Postpartum depression (PPD) affects approximately 10-15% of new mothers worldwide with profound consequences extending to offspring and partners. While the classical "hormonal withdrawal hypothesis" has long emphasized the abrupt decline in estradiol, progesterone, and cortisol following childbirth, emerging evidence demonstrates that these endocrine perturbations converge with dysregulated neuroimmune pathways as central drivers of PPD pathophysiology. This narrative review integrates mechanistic evidence linking reproductive hormone withdrawal, HPA axis dysregulation, neurotransmitter imbalances, and peripheral immune activation to central neuroinflammatory pathways in PPD, with the goal of providing a unified framework for understanding pathophysiology and identifying translational therapeutic opportunities. We synthesize evidence on increased inflammatory cytokines, including IL-6, TNF-α, and IL-1β, blood-brain barrier disruption, microglial activation, and neuroinflammatory signaling pathways. Additionally, we examine structural and functional neuroimaging abnormalities in limbic-prefrontal circuits and metabolic disturbances in monoaminergic, glutamatergic, and GABAergic systems. We evaluate established and emerging therapeutic strategies, including conventional antidepressants, FDA-approved neuroactive steroids (brexanolone, zuranolone), and novel immune-targeted interventions (NLRP3 inhibitors, cytokine antagonists). By integrating biological, genetic, and psychosocial risk factors, this review provides a precision-medicine framework for targeting neuroinflammatory pathways, particularly TLR-mediated immune activation, alongside conventional treatments, while identifying NLRP3 inflammasome signaling as a promising but clinically unvalidated therapeutic target warranting direct investigation in postpartum populations.

Motivational factors representing approach and avoidance mechanisms (i.e., behavioral inhibition system, behavioral activation system) have been implicated with depression and anxiety, and have a negative impact on functional outcomes. The independent effects of withdrawal mechanisms, anhedonia and social anxiety, have been established, but are often examined in isolation of one another. The potential modulating or additive relationship between these motivational factors and withdrawal mechanisms remains unclear. Thus, the current study examined the additive and interactive effects of trait level motivational factors and withdrawal mechanisms on impairment in key domains of life. Participants (N = 110) with depression and anxiety symptoms ranging from none to severe completed measures of behavioral inhibition (BIS) and behavioral activation (BAS), anhedonia, social anxiety, and functional outcomes. Linear regressions were conducted to assess the interactive and main effects of these factors on life functioning. While no significant interactions emerged, the main effects of anhedonia and social anxiety were stable predictors of life impairment. Additionally, while behavioral inhibition initially exhibited a significant main effect on life impairment in some of the models, this effect appeared to be accounted for by social anxiety; suggesting they measure components of the same underlying construct. These findings suggest that anhedonia and social anxiety are more stable predictors of proximal functional impairment, as we observed no evidence that the interactive relationship between motivational and withdrawal mechanisms resulted in worse functioning.

In addition to their effects on physical and metabolic health, high-fat, high-sugar (HFHS) diets are associated with neurocognitive impairment and behavioural effects. It is not clear whether these impairments persist or recover when the HFHS diet is replaced with a healthy diet, i.e. diet reversal. We performed a systematic review and meta-analysis of the effects of diet reversal on cognition and behaviour in rodent studies. Our review included 27 studies which fed rodents HFHS diets for a minimum of two weeks, replaced this diet with healthy chow for at least 24 h, and then assessed cognition, anxiety, depression, motivation or locomotor activity. Meta-analyses revealed that diet reversal significantly improved memory performance relative to rodents maintained on HFHS diets ( = 0.46, 95% [0.16, 0.76]  .004) but did not restore memory to the level of chow-fed controls ( = -0.28 [-0.49, - 0.06]  .013). Meta-regressions revealed test- and diet-dependent effects of diet reversal, with significant memory improvements in studies using the novel object location test, or high-fat diets, but not high-sugar or combined HFHS diets. Diet reversal had no significant effects on tests of anxiety-like or depression-like behaviour, motivation, or locomotor activity. Heterogeneity estimates were moderate to high across domains, and risk of bias was generally low. Results demonstrate that diet-induced cognitive impairments are amenable to healthy diet intervention in controlled animal models, underscoring the need for public health nutrition strategies designed to reduce intake of foods high in sugar and fat.

INTRODUCTION: Adults with serious mental illness (SMI) have elevated morbidity and mortality, largely attributable to increased cigarette smoking. Effective smoking cessation interventions remain a critical need for this population. This study tested the Parks and Recreation Quit Smoking Program (PARQuit), a multi-component treatment program for adults with SMI. The aims were to compare the effectiveness of the PARQuit physical activity and PARQuit sedentary groups on smoking cessation, smoking reduction, and psychiatric symptom reduction. METHODS: Ninety-nine participants with SMI were randomized to a physical activity intervention or a sedentary control group, each receiving pharmacotherapy (nicotine replacement therapy (NRT) or bupropion SR) and cessation counseling for 12 weeks in the United States of America, from 2019 through 2025. The PARQuit physical activity group engaged in game-based group exercise (50 minutes, 3 times/week), whereas the PARQuit sedentary group participated in sedentary group activities. Outcomes included smoking cessation (measured at baseline, 6, and 12 weeks) and psychiatric symptoms assessed via the Brief Psychiatric Rating Scale. RESULTS: At baseline, participants smoked a mean of 76 cigarettes per week, declining to 35 cigarettes at 12 weeks. Both groups showed a significant linear decline in cigarette consumption over time (mean change: -3.7 cigarettes/week; 95% CI: -5.2, -2.4), with no significant between-group difference. Smoking abstinence increased significantly (McNemar χ2=5.33, p<.05). Psychiatric symptoms decreased continually, with scores dropping by 0.29 units per week (95% CI: -0.50, -0.09) in both groups. CONCLUSIONS: Although there were no significant differences between study groups, both study groups showed a significant reduction in cigarettes smoked each week and in psychiatric symptoms. Group-based counseling and pharmacotherapy likely contributed to these improvements. Future research should assess longer-term outcomes in sustaining smoking cessation. Clinical Trials Registration Number: NCT03950427.

BACKGROUND: Chair-based exercise may represent a practical alternative for individuals with chronic obstructive pulmonary disease (COPD) who experience balance limitations, fatigue, or difficulty performing standing exercises. OBJECTIVES: To compare the effects of chair-based and standard home-based exercise programmes in people with COPD. METHODS: In this randomized controlled trial, 64 clinically stable patients with COPD were allocated to a Standard Exercise Group (SGr,n = 32) or a Chair-Based Exercise Group (ChGr,n = 32). Both groups completed an 8-week home-based exercise programme (5 days/week) supported by exercise videos, two live online supervised sessions, and weekly follow-up calls; no blinding was applied. Outcomes included the 6-minute walk test (6MWT), modified Medical Research Council dyspnoea scale (mMRC), Fatigue Severity Scale (FSS), pulmonary function, maximal inspiratory and expiratory pressures (MIP/MEP), peripheral muscle strength, Hospital Anxiety and Depression Scale (HADS), International Physical Activity Questionnaire-Short Form (IPAQ-SF), and Saint George's Respiratory Questionnaire (SGRQ). Adverse events were monitored. RESULTS: Both groups showed significant improvements in dyspnoea, fatigue, HADS scores, total physical activity, and all SGRQ domains (p < 0.01). In the chair-based group, 6MWT distance (p = 0.003), MIP and MEP (p = 0.025 and p = 0.028), and peak expiratory flow percentage (PEF%; p = 0.044) increased significantly. Between-group differences were observed only for changes in MEP% (p = 0.032) and PEF% (p = 0.01), favouring the chair-based group. No adverse events were reported. CONCLUSION: Both interventions improved symptoms, physical activity, and quality of life, while significant improvements in functional capacity and selected respiratory parameters were observed only in the chair-based group.

Munchausen syndrome is a psychiatric condition in which individuals feign or induce illness to gain attention, care, and sympathy. Despite being clinically recognized, its biological underpinnings remain largely unexplored, highlighting the need for suitable animal models. Male mice were subjected to social isolation and restraint stress (2 h daily for 7 days) to induce chronic stress. Behavioral changes were assessed using a social interaction test with freely moving or confined juvenile and adult male conspecifics. Anxiety-like behaviors were evaluated by the open field test and elevated plus maze. Concentration of the interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the brain was quantified by using enzyme-linked immunosorbent assay (ELISA). Stressed mice exhibited increased social interaction with freely moving unfamiliar conspecifics but reduced interaction with confined ones. These animals displayed heightened anxiety-like behaviors and elevated levels of IL-6 and TNF-α in the brain. Currently, no preclinical models exist for screening factitious disorder. This study represents the first attempt to develop an animal model to identify Munchausen syndrome-like behaviors. Stress and anxiety significantly modulate social behavior in mice. Notably, enhanced interaction with freely moving conspecifics may mimic attention-seeking behavior, providing a potential model for investigating Munchausen syndrome-like traits. This model may offer insights into the neurobiological basis and aid in the development of targeted therapeutic strategies.

BACKGROUND AND AIM: Cancer patients frequently experience both physical pain and emotional distress, often intensified by exposure to past traumatic events. These psychological and physiological burdens can adversely affect treatment outcomes and quality of life. This study aimed to examine the relationship between past trauma, emotional well-being, and pain among cancer patients undergoing chemotherapy across Iraq. METHOD: This cross-sectional study was conducted from September 1st, 2024, to February 13th, 2025, across four major hospitals in Iraq, using convenience sampling. Data were collected using three standardized instruments: the Trauma History Questionnaire (THQ), the Pain Assessment Numerical Rating Scale (NRS), and the Hospital Anxiety and Depression Scale (HADS), along with a sociodemographic form. Statistical analyses were performed using SPSS version 26.0 and PROCESS Macro version 4.2. Descriptive statistics, Pearson's correlation, multivariable and hierarchical regression, and mediation analysis with 5000 bootstrap samples were employed. RESULTS: A total of 409 patients participated in the study. The Findings revealed significant positive correlations between trauma exposure and pain (r = 0.26-0.31), anxiety (r = 0.33-0.41), and depression (r = 0.29-0.38) (p < .05). Regression models indicated that trauma and emotional well-being significantly predicted pain (Adjusted R = 0.39, p < .001). Mediation analysis demonstrated that anxiety and depression partially mediated the trauma-pain relationship, accounting for 38-46% of the total effect. CONCLUSIONS: Past trauma was significantly associated with both emotional well-being and pain severity among cancer patients. Integrating trauma-informed psychological care into oncology settings may help reduce pain and enhance emotional resilience among patients.

BACKGROUND: Social isolation and loneliness represent significant public health issues in society. Irritable bowel syndrome (IBS) severely impacts quality of life and requires early prevention. However, the relationship between social isolation, loneliness, and IBS remains uncertain. We aim to investigate the association between social isolation, loneliness, and the incidence of IBS in a large-scale population cohort. METHODS: This prospective cohort study involved 369,653 participants without IBS from the UK Biobank. The genetic risk of IBS was evaluated using polygenic risk scores. The Cox proportional hazards model was employed to analyze the relationship between social isolation, loneliness, and the risk of IBS incidence. We examined whether depression and anxiety mediate the association between social isolation, loneliness, and IBS risk. RESULTS: Among the 369,653 participants (mean age: 56.7 ± 8.1 years; 47.7% male), 7,663 individuals were diagnosed with IBS during a median 13.6 years of follow-up. After comprehensive adjustment for socioeconomic status, lifestyle factors, health status, and genetic susceptibility, the HR for IBS incidence was 1.156 (1.073, 1.245) among socially isolated participants compared to non-socially isolated participants. The HR for IBS incidence was 1.361 (1.244, 1.490) among lonely participants compared to non-lonely participants. Subgroup analysis showed that, compared to participants without social isolation, the risk of developing IBS in participants without diabetes and those with diabetes under social isolation was 1.133 times (95% CI: 1.050-1.223) and 1.655 times (95% CI: 1.214-2.257) higher, respectively, with the risk being greater in the diabetic group (P for interaction = 0.022). CONCLUSION: Social isolation and loneliness were associated with an increased risk of developing IBS, although loneliness may have a more significant effect on risk. Participants with diabetes have a higher risk of developing IBS under conditions of social isolation. Depression and anxiety mediated the association between social isolation, loneliness, and the risk of developing IBS.

BACKGROUND: Trial teams frequently make language-related, non-clinical eligibility decisions during recruitment. They need to ensure that patients understand the conditions and implications of trial participation and either have the necessary language skills to participate, or receive appropriate accommodations (e.g. translation or interpreting). Fair and consistent assessments are necessary to avoid unduly excluding patients, which could limit external validity and exacerbate inequalities. This study examines how trial teams make language-related eligibility decisions. METHODS: We conducted a systematic review of National Institute for Health and Care Research (NIHR) research reports (2010-2022) for UK-based randomised controlled trials (RCTs) recruiting adults for two conditions that disproportionately affect ethnic minority populations: clinical depression and type 2 diabetes mellitus (T2DM). Two researchers independently screened titles and abstracts and extracted data. We analysed the communication demands of the interventions and primary outcome measures in relation to how language screening was reported, including procedures or instruments used as proxies for language-related gatekeeping. RESULTS: We assessed 185 titles and abstracts from NIHR monographs. Thirty-two RCTs (23 depression, 9 T2DM) ultimately met our inclusion criteria. Ethnic diversity was minimal, particularly in the depression RCTs, where the median proportion of White participants was 97%. Language screening practices were inconsistent across studies and were often poorly aligned with the actual linguistic demands of the trial. Half of the included RCTs explicitly reported a language-based eligibility criterion, including 63% of trials evaluating talking therapies for depression compared to 27% of trials assessing pharmacological, device-based, or surgical interventions. Explicit and implicit language-related gatekeeping measures included the ability to complete research assessments involving language (sometimes to a prespecified score cut-point), provide informed consent, and engage in the intervention as judged by recruiters. Translation and interpreting support were mentioned in one depression study. CONCLUSIONS: This review exposes methodological practices that may impede diverse patients' participation. Linguistic demands of the interventions and outcomes need to be considered in justifying language-related screening and accommodations. Participants' language variables need to be disentangled from ethnicity through routine data collection. A purpose-built screening tool that is universally applied to all participants could lead to fairer, more consistent assessments. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021267905. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=267905. Registered on October 21 2021.

BACKGROUND: Consultation-Liaison Psychiatry (CLP) services are essential for addressing the psychiatric needs of patients with complex medical conditions in general hospitals. AIMS: The study aims to characterize profiles of inpatient psychiatry referrals and describe referral patterns and evaluate temporal trends between referrals, patient demographics, and psychiatric and somatic diagnoses. METHOD: Data from January 2020 to December 2023 were collected from a CLP service during and after the pandemic, using psychiatric diagnoses from the International Classification of Diseases, Tenth Revision (ICD-10). Statistical analyses, including interrupted time series analysis with four periods, and including linear and segmented analyses, plus selective use of autocorrelation tests, were conducted to examine referral patterns and their associations with socio-demographic factors. RESULTS: 6,105 patients were referred to the CLP Service during the study period, which was 6.73% of all hospital admissions. Internal medicine and Pneumology exhibited consistently high referrals, while services like Rheumatology and Endocrinology had lower rates. Common somatic diagnoses included neoplasms (20.7%) and respiratory diseases (9.4%), while neurotic, stress-related, and somatoform disorders were prevalent psychiatric diagnoses (42.5%). Interrupted time series analysis revealed fluctuations in monthly care visits, with notable decreases coinciding with the onset of the COVID-19 pandemic. CONCLUSIONS: Our study elucidated the characteristics of patients receiving CLP services at a major Peruvian general hospital, revealing depression as a prevalent reason for consultation, and highlighting the dynamic nature of psychiatric care delivery, especially amidst the COVID-19 pandemic. CLINICAL TRIALS REGISTRATION NUMBERS: Not applicable.

BACKGROUND: Immune dysregulation and cognitive deficits are increasingly recognized in adolescent major depressive disorder (MDD), yet their interrelationship remains unclear. This study aimed to investigate peripheral immune-inflammatory alterations and natural killer (NK) cell phenotypes, and explore their association with cognitive function in adolescent MDD. METHODS: Fifty-four first-episode, drug-naïve adolescents with MDD and 33 matched healthy controls (HCs) were enrolled. Group differences in peripheral blood immune-inflammatory indices (NLR, PLR, MLR, SII, SIRI), NK cell surface receptors (HLA-DR, NKp46, NKp30, NKG2A, NKG2C, KIR2DL1, ILT2, CD57), and cognitive function were analyzed, along with their intercorrelations. RESULTS: Compared with HCs, patients with MDD showed lower NEU, NLR, PLR, and SII levels, alongside elevated LYM counts. NK cells exhibited reduced overall proportions but increased expression of HLA-DR, NKp46, NKG2A, and ILT2, with decreased CD57 expression in the MDD group. Significant cognitive impairments were observed in speed of processing, reasoning and problem solving, and social cognition. CONCLUSION: Exploratory analyses suggested potential links between immune measures and cognitive performance, which require confirmation in larger samples. The observed immune and cognitive alterations warrant further investigation into potential neuroimmune mechanisms in adolescent MDD. This study provides novel insight into potential biomarkers and immunomodulatory targets for early intervention in adolescent MDD. CLINICAL TRIAL NUMBER: Not applicable.

BACKGROUND: The number of refugees and people seeking asylum worldwide has risen significantly over the past 10 years. These individuals are often placed in immigration detention facilities following their migration journey. Previous studies, including a systematic review conducted in 2018, indicate that detention may be associated with an increase in mental health difficulties. The present review aimed to update the 2018 review by reporting on more recent studies investigating the prevalence of mental disorders and symptoms in immigration detainees, and whether the length of detention increases the likelihood of such disorders. METHODS: Six databases were searched for quantitative, peer-reviewed studies reporting on the prevalence of psychiatric symptoms or disorders in adults and children who had experienced immigration detention. The quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. The findings were presented narratively. RESULTS: Fourteen studies were included, reporting on a total of 2777 participants. The prevalence of significant mental health problems was high in both adults and children subjected to immigration detention. The most common disorders reported were post-traumatic stress disorder (PTSD), anxiety, and depression. Children also experienced high levels of emotional dysregulation and behavioural symptoms. In adults, longer durations of detention were consistently associated with a higher likelihood of experiencing mental health difficulties. Factors related to detention environments were also associated with the prevalence of psychological symptoms and diagnosable mental health conditions. CONCLUSIONS: Overall, this review confirms that immigration detention has negative mental health consequences across a variety of immigration detention facilities and detainee characteristics. Recommendations based on findings are presented, including eliminating child detention, imposing upper limits to the duration of adult detention, improving mental health screening pre-detention, and providing evidence-based psychological care during detention. PROSPERO REGISTRATION NUMBER: CRD42023487205.

STUDY DESIGN: A prospective study. BACKGROUND: In clinical practice, it is challenging to tell major depressive disorder (MD-D) apart from bipolar disorder depressive episodes (BD-D). This study focuses on using inflammatory proteins as biomarkers to differentiate MD-D from BD-D. MATERIALS AND METHODS: Admission plasma was collected from 30 healthy participants, 30 BD-D patients, and 30 MD-D patients. Ten samples from each group were randomly chosen for analysis using Olink Proteomics, and all samples were confirmed with ELISA. Then, we established a nomogram prediction model to assess the diagnostic potential biomarkers and their cut-off points. RESULTS: The study revealed that patients with MD-D exhibited notably elevated levels of IL6, MCP-3, TGF-α, TNFRSF9, and IL17-A compared to healthy control, with their cut-off values being 2.705 pg/ml, 374.5 pg/ml, 51.5 pg/ml, 328.5 pg/ml, and 2.905 pg/ml, respectively. Significantly higher levels of IL17-A and IFN-γ were found in MD-D patients compared to BD-D individuals and their cut-off values were 3.645 pg/ml, and 40.4 pg/ml, respectively. Subsequently, we created a nomogram prediction model that exhibited excellent consistency in the correction curve and proved to be clinically practical based on decision curve analysis. CONCLUSIONS: Our research indicated plasma inflammatory proteins associated with MD-D and could serve as potential biomarkers for it. Moreover, we discovered their cut-off values. A prediction model was created by us to accurately predict MD-D from BD-D patients, giving clinicians a novel approach to quickly distinguish MD-D and implement early targeted treatments. Larger samples are also necessary to further verify our results.

We aimed to examine the association between sleep duration and thirst level, indicator of altered hydration status. We performed a secondary analysis of the 2018 Korean Sleep-Headache Study, a nationally representative cross-sectional survey conducted in the Republic of Korea. Of 2,501 participants who completed the survey, 2,468 were included in the final analysis (age, 47.9 ± 16.4 years; 49.8% male). Participants were categorized into the high- or low-thirst group based on self-reported thirst frequency. Sleep duration was grouped as ≤ 6, > 6-7, > 7-8, and > 8 h. Logistic regression assessed the relationship between sleep duration and high thirst, adjusting for multiple lifestyle and health variables. Short sleep duration (≤ 6 h) was significantly associated with high thirst (adjusted OR 1.69; 95% CI, 1.00-2.86; p = 0.049), compared to the reference group (> 7-8 h). Age-stratified analyses revealed that adults ≥ 50 years showed a significant association between sleep duration of > 6-7 h and high thirst (OR 2.26; 95% CI, 1.23-4.12; p = 0.01). Sensitivity analyses indicated diabetes and habitual snoring as key contributors, and depressive mood consistently predicted high thirst. These findings suggest a complex interplay between sleep, thirst perception, and hydration, potentially mediated by metabolic and sleep-related disorders.

Subjective cognitive performance in multiple sclerosis (MS) correlates weakly with objective performance, but is more strongly associated with depression. We aimed to identify symptoms and brain MRI volumes related to subjective and objective cognitive performance. 205 MS subjects, diagnosed within the last 15 years, completed the SymptoMScreen, patient-reported Expanded Disability Status Scale, Neuro-QoL subjective cognitive and fatigue sub-scores, and Beck Depression Inventory. For the objective cognitive assessment the smartphone-based icompanion Symbol test was used. Volumetric variables were calculated from the 52 available brain MRIs using icobrain. A weak correlation was observed between subjective and objective performance (rho = 0.21, p = 0.002). Subjective performance was negatively associated with pain, dizziness, fatigue and depression, while objective performance was negatively related to walking impairment. Objective performance significantly correlated with thalamic volume, while subjective performance did not correlate with any brain volumes. In other words, subjective and objective cognitive performance are related to different clinical markers: subjective performance is linked to invisible symptoms, while objective performance is linked to more visible measurable clinical markers. Integrating both perspectives in clinical practice may provide a more holistic understanding of cognition in MS, allowing for tailored interventions that enhance patient care and quality of life.

Self-focused rumination, defined as an excessive attentional focus on one's depressive symptoms and their causes, meanings, and consequences, is well-established for its contribution to the onset and maintenance of depressive and anxiety symptoms. However, it remains unclear how this cognitive style can be manifested in older adults and how it might bridge the influences of different stressful life events (SLEs), namely dependent SLEs (partially attributable to one's behaviours) and independent SLEs (entirely beyond personal control), with the two symptom dimensions. Data were from 1868 community-dwelling older adults (mean age = 73.4; 83.1% female) as part of a territory-wide stepped-care intervention in Hong Kong for those with mild-to-moderately severe depressive symptoms (Patient Health Questionnaire-9 = 5-19). We investigated whether self-focused rumination would link dependent and independent SLEs to depressive and anxiety symptoms using both path and network analyses. In the path model, both SLE types were associated with self-focused rumination. Dependent SLEs were directly associated only with depressive symptoms, while independent SLEs were directly associated only with anxiety symptoms. Self-focused rumination linked SLEs to both symptom dimensions. With all symptoms accounted for in the network model, self-focused rumination also presented as the most central bridge symptom between the two SLEs and depressive and anxiety symptoms. Our study provided novel evidence to suggest the potential for targeting this cognitive response style in future interventions to reduce depressive and anxiety symptoms in older adults, particularly amid ongoing stressors.

Somatic symptom disorder (SSD) is characterized by persistent physical symptoms that cannot be fully explained by structural abnormalities or laboratory findings. However, the underlying neural mechanisms of SSD remain poorly understood. This study aimed to investigate functional brain abnormalities in SSD patients presenting predominantly with chest pain using resting-state functional magnetic resonance imaging (rs-fMRI). A total of 102 participants were prospectively enrolled, including 56 patients with SSD and 46 healthy controls (HCs). All participants underwent clinical assessments and structural MRI examinations, including T2-weighted imaging (T2WI), T1-weighted imaging (T1WI), diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), and rs-fMRI. The rs-fMRI metrics included regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional ALFF (fALFF). Group comparisons were conducted to identify differences in brain activity, and correlation analyses were performed to examine associations between brain activity and clinical symptoms. No significant differences were observed between the two groups in demographic variables, including age, gender, and education level. Clinical assessments revealed that SSD patients scored significantly higher than HCs on the Patient Health Questionnaire-15 (PHQ-15), Somatic Symptom Scale (SSS), Generalized Anxiety Disorder-7 (GAD-7), and Hamilton Depression Scale (HAMD). ALFF, fALFF, and ReHo analyses demonstrated significant alterations in spontaneous neural activity in SSD patients compared with HCs. Specifically, increased activity was observed in the left inferior frontal gyrus and precuneus, whereas decreased activity was detected in the hippocampus and insula. Correlation analyses revealed significant associations between these abnormal brain activity patterns and clinical symptom severity in SSD patients. This study highlights regional functional brain abnormalities in SSD, particularly in regions associated with emotion regulation, memory, and sensory processing. These findings provide novel insights into the neural mechanisms underlying SSD and suggest potential neuroimaging targets for therapeutic interventions that may help alleviate symptoms and improve patient outcomes.

Patients with COPD and comorbid depression/anxiety are at risk of reduced health status. This study aimed to assess health status in COPD patients with depression/anxiety, the occurrence of severely reduced health status in this group, and to investigate associations between severely reduced health status and patient-related clinical factors. This cross-sectional study included 2245 randomly selected COPD patients from primary care and hospital outpatient clinics in Sweden. The COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) were used to assess health status. Severely reduced health status was defined as CAT ≥ 20 or CCQ ≥ 2. The 524 patients (23.3%) who reported depression/anxiety had higher mean CAT scores (18.3 vs. 15.2, p < 0.001) and CCQ scores (2.37 vs. 1.83, p < 0.001) than patients without depression/anxiety. In this group, 48% had CAT ≥ 20 and 57% had CCQ ≥ 2. In patients with depression/anxiety, factors associated with CAT ≥ 20 were: onset of COPD symptoms before 60 years of age (OR = 2.62 [95% CI 1.37-5.04]), frequent symptoms of depression in the previous three months (2.59 [1.55-4.30]), one or more COPD exacerbations in the previous six months (2.37 [1.41-4.00]) and physical inactivity (1.89 [1.11-3.22]). Apart from physical inactivity, factors associated with CCQ ≥ 2 were the same as for CAT ≥ 20. Approximately half of the COPD patients with comorbid depression/anxiety reported severely reduced health status. Exacerbations, frequent depressive symptoms and physical inactivity were factors associated with severely reduced health status, and constitute important treatable and preventable traits of COPD.

Major depressive disorder is known to disturb the hippocampus, but how this impacts signal processing performed by the structure remains poorly understood. Here, we report that single housing (7-10 days) promotes a depression-like phenotype in young adult mice that is associated with a robust, yet surprisingly discreet defect in information flow across the primary hippocampal circuit. In addition to sociability disturbances and despair-like behavior, single housing eliminated preference for novelty and impaired episodic memory encoding. Additionally, the lateral habenula, an epithalamic structure critically involved in depression, was hyperactive. Although the CA1 waveform and associated spike output elicited by single-pulse lateral perforant path (LPP) activation of hippocampus was largely unaffected by single housing, pronounced disturbances emerged when the circuit was activated with physiologically relevant frequencies and patterns. The characteristic 'theta/gamma' pattern was distorted such that a pronounced facilitation was present in the single-housed group, while the filtering of CA1 output to brief beta (25 Hz) and gamma (50 Hz) frequency LPP stimulation evident in group-housed slices was absent. Within field CA3, the recruitment of inhibitory interneurons suppresses spike output, and subsequent signal propagation to CA1, in response to beta frequency LPP inputs but not those arriving at gamma frequencies. This CA3 beta filter was significantly impaired following single housing. These results suggest that a depression phenotype is associated with a highly selective and partial loss of inhibition within the CA3 and CA1 links of the hippocampal circuit, providing new insights into the relationship between depression and hippocampal function.

OBJECTIVES: To assess longterm weight and comorbidity outcomes following bariatric surgery at a publicly funded obesity service. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Cohort of 203 individuals who underwent bariatric surgery between 1 October 2009 and 1 June 2024 were followed for 1-10 years postoperatively. Major obesity-related comorbidities assessed included type 2 diabetes mellitus (T2DM), dyslipidaemia, hypertension, obstructive sleep apnoea (OSA), arthritis and arthralgia, and depression and anxiety. MAIN OUTCOME MEASURES: Percentage change in weight over time and change in prevalence of obesity-related comorbidities. RESULTS: At baseline the mean age was 50.4 years (SD, 11 years), mean weight 134.6 kg (SD, 30.3 kg), mean BMI 49.3 kg/m (SD, 9.5 kg/m) and 59.6% (n = 121) of the cohort had ≥ three of the six comorbidities. Maximal weight loss occurred at 18-months post-surgery with a mean 26.6% (SD, 9.8%) weight reduction. Data were available for 45% (n = 73/162) at 5 years and 38% (n = 19/50) of the cohort at 10 years, with mean weight loss of 23% and 21.9%, respectively. Compared to baseline, at 5 years there was a significant reduction in the proportion of the cohort with T2DM (-13.2%, p < 0.001), OSA (-11.4%, p < 0.001), hypertension (-10.4%, p < 0.002) and dyslipidaemia (-9.2%, p < 0.003), but there was no change in the proportion with anxiety, depression, arthritis or arthralgia. CONCLUSIONS: Bariatric surgery in a publicly funded service was shown to have long-term efficacy, with weight loss maintained to 10 years follow-up and a reduction in the incidence of four major obesity-related comorbidities after 5 years.

RATIONALE AND OBJECTIVES: Some patients with angina and non‑obstructive coronary artery disease (ANOCA) frequently present with anxiety. Mental stress can induce myocardial ischemia in patients with anxiety. This study aimed to assess myocardial microcirculation using dynamic CT myocardial perfusion imaging (CT-MPI) with mental stress test (MST) and pharmacologic stress test (PST) in ANOCA patients with anxiety. MATERIALS AND METHODS: ANOCA patients underwent CT-MPI with MST using a series of the standardized color word/arithmetic stressors and PST using regadenoson, and divided into anxiety group and non-anxiety group according to the generalized anxiety disorder scale. Myocardial blood flow (MBF) and myocardial blood flow reserve (MFR) were analyzed, using a 17-segment model. RESULTS: Sixty patients with 1020 segments were included for final analysis, including 29 patients with anxiety and 31 patients without anxiety. After MST, MBF value of the anxiety group was lower than that at rest (P < 0.05), and the anxiety group had a lower MFR compared to the non-anxiety group (P < 0.05); Anxiety severity was negatively correlated with global MFR and ΔGlobal-MBF value (r = -0.633, P < 0.001, r = -0.667, P < 0.001) and positively correlated with decreased global MBF value (r = 0.561, P = 0.01). In contrast, no significant differences or correlations were observed between the two groups after PST (P > 0.05). Multivariate logistic regression analysis revealed that anxiety is an independent risk factor for MBF reduction after MST in patients with ANOCA (OR=3.294, 95% CI: 1.009-10.754, P=0.046). CONCLUSIONS: Anxiety is associated with myocardial microcirculation dysfunction (MMD) in patients with ANOCA. Anxiety is a risk factor for MMD under mental stress in ANOCA patients.

Anorexia is a clinically significant condition in companion animals, particularly cats, that disrupts metabolic homeostasis and impedes recovery from underlying diseases. Mirtazapine (MRZ), a commonly prescribed appetite stimulant in veterinary medicine, has limited clinical utility due to its intense bitterness and suboptimal bioavailability in conventional dosage forms. To address these limitations, we developed a novel drug delivery system integrating microencapsulation technology with an orally disintegrating tablet (ODT) formulation. Using an optimized emulsification-solvent diffusion method, we produced ethyl cellulose-based microspheres exhibiting high encapsulation efficiency (93.19 ± 0.71%), uniform particle size distribution (106.12 ± 1.49 μm), and pH-responsive drug release characteristics. Comprehensive physicochemical characterization confirmed the structural integrity of the microspheres and the absence of detrimental drug-polymer interactions. Furthermore, the ODT formulation exhibited excellent pharmaceutical properties, including rapid disintegration and complete drug release under gastric conditions, and effective masking of MRZ's bitter taste in the oral cavity. In vivo evaluations revealed significantly improved palatability (p < 0.05) and preliminary evidence of appetite stimulation (p < 0.05) compared with conventional formulations, supporting further clinical development. Stability studies indicated robustness under standard storage conditions. This advanced delivery system successfully overcomes the major limitations of current MRZ therapies, offering a promising solution for enhancing treatment compliance and therapeutic outcomes in veterinary practice. Moreover, the developed technology platform provides valuable insights for formulating other challenging active pharmaceutical ingredients requiring taste masking and controlled release.

INTRODUCTION: Atopic dermatitis (AD) is a common chronic inflammatory disease that presents differences in clinical expression according to sex. The aim of this study was to evaluate the influence of sex on disease severity, comorbidities, treatments, and adverse events in patients with moderate-to-severe AD included in the Spanish BIOBADATOP registry. METHODS: We conducted a prospective observational study using data from the BIOBADATOP registry from March 2020 through February 2025. Demographic variables, severity scales (EASI, DLQI, POEM, pruritus VAS), comorbidities, treatments, and adverse events were collected. Statistical analysis was performed using chi-square, Student's t-test, and Mann-Whitney tests, considering statistical significance at P < .05. RESULTS: A total of 507 adult patients on systemic treatment were included (53.1% men, 46.9% women). Men showed greater disease severity according to EASI (21.7 vs 21.0) and higher serum IgE levels (1323 vs 638 KU/L). Women reported greater pruritus intensity and worse POEM scores. Anxiety (26% vs 13%) and depression (15% vs 5%) were more frequent among women. No differences were observed in family history or atopic comorbidities. Similarly, no relevant differences were found in treatments received, treatment duration, or clinical response at 3, 6, and 12 months. However, women showed a higher rate of GI adverse events (97/1000 vs 19/1000 patient-years). CONCLUSIONS: Clinical and comorbidity differences according to sex exist in moderate-to-severe AD. Men show greater disease severity and higher IgE levels, whereas women experience a greater perceived disease burden, pruritus, psychiatric comorbidities, and more GI adverse events. These findings support the need to consider sex as a factor in the evaluation and comprehensive management of AD.

Behavioral depression is a cardinal sign of clinically relevant pain and a target of pain treatment. Accordingly, preclinical assays of pain-depressed behavior can serve as tools for translational research on the expression and treatment of this key manifestation of pain. We recently validated a procedure to assess expression and pharmacological treatment of acute pain-related depression of locomotor activity produced in mice by acute treatment with intraperitoneal lactic acid (IP acid). The present study evaluated the utility of this procedure for research on locomotor depression produced by four putative models of chronic pain: (1) a model of episodic visceral pain produced by repeated daily IP acid injection, (2) a laparotomy model of postsurgical pain, (3) a cutaneous inflammatory pain model produced by intraplantar injection of complete Freund's adjuvant (Ipl CFA), and (4) a spared nerve injury (SNI) model of neuropathic pain. Locomotor activity in male and female ICR mice was objectively and quantitatively assessed in chambers with two compartments separated by a wire-mesh barrier that could be surmounted to cross between compartments. Primary dependent measures were vertical activity represented by Crosses between compartments and horizontal activity represented by the sum of photobeam breaks (Movement Counts) within each compartment. Repeated IP acid and laparotomy depressed both Crosses and Movement, and effects were alleviated by analgesics. Ipl CFA and SNI produced weak effects too small and variable to permit drug testing. These results support utility of repeated IP acid and laparotomy models for research on pain-related behavioral depression using locomotor endpoints in mice. PERSPECTIVE: Clinically relevant pain commonly produces behavioral depression. This article compared locomotor depression in mice produced by four chronic pain models. Two models (episodic visceral pain, postsurgical pain) produced locomotor depression alleviated by analgesics. Inflammatory and neuropathic pain models produced weak effects that limit their utility for research on pain-depressed behavior.

Adolescence is a sensitive neurodevelopmental period marked by remodeling of brain circuits that support cognitive development and emotion and behavior regulation. These maturation processes heighten psychiatric vulnerability to environmental exposures, including to toxicants such as insecticides. Epidemiological studies show widespread adolescent insecticide exposure and increasingly link this with psychiatric outcomes, yet underlying neural mechanisms remain poorly understood. Preclinical studies can clarify these associations and identify insecticide-induced mechanisms that may disrupt neurodevelopment and produce consequent long-term behavioral outcomes. Here, we performed a systematic review of rodent studies following PRISMA guidelines. 50 articles met inclusion criteria, examining neurotoxic outcomes following insecticide exposure during early (juvenile), middle, and late adolescent ages (postnatal days 21-60). Outcomes were categorized into four domains: neurocognitive, neuropsychiatric, neurobiological, and general neurotoxicity. Risk of bias was assessed using the SYRCLE Risk of Bias tool. Across studies, adolescent insecticide exposure led to learning and memory impairments and tended to increase depression-relevant behaviors, alter locomotor activity, and produce general neurotoxic effects. Mechanistic findings highlighted disruptions in cholinergic and monoaminergic signaling, oxidative stress, neuroimmune changes, and cell death and other neurodegenerative processes. Together, findings indicate adolescent insecticide exposure disrupts multiple neural systems with behavioral consequences relevant to adolescent development and psychiatric risk. Future research should model real-world exposures (e.g. dose, timing) to better inform translational understanding of adolescent psychiatric vulnerability. Because many life-long neuropsychiatric disorders emerge in adolescence, identifying how modifiable environmental exposures shape risk offers an opportunity for prevention and intervention strategies to alter the course of disease across the lifespan.