OBJECTIVES: Perinatal depression (PND) impacts a substantial subset of females globally and confers significant risk to maternal-infant health and offspring development, but current evidence on the association between thyroid peroxidase antibody (TPOAb) positivity and the risk of PND is uncertain. This study aims to evaluate the association between TPOAb positivity and the risk of PND. METHODS: We systematically searched PubMed, Web of Science, Embase, the Cochrane Library, and PsycINFO from their inception to March 1, 2025. Cohort, case-control, and cross-sectional studies evaluating the association between TPOAb positivity and the risk of PND were included. This meta-analysis was conducted according to the PRISMA 2020 checklist. The risk of bias in the included studies was assessed by the Newcastle-Ottawa Scale (NOS). Data synthesis was performed using random-effects model and fixed-effects model. RESULTS: After screening, 11 studies with 10,559 patients were eligible. The pooled relative risk (RR) indicated that females positive for TPOAb exhibited a significantly higher risk to develop PND (RR=1.52, 95 %CI [1.16-1.99], p<0.05). A moderate degree of heterogeneity was presented among the included studies (I=52 %). CONCLUSIONS: This meta-analysis demonstrated that perinatal TPOAb positivity is associated with an increased risk of PND. However, given the moderate heterogeneity and the limited number of included studies, future well-designed prospective studies assessing TPOAb positivity at specific time points during pregnancy are warranted to improve the quality of evidence.

OBJECTIVE: Traumatic brain injury (TBI) affects approximately two million individuals in the United States annually, with most cases classified as mild (mTBI). Reported prevalence of insomnia, excessive daytime sleepiness, or obstructive sleep apnea (OSA) ranges from 30% to 70% in patients with mTBI. Sleep disorders may interfere with recovery and contribute to disability. This study characterizes self-reported impairments in sleep and mood among patients with mTBI. METHODS: This cross-sectional retrospective study at a Level 1 trauma center included adults with mTBI (Glasgow Coma Scale ≥ 13) diagnosed ≥ 6 months prior. Patients with substance dependence were excluded. Patients completed the Neurobehavioral Symptom Inventory (NSI), Epworth Sleepiness Scale (ESS), STOP-BAG, Insomnia Severity Index (ISI), Functional Outcome of Sleep Questionnaire-10 (FOSQ-10), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7). Regression analyses controlling for age, body mass index, and time from injury were performed. RESULTS: We recruited 46 subjects, of which 74% (34) were male and 61% (28) were White. Mean (±SD) age was 53 (±17.07) years. Mean (±SD) scores were ESS 8.32 (±5.86), STOP-BAG 2.5 (±1.57), ISI 10.05 (±8.87), FOSQ-10 13.02 (±6.90), PHQ-9 7.02 (±6.72), and GAD-7 6.71 (±6.81). Univariate analyses showed significant associations between NSI and each of ESS, ISI, FOSQ-10, PHQ-9, and GAD-7 (p < 0.01). CONCLUSION: Patients with mTBI commonly report chronic impairments in sleep and psychological well-being. These findings emphasize the need for comprehensive management and identify the importance of screening for sleep disorders in this population.

BACKGROUND: Insomnia, social dysfunction, suicidality, and depressive symptoms commonly co-occur in schizophrenia. Their joint cross-sectional associations and potential sex differences among rural adults with schizophrenia remain unclear. METHODS: This multicenter cross-sectional study included 931 rural adults with schizophrenia in Chaohu, China. Depressive symptoms, insomnia severity, social dysfunction, and suicidality were assessed using the Patient Health Questionnaire-9, Insomnia Severity Index, Social Disability Screening Schedule, and a composite suicidality score, respectively. Sex-stratified logistic regression and exploratory indirect-association analyses with 5,000 bootstrap resamples were conducted. A sensitivity analysis used a non-overlapping Patient Health Questionnaire-7 score excluding the sleep and suicidality items. RESULTS: Of 931 participants, 457 were male and 474 were female. Female participants had higher depressive-symptom, insomnia, suicidality, and social-dysfunction scores than male participants (all P≤0.005). In both sex-stratified models, higher insomnia, suicidality, and social-dysfunction scores were associated with greater odds of at least mild depressive symptoms. In the exploratory model, insomnia severity was directly associated with depressive-symptom score (b=0.388, 95% bootstrap confidence interval [CI], 0.345-0.431). Indirect associations via social dysfunction (0.042, 95% CI, 0.028-0.057) and suicidality (0.038, 95% CI, 0.021-0.058) were supported, whereas the serial indirect association was not (0.002, 95% CI, -0.0001 to 0.005). Sex did not moderate the indirect associations. CONCLUSION: Women reported higher symptom and social-dysfunction scores than men, but sex did not moderate the estimated indirect associations. Insomnia, social dysfunction, suicidality, and depressive symptoms formed a clinically relevant cross-sectional pattern; however, temporal ordering and causality cannot be inferred. Longitudinal studies with non-overlapping measures and broader clinical covariates are needed.

Although sexual orientation change efforts are generally understood to be ineffective and health-undermining, this understanding is based almost entirely on retrospective, cross-sectional data. We present prospective, longitudinal data from a sample of 315 sexual minority current/former members of the Church of Jesus Christ of Latter-day Saints to examine the efficacy and impact of self-initiated sexual orientation change efforts (SISOCE). We found that 74.6% of participants engaged in SISOCE at some point in their lives. Of the 13.7% of participants who were engaged with SISOCE at the start of the study, 62.8% terminated their SISOCE in the 2-year window of the study. We failed to find significant differences in sexual attraction, aversion, or behavior two years later between those who were actively engaged in SISOCE and those who were not. At baseline, participants engaged in SISOCE reported more religiousness, self-alienation, desires to be exclusively heterosexual (i.e., internalized homonegativity), and concealment than participants not engaged in SISOCE. We also found that participants engaged in SISOCE reported less social support, well-being, and self-rated health alongside more depression than participants not engaged in SISOCE at baseline. Two years later, participants who engaged in SISOCE at baseline reported more depression and less social support than participants not engaged in SISOCE. Results support the idea that trying to change one's sexual orientation is health-undermining and ineffective with caveats on how health-undermining, whether we know it is ineffective for everyone, and whether it is always health-undermining. We recommend therapists provide acceptance-focused and person-affirming assessments/interventions that promote identity development.

BACKGROUND: Although obesity and mental health problems represent two of the most pressing public health challenges, their developmental interplay remains insufficiently understood. Thus, we examined how depressive and anxiety symptoms, self-esteem, and psychological resilience are associated with weight development during adolescence. METHODS: We included 1280 11-year-old children from the Finnish Health in Teens cohort, following 814 of them for 4.3 years. Mental health was assessed with validated self-administered scales at age 11. Psychological resilience was determined by complete mental health after exposure to stressful life events. Body mass index z-score (BMIz) and waist-to-height ratio (WtHr) were calculated at ages 11 and 16. RESULTS: In models adjusted for sex, age, physical activity, dietary pattern, puberty status, caregivers' BMI and education level, depressive symptoms were associated with higher baseline BMIz but smaller increases in mean BMIz thereafter (p = 0.030). High self-esteem was associated with lower baseline BMIz, yet with steeper increases over follow-up (adjusted model, p = 0.021). Anxiety symptoms and resilience were not associated with BMIz after adjustments. Similar patterns were observed for WtHr. CONCLUSION: Findings highlight that mental health is associated with physical growth in adolescence, emphasizing the need to consider mental health in understanding and addressing patterns of weight development and their underlying dynamics. IMPACT: This study provides up-to-date, longitudinal evidence on how mental health shapes subsequent weight development during the critical and rapid growth period of adolescence. Both positive and negative dimensions of mental health play a role in shaping adolescent weight development, with evidence that some youths experiencing mental health difficulties exhibited smaller increases in BMI z-score, even when starting from a higher baseline BMI. It should be acknowledged that in contemporary society, adolescents with mental health difficulties may not necessarily present immediate excessive weight gain but instead follow stable or even declining weight trajectories.

BACKGROUND: Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are common conditions associated with significant impairment and distress across multiple domains of functioning, including academic and occupational settings. Although menstruation, and with it the potential onset of PMS or PMDD, typically begins in early adolescence, research in adolescent populations remains limited. Therefore, the present study was conducted to examine the prevalence of PMS and PMDD in German-speaking adolescents, and to evaluate the psychometric properties of the adolescent-adapted version of the Premenstrual Impact Questionnaire (PMS-I-Y). METHODS: In this cross-sectional online study, 521 adolescents aged 14-18 years from Germany, Austria and Switzerland were recruited via Instagram. Premenstrual symptoms were assessed using the PMS-Q-Y. Participants meeting criteria for at least mild PMS completed the PMS-I-Y to assess symptom-related impairment. Severity classifications were based on operationalized questionnaire criteria derived from DSM-5 and PSST-A frameworks. Confirmatory and exploratory factor analyses were conducted to examine factorial validity. Convergent and discriminant validity were assessed using correlations with symptom severity and personality traits. RESULTS: A substantial proportion of participants reported clinically relevant premenstrual burden, with 46.6% meeting criteria for moderate-to-severe PMS and 22.5% meeting criteria for PMDD. Factor-analytic results indicated a strong general factor of premenstrual impairment alongside psychological and functional components. Convergent validity was supported by strong associations with symptom severity (r = .65 - .75). Discriminant validity was indicated by negligible correlations with openness, extraversion, and agreeableness (all r ≤ .08), small negative correlations with conscientiousness (r = - .11 to - 0.13), and small to moderate positive correlations with neuroticism (r = .16 - .33). CONCLUSIONS: Premenstrual symptoms are highly prevalent and associated with substantial psychological and functional burden in adolescents. The PMS-I-Y, an adolescent-adapted version of an existing instrument, shows promising psychometric properties for assessing premenstrual impairment in this age group. However, findings should be interpreted with caution due to the use of retrospective self-report measures, potential sampling bias resulting in a self-selected sample, and the lack of prospective diagnostic assessment. Accordingly, prevalence estimates reflect retrospective symptom reporting operationalized questionnaire criteria rather than clinical diagnoses.

BACKGROUND/OBJECTIVES: Decreased appetite in older adults is associated with physical activity. Prior research findings have been inconsistent or limited due to methodological differences. Many studies did not adequately control for psychological or social confounders on appetite. Therefore, we aimed to assess the relationships among appetite, physical activity, psychological factors, and social factors in community-dwelling older adults. We investigated how physical activity intensity and time of day could be associated with appetite. METHODS: This cross-sectional study included 100 community-dwelling older adults. Appetite was assessed using the Japanese version of the Simplified Nutritional Appetite Questionnaire. Physical activity was evaluated using an accelerometer. Physical activity intensity was classified into sedentary behavior, light-intensity activity, and moderate- to vigorous-intensity activity. Multiple regression analysis was performed with Japanese version of the Simplified Nutritional Appetite Questionnaire as the dependent variable, whereas physical activity, depression (Geriatric Depression Scale-15), and social isolation (Lubben Social Network Scale-6) were the independent variables. RESULTS: The mean Japanese version of the Simplified Nutritional Appetite Questionnaire score in all participants was 15.2. Physical activity and social isolation were not associated with appetite, whereas higher levels of depression were significantly associated with lower appetite. CONCLUSIONS: No association was observed between objectively measured physical activity and appetite among community-dwelling older adults. Appetite was significantly associated with depressive symptoms. These findings highlight the importance of addressing psychological factors, such as depression, for maintaining or improving appetite in older adults. Significance/Implications: Interventions targeting psychological factors might be important for maintaining and improving appetite in older adults.

The tumor suppressor protein p53 is a known modulator of neurodegenerative disease (ND) processes. Although p53 expression is increased in the brains of patients with Alzheimer's disease, Parkinson's disease, and ischemic stroke, its role in mood disorders such as anxiety and depression remains unclear. To investigate the role of p53 in behavioral responses to chronic stress, we examined behavioral and molecular alterations in p53 knockout (p53) mice and wild type mice. In p53 mice, increased vulnerability to chronic unpredictable mild stress (CUMS)-induced anxiety- and depression-like behaviors was observed following CUMS exposure. In parallel with these behavioral changes, BDNF expression was reduced, whereas glutamate levels were elevated in the prefrontal cortex of p53 mice. Increased calcium-associated staining and NMDAR2B expression were observed together with increased neuronal injury- and cell death-related markers. In primary cortical neurons derived from p53 mice, corticosterone treatment resulted in greater increases in glutamate levels, NMDAR2B expression compared to wild-type controls. Cell death markers (cleaved caspase-3, p-p38, p-JNK) were upregulated, while neuroprotective signals (BDNF, p-Akt, p-ERK, p-CREB) were suppressed in p53 mice, and corticosterone-treated primary neuronal cells from p53 mice. These findings indicate that p53 deficiency is associated with enhanced vulnerability to CUMS-induced anxiety- and depression-like behaviors and is accompanied by alterations in calcium handling, glutamate homeostasis, neuronal injury-related markers, and BDNF-associated neuroprotective signaling.

INTRODUCTION: Cannabis use disorder (CUD) is one of the highest prevalence mental health conditions globally. Psychosocial treatments for CUD have modest efficacy. There are currently no approved adjunctive pharmacological approaches for CUD. Varenicline, a nicotinic receptor partial agonist approved for use in smoking cessation, has shown promise as a treatment for CUD. This study aims to synthesise the literature on the efficacy of varenicline in treating CUD. A secondary aim is to examine the tolerability of varenicline and its effect on concurrent tobacco use within CUD treatment. METHODS: A pre-registered systematic review of records extracted from Ovid MEDLINE ALL, CINAHL Complete, APA PsycInfo, Embase, Cochrane Central Register of Controlled Trials, Web of Science Core Collection, Scopus, Clinicaltrials.gov, the WHO International Clinical Trials Registry, and Google Scholar (final extraction March 2025). Original peer-reviewed studies assessing the effect of varenicline on cannabis use or CUD in adolescents (13-18 years) or adults (18-65 years) were included. Risk of bias and study quality assessments were conducted. RESULTS: Five studies were identified as eligible for inclusion (total N = 299). Four studies were Randomized Controlled Trials and one was a case series. Two studies were assessed as poor quality, two as fair quality and one good quality. Narrative synthesis of studies was conducted because of lack of compatible study methodologies required for meta-analytic approaches. Mixed results were found on the efficacy of varenicline on cannabis use across studies. The single high-quality study demonstrated significant reductions in cannabis use and cannabis withdrawal symptoms. The three studies reporting on the secondary outcome of tolerability also demonstrated inconsistent findings. The high-quality study found no difference in participants experiencing at least one adverse event between the varenicline and placebo groups, however nausea was reported more frequently in the varenicline group. Inconsistent findings were observed across the four studies that measured concurrent tobacco use, with the one high-quality study reporting no differences in cigarettes per day over the treatment phase between the varenicline and placebo groups. CONCLUSIONS: There is currently insufficient data to draw confident conclusions about the efficacy and tolerability of varenicline as treatment for CUD in youth and adult populations.

Perioperative neurocognitive disorders (PND), comprising postoperative delirium and postoperative cognitive dysfunction, represent prevalent complications during the perioperative period, particularly among elderly patients. PND not only impedes patient recovery but also imposes a substantial socioeconomic burden. Consequently, effective prevention and management of PND across the preoperative, intraoperative, and postoperative phases hold significant clinical and public health importance. However, existing clinical interventions remain limited in efficacy, posing ongoing challenges in PND care. Through a comprehensive literature review, this study examines the potential of acupuncture, as a clinical intervention for PND. We synthesize current evidence on acupuncture's diversified protocols, mechanistic framework, and clinical value in PND prevention. We propose that these perioperative risk factors, including anxiety, pain, sleep disruption, inflammation, and thermoregulatory disturbance, do not act in isolation; rather, they may interact through shared pathways to collectively contribute to PND risk. Acupuncture, particularly electroacupuncture and transcutaneous acupoint stimulation, counteracts this network through multi-target regulation centered on the gut-brain axis: it modulates gut microbiota and metabolites, balances key neural circuits, maintains neurochemical and synaptic homeostasis, and simultaneously intercepts multiple risk pathways. By integrating these actions across peripheral and central systems, acupuncture constructs a coordinated neuroprotective network that reduces PND incidence and accelerates cognitive recovery. This review provides a theoretical basis for optimizing perioperative management strategies and guiding mechanistic research on acupuncture-based neuroprotection.

Temozolomide (TMZ), the gold standard drug used for the treatment of glioblastoma, is known to affect healthy brain proliferating cells, inhibiting adult hippocampal neurogenesis. Since most antidepressants mediate their beneficial effect through this process and given the large proportion of glioblastoma patients with depressive symptoms, this preclinical study evaluated the interaction between TMZ and cannabidiol (CBD), a cannabinoid compound with antidepressant-like potential. To do so, adult female nude mice were intracranially implanted with GL261 tumor cells and treated with TMZ (5 mg/kg) or PBS twice a week. Additionally, animals received CBD (30-45 mg/kg) 5 days/week (1 dose/day) rendering two groups (PBS-CBD vs. TMZ-CBD). To control for the effects of TMZ alone a group of mice was treated with vehicle (TMZ-Veh). MRI was used to evaluate tumor growth and/or its suppression by treatment. Antidepressant-like responses were assessed under stressful settings (forced-swim or tail-suspension tests) and brain samples were collected to evaluate hippocampal neuroplasticity/neurotoxicity markers. The main results showed that the combined treatment with TMZ-CBD decreased tumor volume, induced signs of antidepressant-like responses, while modulated hippocampal FADD as compared to PBS-CBD female mice. However, these effects were no different than the ones observed by TMZ-Veh, suggesting that TMZ alone was sufficient to observe the behavioral and neurochemical responses, and that adding a concomitant CBD treatment did not change that outcome. This data adds to our recent studies suggesting some beneficial affective-like responses induced by TMZ in rodents, while validating them in a female mice model with induced glioblastoma.

BACKGROUND: This post-hoc analysis examined the effect of sustained psychiatric medication on suicide reattempt risk among Korean patients with depression following an initial attempt. METHODS: Using the Korean Health Insurance Review and Assessment Service (HIRA) database, we identified adults aged 18 years and older diagnosed with depressive disorder who attempted suicide in 2014 (N = 4925; mean age 47.4 ± 17.3 years, range 19-96). Sustained psychiatric medication was defined as receiving antidepressant or antipsychotic treatment for ≥75% of the six months after the index attempt. Stabilized inverse-probability-of-treatment weighting (IPTW) based on propensity scores addressed baseline imbalances. Logistic regression assessed one-year reattempt risk; survival analyses examined long-term risk over up to seven years (from index through August 31, 2020; median follow-up 5.9 years, maximum 6.7 years). Exploratory subgroup analyses compared patients <65 and ≥ 65 years. RESULTS: After IPTW, baseline characteristics were balanced. The one-year reattempt rate was 5.3% with medication versus 7.9% without (OR:0.65, 95% CI:0.504-0.846, P = 0.001). Survival analyses over the seven-year follow-up showed no significant long-term difference (IPTW-adjusted log-rank P = 0.886). The protective effect was evident only in patients <65 years (OR:0.621, 95% CI:0.471-0.822, P < 0.001), with no significant effect in those ≥65 years. CONCLUSIONS: Sustained psychiatric medication after a suicide attempt reduces one-year reattempt risk in patients with depression, in particular in those aged under 65 years. The benefit of initial treatment did not persist over seven years, suggesting that the effect of continued treatment beyond six months warrants future investigation.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

BACKGROUND: Osteoporosis is a major complication in patients with arthritis, yet the long-term protective effect of physical activity (PA) and its underlying mechanisms are not fully understood. METHODS: This study utilized two large aging cohorts, the U.S. Health and Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA). All exposures and outcomes, including PA and physician-diagnosed arthritis and osteoporosis, were based on self-reported data. Cross-sectional analyses assessed the association between PA and arthritis-osteoporosis comorbidity. Longitudinal Cox models examined the effect of baseline PA on new-onset osteoporosis in patients with arthritis. Subgroup, E-value, and mediation analyses were performed to explore effect heterogeneity, robustness, and the mediating role of depression. An exploratory reverse analysis assessed the association of PA with new-onset arthritis in osteoporosis patients. RESULTS: Among 20,175 HRS and 10,525 ELSA participants in the cross-sectional analysis, and 8032 HRS and 2984 patients with arthritis in the prospective analysis, PA was associated with lower comorbidity prevalence (HRS: OR = 0.78; ELSA: OR = 0.69). In longitudinal analyses, active PA was independently associated with reduced osteoporosis risk (HRS: HR = 0.86; ELSA: HR = 0.70) in patients with arthritis. The effect was more pronounced in younger patients and those with heart disease or depression. In HRS, depression significantly mediated 36.55% of the protective effect, whereas this mediation pathway was non-significant in ELSA. No significant association was found between PA and new-onset arthritis in osteoporosis patients. CONCLUSION: Regular physical activity was associated with a lower risk of osteoporosis in patients with arthritis; the association may be partly explained by improvements in depressive symptoms. Promoting PA should be integral to clinical management.

BACKGROUND: Women living with HIV (WLWH) experience often poorer mental health. Family plays a central role in Chinese society and family influence would be particularly salient for Chinese WLWH. Current literature predominantly focuses on how family influences on mental health. Little is known about how mental health affects family functioning, and specifically, this reciprocal dynamic within this population. AIMS: To examine the reciprocal relationship between family functioning and depressive symptoms among Chinese WLWH over a 4-year period. METHODS: A three-wave longitudinal study was conducted among Chinese WLWH, at baseline, 2-year, and 4-year follow-up. Data were collected via individual face-to-face interviews, using structured questionnaires. Cross-lagged panel model (CLPM) was performed in data analysis. RESULTS: A total of 382 participants (Mean age: 36.77 years) were included at baseline; 379 (99.2%) and 372 (97.4%) completed the 2-year and 4-year follow-ups, respectively. Bivariate correlations indicated that family functioning and depressive symptoms were significantly and negatively correlated at each wave. Results from CLPMs revealed a consistent unidirectional relationship: higher family functioning at both baseline and the 2-year follow-up significantly predicted reduced depressive symptoms at the subsequent time point (β = -0.13, p < .05) among WLWH. Conversely, neither depression at baseline nor 2-year follow-up were significant in predicting subsequent family functioning. CONCLUSION: The findings highlight the protective role of family functioning in reducing depressive symptoms among Chinese WLWH over time, suggesting that family support can serve as a buffer against depression. The development of tailored family-based interventions to enhance family dynamics is strongly warranted for this population.

Depression is a highly prevalent affective disorder, and current pharmacotherapies are often limited by suboptimal efficacy and adverse effects. Diosmetin, a dietary flavonoid, exhibits neuroprotective properties through antioxidant and anti-inflammatory mechanisms; however, its antidepressant potential remains insufficiently explored. This study evaluated the antidepressant-like effects of diosmetin in a chronic unpredictable mild stress (CUMS)-induced mouse model. For the induction of depression-like behavior, male BALB/c mice were subjected to a different stressor protocol. Diosmetin (10, 20, and 40 mg/kg (p.o.)) was administered for 4 weeks alongside continued stress exposure. Behavioral outcomes were complemented by photoacoustic imaging, followed by biochemical, molecular, and histological analyses of brain tissues. Colon tissues were also assessed for oxidative stress and histopathological changes, and fecal samples were analyzed for short-chain fatty acid (SCFA) levels. CUMS exposure induced significant depressive-like behavior and cognitive deficits, which were markedly attenuated by diosmetin treatment. Diosmetin reduced oxidative stress (decreased ROS and nitrite; increased GSH) and upregulated antioxidant markers NRF2 and HO-1. It also suppressed neuroinflammation (reduced iNOS and NLRP3), inhibited apoptosis (decreased cytochrome c and cleaved caspase 3), and restored BDNF levels. Imaging findings indicated improved cerebral hemodynamics, while histological analysis showed reduced neuronal degeneration with diosmetin treatment. Additionally, diosmetin ameliorated colonic oxidative stress and restored altered SCFA profiles. Overall, diosmetin exhibited significant antidepressant-like effects that were associated with normalization of the NRF2/HO-1 antioxidant and NLRP3 inflammasome pathways, reduced apoptosis, improved neurotrophic signaling, and restoration of SCFA levels. These findings suggest that the interconnected pathways may contribute to the antidepressant-like effects of diosmetin, warranting further mechanistic investigation.

Prolonged opioid use is associated with many complications, including significant memory deficits. Celosia cristata, a traditionally used medicinal plant, exhibits diverse pharmacological activities; however, its neurocognitive potential remains unexplored. This study is designed to investigate the effects of the methanolic extract of C. cristata (MECC) on morphine-induced cognitive impairment in mice. Phytochemical profiling using GC-MS identified 21 bioactive compounds, including fatty acid derivatives, phenolics, and alkaloids. Following behavioral screening to exclude the anxiety- or depression-related bias, behaviorally naive mice were subjected to the Morris Water Maze Test (MWMT) and Novel Object Recognition Test (NORT) to evaluate the learning and memory performance. MECC-treated mice exhibited significantly greater spending time in the targeted quadrant of the MWM apparatus (p < 0.05) compared to the morphine-only control, indicating enhanced spatial memory. On the other hand, in NORT, MECC (250 and 500 mg/kg b.w. of mice) increased the exploration time around the novel object by 1.5-2-fold relative to morphine-only mice (p < 0.05), demonstrating dose-dependent improvement of the recognition memory. In-silico analyses identified methyl 9-cis,11-trans-octadecadienoate, 13-octadecenoic acid methyl ester, and tetradecanoic acid 10,13-dimethyl methyl ester as potential neuroactive constituents with strong affinities for AMPA-R and NMDA-R. These compounds also fulfilled key ADMET criteria, including BBB and Caco-2 permeability, and non-mutagenicity. Hence, the ameliorating effects of MECC may be associated with the presence of these compounds, while the docking results provide preliminary mechanistic hypotheses suggesting possible modulation of glutamatergic receptor pathways that warrant further experimental validation. To our knowledge, this is the first report demonstrating the memory-enhancing effects of MECC. Further studies are warranted to isolate the active compounds and elucidate their molecular mechanisms for potential therapeutic development.

Lead (Pb) is a neurotoxic heavy metal that crosses the placental barrier and may affect fetal development. However, the effects of chronic developmental Pb exposure on oxidative stress, stress-related endocrine responses, and depression-like behavior, particularly regarding sex differences, remain unclear. This study evaluated the effects of chronic Pb exposure from gestation to adulthood on redox balance, corticosterone responses, and depression-like behavior in male and female mice. Pregnant C57BL/6J mice received 250 ppm lead acetate in drinking water from gestational day 0 until offspring reached adulthood. Depression-like behavior was assessed using the forced swimming and tail suspension tests. Reactive oxygen species and lipid peroxidation were measured in the prefrontal cortex and hippocampus, and plasma corticosterone was quantified following behavioral stress. Chronic Pb exposure increased immobility in both behavioral tests and increased oxidative stress markers in the prefrontal cortex and hippocampus, with sex- and region-dependent differences. Pb exposure also altered corticosterone dynamics in both sexes: males showed a delayed corticosterone peak, whereas females exhibited a prolonged response that remained elevated 24 h after stress. Overall, chronic developmental Pb exposure was associated with depression-like behavior, oxidative imbalance, and altered corticosterone responses in a sex-dependent manner. These findings highlight biological sex as an important factor influencing the neurobehavioral, redox, and stress-related endocrine consequences of chronic developmental Pb exposure.

Anxiety disorders are among the most common mental health conditions affecting women of reproductive age, and a significant proportion of pregnant women experience clinically relevant anxiety symptoms. In some cases, pharmacological treatment may be required to manage severe or persistent symptoms; however, concerns remain regarding the potential impact of prenatal exposure to anxiolytic medications on fetal brain development. The developing nervous system undergoes critical processes during gestation, including neuronal proliferation, migration, and synaptic formation, which may be sensitive to pharmacological influences. This review examines available clinical and preclinical evidence regarding the neurodevelopmental consequences of prenatal exposure to commonly used anxiolytic medications, especially benzodiazepines (BZDs) and azapirones (AZPs). Evidence from observational human studies has shown associations between prenatal exposure to BZDs and certain neonatal and neurodevelopmental outcomes. However, results remain inconsistent and may be influenced by confounding factors, including maternal psychiatric conditions, co-medication use, and environmental variables. In contrast, data on prenatal exposure to AZPs, especially buspirone, are relatively limited, with most of the available evidence coming from small cohorts and preclinical models. Experimental studies provide mechanistic insights suggesting that early-life exposure to anxiolytic agents may influence neurotransmitter systems, neuronal morphology, and behavioral development in offspring. However, translating findings from animal models to the human clinical context remains challenging. Overall, the current literature highlights substantial knowledge gaps regarding dose-dependent effects, critical developmental windows, and long-term neurobehavioral outcomes. Further well-controlled longitudinal and translational studies are needed to clarify the potential implications of prenatal exposure and to support evidence-based clinical decision-making during pregnancy.

OBJECTIVE: Although sleep disturbances increase during pregnancy, sleepiness does not appear to follow a similar trajectory. Given that the relationship between sleep disturbances and sleepiness during pregnancy is understudied, we examined their associations to determine whether these relationships strengthen with advancing gestation. METHODS: For this prospective longitudinal survey, we enrolled 3808 women, of whom 3286 responded. Sleep disturbances were assessed in early pregnancy, midpregnancy, and late pregnancy and at delivery. Mixed-effects models were constructed with adjustments for age, body mass index, parity, maternal smoking, and depressive symptoms. RESULTS: Sleepiness decreased from early to midpregnancy and increased thereafter, being highest at delivery. In contrast, the proportion of women with insomnia increased from 19.1% in early pregnancy to 59.1% at delivery. The proportion of habitual snorers (three or more times per week) and short sleepers (<7 h per night) increased as pregnancy progressed, whereas the proportion of long sleepers (>9 h per night) remained stable. Significant sleep loss (>2 h) increased particularly at delivery. Greater sleepiness was consistently associated with insomnia symptoms (all P < 0.001), with stronger effect size estimates in late pregnancy. Sleepiness was also associated with habitual snoring from midpregnancy onwards. Short sleep duration and sleep loss were related to greater sleepiness throughout pregnancy (all P < 0.001), but long sleep duration was associated with greater sleepiness only in early pregnancy. CONCLUSION: Sleepiness during pregnancy followed a U-shaped trajectory but was consistently associated with insomnia, short sleep duration, sleep loss, and snoring from midpregnancy onwards. Screening for underlying sleep disturbances among pregnant women reporting sleepiness may provide an opportunity for timely identification and management, potentially improving maternal well-being.

Recent years have seen unprecedented increases in compulsive behaviors, even in previously undiagnosed populations. Yet, despite their rising prevalence and the fact that compulsions-notably associated with obsessive-compulsive disorder (OCD), but also a key feature of other disorders such a hoarding or body dysmorphic disorder-significantly hamper daily function, the specific mechanisms of their formation remain unknown. Previous research holds mixed findings on compulsivity-linked cognitive deficits, and, while many accounts assume that compulsions aim to reduce anxiety, most individuals with anxiety do not develop compulsions-suggesting that the anxiety-reduction account is incomplete. We propose here a broader, uncertainty-resolving account of compulsivity, that bypasses the commonly-used, single-goal structure of many cognitive tasks to leverage the real-world hierarchical structure of goals-with " (e.g., "how do I clean my hands?") in the service of ("how do I stay healthy?"). In that framework, we suggest that compulsivity may reflect a deficit in integrating uncertainty from local to global goals, which still spares the basic circuitry of reward and learning. We tested 20 OCD patients and 20 healthy volunteers in a predictive inference task with a hierarchical structure of local uncertainty reduction in the service of global uncertainty reduction. Both groups learned the reward structure of the local environment based on observed data; however, only the healthy volunteers showed evidence of integrating learned knowledge at the local level to reduce uncertainty about the higher level of the task hierarchy. This indicates a potential mechanism for compulsions that relies on the inability to adaptively integrate, prioritize, and "toggle" among different local goals in the service of global goals.

INTRODUCTION: Poststroke depression (PSD) is a prevalent and debilitating complication that adversely affects recovery and quality of life among stroke survivors globally. While PSD prevalence ranges between 28% and 45%, data on severe PSD in older adults with prolonged poststroke disability in Nigeria remain limited. This study aimed to determine the prevalence of severe PSD and identify its key sociodemographic and clinical predictors among older Nigerian adults with chronic poststroke disabilities. METHODS: A multisite, hospital-based cross-sectional survey was conducted from March 2024 to July 2025 across six tertiary healthcare institutions representing Nigeria's geopolitical zones. A total of 305 adults aged ≥60 years with physician-confirmed poststroke disabilities were recruited using a multistage sampling technique (stratified purposive hospital selection and consecutive sampling of eligible patients). Depression severity was assessed using the Geriatric Depression Scale-15 (GDS-15). χ tests evaluated associations between severe depression and predictor variables, with ORs calculated for significant factors (p<0.05). RESULTS: Severe depression was identified in 66.6% (n=203) of participants, substantially exceeding prior regional estimates. Participants aged ≥70 years had higher odds of severe PSD (OR=1.85; 95% CI 1.07 to 3.21; p=0.01). Female gender was associated with increased depression severity (OR=0.56; 95% CI 0.34 to 0.93; p=0.03). Christian religious affiliation showed a strong positive association (OR=4.30; 95% CI 2.57 to 7.20; p<0.001). Being married (OR=1.82; 95% CI 1.13 to 2.92; p=0.02) and living with family (OR=4.68; 95% CI 2.77 to 7.91; p<0.001) were protective. Longer poststroke duration (≥5 years) (OR=2.01; 95% CI 1.23 to 3.29; p=0.01) and continuous medication dependence (OR=2.54; 95% CI 1.01 to 6.35; p=0.04) significantly increased odds of severe PSD. CONCLUSION: This study reveals an alarmingly high prevalence of severe PSD among older Nigerian adults with chronic poststroke disabilities, driven by demographic, cultural and clinical factors. Integration of routine depression screening and culturally sensitive psychosocial interventions, leveraging social support networks, is imperative to address this substantial mental health burden within stroke rehabilitation programmes in resource-limited settings.

INTRODUCTION: Frailty is recognised as a significant health challenge among adults living with HIV. The increasing ageing population in more than 21.1 million people living with HIV (PLHIV) in Eastern and Southern Africa is of public health concern; however, data on the prevalence and associated factors of frailty in this population are limited. This study aimed to determine the prevalence of pre-frailty, frailty, identify associated factors and assess its impact on quality of life (QoL) among adult PLHIV attending Muhimbili National Hospital in Tanzania. METHODS: A hospital-based, cross-sectional study was done in 2023 at the Care and Treatment Clinic (CTC). Adult PLHIV aged 35 years and above were enrolled using a linear systematic sampling. Frailty was assessed using the FRAIL scale which measured fatigue, resistance, ambulation, illnesses and loss of weight, where scores of 3-5, 1-2 and 0 indicated frailty, pre-frailty and healthy, respectively. WHOQOL-HIV BREF instrument measured QoL scores (4-20) using physical, psychological, level of independence, social relationships, environmental health and belief domains. Factors associated with frailty were determined using ordinal logistic regression. Comparison of QoL scores between frailty groups was determined using one-way Analysis of Variance (ANOVA). Statistical significance was set at p<0.05. RESULTS: A total of 268 PLHIV were included with a mean age of 51.8±10.0 years. Prevalence of pre-frailty and frailty was 23.5% and 27.6%, respectively. Factors associated with frailty included older age (≥50 years), being female and ever being diagnosed with a mental disorder. The QoL score was 16.2±1.6. Low scores in physical health and level of independence domains were significantly associated with increasing frailty severity status. CONCLUSION: More than 50% of adult PLHIV had pre-frailty and frailty status. This is a multifactorial condition not solely a consequence of HIV infection itself. Its association with reduced QoL highlights the importance of integrating routine frailty screening into CTC care.

BACKGROUND: Evidence suggests that people with glaucoma may experience more depressive symptoms than those without glaucoma, but prior estimates have been limited by heterogeneous ascertainment and insufficient separation of comparative, prevalence, and longitudinal evidence. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, SinoMed, Wanfang, VIP, CNKI, ChiCTR, and ClinicalTrials.gov to March 27, 2026. Eligible studies reported depression outcomes among individuals with glaucoma; studies included in the primary comparative analysis additionally required a non-glaucoma comparison group. Two reviewers independently screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale (NOS) for cohort/case-control studies and Joanna Briggs Institute (JBI) tools for cross-sectional studies. Random-effects meta-analyses used restricted maximum likelihood (REML) as the primary estimator; DerSimonian-Laird models were sensitivity analyses. Certainty of evidence was assessed using the GRADE framework adapted for observational evidence. RESULTS: Forty-nine studies were included qualitatively. Sixteen studies including 14,030 glaucoma participants and 4,472,723 controls contributed to the primary odds ratio meta-analysis. Glaucoma was associated with higher odds of depression (OR, 2.80; 95% CI, 1.66-4.74;  = 95.95%; approximate prediction interval 0.32-24.47). Results remained significant across sensitivity analyses excluding self-reported glaucoma studies, unclear glaucoma ascertainment, and a very large database study. Thirty-eight studies including 21,705 patients with glaucoma contributed to the single-group prevalence meta-analysis; pooled depression prevalence was 26.03% (95% CI, 21.10%-31.64%; prediction interval 5.98%-66.04%). Longitudinal evidence was limited and heterogeneous; one UK Biobank cohort suggested a longitudinal association with incident hospitalized depression among participants with glaucoma (HR, 1.54; 95% CI, 1.01-2.34). GRADE certainty was very low for the comparative, prevalence, and longitudinal evidence domains. CONCLUSIONS: Very low-certainty observational evidence suggests that depression or depressive symptoms are more common among individuals with glaucoma; however, whether glaucoma precedes, contributes to, or results from depressive symptoms remains uncertain. The observed association may reflect complex bidirectional relationships between glaucoma-related visual burden and depressive symptoms. Ophthalmic care should incorporate pragmatic depression awareness and referral pathways, while future longitudinal studies should use standardized glaucoma and depression ascertainment with adequate adjustment for visual, clinical, and socioeconomic confounders.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a chronic psychiatric condition that frequently presents with comorbid depressive disorders. For patients exhibiting treatment-refractory OCD and concurrent depressive disorder(s), there is growing clinical interest in the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine as a rapid-acting intervention. This case report describes a 27-year-old female patient with severe, treatment-refractory OCD and comorbid depressive symptoms, detailing her response to a single intramuscular (IM) ketamine administration. CASE PRESENTATION: The patient's primary compulsion was that of handwashing, which she would partake in for ~6 h per handwashing session at the time of the first ketamine administration. This occurred daily over a 3.5-month period, wherein a single day would consist of up to 18 total hours of handwashing. These extreme compulsions resulted in severe in-home isolation, precluding in-person psychotherapy and employment. Despite ongoing management by an independent telepsychiatrist, the patient reported no symptom relief from her prescribed regimen of fluoxetine (80 mg) and alprazolam (1 mg, four times daily)-a pharmacotherapeutic approach that may have been clinically suboptimal given the potential for high-dose benzodiazepines to exacerbate obsessive-compulsive symptoms. Given the severity of her condition, she subsequently pursued treatment at an unaffiliated outpatient ketamine clinic. CONCLUSION: Following a single IM ketamine administration, the patient experienced an acute, ~97% reduction in handwashing duration (from 6 h sessions to 5-10 min sessions) sustained over a 10-day period. This observation highlights an acute change in the patient's primary compulsive behavior. However, concurrent pharmacotherapy may confound the results, and prospective controlled trials are required to fully evaluate the efficacy of this intervention.