The purpose of this study was to assess the impact of Stargardt disease (STGD) on activities of daily living and mental health, correlating patient-reported outcome (PRO) measures from the Michigan Retinal Degeneration (MRDQ) and Vision-Related Anxiety Questionnaires (MVAQs) with clinical data.

Patients with STGD with biallelic pathogenic ABCA4 mutations were recruited from the University of North Carolina (UNC) at Chapel Hill and Foundation Fighting Blindness (FFB) databases. Participants completed MRDQ and MVAQ testing. Best-corrected visual acuity (BCVA), electroretinogram (ERG), and fundus autofluorescence (FAF) were retrospectively analyzed for UNC patients.

Fifty participants (mean age = 48.8 ± 18.5) were included. Median θ for MRDQ: central vision (0.138), color vision (0.143), contrast sensitivity (0.122), and photosensitivity (0.185). Median MVAQ θ scores for cone- and rod-related anxiety were 0.005 and -0.055, respectively. The following additional analyses were performed using the UNC subset of participants (n = 12): BCVA correlated with contrast sensitivity (P = 0.027). Rod ERG response correlated with scotopic vision (P = 0.044). Central FAF lesion extent correlated with central vision (P = 0.039) and contrast sensitivity (P = 0.032). Rod-related anxiety correlated with rod ERG response (P = 0.048), color vision (P < 0.001), contrast sensitivity (P < 0.001), photopic peripheral vision (P < 0.001), cone-related anxiety (P < 0.001), photosensitivity (P = 0.014), mesopic peripheral vision (P < 0.001), and scotopic vision (P < 0.001). Cone-related anxiety correlated with color vision (P = 0.026), contrast sensitivity (P = 0.013), photopic peripheral vision (P < 0.001), mesopic peripheral vision (P < 0.001), and scotopic vision (P < 0.001).

In patients with STGD, structural and functional measures correlated with reduced functional vision and increased vision-related anxiety per PRO criteria. These findings provide insight into patient-perceived disease burden and may help inform future STGD interventions.

Perinatal depression is common in sub-Saharan Africa, yet treatment gaps are substantial. Cognitive behavioral therapy (CBT) is effective but relies on written materials.

To evaluate the efficacy of a culturally adapted CBT intervention delivered by lay counselors to women with perinatal depression in rural Sierra Leone.

This study was an individually randomized, outcomes assessor- and investigator-blinded, clinical trial of an adapted CBT intervention vs enhanced usual care. The trial was conducted in 6 government-run antenatal clinics in Pujehun District, Sierra Leone, which has limited infrastructure, low literacy, high maternal undernutrition, and no perinatal mental health services. Participants were drawn from a concurrent antenatal nutritional supplementation trial between November 2023 and April 2025. Eligible participants were pregnant and postpartum women who were undernourished and had depression (scoring ≥9 on the adapted Patient Health Questionnaire-9 [aPHQ-9]).

Participants were randomized 1:1 to receive 6 weekly sessions of CBT adapted for delivery without written materials or only enhanced usual care. All participants received enhanced usual care, which consisted of antenatal nutritional supplementation, monthly malaria chemoprophylaxis, and 2 doses of azithromycin.

The primary outcome was aPHQ-9 score at 8 weeks. Secondary outcomes included clinically meaningful symptom reduction (decrease of >3 points) and remission (aPHQ-9 score <5).

Among 881 women screened, 155 (median [IQR] age, 19 [18 to 22] years) were randomized to CBT (80 women) or control (75 women) groups. Postintervention data were available for 140 of 153 eligible participants (91.5%). Median aPHQ-9 scores at postintervention were lower in the CBT group than the control group (median difference, -4; 95% CI, -5 to -3; P < .001). Clinically meaningful symptom reductions were more common with CBT vs control (72 participants [96.0%] vs 36 participants [55.4%]; odds ratio, 19.33; 95% CI, 6.33 to 84.59; P < .001), and 59 CBT participants (78.6%) achieved remission compared with 22 participants (33.8%) in the control group (odds ratio, 7.21; 95% CI, 3.39 to 15.33; P < .001). Attenuated effects persisted through 9 months after pregnancy (median difference in aPHQ9 for intervention vs control, -1; 95% CI, -2 to 0; P = .02).

In this study, a culturally adapted CBT intervention delivered by lay counselors reduced depressive symptoms approximately 8 weeks after enrollment compared with enhanced usual care. These findings suggest that CBT adapted for low-literacy settings may offer a scalable model for treatment where mental health professionals are scarce.

ClinicalTrials.gov Identifier: NCT05949190.

Blood-based neural biomarkers linked to aging may provide insights into the biological end point of the human lifespan. However, the key biomarker associated with cognition and mortality in centenarians remains unclear.

To investigate the associations between 3 neural biomarkers-amyloid-β42 and amyloid-β40 ratio (Aβ42/40), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL)-and both cognitive function and all-cause mortality in centenarians.

This population-based cohort study included Japanese centenarians aged 100 years or older who were enrolled between September 2000 and January 2021. Participants underwent baseline cognitive assessments and blood sampling and were followed up for 17 years for mortality. Data analysis was performed in February 2026.

Baseline plasma levels of Aβ42/40, p-tau181, and NfL measured using ultrasensitive immunoassays.

Cognitive function at baseline, measured using the Mini-Mental State Examination (MMSE), and all-cause mortality.

Of 495 participants (398 [80.4%] women; mean [SD] age 104.1 [3.0] years), 419 completed a cognitive assessment (mean [SD] MMSE, 14.9 [6.9]). During 17 years of follow-up, 466 participants (95.5%) died. Lower Aβ42/40 (β = 0.99; 95% CI, 0.46 to 1.52) and higher NfL levels (β = -0.92; 95% CI, -1.62 to -0.23) were significantly associated with lower MMSE scores after adjusting for confounders. Higher NfL levels were also associated with increased mortality (hazard ratio, 1.36; 95% CI, 1.17 to 1.57), showing the greatest point estimate among the biomarkers, all of which were standardized and statistically significant (change in Akaike Information Criterion, likelihood ratio test, χ2 = 30.16; P < .001). Aβ42/40 and p-tau181 were not statistically significant after full adjustment.

In this cohort study of centenarians, higher plasma NfL levels were associated with lower cognitive function and increased all-cause mortality, whereas Aβ42/40 and p-tau181 showed no associations. These findings suggest that plasma NfL was associated with neurodegeneration in extreme aging. Further studies are needed to confirm its clinical utility before routine implementation.

Circadian rest-activity rhythms (RARs) are increasingly viewed as aging-relevant behavioral phenotypes, but links to DNA methylation-based epigenetic age acceleration (EAA) are not well defined.

To evaluate associations between multidimensional actigraphy-derived 24-hour RAR metrics (strength and robustness, regularity and fragmentation, and timing) and EAA across 4 epigenetic clocks.

This cross-sectional study used data from the Baltimore Epidemiologic Catchment Area Study, wave 5 (2017-2022). The cohort included community-dwelling adults in eastern Baltimore, Maryland, with 7-day wrist actigraphy and blood DNA methylation data. Analyses were conducted from January to December 2025.

Seven-day wrist actigraphy-derived parametric and nonparametric RAR metrics, including rhythm strength and robustness (amplitude, mesor, relative amplitude, and mean activity during the least active continuous 5-hour period [L5] and most active continuous 10-hour period [M10]), regularity and fragmentation (interdaily stability [IS] and intradaily variability [IV]), timing (acrophase, L5 and M10 start times, and rest and sleep midpoints), and day-to-day timing variability (rest midpoint variability [RMV] and sleep midpoint variability [SMV]).

Associations between EAA for 4 clocks (Horvath, Hannum, PhenoAge, and GrimAge) and each RAR metric, evaluated using linear regression models.

A total of 207 participants were included (mean [SD] age, 68.42 [7.48] years; 135 [65.2%] female). In fully adjusted models, each 1-SD increase in amplitude, relative amplitude, and IS was associated with lower GrimAge acceleration (amplitude: β, -0.67 [95% CI, -1.24 to -0.09]; P = .02; relative amplitude: β, -0.77 [95% CI, -1.31 to -0.23]; P = .005; IS: β, -0.65 [95% CI, -1.20 to -0.09]; P = .02). Each 1-SD increase in amplitude and IS was also associated with lower PhenoAge acceleration (amplitude: β, -1.20 [95% CI, -2.26 to -0.15]; P = .03; IS: -1.35 [95% CI, -2.36 to -0.34]; P = .009). Higher L5 activity and IV were associated with higher GrimAge acceleration (L5: β, 0.60 [95% CI, 0.06-1.13]; P = .03; IV: β, 0.72 [95% CI, 0.17-1.28]; P = .01). There were nonsignificant but directionally consistent outcomes for the Horvath and Hannum clocks. RAR-EAA effect sizes were generally larger in women than in men (amplitude, mesor, M10, RMV, and SMV; P < .05 for interaction) and in White participants compared with those in other race and ethnicity categories (mesor, IV, and M10; P < .05 for interaction); associations for rhythm-timing metrics varied with age; and Shapley additive explanations analyses identified IS, RMV, and amplitude as 3 of the most influential RAR factors in epigenetic age acceleration.

In this exploratory cross-sectional study, higher strength and stability of circadian RARs were associated with lower acceleration of epigenetic age (particularly GrimAge and PhenoAge), whereas greater irregularity and more variable activity timing were associated with greater acceleration, supporting the interpretation of RARs as markers of biological aging.

In multiple sclerosis (MS), symbol digit modalities test (SDMT) scores are often influenced by practice effects. We evaluated the SDMT practice effect as a proxy of cognitive performance by relating it to disease severity and future performance.

People with MS (pwMS) and healthy controls (HCs) were evaluated at baseline and five-year follow-up. Practice effects were modeled using two-part piecewise linear regression on daily smartphone SDMT (sSDMT) scores. Cognitive impairment (CI) and preservation (CP) were defined relative to HC baseline sSDMT z-scores (CI: z < -1.67, CP: z ≥ -1.67). Practice outcomes across HC/CP/CI were compared using ANCOVA and correlated to baseline variables. They were also assessed in relation to clinical outcomes and brain volumes in cross-sectional and baseline-follow-up models.

85 pwMS (CP/CI: 66/19) and 20 HCs were analyzed. 73 pwMS completed follow-up (5.39 ± 0.38y). A practice plateau occurred in 80%/82%/100% of HC/CI/CP. Higher baseline sSDMT was related to higher plateau sSDMT (ρ = 0.930, p < 0.001) and lower %-increase (ρ = -0.266, p = 0.013). %-increase was higher in CI than CP (CI/CP = 22.0%/15.5 adj.p = 0.004), but the absolute ∆-increase and breakpoint were similar across groups. Associations of disability, cognition, and brain volumes with the plateau sSDMT were stronger when compared to the baseline sSDMT. No other associations were found cross-sectionally and in the baseline-follow-up models.

Early-phase sSDMT practice effects were related to cognitive performance but were unique to disease status or associated with disease severity in pwMS. Plateau sSDMT showed stronger associations with disability and brain volumes than baseline performance. Interpretation of SDMT performance should therefore consider practice effects.

Partner support is both an important protective and risk factor for women's mental health perinatally. Although there is likely a bidirectional relationship between support and mental health, a research gap exists in understanding changes in women's experience of partner support over pregnancy and early childhood, and whether this differs for women with Major Depressive Disorder (MDD). This study examines whether women diagnosed with MDD antenatally are at increased risk of deteriorating partner support over the perinatal period, after accounting for demographic effects, ongoing depressive symptoms, stressful life events, and attachment orientation.

731 women recruited into a longitudinal pregnancy cohort study, the Mercy Pregnancy Emotional Wellbeing Study, were included, of whom 124 were diagnosed with MDD first trimester using the Structured Clinical Interview for the DSM (SCID). Perceived partner support was measured with the Social Support Effectiveness Questionnaire (SSEQ) in third trimester, 6 and 12 months, and 4 years postpartum. Partner support changes over time were analysed with mixed effects modelling.

There was an overall small but significant decline in partner support over time for all women. However, this decline was larger for women with MDD between 12 months and 4 years postpartum. Ongoing depressive symptoms, stressful life events, and insecure attachment orientation contributed to perceptions of lower partner support.

The perinatal and early childhood period poses an increased risk for the partner relationship for all women, but this risk is increased for women with MDD. This knowledge could be translated into identifying vulnerable women and offering appropriate interventions.

This scoping review synthesizes empirical research on how autistic family members shape family dynamics across relational subsystems, cultural contexts, and developmental stages. A comprehensive search conducted in January 2025 across five databases using the SPIDER framework yielded 102 studies analysed through convergent integrated three-stage thematic analysis informed by family systems theory. Five interconnected themes emerged: family identity reconstruction and role adaptation; emotional climate and communication patterns; cultural, societal, and structural contexts; pathways to resilience and positive adaptation; and developmental trajectories across the lifespan. These themes were integrated into an interpretive conceptual model in which communication emerged as a cross-cutting relational process, family adaptation unfolded across developmental time, and contextual conditions shaped which adaptive pathways were more or less available. Across studies, adaptive flexibility was a recurring feature of more positively adapting families, and caregiver mental health, especially maternal mental health in a mother-dominated evidence base, appeared closely linked to family emotional climate. A dedicated analysis reinterprets findings through a neurodiversity-informed lens, proposing foundational shifts toward investigating family adaptation with rather than to autism. Critically, autistic perspectives remain largely absent: of the 102 included studies, only five included autistic self-report as a primary data source. Future research must centre autistic voices, employ integrated longitudinal designs, and address structural barriers supporting equitable family systems.

This study examined behavioral, clinical, and hematologic factors associated with HIV-associated neurocognitive disorder (HAND) among people with HIV (PWH) using the International HIV Dementia Scale (IHDS) within a randomized clinical trial. This secondary analysis used data from the Hospital Visit as Opportunity for Prevention and Engagement for HIV-Infected Drug Users (HOPE) study, which enrolled 801 PWH who use substances from 11 U.S. hospitals. CD4 cell count, HIV-1 viral load, Global Severity Index (GSI), Global Assessment of Functioning (GAF), and Physical and Mental Component Scores (PCS, MCS) were assessed at baseline, 6 months, and 12 months. HAND was defined as an IHDS score ≤ 10. Multivariable linear and logistic regression models were used to identify baseline correlates of IHDS score and HAND, respectively. Linear mixed models were applied to evaluate the longitudinal changes in clinical outcomes. HAND prevalence was 76.3% (84.2% for females and 72.5% for males). Multivariable linear models revealed that obesity, CD4 cell counts < 200 cells/ µL, higher hemoglobin level and hematocrit, and higher GAF scores were significantly associated with IHDS score (p < 0.05). Furthermore, logistic models showed that recent alcohol use, obesity, viral suppression (≤ 200 copies/mL), hemoglobin and hematocrit levels, and GAF scores were associated with lower odds of HAND, whereas platelet count was linked to higher odds. Longitudinal analyses demonstrated significant increases in hemoglobin, hematocrit, PCS, and MCS over time, alongside decreases in platelet count and GSI. Compared with participants without HAND, those with HAND consistently exhibited lower hemoglobin, hematocrit, GAF, and GSI scores, and higher platelet counts and MCS scores across follow-up. These findings underscore the complex interplay between hematologic and mental health, substance use, and functional status in shaping neurocognitive outcomes among PWH. Targeting modifiable hematologic, behavioral, and psychosocial factors may help reduce HAND risk and improve long-term cognitive and functional outcomes. ClinicalTrials.gov ID: NCT01612169.

Incisional hernia is a common long-term complication of abdominal surgery and is traditionally seen as a structural defect. However, recent patient-centered research suggests that abdominal wall pathology may also impose substantial psychological burden. Whether incisional hernia is associated with an increased risk of clinically diagnosed depression at the population level remains unclear.

This retrospective cohort study used data from the German Disease Analyzer database (IQVIA). Adults with a first documented diagnosis of incisional hernia (ICD-10: K43.0-K43.2) between 2005 and 2024 were identified. Individuals with recent psychiatric disorders were excluded to assess incident depression. Patients were matched 1:1 to controls without hernia using propensity scores based on age, sex, index year, consultation frequency, somatic comorbidities, and remote history of depression. The primary outcome was incident depression (ICD-10: F32, F33) within five years. Associations were analyzed using conditional Cox regression.

A total of 10,075 patients with incisional hernia were matched to 10,075 patients without hernia. During five years of follow-up, 18.4% of patients with and 16.5% without incisional hernia were diagnosed with depression. Incisional hernia was associated with a slightly increased risk of incident depression (hazard ratio 1.12; 95% confidence interval 1.04-1.20). The association was more pronounced among women and among individuals without prior depression.

Incisional hernia is associated with a slightly increased risk of clinically diagnosed depression. These findings indicate a modest statistical association between incisional hernia and subsequent depression diagnoses in routine care. While the magnitude of the association was small, awareness of potential psychosocial comorbidity may be relevant in selected clinical contexts.