Modulating intracellular signaling may extend drug effects.
Synaptic alterations are preceding the axonal loss in optic atrophy of Wolfram syndrome mouse model
BackgroundWolfram syndrome is a rare autosomal recessive disorder characterized by antibody-negative early-onset diabetes mellitus, optic atrophy, sensorineural hearing loss, arginine-vasopressin deficiency, and progressive neurodegeneration of the brainstem and cerebellum. It is caused primarily by pathogenic variants in the WFS1 gene, which encodes a transmembrane endoplasmic reticulum–resident protein involved in the unfolded protein response and cellular calcium homeostasis. Although multiple rodent models of Wolfram syndrome have been developed and shown to exhibit visual defects, some studies have reported significant vision loss prior to any detectable axonal degeneration or myelin abnormalities, and the mechanisms underlying these early visual deficits remain poorly understood.ObjectiveRecent in vitro studies have demonstrated altered synaptic contacts and aberrant neurite morphology in WFS1-deficient cerebral organoids and human iPSC-derived neurons, respectively. These findings prompted us to investigate, for the first time in vivo, whether synaptic and dendritic abnormalities occur in the retina of Wfs1 knockout mice.MethodsUsing confocal microscopy, we examined retinal and optic nerve histology in Wfs1 knockout mice at 4 and 7 months of age.ResultsOur analysis reveals progressive synaptic alterations in the inner plexiform layer, driven by early presynaptic compartment failure. These changes represent the earliest detectable phenotype associated with vision loss in this model and precede overt axonal degeneration.ConclusionThese findings identify early synaptic preservation as a promising therapeutic target for vision loss in Wolfram syndrome.
Correction: Detection of differentially expressed genes in spatial transcriptomics data by spatial analysis of spatial transcriptomics: A novel method based on spatial statistics
The triple-hit hypothesis of Alzheimer’s disease: blood–brain barrier breakdown, infection, and neuroimmune activation as a unified etiological framework
Studies of Alzheimer’s disease (AD) have long been dominated by the amyloid cascade hypothesis, although mounting evidence suggests that amyloid-β (Aβ) deposition might be a late downstream event, rather than the initiating trigger of AD. Here, I propose a unifying Triple-Hit Hypothesis in which AD develops through a sequential interaction among three causative processes that have been individually implicated before in the onset of Alzheimer’s disease: (1) early blood–brain barrier (BBB) breakdown, (2) entry or reactivation of microbial agents within the brain, and (3) maladaptive innate immune responses that produce chronic neuroinflammation and Aβ accumulation. Converging data from human imaging, neuropathology, infectious disease studies, genetics, and vascular medicine could suggest that these three processes, which were in some previous studies linked to AD, might not be independent but rather that their temporal synergy could drive disease progression. This new conceptual framework integrates long-standing but fragmented lines of evidence and, if confirmed by experimental studies, offers the possibility for the development of new diagnostic biomarkers, new therapeutic entry points, and prevention strategies for AD. I argue that understanding AD as a disorder of the blood-brain barrier, immunity, and host–pathogen interactions should be taken into account in future research on the etiology and clinical progression of AD.
Reading speed, visual deficits, and cerebral white matter integrity in veterans with and without mild traumatic brain injury
IntroductionSince 2001, approximately 17.3% of enlisted personnel have experienced a traumatic brain injury (TBI) according to the United States military. Visual deficits (e.g., convergence insufficiency or pursuit abnormalities) are reported as chronic, persistent symptoms of TBI, which can impact daily activities such as reading, computer work, and driving.MethodsIn the present study, diffusion-weighted imaging (DWI) data and behavioral and survey data related to visual function were analyzed for 63 combat veterans with and without mild TBI (mTBI). We also tested the hypothesis that white matter damage, measured as either decreased fractional anisotropy of white matter or “potholes” evident in the DWI data, would predict visual behaviors (reading speed, smooth pursuit catch-up saccades, and/or convergence insufficiency).ResultsOur key finding is that scores on the Convergence Insufficiency Symptom Survey (CISS) predicted whether the use of a color overlay would increase reading speed for participants with mTBI, but not for control participants. General linear model analyses found a relationship between smooth pursuit catch-up saccades and the cumulative number of white matter “potholes” found in white matter across the cerebrum. However, the sample size was too small to conclude that these correlations were uniquely related to TBI status.DiscussionThese findings point toward the importance of additional research to determine exactly how mTBI is associated with reduced reading speed and why altering the color of the page improves performance for individuals with mTBI and convergence insufficiency.
Beyond the auditory: anxiety bridges sleep disturbances and depressive symptoms to tinnitus handicap
BackgroundTinnitus is closely associated with psychological factors including anxiety, depression, and sleep disturbances. However, how these variables interact to influence tinnitus severity remains poorly understood, warranting further exploration.MethodsThis retrospective study analyzed data from 285 patients with tinnitus, utilizing the Tinnitus Handicap Inventory (THI), Self-Rating Depression Scale (SDS), Self-Rating Scale of Sleep (SRSS), and Self-Rating Anxiety Scale (SAS) as assessment instruments. Univariate and multivariate regression analyses were performed to identify psychosocial factors associated with THI scores. Structural equation modeling (SEM) was employed to examine the mediating role of anxiety—specifically, whether sleep disturbances and depression exacerbate tinnitus handicap indirectly through heightened anxiety. Subgroup analyses were further conducted to evaluate the stability of this psychological mediation pathway across different demographic and clinical subgroups (e.g., age, gender, disease duration).ResultsTinnitus severity was significantly positively correlated with scores on the SRSS, SDS, and SAS (all P < 0.05). Multivariate regression analysis identified age, sleep quality (SRSS), and anxiety (SAS) as independent predictors of increased Tinnitus Handicap Inventory (THI) scores. Structural equation modeling further confirmed that SAS partially mediated the relationship between SRSS and THI (mediation effect: 31.7%) and fully mediated the relationship between SDS and THI. Subgroup analyses revealed that the mediating effect of anxiety was more pronounced in middle-aged and elderly individuals, females, and patients with left-sided tinnitus.ConclusionAnxiety serves as a central mediating mechanism linking sleep disturbances and depressive symptoms to tinnitus severity. The present findings demonstrate that anxiety not only directly exacerbates tinnitus-related handicap but also mediates the influence of sleep and mood disturbances on tinnitus distress. These findings underscore the critical role of anxiety in personalized tinnitus treatment.
Does the phubbing scale measure the same construct across sexes? Evidence from a Nigerian sample
IntroductionPhubbing is associated with excessive use of digital technologies, and the Phubbing Scale (PS) is widely used to measure it. The PS may be influenced by cultural variations, so it is advisable to validate it before applying it in a new cultural context. Phubbing has emerged as a construct of interest in Nigeria, yet no validation studies for the PS have been conducted in this population.MethodsTo address this gap, the PS, along with scales measuring technological addictions and digital life balance, was administered to 396 Nigerian university students (18 to 25 years old; 80.6% female). Confirmatory Factor Analysis was used to test two 10-item models and one 8-item model. The best-fitting model was subsequently tested. Internal and external validity, and measurement invariance across sexes were assessed.ResultsThe 8-item correlated two-factor model (PS-8) showed the best results. For PS-8, internal and external validity, and strict measurement invariance across sexes were supported based on global fit indices. However, parameter estimates suggested potential sex-related differences in the construct. In females, factor loadings and the correlation between factors were adequate, whereas in males several items of Factor 2 showed low loadings, and the correlation between factors was negligible.ConclusionIn conclusion, the PS-8 appears suitable for measuring phubbing in this population, although potential sex-related differences should be considered. These differences may stem from psychometric limitations in the Smartphone Obsession factor items and/or from variations in how the PS construct manifests across sexes, which could affect interventions or comparative studies. Considering the limitations of the study, future research will be necessary to corroborate these findings.
Association between neurodegenerative plasma biomarkers and geriatric depression in older adults with and without clinical dementia in Kinshasa, Democratic Republic of the Congo
IntroductionPrevious Western studies have shown an association between neurodegenerative plasma biomarkers and geriatric depression. However, few studies have examined this relationship in sub-Saharan African countries. This article examines this association in older adults with or without clinical dementia in Kinshasa, Democratic Republic of Congo.MethodsThis cross-sectional study included eighty-one people aged 65 years and older assessed for dementia using the Community Dementia Screening Instrument (CSID) and the Alzheimer’s Disease Questionnaire. Depression and cognitive impairment were assessed using the Geriatric Depression Scale and the African Neuropsychological Battery (ANB), respectively. Plasma biomarkers measured included β-amyloid (Aβ) 40/42, phosphorylated tau 181 (p-tau), neurofilament light chain (NfL), glial fibrillar acid protein (GFAP), interleukins (IL-1β, IL-10), and tumor necrosis factor-α (TNF-α). Logistic regression models were used to estimate the likelihood that these biomarkers are associated with depression, adjusting for sex, age, and education level.ResultsThe mean age of the participants was 72.9 years. Of those suspected of suffering from Alzheimer’s disease (AD), 80% had geriatric depression. High blood pressure was common in participants with suspected AD (60%). People with dementia had significantly lower cognitive scores on all ANB tests than those without dementia. GFAP and NfL were significantly associated with higher odds of geriatric depression, with odds ratios of 1.98 (1.17–3.67; p = 0.02) and 1.76 (1.06–3.20; p = 0.04), respectively. Other biomarkers were not associated with depression.ConclusionThis study suggests a potential role of nonspecific biomarkers of AD, neurodegeneration, and astrocytic glial activation in geriatric depression in older adults in sub-Saharan Africa.
Unseen intimate partner violence: regional differences in controlling behaviours
IntroductionControlling behaviour is considered a form of emotional abuse and restricts an individual’s autonomy. This study aims to determine the factors associated with women’s exposure to controlling behaviour by their spouse/partner in the last year, as of the time the survey was conducted, by place of residence in Türkiye.MethodsThis study utilised microdata obtained from the National Research on Domestic Violence against Women in Türkiye. Binary logistic regression analysis was employed to determine the factors associated with women’s exposure to controlling behaviour by their spouse/partner.ResultsThe results of the study showed that age, educational level, the woman’s greater contribution to household income, suicidal thoughts, previous pregnancies, the educational level of the spouse/partner, whether or not the man beating his wife is considered acceptable, the educational level of the spouse/partner, fear of the spouse/partner, the spouse/partner fighting with the man in a way that involves physical violence, the spouse/partner experiencing physical violence from their own family, exposure to other types of violence by the spouse/partner, knowledge of preventive measures against violence, and household size were found to be associated with exposure to controlling behaviour.DiscussionThe study found that the significance and effect of variables related to exposure to controlling behaviour also differed by women’s place of residence. According to the study, appropriate strategies to reduce controlling behaviour should be developed, taking into account public health programmes to raise awareness of controlling behaviour towards women, based on their place of residence, and considering the determinants that influence exposure to controlling behaviour.
Remote EMDR versus CBT for PTSD after the Kahramanmaraş earthquakes: a randomized trial
BackgroundLarge-scale earthquakes are associated with high and persistent rates of post-traumatic stress disorder (PTSD), depression, and anxiety. Although Eye Movement Desensitization and Reprocessing (EMDR) and Cognitive Behavioral Therapy (CBT) are both guideline-recommended treatments for PTSD, direct randomized comparisons—particularly in post-disaster settings and via remote delivery—remain limited.MethodsIn this randomized, controlled, parallel-group trial (ClinicalTrials.gov Identifier: NCT06758362), 89 adult survivors of the 2023 Kahramanmaraş earthquakes in Türkiye who met DSM-5 criteria for PTSD were assigned to 12 sessions of remotely delivered EMDR (n = 30), CBT (n = 30), or a wait-list control group (n = 29). PTSD severity was the primary outcome, with depression, anxiety, and emotion regulation as secondary outcomes. Assessments were conducted at baseline, mid-treatment, and post-treatment. Analyses followed an intention-to-treat framework using mixed-effects models.ResultsBoth EMDR and CBT produced large reductions in PTSD symptoms compared with the control condition (Cohen’s d ≈ 1.9), alongside moderate-to-large improvements in depression (d ≈ 1.4) and anxiety (d ≈ 1.3). Symptom improvement was evident by mid-treatment and increased through post-treatment. Direct comparisons between EMDR and CBT yielded overlapping confidence intervals, indicating comparable overall efficacy. However, EMDR showed a tendency toward greater reduction in core PTSD symptoms, whereas CBT demonstrated relatively stronger effects on depressive symptoms. Improvements in emotion regulation were observed in both treatment groups but did not reach statistical significance.DiscussionThe findings suggest that both EMDR and CBT are highly effective when delivered remotely in the aftermath of a large-scale natural disaster. Differential response patterns likely reflect distinct therapeutic mechanisms—direct trauma memory processing in EMDR versus cognitive restructuring and behavioral activation in CBT—highlighting their potential complementarity rather than superiority of one approach over the other. The absence of spontaneous improvement in the control group underscores the necessity of structured psychological intervention following earthquake exposure.ConclusionRemotely delivered EMDR and CBT are feasible, effective, and clinically valuable interventions for earthquake-related PTSD. Their comparable efficacy and partially distinct symptom profiles support flexible, needs-based integration of both treatments within disaster mental-health systems.Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT06758362, identifier NCT06758362.