct attributes pertaining to suicide-related characteristics and clinical symptoms, covering domains such as anxiety, externalizing and internalizing behaviors, and feelings of hopelessness. Cluster 1, identified as the low-suicide risk group, exhibited less frequent suicidal ideation, planning, and multiple attempts. In the high-suicide risk groups, Cluster 2 displayed pronounced externalizing symptoms, whereas Cluster 3 was primarily defined by internalizing and hopelessness symptoms. Bipolar disorders were most common in Cluster 2, while depressive disorders were predominant in Cluster 3. DISCUSSION: Our findings suggest the possibility of differentiating psychiatric outpatients into distinct, clinically relevant subgroups predicated on their suicide risk. This research potentially paves the way for personalizing interventions and preventive strategies that address cluster-specific characteristics, thereby mitigating suicide-related mortality among psychiatric outpatients.

A Comparative Study of Endoscopic versus Percutaneous Epidural Neuroplasty in Lower Back Pain: Outcomes at Six-Month Follow Up.

Background and Objectives: Endoscopic epidural neuroplasty (EEN) facilitates adhesiolysis through direct epiduroscopic visualization, offering more precise neural decompression than that exhibited by percutaneous epidural neuroplasty (PEN). We aimed to compare the effects of EEN and PEN for 6 months after treatment with lower back and radicular pain in patients. Methods: This retrospective study compared the visual analog scale (VAS) and Oswestry disability index (ODI) scores in patients with low back and radicular pain who underwent EEN or PEN with a steering catheter. The medical records of 107 patients were analyzed, with 73 and 34 undergoing EEN and PEN, respectively. Results: The VAS and ODI scores decreased at all time points after EEN and PEN. VAS and ODI scores decreased more in the EEN group than those in the PEN group at 1 day and 1- and 6-months post-procedure, indicating superior pain relief for both lower back and radicular pain through EEN. Conclusions: EEN is a superior treatment of pain control than PEN in lower back and radicular pain patients.

Gray matter volume reduction in the emotional brain networks in adults with anosmia.

Loss of olfaction, or anosmia, frequently accompanies emotional dysfunctions, partly due to the overlapping brain regions between the olfactory and emotional processing centers. Here, we investigated whether anosmia was associated with gray matter volume alterations at a network level, and whether these alterations were related to the olfactory-specific quality of life (QOL) and depressive symptoms. Structural brain magnetic resonance imaging was acquired in 22 individuals with postinfectious or idiopathic anosmia (the anosmia group) and 30 age- and sex-matched controls (the control group). Using independent component analysis on the gray matter volumes, we identified 10 morphometric networks. The gray matter volumes of these networks were compared between the two groups. Olfactory-specific QOL and depressive symptoms were assessed by self-report questionnaires and clinician-administered interviews, respectively. The anosmia group showed lower gray matter volumes in the hippocampus-amygdala and the precuneus networks, relative to the control group. Lower gray matter volumes in the hippocampus-amygdala network were also linearly associated with lower olfactory-specific QOL and higher depressive symptom scores. These findings suggest a close relationship between anosmia and gray matter volume alterations in the emotional brain networks, albeit without determined causal relations.

Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study.

OBJECTIVE: Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis. METHODS: We built gene expression predictive models in blood B cells, CD4+ and CD8+ T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches. RESULTS: TWAS identified 171 genes for SLE (p<1.0×10-5); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association between CD83 and SLE (p<7.7×10-8). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5×10-9) around CD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect on ACAP1, and that presence of the SLE risk allele decreased ACAP1 expression. CONCLUSIONS: Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

Large-scale meta-analysis across East Asian and European populations updated genetic architecture and variant-driven biology of rheumatoid arthritis, identifying 11 novel susceptibility loci.

OBJECTIVES: Nearly 110 susceptibility loci for rheumatoid arthritis (RA) with modest effect sizes have been identified by population-based genetic association studies, suggesting a large number of undiscovered variants behind a highly polygenic genetic architecture of RA. Here, we performed the largest-ever trans-ancestral meta-analysis with the aim to identify new RA loci and to better understand RA biology underlying genetic associations. METHODS: Genome-wide RA association summary statistics in three large case-control collections consisting of 311 292 individuals of Korean, Japanese and European populations were used in an inverse-variance-weighted fixed-effects meta-analysis. Several computational analyses using public omics resources were conducted to prioritise causal variants and genes, RA variant-implicating features (tissues, pathways and transcription factors) and potentially repurposable drugs for RA treatment. RESULTS: We identified 11 new RA susceptibility loci that explained 6.9% and 1.8% of the single-nucleotide polymorphism-based heritability in East Asians and Europeans, respectively, and confirmed 71 known non-human leukocyte antigens (HLA) susceptibility loci, identifying 90 independent association signals. The RA variants were preferentially located in binding sites of various transcription factors and in cell type-specific transcription-activation histone marks that simultaneously highlighted the importance of CD4+ T-cell activation and the potential role of non-immune organs in RA pathogenesis. A total of 615 plausible effector genes, based on gene-based associations, expression-associated variants and chromatin interaction, included targets of drugs approved for RA treatments and potentially repurposable drugs approved for other indications. CONCLUSION: Our findings provide useful insights regarding RA genetic aetiology and variant-driven RA pathogenesis.

Genetic variants shape rheumatoid arthritis-specific transcriptomic features in CD4+ T cells through differential DNA methylation, explaining a substantial proportion of heritability.

OBJECTIVE: CD4+ T cells have been suggested as the most disease-relevant cell type in rheumatoid arthritis (RA) in which RA-risk non-coding variants exhibit allele-specific effects on regulation of RA-driving genes. This study aimed to understand RA-specific signatures in CD4+ T cells using multi-omics data, interpreting inter-omics relationships in shaping the RA transcriptomic landscape. METHODS: We profiled genome-wide variants, gene expression and DNA methylation in CD4+ T cells from 82 patients with RA and 40 healthy controls using high-throughput technologies. We investigated differentially expressed genes (DEGs) and differential methylated regions (DMRs) in RA and localised quantitative trait loci (QTLs) for expression and methylation. We then integrated these based on individual-level correlations to inspect DEG-regulating sources and investigated the potential regulatory roles of RA-risk variants by a partitioned-heritability enrichment analysis with RA genome-wide association summary statistics. RESULTS: A large number of RA-specific DEGs were identified (n=2575), highlighting T cell differentiation and activation pathways. RA-specific DMRs, preferentially located in T cell regulatory regions, were correlated with the expression levels of 548 DEGs mostly in the same topologically associating domains. In addition, expressional variances in 771 and 83 DEGs were partially explained by expression QTLs for DEGs and methylation QTLs (meQTLs) for DEG-correlated DMRs, respectively. A large number of RA variants were moderately to strongly correlated with meQTLs. DEG-correlated DMRs, enriched with meQTLs, had strongly enriched heritability of RA. CONCLUSION: Our findings revealed that the methylomic changes, driven by RA heritability-explaining variants, shape the differential expression of a substantial fraction of DEGs in CD4+ T cells in patients with RA, reinforcing the importance of a multidimensional approach in disease-relevant tissues.

Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations. METHODS: We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations. RESULTS: We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10-8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=-0.242) and non-albumin protein (rg=0.238). CONCLUSION: This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

Late Mortality Prediction of Neutrophil-to-Lymphocyte and Platelet Ratio in Patients With Trauma Who Underwent Emergency Surgery: A Retrospective Study.

BACKGROUND: We aimed to evaluate the usefulness of neutrophil-to-lymphocyte (N/L) and neutrophil-to-lymphocyte platelet (N/LP) ratios in predicting late mortality of patients with trauma who underwent emergency surgery. MATERIALS AND METHODS: We retrospectively evaluated patients with trauma older than 19 y who underwent emergency surgery at our level I trauma center. Blood count-based ratios (N/L and N/LP at days 1, 3, and 7 of hospitalization) and trauma scores were analyzed. Statistical analysis was performed using univariable logistic regression and receiver operating curves. RESULTS: A total of 209 patients were evaluated. N/LP at day 7, N/L at day 7, Trauma Injury Severity Score, Revised Trauma Score, and Injury Severity Score were significantly associated with late mortality. Area under the receiver operating characteristic curves for predicting mortality was highest for N/LP at day 7 (0.867 [95% confidence interval 0.798-0.936], P < 0.001). The group with N/LP greater than the cutoff value (9.3, sensitivity 77.3%, specificity 83.1%) at day 7 showed higher mortality than the group with N/LP less than the cutoff value (35.4% versus 3.2%, P < 0.001, respectively) at day 7. CONCLUSIONS: N/LP at day 7 may be a superior predictor of late mortality compared with preexisting trauma scores in patients with major trauma undergoing emergency surgery, by better reflecting the systemic inflammation status.

Hippocampal cerebral blood flow increased following low-pressure hyperbaric oxygenation in firefighters with mild traumatic brain injury and emotional distress.

BACKGROUND: Recent evidence suggests that hyperbaric oxygenation (HBO), which has been used as an effective treatment for certain types of tissue injury, may change neural activities in the human brain and subsequently improve symptoms of psychiatric disorders. To scrutinize the neural mechanism of HBO in the human brain, we investigated whether 20 sessions of HBO changed regional cerebral blood flow (rCBF) of the limbic system in firefighters with mild traumatic brain injury (mTBI) and subjective emotional distress. METHODS: Twenty firefighters with mTBI and mild emotional distress were treated with HBO at a relatively low pressure of 1.3 atmospheres absolute for 45 min a day for 20 consecutive days (the mild emotional distress group). The rCBF of the limbic system was measured using an arterial spin labeling perfusion magnetic resonance imaging before and after the HBO. Analyses were performed on the data from fourteen individuals who completed the study and 14 age- and sex-matched healthy firefighters (the comparison group). RESULTS: Firefighters in the mild emotional distress group showed increase rCBF following HBO in a cluster encompassing the right hippocampal and parahippocampal regions (peak t = 4.31; cluster size = 248 mm3)(post-hoc analysis, z = 5.92, p < 0.001) that had lower rCBF relative to the comparison group at baseline (post-hoc analysis, t = -2.20, p = 0.04). CONCLUSION: The current study demonstrated that low-pressure HBO might increase rCBF of the hippocampal and parahippocampal regions, suggesting a potential underpinning mechanism of HBO in the human brain.

Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis.

OBJECTIVE: Genome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. As a continuous effort, we conducted GWAS in a large Korean RA case-control population. METHODS: We newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations. RESULTS: We identified six new RA-risk loci (SLAMF6, CXCL13, SWAP70, NFKBIA, ZFP36L1 and LINC00158) with pmeta<5×10-8 and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases. CONCLUSION: This study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.

Altered functional connectivity in the fear network of firefighters with repeated traumatic stress.

BACKGROUND: Firefighters are routinely exposed to various traumatic events and often experience a range of trauma-related symptoms. Although these repeated traumatic exposures rarely progress to the development of post-traumatic stress disorder, firefighters are still considered to be a vulnerable population with regard to trauma.AimsTo investigate how the human brain responds to or compensates for the repeated experience of traumatic stress. METHOD: We included 98 healthy firefighters with repeated traumatic experiences but without any diagnosis of mental illness and 98 non-firefighter healthy individuals without any history of trauma. Functional connectivity within the fear circuitry, which consists of the dorsal anterior cingulate cortex, insula, amygdala, hippocampus and ventromedial prefrontal cortex (vmPFC), was examined using resting-state functional magnetic resonance imaging. Trauma-related symptoms were evaluated using the Impact of Event Scale - Revised. RESULTS: The firefighter group had greater functional connectivity between the insula and several regions of the fear circuitry including the bilateral amygdalae, bilateral hippocampi and vmPFC as compared with healthy individuals. In the firefighter group, stronger insula-amygdala connectivity was associated with greater severity of trauma-related symptoms (ß = 0.36, P = 0.005), whereas higher insula-vmPFC connectivity was related to milder symptoms in response to repeated trauma (ß = -0.28, P = 0.01). CONCLUSIONS: The current findings suggest an active involvement of insular functional connectivity in response to repeated traumatic stress. Functional connectivity of the insula in relation to the amygdala and vmPFC may be potential pathways that underlie the risk for and resilience to repeated traumatic stress, respectively.Declaration of interestNone.

Brain Age Prediction Using Multi-Hop Graph Attention Combined with Convolutional Neural Network.

Convolutional neural networks (CNNs) have been used widely to predict biological brain age based on brain magnetic resonance (MR) images. However, CNNs focus mainly on spatially local features and their aggregates and barely on the connective information between distant regions. To overcome this issue, we propose a novel multi-hop graph attention (MGA) module that exploits both the local and global connections of image features when combined with CNNs. After insertion between convolutional layers, MGA first converts the convolution-derived feature map into graph-structured data by using patch embedding and embedding-distance-based scoring. Multi-hop connections between the graph nodes are modeled by using the Markov chain process. After performing multi-hop graph attention, MGA re-converts the graph into an updated feature map and transfers it to the next convolutional layer. We combined the MGA module with sSE (spatial squeeze and excitation)-ResNet18 for our final prediction model (MGA-sSE-ResNet18) and performed various hyperparameter evaluations to identify the optimal parameter combinations. With 2788 three-dimensional T1-weighted MR images of healthy subjects, we verified the effectiveness of MGA-sSE-ResNet18 with comparisons to four established, general-purpose CNNs and two representative brain age prediction models. The proposed model yielded an optimal performance with a mean absolute error of 2.822 years and Pearson's correlation coefficient (PCC) of 0.968, demonstrating the potential of the MGA module to improve the accuracy of brain age prediction.

Alterations in Brain Morphometric Networks and Their Relationship with Memory Dysfunction in Patients with Type 2 Diabetes Mellitus.

Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years' duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups' gray matter volumes were compared, and distinctions in memory performance were assessed. In the T2DM group, the relationship between changes in gray matter volume within these networks and declines in memory performance was examined. Among the identified morphometric networks, the T2DM group exhibited reduced gray matter volumes in both the precuneus (Bonferroni-corrected p=0.003) and insular-opercular (Bonferroni-corrected p=0.024) networks relative to the control group. Patients with T2DM demonstrated significantly lower memory performance than the control group (p=0.001). In the T2DM group, reductions in gray matter volume in both the precuneus (r=0.316, p=0.001) and insular-opercular (r=0.199, p=0.047) networks were correlated with diminished memory performance. Our findings indicate that structural alterations in the precuneus and insular-opercular networks, along with memory dysfunction, can manifest within the first 5 years following a diagnosis of T2DM.

Changes in Structural Covariance among Olfactory-related Brain Regions in Anosmia Patients.

Anosmia, characterized by the loss of smell, is associated not only with dysfunction in the peripheral olfactory system but also with changes in several brain regions involved in olfactory processing. Specifically, the orbitofrontal cortex is recognized for its pivotal role in integrating olfactory information, engaging in bidirectional communication with the primary olfactory regions, including the olfactory cortex, amygdala, and entorhinal cortex. However, little is known about alterations in structural connections among these brain regions in patients with anosmia. In this study, high-resolution T1-weighted images were obtained from participants. Utilizing the volumes of key brain regions implicated in olfactory function, we employed a structural covariance approach to investigate brain reorganization patterns in patients with anosmia (n=22) compared to healthy individuals (n=30). Our structural covariance analysis demonstrated diminished connectivity between the amygdala and entorhinal cortex, components of the primary olfactory network, in patients with anosmia compared to healthy individuals (z=-2.22, FDR-corrected p=0.039). Conversely, connectivity between the orbitofrontal cortex-a major region in the extended olfactory network-and amygdala was found to be enhanced in the anosmia group compared to healthy individuals (z=2.32, FDR-corrected p=0.039). However, the structural connections between the orbitofrontal cortex and entorhinal cortex did not differ significantly between the groups (z=0.04, FDR-corrected p=0.968). These findings suggest a potential structural reorganization, particularly of higher-order cortical regions, possibly as a compensatory effort to interpret the limited olfactory information available in individuals with olfactory loss.

Impact of sleep disturbance in shift workers on hippocampal volume and psychomotor speed.

STUDY OBJECTIVES: Shift work interferes with circadian rhythms, affecting sleep quality and cognitive function. Poor sleep quality in shift workers can impair psychomotor performance due to fatigue and sleepiness, increasing the risk of errors, accidents, and reduced productivity. Given the potential for atrophic changes in the hippocampus due to sleep disturbances, our study investigates how poor sleep quality correlates with hippocampal structural alterations and impacts psychomotor performance among shift workers. METHODS: We recruited 100 shift workers, classifying them based on sleep quality into two groups: good sleep-SW group (n = 59) and poor sleep-SW group (n = 41). Sleep quality was assessed using both 7-day actigraphy for sleep efficiency and the Pittsburgh Sleep Quality Index. A control group of 106 non-shift workers without sleep problems (non-SW group) was also included for comparison. The outcome measures were psychomotor speed and hippocampal volumes, both total and by subfield. RESULTS: The poor sleep-SW group showed significantly smaller hippocampal volumes than both the good sleep-SW group (P<0.001) and the non-SW group (P=0.003). Longer shift work years correlated with greater reductions in hippocampal volume in this group (r=-0.42, P=0.009), unlike in the good sleep-SW group (r=0.08, P=0.541). Furthermore, they demonstrated declines in psychomotor speed relative to the non-SW group (P=0.006), which correlated with smaller hippocampal volumes (r=0.37, P=0.020). CONCLUSIONS: Shift workers with poor sleep quality exhibit significant hippocampal volume reductions and psychomotor speed decline, underscoring the importance of early intervention and support for sleep issues in this population.

Combing Genome-Wide Association Studies and Single-Cell Analysis to Elucidate the Mechanisms of Kidney Disease: Proceedings of the Henry Shavelle Professorship.

Background: Kidney diseases pose a significant global health burden; there is an urgent need to deepen our understanding of their underlying mechanisms. Summary: This review focuses on new innovative approaches that merge genome-wide association studies (GWAS) and single-cell omics (including transcriptomics) in kidney disease research. We begin by detailing how GWAS has identified numerous genetic risk factors, offering valuable insight into disease susceptibility. Then, we explore the application of scRNA-seq, highlighting its ability to unravel how genetic variants influence cellular phenotypes. Through a synthesis of recent studies, we illuminate the synergy between these two powerful methodologies, demonstrating their potential in elucidating the complex etiology of kidney diseases. Moreover, we discuss how this integrative approach could pave the way for precise diagnostics and personalized treatments. Key Message: This review underscores the transformative potential of combining GWAS and scRNA-seq in the journey toward a deeper understanding of kidney diseases.

Cerebral cortical thinning in brain regions involved in emotional regulation relates to persistent symptoms in subjects with posttraumatic stress disorder.

A considerable proportion of individuals exposed to trauma experience chronic and persistent posttraumatic stress disorder (PTSD). However, the specific brain and clinical features that render trauma-exposed individuals more susceptible to enduring symptoms remain elusive. This study investigated 112 trauma-exposed participants who had been diagnosed with PTSD and 112 demographically-matched healthy controls. Trauma-exposed participants were classified into those with current PTSD (persistent PTSD, n = 78) and those without (remitted PTSD, n = 34). Cortical thickness analysis was performed to discern group-specific brain structural characteristics. Coping strategies and resilience levels, assessed as clinical attributes, were compared across the groups. The persistent PTSD group displayed cortical thinning in the superior frontal cortex (SFC), insula, superior temporal cortex, dorsolateral prefrontal cortex, superior parietal cortex, and precuneus, relative to the remitted PTSD and control groups. Cortical thinning in the SFC was associated with increased utilization of maladaptive coping strategies, while diminished thickness in the insula correlated with lower resilience levels among trauma-exposed individuals. These findings imply that cortical thinning in brain regions related to coping strategy and resilience plays a vital role in the persistence of PTSD symptoms.

Disturbed insular functional connectivity and its clinical implication in patients with complex regional pain syndrome.

BACKGROUND: Complex regional pain syndrome (CRPS) is characterized by continued amplification of pain intensity. Given the pivotal roles of the insula in the perception and interpretation of pain, we examined insular functional connectivity and its associations with clinical characteristics in patients with CRPS. METHODS: Twenty-one patients with CRPS and 49 healthy controls underwent resting-state functional magnetic resonance imaging. The seed-to-seed functional connectivity analysis was performed for the bilateral insulae and cognitive control regions including the dorsal anterior cingulate cortex (dACC) and bilateral dorsolateral prefrontal cortex (DLPFC) between the two groups. Correlations between altered functional connectivity and clinical characteristics were assessed in CRPS patients. RESULTS: CRPS patients exhibited lower functional connectivity within the bilateral anterior insulae, between the insular and cognitive control regions (the bilateral anterior/posterior insulae-dACC; the right posterior insula-left DLPFC), as compared with healthy controls at false discovery rate-corrected p < 0.05. In CRPS patients, pain severity was associated negatively with the left-right anterior insular functional connectivity (r = -0.49, p = 0.03), yet positively with the left anterior insula-dACC functional connectivity (r = 0.51, p = 0.02). CONCLUSIONS: CRPS patients showed lower functional connectivity both within the bilateral anterior insulae and between the insular and cognitive control regions. The current findings may suggest pivotal roles of the insula in dysfunctional pain processing of CRPS patients.

Aberrant Resting-state Functional Connectivity in Complex Regional Pain Syndrome: A Network-based Statistics Analysis.

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder. Pain catastrophizing, characterized by magnification, rumination, and helplessness, increases perceived pain intensity and mental distress in CRPS patients. As functional connectivity patterns in CRPS remain largely unknown, we aimed to investigate functional connectivity alterations in CRPS patients and their association with pain catastrophizing using a whole-brain analysis approach. Twenty-one patients with CRPS and 49 healthy controls were included in the study for clinical assessment and resting-state functional magnetic resonance imaging. Between-group differences in whole-brain functional connectivity were examined through a Network-based Statistics analysis. Associations between altered functional connectivity and the extent of pain catastrophizing were also assessed in CRPS patients. Relative to healthy controls, CRPS patients showed higher levels of functional connectivity in the bilateral somatosensory subnetworks (components 1~2), but lower functional connectivity within the prefronto-posterior cingulate (component 3), prefrontal (component 4), prefronto-parietal (component 5), and thalamo-anterior cingulate (component 6) subnetworks (p<0.05, family-wise error corrected). Higher levels of functional connectivity in components 1~2 (ß=0.45, p=0.04) and lower levels of functional connectivity in components 3~6 (ß=-0.49, p=0.047) were significantly correlated with higher levels of pain catastrophizing in CRPS patients. Higher functional connectivity in the somatosensory subnetworks implicating exaggerated pain perception and lower functional connectivity in the prefronto-parieto-cingulo-thalamic subnetworks indicating impaired cognitive-affective pain processing may underlie pain catastrophizing in CRPS.