BackgroundPost-translational modifications, particularly SUMOylation, plays a crucial role in α-synuclein (α-syn) aggregation, a key pathological feature of Parkinson’s disease (PD). Curcumin, a natural polyphenol, has shown neuroprotective potential, but its effects on SUMOylation-related signaling in PD remain unclear.ObjectiveThis study aimed to investigate whether curcumin modulates α-syn SUMOylation and to elucidate the underlying molecular mechanisms in PD model mice.MethodsA PD model was established in male C57BL/6 mice via unilateral intrastriatal injection of α-syn preformed fibrils (PFFs). Six months after α-syn PFFs injection, mice were treated intravenously with curcumin (25 mg/kg/day) or vehicle for 1 month. Behavioral tests (open field, rotarod) assessed motor function. Neuropathology was evaluated by immunohistochemistry and western blotting for tyrosine hydroxylase (TH), phosphorylated α-syn (p-syn), SUMOylation pathway components (SUMO1, SAE2, UBC9, PIAS1/2), and ubiquitin. Striatal dopamine levels were measured by HPLC.ResultsCurcumin treatment ameliorated motor deficits and anxiety-like behaviors in PD mice. It partially preserved dopaminergic neurons and reduced p-syn aggregation in the substantia nigra, accompanied by increased striatal dopamine levels. Mechanistically, curcumin was associated with reduced SUMO1 and increased ubiquitin levels, suggesting modulation of SUMOylation-related signaling. Among SUMOylation enzymes, UBC9 expression was decreased, whereas E1 (SAE2) and E3 (PIAS1/2) components were not substantially affected.ConclusionOur findings demonstrated that curcumin exerted neuroprotective effects in a PD model by attenuating α-syn pathology. The protective mechanism involves the inhibition of α-syn SUMOylation, primarily through the downregulation of the UBC9 enzyme. This study identifies UBC9-mediated SUMOylation as a potential target for curcumin and highlight a promising strategy for modifying α-syn-associated pathology in PD.
Subcortical gray matter atrophy and iron deposition in patients with vascular dementia: a multimodal MRI study
PurposeVascular dementia (VAD) is the second most common type of dementia worldwide. Therefore, early detection and diagnosis, along with a clear understanding of its pathogenesis are critical for mitigating disease progression. In the present study, we aimed to elucidate the associations of brain volume and iron deposition with VAD based on structural brain and iron content analyses.MethodsFifty-three patients with VAD and 43 control participants were recruited for this study. All participants underwent the Mini-Mental State Examination (MMSE) and brain MRI scans. This study primarily focused on the volume of specific brain regions (assessed using FreeSurfer) and iron deposition (evaluated using quantitative susceptibility mapping [QSM]). Linear regression analysis was also performed.ResultsPatients with VAD exhibited significant reductions in brain volume in the left putamen (β = −0.342, 95% CI: −0.581 to −0.104), left pallidum (β = −0.099, 95% CI: −0.187 to −0.001), left hippocampus (β = −0.138, 95% CI: −0.271 to −0.004), and right hippocampus (β = −0.235, 95% CI: −0.420 to −0.051). Additionally, significant increases in iron levels were identified in the left (β = 0.006, 95% CI: 0.002 to 0.010) and right (β = 0.005, 95% CI: 0.001 to 0.009) hippocampus.ConclusionsThese findings indicate that brain volume reduction and increased iron levels in specific regions may be associated with cognitive deficits in patients with VAD.
Editorial: eHealth and personalized medicine in mental health and neurodevelopmental disorders: digital innovation for diagnosis, care, and clinical management
Illness perception, family resilience, and emotional distress among hospitalized older adults with multimorbidity in Xinjiang, China: a latent profile and mediation analysis
BackgroundOlder adults with multimorbidity frequently encounter significant psychological challenges, with negative illness perception being a prevalent issue. Such perceptions can intensify emotional distress. Family resilience—the ability of a family system to adapt positively to adversity—plays a crucial role in alleviating negative emotions, including anxiety and depression. This study aimed to investigate the heterogeneity of illness perception among older patients with multimorbidity and to assess the mediating effect of family resilience on the relationship between illness perception and emotional distress.Materials and MethodsBetween October 2025 and January 2026, 420 multimorbid older patients were recruited in three tertiary hospitals of Xinjiang Province. The evaluation was done based on the Brief Illness Perception Questionnaire, the Chinese version of the Family Resilience Assessment Scale, and the Hospital Anxiety and Depression Scale. The two methods of analysis were the latent profile analysis used to determine the unique patterns of illness perception and the bootstrap-based mediation analysis to determine whether family resilience mediates.ResultsThree distinct illness perception profiles were identified: low (32.6%), moderate (47.6%), and high (19.8%) illness perceptions. Using the low illness perception group as the reference, family resilience showed a significant partial mediating effect between moderate illness perception and anxiety (indirect effect = 0.510, 95% CI: 0.325–0.724), moderate illness perception and depression (indirect effect = 0.450, 95% CI: 0.283–0.631), high illness perception and anxiety (indirect effect = 1.263, 95% CI: 0.819–1.739), and high illness perception and depression (indirect effect = 1.114, 95% CI: 0.707–1.555).DiscussionThe results demonstrated heterogeneity in the perception of illness among older multimorbid patients, as a substantial percentage of the sample had moderate-to-high levels. Family resilience played a major partial mediating role between illness perception and emotional distress. The findings suggest the significance of shifting the clinical emphasis to the family system and integrating family resilience improvement as one of the psychological support measures for chronic patients.
Remimazolam versus propofol on seizure adequacy in electroconvulsive therapy: a retrospective cohort study
ObjectiveElectroconvulsive therapy (ECT) is a core treatment modality for severe mental disorders, and the choice of anesthetic induction agent directly impacts seizure quality and therapeutic outcomes. This study aimed to compare the effects of remimazolam versus propofol on seizure adequacy during ECT.MethodsThis retrospective secondary analysis was conducted using data from a prospective observational cohort. A total of 859 ECT sessions from 114 patients were included. The primary outcome was the rate of adequate seizure, defined as an electroencephalographic (EEG) ictal duration of ≥15 seconds. Secondary outcomes included EEG seizure duration, post-ictal suppression index (PSI), maximum sustained power (MSP), and average seizure energy index (ASEI). Stabilized inverse probability of treatment weighting was employed to balance baseline covariates between groups, with balance assessed by standardized mean differences. Generalized linear mixed models were used to compare intergroup differences, accounting for random effects at the patient level. Subgroup analysis, E-value calculation, and propensity score matching (PSM) at 1:1 and 1:2 ratios were performed as sensitivity analyses to assess the robustness of the results. ResultsA total of 859 ECT sessions were included, with 179 in the remimazolam group and 680 in the propofol group. Baseline characteristics were well-balanced between groups after weighting. The remimazolam group exhibited a significantly higher rate of adequate seizures compared with the propofol group (adjusted odds ratio: 12.054, 95% confidence interval: 5.758–25.233, P < 0.001), along with prolonged EEG seizure duration and elevated MSP. No significant between-group differences were observed in PSI or ASEI. The results of all sensitivity analyses were consistent with those of the primary analysis.ConclusionRemimazolam was associated with a higher rate of EEG seizure adequacy and longer EEG seizure duration; however, whether this electrophysiological advantage translates into better clinical outcomes remains to be investigated in prospective studies.
Latest developments in the use of e-cigarettes by people with schizophrenia spectrum disorders who smoke: a scoping review
BackgroundTobacco use is significantly more prevalent among individuals with schizophrenia spectrum disorders (SSD) compared to the general population, contributing to elevated rates of premature mortality from smoking-related diseases. Despite a decline in smoking prevalence in the general population, individuals with SSD continue to smoke at persistently high rates, driven by biological, psychological, and social factors. Standard smoking cessation approaches yield markedly poorer outcomes in this group compared to non-psychiatric populations. This scoping review aimed to map the emerging evidence on the use of e-cigarettes among individuals with SSD or serious mental illness (SMI).MethodsThis scoping review was conducted in accordance with the Population–Concept–Context (PCC) framework and reported following the PRISMA extension for Scoping Reviews (PRISMA-ScR) guidelines. The review focused on studies published between January 2020 and February 2026, searched on PubMed and EMBASE, providing an up-to-date synthesis of emerging evidence on e-cigarette use in this vulnerable population.ResultsThree studies reported across four publications were included (total N = 323); one research group (Pratt et al.) contributed two separate publications reporting distinct outcomes from the same study cohort. Findings suggest that e-cigarette-based interventions are feasible and acceptable in individuals with SSD and SMI, with preliminary evidence of smoking reduction and decreased exposure to tobacco-related carcinogens. However, sustained harm reduction appeared dependent on a combined approach considering that device provision was empowered in its efficacy to sustain harm reduction over time when integrated with behavioral support.ConclusionsThe available evidence, while preliminary and limited by the small number of included studies, should be interpreted with caution regarding generalizability to patients with Schizophrenia Spectrum Disorders exclusively, as three of the four included publications recruited participants with broader SMI diagnoses of which SSD represents only a subset. Further research, including larger adequately powered trials with standardized outcome measures and longer follow-up, is needed to establish the generalizability and long-term impact of these interventions.
A Study to Assess the Efficacy and Safety of Solriamfetol in Adolescents With ADHD
Conditions: ADHD
Interventions: Drug: Solriamfetol Dose A; Drug: Solriamfetol Dose B; Drug: Placebo
Sponsors: Axsome Therapeutics, Inc.
Recruiting
Interventions: Drug: Solriamfetol Dose A; Drug: Solriamfetol Dose B; Drug: Placebo
Sponsors: Axsome Therapeutics, Inc.
Recruiting
A Study to Assess the Efficacy and Safety of Solriamfetol in Children With ADHD
Conditions: ADHD
Interventions: Drug: Solriamfetol Dose A; Drug: Solriamfetol Dose B; Drug: Placebo
Sponsors: Axsome Therapeutics, Inc.
Recruiting
Interventions: Drug: Solriamfetol Dose A; Drug: Solriamfetol Dose B; Drug: Placebo
Sponsors: Axsome Therapeutics, Inc.
Recruiting
Home Play-based Intervention for Parents and Infants
Conditions: Attention-Deficit/Hyperactivity Disorder (ADHD); Autism Spectrum Disorder; Premature Birth; Global Developmental Delay
Interventions: Behavioral: SPRINT Intervention; Other: Waitlist Protocol
Sponsors: Nanyang Technological University; Agency for Science, Technology and Research (A*STAR); KK Women’s and Children’s Hospital; Institute for Human Development and Potential (IHDP), Singapore
Not yet recruiting
Interventions: Behavioral: SPRINT Intervention; Other: Waitlist Protocol
Sponsors: Nanyang Technological University; Agency for Science, Technology and Research (A*STAR); KK Women’s and Children’s Hospital; Institute for Human Development and Potential (IHDP), Singapore
Not yet recruiting
Defining and Assessing Empathic Communication in Patient Portal Secure Messages: Adapted Coding Framework Development Study
Background: Empathic communication in the clinical setting has been associated with improved clinical outcomes, decreased anxiety, and increased patient satisfaction, treatment adherence, and trust. Despite the recent growth in patient portal use, the expression of empathic communication through patient portal secure messages is not well understood. Objective: This study aimed to construct a coding schema to define and assess empathic opportunities initiated by patients and primary care clinicians’ responses to these opportunities within a patient portal messaging environment. Methods: Data for this study included adult patient secure messages and responding messages from clinicians working in family practice clinics within a regional health care system serving central and northeast Pennsylvania between January 2018 and December 2023. We conducted a manual review of messages using the Empathic Communication Coding System as a guiding framework, which defines empathic opportunities created by patients and corresponding empathic responses by clinicians. We double-coded 500 patient messages for 3 empathic opportunity types: statements of emotion, progress, and challenge. Coding definitions were iteratively updated to describe specific textual cues unique to the patient portal context. This procedure was repeated to code for empathy in clinician responses to empathic opportunities. An additional 100 patient messages were double-coded for interrater reliability testing, and 500 patient messages were single-coded using the finalized coding schema. Results: Among 1100 patient messages coded, 576 (52.4%) included an empathic opportunity. Of these messages, 100 (17.3%) included a statement of emotion, 85 (14.7%) included a statement of progress, and 539 (93.6%) included a statement of challenge. Statements of challenge were primarily characterized by patients explicitly describing physical or mental health issues, a barrier in care, or difficulties in their personal lives. Among the 576 patient messages with empathic opportunities, 446 (77.4%) received at least 1 response from a clinician. Clinicians sent 483 response messages, of which 64 (13.2%) expressed empathy. Conclusions: While patients created empathic opportunities in over half of patient portal secure messages, primary care clinicians infrequently responded with empathy. The findings of this study provide initial evidence of gaps in empathic communication within patient portal secure messages and lay the groundwork for using artificial intelligence models to systematically measure and improve this communication across the patient portal messaging system.
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