Tumor necrosis factor-alpha (TNF-α) is a key mediator in the inflammatory mechanisms of depression, yet its peripheral levels and contributors remain unclear in patients with depression without comorbid physical diseases. This study aimed to compare peripheral TNF-α levels between healthy controls and individuals with depression without physical diseases, and to investigate the associations of stressful life events and modifiable lifestyle factors with peripheral TNF-α levels.

Participants were derived from the Depression Cohort in China study. Adults aged 18-65 years were included in the study. Participants included healthy controls and individuals with subthreshold depressive symptoms (SDS) or major depressive disorder (MDD), all of whom were free of physical diseases. Peripheral TNF-α was measured by ELISA. Stressful life events and lifestyle factors were assessed using questionnaires. General linear models were used to assess the associations of stressful life events and lifestyle factors with TNF-α. Dominance analysis was used to rank the relative importance of predictors, and Blinder-Oaxaca decomposition was used to quantify the extent to which these factors statistically explained the TNF-α difference between healthy controls and individuals with depression.

A total of 414 physically healthy adults were recruited, including 154 healthy controls and 260 individuals with depression. Among those with depression, 185 had SDS and 75 had MDD. Compared with healthy controls, peripheral TNF-α was mildly but significantly elevated in SDS (Cliff's delta = 0.293, P < 0.001), and MDD (Cliff's delta = 0.261, P < 0.01). Multivariate general linear model found that smoking in the past month (β = 2.15, P = 0.003), sleep duration < 6 h per day (β = 1.95, P = 0.004), and experience ≥ 3 stressful life events (β = 3.14, P = 0.001) were significantly contributed to the total variance of peripheral TNF-α in all participants. Blinder-Oaxaca decomposition indicated that 44.7% of the difference in peripheral TNF-α between healthy controls and depression was attributable to lifestyle factors and stressful life events. Within this explained portion, smoking contributed 25.1%, sleep duration < 6 h contributed 32.5%, and experiencing ≥ 3 stressful life events contributed 29.8%. Stratified analyses suggested that stressful life events might moderate the effect of drinking alcohol on TNF-α.

Peripheral TNF-α was mildly elevated in physically healthy adults with depression, with comparable levels observed in SDS and MDD. Stressful life events and lifestyle factors were associated with peripheral TNF-α levels in this population.

Not applicable.

Alzheimer's disease (AD) is biologically defined by amyloid-β (Aβ) and tau pathology but clinically manifests as progressive synaptic dysfunction and cognitive decline. Although anti-amyloid and anti-tau therapies modestly slow disease progression, they do not directly restore cognition or synaptic function.

Phase II trials of cognition‑enhancing therapies in AD and prodromal AD were reviewed to identify factors behind success or failure. Trials from ClinicalTrials.gov and the EU Clinical Trials Register with cognitive endpoints were assessed by mechanism, design, population, and outcomes. Strategies included synaptic, inflammatory, metabolic, vascular, and regenerative approaches.Most therapies showed limited or inconsistent cognitive effects, and many trials did not demonstrate clear efficacy.

Phase II cognition‑enhancing trials in AD show biological plausibility but remain methodologically limited. Cognitive signal detection depends on the fit between mechanism, disease stage, and trial design, and on the statistical approach used to capture subtle change. Outcome variability highlights the need for sensitive cognitive measures and adequate power. Progress will require precision‑enriched designs, with biomarker‑defined populations, cognitive‑trajectory modeling, and integrated cognitive and functional endpoints.

In the United States, the suicide death rate for military veterans is higher than the rate for the general population. Several risk factors of suicide (e.g., housing instability) occur at elevated prevalence among veterans, and gender is a well-documented moderator of suicide. The objective of the present study was to parse factors risk for suicide attempts at the intersection of gender and housing instability among veterans.

Data were from Veterans Health Administration electronic health records (EHR) from 2013 to 2017 for veterans with indicators of housing instability (n = 659,987). Because EHR did not include gender identity data, gender was defined by sex recorded in the EHR (male or female) and transgender and gender diverse (TGD) status using ICD-10 diagnosis codes related to gender dysphoria. A discrete-time survival analysis was used, with person-month as the unit of analysis, to examine correlates of suicide attempt over time within each gender group (i.e., cisgender men, cisgender women, or TGD).

TGD veterans had 2 × to 3 × greater prevalence of suicide attempt than cisgender men and women veterans. Suicide attempt during follow-up was lower than suicide attempt at baseline for both cisgender men veterans and TGD veterans, however, for cisgender women veterans, suicide attempt during follow-up was greater than at baseline. Both baseline and recent suicidal ideation were strong predictors of suicide attempt during follow-up across all 3 gender groups. Utilization of social services was positively related to suicide attempt for cisgender males.

Among a population of veterans with high risk for suicide (i.e., experienced housing instability), TGD veterans had the greatest prevalence of suicide attempt. Future studies are needed to determine how VA suicide prevention efforts reach TGD veterans. Social service programs may indicate acute risk, particularly cisgender men, and may benefit from greater synergy with suicide prevention efforts.

To evaluate retinal structural parameters and layer-specific microvascular perfusion using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in patients with chronic methamphetamine use disorder.

This prospective, cross-sectional study included 45 patients with methamphetamine use disorder and 45 age-and sex-matched healthy controls. All participants underwent comprehensive ophthalmologic examination and standardized OCT and OCTA imaging. Central macular thickness, peripapillary retinal nerve fiber layer (RNFL) thickness, and subfoveal choroidal thickness were assessed by OCT. OCTA was used to quantify foveal avascular zone (FAZ) area, vessel density of the superficial and deep capillary plexuses (SCP and DCP), and flow areas of the outer retina and choriocapillaris. Correlations with duration and cumulative methamphetamine exposure were analyzed.

Total and superior quadrant RNFL thicknesses were significantly higher in the methamphetamine group(p=0.039 and p=0.030, respectively). Although SCP-VD was lower in the methamphetamine group, this difference did not reach statistical significance(p>0.05). In contrast, DCP-VD was significantly reduced in the methamphetamine group across total, parafoveal, and perifoveal regions(all p<0.001). Choriocapillaris flow area was also significantly lower in methamphetamine users(p=0.001). No clinical signs of retinopathy were observed in the patient group. Total and superior RNFL thicknesses were positively correlated, and outer retinal flow was negatively correlated, with both duration and cumulative methamphetamine exposure(p<0.05).

Chronic methamphetamine use was associated with reduced DCP vessel density and decreased choriocapillaris flow despite the absence of clinically apparent retinopathy. These findings suggest layer-specific subclinical microvascular alterations detectable by OCTA. Longitudinal studies are needed to determine their progression and clinical relevance.

Adults formerly placed out-of-home (care leavers) often accumulate multiple psychosocial adversities that can lead to poor quality of life (QoL) and place them at high risk for developing mental disorders persisting into adulthood. This study examines the development of mental disorders among care leavers and their QoL, differentiating by disorder groups.

The sample consisted of 119 young adults formerly placed out-of-home (M_{age at baseline} = 15.0 years; M_{age at follow-up} = 25.4 years). Mental disorders were assessed at baseline using the Kiddie Schedule for Affective Disorder and Schizophrenia-Present and Lifetime Version and at a 10-year follow-up with the Structured Clinical Interview for DSM-5 Disorders-Clinician Version. Personality disorders were evaluated at both time points using the Structured Clinical Interview for DSM-IV-TR Axis II. QoL was measured at follow-up using the World Health Organization QoL-BREF questionnaire.

Four groups based on the presence or absence of mental disorders at baseline and follow-up were identified: resilient (n = 24, 20.2%), persistent (n = 56, 47.0%), remitted (n = 25, 21.0%), and newly occurring (n = 14, 11.8%). Regarding the mental disorder groups, internalizing disorders at baseline (β = -0.44, p < .05, 95% CI [-0.85, -0.04]) and internalizing (β = -0.78, p < .001, 95% CI [-1.14, -0.43]) and externalizing disorders (β = -0.50, p < .01, 95% CI [-0.86, -0.13]) at follow-up were negatively associated with QoL in young adulthood.

Mental disorder trajectories from childhood to young adulthood can negatively impact care leavers' QoL. Prevention and early intervention, as well as addressing mental health during out-of-home placement and transition into young adulthood, are important to reduce the risk of persistent psychopathology and lower QoL.

Schizophrenia (SCZ) is widely considered to be closely associated with n-methyl-d-aspartate receptor (NMDAR) dysfunction. As important modulators of NMDAR, abnormalities in d-amino acid levels and their metabolic pathways may play a critical role in the pathophysiology of SCZ. Emerging evidence suggests that alterations in d-amino acid-related indicators in the plasma and brain tissue of patients with SCZ are associated with disease progression. Monitoring blood concentrations of d-amino acids may therefore provide novel peripheral biomarkers for the auxiliary diagnosis of schizophrenia. Although direct activation of NMDAR has not yielded satisfactory therapeutic outcomes, preliminary progress has been made by modulating its co-agonist sites for glycine and d-serine. d-serine, d-aspartate, and d-cysteine, as NMDAR agonists, represent potential adjunctive therapeutic strategies for schizophrenia. In contrast, d-cycloserine, a partial NMDAR agonist, has demonstrated mixed clinical efficacy in the treatment of schizophrenia. Furthermore, an alternative strategy for enhancing NMDAR function is the inhibition of d-amino acid oxidase (DAAO). Although a variety of DAAO inhibitors have been developed for the treatment of schizophrenia, most of these agents have not yet entered clinical application. Importantly, whether DAAO inhibition can improve therapeutic outcomes in SCZ by increasing d-amino acid levels remains to be further validated. Future research still requires higher-quality preclinical studies and multicenter clinical trials with longer follow-up periods to further elucidate the efficacy, safety, and potential value of peripheral biomarkers associated with d-amino acid-based interventions.

Brief interventions delivered in healthcare settings represent a promising substance use prevention and early intervention strategy for youth in foster care, among whom early life adversity and resulting psychological sequalae increase risk for problematic substance use. Limited research has examined the effectiveness of brief interventions in this subpopulation. This study aimed to examine whether psychological diagnoses were associated with screening positive for problematic substance use, and whether psychological diagnoses impacted effectiveness of a brief intervention for substance use.

Longitudinal observational study of adolescents (ages 10-20 years) seen for mandated health examinations in a foster care clinic. Youth who endorsed substance use and received a brief intervention were invited to complete baseline surveys and follow-ups at 30 days, 60 days and 6 months. Logistic regressions evaluated associations of mental health disorders with endorsing problematic substance use. Generalized linear mixed models examined associations of mental health disorders with trajectories of post-intervention change in substance use.

Midwest, United States.

Adolescents seen for mandated health examinations in a foster care clinic who completed a substance use screening measure [CRAFFT2.1 + N; n = 1656; mean age (SD) = 14.4 (2.6); 53.4% female; 58.4% Black, 31.6% white]. A second subsample included only those adolescents who received a brief intervention for substance use during their clinic visit [n = 287; mean age (SD) = 15.9 (2.1); 59.9% female; 53.7% Black, 35.5% white].

Mental health diagnoses and CRAFFT2.1 + N were extracted from the electronic health record. Youth-reported count of past 30-day use of alcohol, cannabis and nicotine/tobacco at each wave.

A minority (12%) of youth in foster care endorsed problematic substance use. Youth with a mental health diagnosis had 58% to 161% higher odds of reporting problematic substance use [odds ratios (ORs) = 1.58-2.61; 95% confidence intervals (CIs) = (1.16-2.13) - (1.93-3.56)]. Following the intervention, youth who had been diagnosed with internalizing disorders (i.e. anxiety, depressive and trauma disorders), and those with co-occurring internalizing and externalizing disorders, reported smaller decreases or no decreases in their cannabis [ORs = 2.09, 7.03; 95% CIs = (1.17-3.71), (3.43-14.42)] and nicotine use [ORs = 1.95-7.68; 95% CIs = (1.08-3.53) - (4.12-14.32)]. Alcohol use did not vary as a function of mental health diagnoses [ORs = 0.31-13.10; 95% CIs = (0.00-19.37) - (0.19-915.80).

Foster youth in the United States, particularly those with mental health concerns, appear to be at high risk for problematic substance use.

Despite their negative effects on cognitive function and cognitive decline risk, drugs with anticholinergic properties are commonly prescribed, particularly in older individuals. In this observational study we aimed to shed light on the relationships between anticholinergic burden (ACB) and depressive symptoms and cognitive and functional performance in a real-world clinical setting.

The study included individuals seeking care at the old-age psychiatry outpatient clinic of Patras University Mental Health Services. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale; cognitive function was tapped using the Cognitive Telephone Screening Instrument, the Montreal Cognitive Assessment, and the Mini-Mental State Examination; and functional performance was assessed using the Bristol Activities of Daily Living Scale. Differences in demographic and clinical variables across the four diagnostic groups were analyzed. Regression analyses were performed to examine the associations between ACB, cognitive and non-cognitive symptoms, and demographic variables. In addition, clustering analyses were conducted to identify distinct, naturally occurring examinee subgroups and to assess if ACB differed across them.

The study sample consisted of individuals without cognitive impairment (N = 301), people with mild neurocognitive disorder (MiND, N = 264), major neurocognitive disorder caused by Alzheimer's disease (ADMaND, N = 114), or other diseases (nonADMaND, N = 63). Significant associations were detected between ACB and depressive symptoms (0.72, p < 0.001), short-term memory (-0.11, p = 0.017), long-term memory (-0.24, p < 0.001), working memory (-0.24, p = 0.001), attention/concentration (-0.13, p = 0.004), verbal fluency (-0.57, p = 0.003), inductive reasoning (-0.17, p = 0.002), basic activities of daily living (0.29, p = 0.001), and instrumental activities of daily living (0.58, p < 0.001). The clustering analyses indicated that in the cluster including individuals with more advanced cognitive decline, poorer functional status, and more severe depressive symptoms, ACB was higher compared with the second group identified by the analyses (p < 0.001).

ACB is related to different aspects of the clinical phenotype of cognitive decline. Despite the lack of solid evidence regarding causal relationships and need for further research, minimizing ACB in clinical settings may embody a potential pragmatic strategy in managing cognitive decline in ageing.

PurposeTo identify a consensus-based subset of NANDA-I nursing diagnoses (NDs) specifically relevant to mental health and addiction care, facilitating their integration into clinical practice and electronic health records (EHRs).MethodsA multiphase e-Delphi study was realized engaging 33 international nurses with experience in the fields of interest and in standardized nursing languages. Participants evaluated the relevance of 267 NANDA-I NDs (12th edition) using a 9-point scoring system, allowing for the immediate inclusion of 130 NDs with high consensus (median scores of 7-9). Further five uncertain NDs were included after undergoing a second Delphi round.FindingsA total of 135 NDs (50.6% of NANDA-I taxonomy) were identified as essential for mental health and addiction care. Domains such as self-perception, coping/stress tolerance, and interpersonal relationships had the highest inclusion rates, reflecting the psychosocial and cognitive complexity of care in these settings. Conversely, NDs belonging to domains like growth/development, safety/protection, and elimination/exchange were selected in a more focused way, limiting to conditions reflecting expected side effects of psychiatric medications or substance misuse or risks for other- or self-directed injuries.ConclusionsThe identified subset of NDs seems to have the potential to capture the multifaceted nature of mental health and addiction nursing. This targeted approach addresses the unique needs of these populations and highlights nursing's critical role in holistic care delivery.Implications for Nursing PracticeImplementing this NDs subset into EHRs can streamline clinical reasoning, enhance interdisciplinary communication, and align interventions with patient needs. By focusing on a refined set of diagnoses, nurses can improve care quality, optimize outcomes, and contribute to evidence-based decision making in mental health and addiction care. Future research should evaluate the subset's impact on patient outcomes and healthcare efficiency.

Refugees carry a cumulative burden of past trauma and ongoing post-migration stress, yet the mechanisms linking these to mental health functioning remain incompletely understood. Sense of coherence - a salutogenic orientation comprising comprehensibility, manageability, and meaningfulness - may help account for these associations. We tested sense of coherence as a mediator of both associations and compared the relative weight of the two stressor domains.

A cross-sectional sample of 151 refugees and asylum seekers in the Netherlands (84.1% with a residence permit) completed the LEC-5, PMLP, SOC-13, and OQ-45.2 in person with research-assistant support across Dutch, English, and Arabic. We conducted multiple regression and three PROCESS Model 4 mediation analyses, including a parallel mediation with sense of coherence and post-migration stress as simultaneous mediators.

Both stressors predicted poorer functioning, with post-migration stress substantially stronger than trauma exposure (b = .40 vs. .17). Sense of coherence was the strongest correlate of functioning (r = -.57) and statistically mediated both cross-sectional associations. In the parallel mediation, sense of coherence and post-migration stress mediated the trauma-functioning association, and the direct effect was no longer statistically significant once both were included. Family-oriented stressors dominated the burden profile: worries about family in the country of origin (78.8%), missing family (73.5%), and uncertainty about the future (70.9%).

As a personal-resilience construct shaped by - not insulated from - external conditions, sense of coherence warrants sustained attention in this population.