Patients diagnosed with cholelithiasis, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and constipation frequently exhibit comorbid major depressive disorder (MDD). Although the underlying mechanisms remain elusive, potential genetic associations have been proposed. Leveraging extensive genome-wide association study databases, the genetic association patterns between MDD and four digestive diseases (cholelithiasis, GERD, IBS, and constipation) were systematically investigated. A hierarchical analytical approach was adopted: linkage disequilibrium score regression (LDSC), genetic covariance analysis (GNOVA), and high-definition likelihood (HDL) were employed to evaluate genome-wide correlations. Regional genetic variation was analyzed using local variation association analysis (LAVA) to pinpoint significant genomic loci. A bivariate causal mixture model (MiXeR) was further applied to quantify genetic overlap. The conditional/conjunctional false discovery rate (cond/conjFDR) approach was utilized to detect shared loci. Tissue-specific enrichment analyses were conducted using linkage disequilibrium score regression for specifically expressed genes (LDSC-SEG) to identify phenotype-relevant tissue distributions. In addition, a genetics-informed cell-type spatial mapping approach was used to generate single-cell-resolution maps of disease-associated cell populations. The findings revealed statistically significant, positive genome-wide genetic correlations between MDD and all four digestive diseases. Multiple chromosomal regions exhibiting shared genetic signals were identified through local variation analysis. Key overlapping genetic loci were uncovered via cond/conjFDR analysis. MiXeR further indicated substantial genetic overlap among these traits. Furthermore, gene enrichment assessments indicated that MDD, constipation, and IBS demonstrated significant tissue-specific enrichment in various brain regions. Genetics-informed cell-type spatial mapping analyses also revealed similar patterns of cell-type-specific distribution across related tissues. This investigation constitutes the first genomic-level evidence of genetic overlap between MDD and the four digestive diseases, elucidating shared loci that may underlie comorbidity mechanisms. These results suggest novel molecular pathways for integrated clinical prevention and therapeutic strategies.
Abstract Background Using speech as objective markers for major depressive disorder (MDD) has shown promise, yet their generalizability across clinical settings remains largely unvalidated. Objective This study aimed to validate previously identified speech markers of depressive symptoms in an independent clinical cohort, thereby assessing their reproducibility and robustness for cross-site application. Methods Speech data from two independent psychiatric cohorts (RWTH Aachen and University of Oldenburg, Germany) were analyzed, comprising 135 participants (71 healthy controls, 64 MDD patients). Participants completed a positive and a negative storytelling task, over 80 temporal, lexical, and spectral speech features were extracted from the acoustic signal. Statistical analyses assessed group differences and correlations with Beck Depression Inventory (BDI-II) scores. Machine learning models trained on the Aachen data were tested on the Oldenburg cohort. Results Several temporal and spectral speech features, including utterance duration, pause duration, and MFCCs, were consistently associated with MDD diagnosis and symptom severity across both cohorts. Machine learning models trained on Aachen data achieved a classification accuracy (ROC-AUC) of 0.63 on the Oldenburg sample, demonstrating above-chance but modest transfer performance. Voice quality features (shimmer, jitter) showed more variable associations: partial correlations indicated some significant effects (e.g., shimmer and jitter during positive storytelling), whereas moderation analyses revealed interaction effects, particularly for shimmer and jitter in negative storytelling, where MDD patients exhibited higher values in the Aachen cohort but lower values in the Oldenburg cohort compared to healthy controls. Conclusions The study indicates that temporal and spectral markers of speech are relatively robust across independent clinical samples, whereas voice quality markers (shimmer, jitter) show site-dependent inconsistencies, acting as technical artifacts of varying recording conditions rather than robust biomarkers. While current speech-based classifiers remain less accurate than established self-report measures, their integration with clinical scores offers a more balanced trade-off between sensitivity and specificity. Future work should prioritize systematic evaluation across elicitation tasks, languages, and longitudinal settings to delineate which speech features are transferable and which are task-specific.
Abstract Global evidence shows a deterioration in the mental health of children and adolescents during the COVID-19 pandemic, raising questions about how mental health care, including psychotropic medication prescriptions, has adapted. However, it remains unclear how this deterioration affected prescription trends. This scoping review examined quantitative longitudinal studies comparing psychotropic drug prescriptions before and during the pandemic. A search of five databases, PubMed, CINAHL, Web of Science, Scopus, and PsycINFO, yielded 14 studies from 11 OECD countries (Austria, Australia, Canada, Denmark, Israel, Italy, the United States, Portugal, Sweden, Norway, and New Zealand). Included studies were quantitative, longitudinal, in English, and focused on individuals aged 0–19. Most used national health registers or clinical data covering pre-pandemic (2013–2019) and pandemic years (2020–2022). Six studies focused exclusively on adolescents (10–19 or 12–18 years), while others included larger age ranges (0–17/18/19 years). Ten studies reported increases in antidepressant and antipsychotic prescriptions during the pandemic, with two showing initial declines followed by rises; four reported overall decreases. Notable gender and age differences emerged, with girls showing the largest rise in antidepressant use and adolescents exhibiting higher usage than younger children. Stimulant prescription trends varied across countries. Socioeconomic disparities and national policy responses, including school closures and healthcare access, also influenced prescribing patterns. Two studies found higher prescription rates among children from more advantaged backgrounds. Twelve studies focused on the early pandemic period, limiting time generalisability, while only two extended into 2022. This review highlights the need for enhanced monitoring and extended longitudinal research to assess the long-term impact of crises like COVID-19 on youth mental health care. It also emphasises the importance of health system preparedness for managing psychiatric treatment in future public health emergencies. Although an overall shift in psychotropic prescribing among children and adolescents is suggested, the limited number of studies and short follow-up periods restrict conclusions about long-term trends.
Problematic gaming (PG) represents an addictive behavior that is prevalent among young adults and has a significant impact on mental health. Patients diagnosed with bipolar disorder (BD) may be particularly susceptible to PG. Nevertheless, the neural circuits underlying PG in patients with BD remain poorly understood. A total of 73 participants were included in this study, including the group of BD patients with PG (BD-PG, n = 26), the group of BD patients without PG (BD-NPG, n = 23), and the healthy control group (HC, n = 24). All participants completed the VGD-S and underwent resting-state fMRI scanning, while BD patients additionally completed the BDI-II and YMRS within 24 h before scanning. Seed-based functional connectivity (FC) related to cognitive control, emotion, and reward was examined. ANCOVA, FDR correction, a separate BD sensitivity analysis, and partial correlation analysis were performed. After FDR correction, FC between the left thalamus and right amygdala was increased in the BD-PG group compared with both the BD-NPG and HC groups and was also increased in the BD-NPG group compared with the HC group. Partial correlation analysis further showed that FC between the left thalamus and right amygdala was positively associated with VGD-S scores after controlling for age, education years, and medication burden. Increased FC between the left thalamus and right amygdala may represent a preliminary neural correlate of problematic gaming severity among patients with BD. This finding may suggest the potential importance of the thalamus and amygdala in cognitive control and reward processing in BD patients with PG.
The association between thyroid dysfunction, thyroid hormone replacement therapy, and depression remains inconsistent. This study investigated the bidirectional risk association between thyroid dysfunction and depressive symptoms, focusing on the effect of thyroid hormone therapy on depressive symptoms, and exploring the shared molecular basis between hypothyroidism treated with levothyroxine and depression at the genetic level. Part one utilized 2007–2012 National Health and Nutrition Examination Surveys (NHANES) data to analyze associations between thyroid profiles and depressive symptoms. Part two compared molecular expression profiles between levothyroxine-treated hypothyroid patients and major depressive disorder patients using GEO datasets (GSE251778, GSE103305). Part one revealed a bidirectional association between depressive symptoms and hypothyroidism: patients with decreased interest, appetite changes, or feelings of worthlessness/failure were more likely to have hypothyroidism, while hypothyroidism was associated with an increased risk of depressive symptoms in general (PHQ-9 score ≥ 5). Compared with those with normal thyroid function, participants receiving thyroid hormone replacement therapy had a significantly higher risk of PHQ-9 score ≥ 5 (OR = 1.328; 95
Curcumin is a natural polyphenolic compound that is believed to have the potential to treat various ailments, including depressive mood. However, studies on the anti-depressive properties of curcumin have yielded conflicting results. This meta-analysis seeks to assess the clinical benefits of curcumin for patients with depression or depressive symptoms. We systematically reviewed Scopus, PubMed, Web of Science, and Embase, inception February 15, 2025, to identify studies evaluating the impact of curcumin supplementation on depression in adults. The overall effects calculated using random effects model. Nineteen RCTs were included in meta-analysis. A pooled analysis of eight studies showed a significant effect for curcumin supplementation in term of improving depression (SMD: -0.76; 95
Forensic psychiatric patients have a reduced life expectancy, largely due to cardiovascular diseases. Low maximal oxygen uptake is a risk factor for cardiovascular diseases in the general population and may also be essential to the cardiovascular risk among forensic psychiatric patients. The purpose of this study was to verify previous results of very low estimated maximal oxygen uptake levels in a larger group of forensic psychiatric patients and investigate the impact of the length of inpatient forensic psychiatric care on estimated maximal oxygen uptake. Further, we examined the extent to which BMI, level of physical activity, and smoking status were associated with estimated maximal oxygen uptake. We evaluated estimated levels of maximal oxygen uptake based on clinical testing of 115 forensic psychiatric patients and the development of these levels during inpatient care for those who underwent retesting (two tests, n = 66, three tests, n = 30). Mean estimated levels of maximal oxygen uptake were remarkably low, confirming previous findings. Levels correlated negatively with higher body mass index, lower physical activity, and older age; however, no change was observed during forensic psychiatric inpatient care. Estimated physical activity levels tended to increase between tests one and two, but decreased significantly between tests two and three. This Swedish forensic psychiatric cohort had very low cardiovascular fitness. The strongest associated factors were a high BMI and a low level of physical activity. These results make essential contributions to the planning of future studies on treatment strategies aimed at improving metabolic health in forensic psychiatric patients. The importance of aerobic exercise, as well as means to encourage patients to reach and maintain recommended levels of physical activity, needs to be further explored.
Major depressive disorder (MDD) is accompanied by prominent physiological abnormalities, notably sleep disturbances and immune-inflammatory dysregulation. As a serotonin-norepinephrine reuptake inhibitor, antidepressant duloxetine exhibits both anti-inflammatory effects and therapeutic benefits in improving sleep architecture. This study aimed to investigate the effects of duloxetine on objective sleep parameters and serum pro-inflammatory cytokine levels in patients with MDD, and further to explore the correlation between treatment-related improvements in sleep quality and dynamic changes in inflammatory cytokine profiles. This study included 74 patients with MDD who met the DSM-5 criteria, had a baseline 24-item Hamilton Depression Rating Scale score ≥ 20, and no prior use of antidepressants or anti-inflammatory drugs within 3 months. All patients were administered duloxetine at a daily dose of 40–60 mg for 4 consecutive weeks. Objective sleep parameters, including total sleep time (TST), sleep efficiency (SE), wake time after sleep onset (WASO), and rapid eye movement (REM) latency, were evaluated using polysomnography (PSG). Serum levels of 6 pro-inflammatory cytokines, including interleukin‑1β (IL‑1β), IL‑6, IL‑8, IL‑12, tumor necrosis factor‑α (TNF‑α), and interferon‑γ (IFN‑γ), were measured by enzyme-linked immunosorbent assay. Changes from baseline to post-treatment were analyzed using paired t-tests or Wilcoxon signed-rank tests based on data distribution. Correlation analyses were performed using Pearson or Spearman tests, followed by partial correlation analysis adjusting for potential confounders. After 4 weeks of duloxetine treatment, significant improvements in sleep parameters were observed, characterized by increased TST (t = -6.614, P < 0.001) and SE (t = -6.631, P < 0.001), as well as decreased WASO (t = 6.331, P < 0.001). Moreover, serum concentrations of IL‑1β (t = 4.759, P < 0.001), IL‑8 (t = 6.327, P < 0.001), IL‑12 (t = 6.194, P < 0.001), and IFN‑γ (t = 8.713, P < 0.001) were significantly reduced following treatment. Furthermore, at baseline, TST was negatively correlated with serum IL-12 levels (r = -0.306, P = 0.016) in patients with MDD. Similarly, SE was negatively correlated with serum levels of IL‑1β (r = -0.343, P = 0.006), IL‑8 (r = -0.297, P = 0.019), and IL‑12 (r = -0.279, P = 0.028). Additionally, following treatment, the change in TST was negatively correlated with the change in IL-12 levels (r = -0.285, P = 0.025). Likewise, the change in SE was negatively correlated with changes in IL-8 levels (r = -0.263, P = 0.039) and IL-12 levels (r = -0.294, P = 0.020). Four-week duloxetine treatment was associated with improved sleep disturbances and reduced peripheral pro-inflammatory cytokine levels in patients with MDD. The baseline correlations between sleep parameters and pro-inflammatory cytokines, as well as the concurrent changes in these indicators following duloxetine treatment, reveal a potential relationship between sleep improvement and altered inflammatory profiles during duloxetine intervention. These preliminary findings suggest a possible link between duloxetine-related therapeutic effects on sleep and inflammatory regulation in MDD, which warrants further verification in future studies.
This study examined whether the timing of adverse childhood experiences (ACEs) is associated with differences in intellectual ability in adults with autism spectrum disorder (ASD) without intellectual disability. A total of 161 adults with ASD were categorized into three groups based on ACE onset: no ACEs (Group 0), early childhood ACEs (≤ 10 years; Group 1), and adolescent ACEs (11–18 years; Group 2). Intellectual ability was assessed using the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). Findings revealed that Group 1 outperformed Group 2 on the picture completion and figure weights subtests, suggesting that early ACE exposure may be linked to distinct cognitive profiles in ASD. To account for the higher severity of post-traumatic stress disorder (PTSD) symptoms, including hypervigilance, in Group 1 compared to Group 2, we conducted multivariate analyses of covariance and logistic regression to control for potential confounders such as years of education and PTSD symptom severity, given that hypervigilance may influence cognitive task performance. However, the observed differences remained significant. These results suggest a potential association between the timing of ACE exposure and specific cognitive subdomains in adults with ASD. Furthermore, WAIS-IV subtests, particularly picture completion and figure weights, may serve as potential markers for identifying cognitive adaptations associated with early adversity in ASD individuals. Since this study was not a clinical trial, this section does not apply.
Growing research highlights interpretation inflexibility as a key transdiagnostic mechanism across psychopathologies. Yet, few studies have examined its role in everyday socio-emotional processing. This review bridges that gap by exploring how interpretation inflexibility contributes to psychopathology—particularly depression and psychosis—in social contexts. Evidence suggests disrupted interpersonal processes, including rigid interpretations of social scenarios and impressions of others, are central to understanding depressive and psychotic symptoms. Depression is marked by valence-specific, context-dependent inflexibility, with difficulty disengaging from negative biases. In contrast, psychosis shows a broader inflexibility across emotional valences. The review also outlines evolving measures of interpretation inflexibility, emphasizing the need to account for social context in interpretation revision. Current findings highlight the value of examining inflexibility within social frameworks to better understand its role in adaptive functioning and psychopathology. Future research on interpretation inflexibility in social contexts could inform novel interventions and improve clinical outcomes.
Obsessive–compulsive disorder (OCD) is a chronic, early-onset condition often associated with high rates of treatment resistance, and affective disturbances are frequent comorbidities and linked to poorer therapeutic outcomes. Recently, the concept of “demoralization syndrome” has been proposed as not fully overlapping with major depressive episodes. Given the disabling nature of OCD, it is relevant to specifically evaluate the states of demoralization, considering that this condition may have treatment implications partially different from those related to other forms of affective disturbances. The aim of the present exploratory study was to evaluate demoralization in subjects with OCD and its relationship with the severity of OCD-related symptoms. Adults with a primary diagnosis of OCD were consecutively recruited from the OCD outpatient clinic of Azienda Ospedaliero-Universitaria Policlinico Umberto I (Rome, Italy). Participants were assessed with clinical interviews as well as with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for OCD severity, the Demoralization Scale (DS) for demoralization, and the Patient Health Questionnaire (PHQ) and Hamilton Depression Rating Scale (HAM-D) for depressive symptoms. Descriptive and correlational analyses have been performed. A total of 43 adults with OCD were included. Both depressive and demoralization symptoms were highly prevalent, with clinically-significant demoralization observed in 88
Adolescents undergo important developmental changes, characterized by profound biological and psychosocial changes. This period is also associated with increased vulnerability to mental health challenges and engagement in risky/problematic behaviors. Non-suicidal self-injury (NSSI) and internet addiction (IA) are increasingly recognized as prevalent and interconnected behavioral concerns among adolescents, particularly those with depressive disorders. Impulsivity has also been identified as a key psychological factor in both IA and NSSI. This study aimed to investigate the cross-sectional interrelationships among depression, impulsivity, IA, and NSSI in adolescents. A total of 110 adolescents (55 diagnosed with major depressive disorder [MDD] and 55 healthy controls) were recruited from the Child and Adolescent Psychiatry Outpatient Clinic at Suez Canal University Hospital. The severity of depression was assessed using the Children’s Depression Inventory (CDI). All participants completed the Internet Addiction Test (IAT), Deliberate Self-Harm Inventory (DSHI), and Barratt Impulsiveness Scale (BIS-11). Statistical analyses included group comparisons, correlation analyses, logistic regression. Cross-sectional pathway analyses using structural equation modeling (SEM) was conducted to examine indirect associations between IA and NSSI through depression and impulsivity. Adolescents with MDD reported significantly higher levels of NSSI, IA, and impulsivity compared to controls. Significantly positive correlations between IAT, BIS-11, and CDI scores and lifetime NSSI frequency were demonstrated among the depression group. IA and NSSI were significantly associated by indirect pathways through both depression and impulsivity. In serial associational models, the cross-sectional indirect pathway from impulsivity to depression (B = 0.370) was stronger than the reverse direction (B = 0.310). Our findings highlighted the interrelated roles of IA, impulsivity, and NSSI among adolescents with MDD. Impulsivity may be a critical factor linking IA to emotional dysregulation and self-injurious behavior. These results highlight the need for integrated screening and prevention strategies targeting impulsivity and these risk behaviors.
Adolescent depression is a major mental health disorder with increasing prevalence and substantial long-term consequences. Although growing evidence suggests that the gut-brain axis is involved in depression, the relationships among gut microbiota, intestinal mucosal neurotransmitters, and adolescent depression remain insufficiently understood. This knowledge gap limits a better understanding of the pathophysiological mechanisms underlying adolescent depression and the identification of potential microbiota-related targets. Therefore, this study aimed to investigate alterations in gut microbiota and intestinal mucosal neurotransmitters, as well as their correlations, in an adolescent mouse model of depression. We established an adolescent depression mouse model using chronic unpredictable mild stress (CUMS), and collected data with the Smart video tracking system. We collected intestinal contents and mucosal tissues from mice. We analyzed gut microbial composition using metagenomic sequencing and quantified mucosal neurotransmitters with liquid chromatography–tandem mass spectrometry (LC–MS/MS). We analyzed correlations among gut microbiota, intestinal mucosal neurotransmitters, and behavioral indicators. Mice in the CUMS group exhibited a significantly reduced sucrose preference rate in the sucrose preference test (P < 0.001); a significantly prolonged immobility time in the forced swim test (P < 0.01); and a significantly decreased total movement distance in the open field test (P < 0.01). No significant intergroup difference was observed in the tail suspension test. Regarding the gut microbiome, the CUMS group showed significantly lower Simpson index (P = 0.018) and Pielou’s evenness index (P = 0.022). Beta diversity analysis indicated a statistically significant but modest between-group difference in community structure (ANOSIM R = 0.145, P = 0.03); this finding was supported by PERMANOVA (Bray–Curtis; pseudo-F = 1.675, R² = 0.0897, P = 0.033). LEfSe (Linear discriminant analysis Effect Size) analysis suggested 27 candidate taxa with discriminatory signals between groups (nominal P < 0.05; exploratory). Neurotransmitter analysis demonstrated that levels of 5-HIAA (5-hydroxyindoleacetic acid), 5-HT (serotonin), 5-HTP (5-hydroxytryptophan), and Kyn (kynurenine) in the colon were significantly decreased in the CUMS group, whereas levels of PA (phenylethylamine) and NE (norepinephrine) were significantly elevated (P < 0.05). Spearman correlation analysis found that Lactobacillus and Lactobacillus acidophilus correlated positively with sucrose preference and negatively with immobility in the forced swim test. Lactobacillus acidophilus also showed a positive correlation with 5-HT pathway metabolites: 5-HIAA, 5-HT, 5-HTP, and Kyn. Adolescent mice exposed to CUMS showed depression-relevant behavioral alterations, shifts in gut microbiota composition, and changes in 5-HT pathway metabolites. Gut microbiota dysbiosis was significantly associated with alterations in 5-HT pathway metabolites. Because this study is correlational, causal relationships require validation in future interventional studies.
The objective of this study was to examine the association between generalized anxiety disorder (GAD) and health-related quality of life (HRQOL) in the general Korean population, and whether this relationship differed by multimorbidity profiles and household income. We included 5,542 participants aged 19 years or older from the data of the 2021 Korean National Health and Nutrition Examination Survey. The GAD was assessed using the Generalized Anxiety Disorder 7-item scale (GAD-7). Participants with a GAD-7 score ≥ 10 were classified as having GAD. HRQOL was measured using the Health-related Quality of Life Instrument with 8 Items (HINT-8). Multimorbidity profiles were derived using latent class analysis. Survey-weighted regression models were used to evaluate associations and interaction effects. The weighted prevalence of GAD was 4.23
To investigate the discriminative value of the combination of lymphocyte-to-high-density lipoprotein ratio (LHR), neutrophil-to-lymphocyte ratio (NLR), and platelet count for patients with first-episode schizophrenia (FES). A retrospective analysis was performed on 181 antipsychotic-naïve inpatients with FES admitted to Zhenjiang Mental Health Center between January 2015 and February 2025.189 participants, including staff members who underwent health check-ups at the same center from July 2024 to November 2025, were prospectively recruited as the healthy control group. Both groups underwent fasting blood cell analysis. Univariate analysis, binary Logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were employed to assess the diagnostic performance of the combined use of LHR, NLR, and platelet count for FES. Univariate analysis revealed that white blood cell count, neutrophil count, monocyte count, platelet count, high-density lipoprotein (HDL), neutrophil-to-high-density lipoprotein ratio (NHR), LHR, platelet-to-lymphocyte ratio (PLR), NLR, and systemic immune-inflammation index (SIRI) were statistically significant influencing factors associated with FES (all P < 0.05) when comparing the FES group with the healthy control group. Binary Logistic regression analysis further identified platelet count, LHR, and NLR as independent predictors of FES relative to healthy controls (all P < 0.05). The ROC curve analysis demonstrated that the combination of platelet count, LHR, and NLR yielded an area under the curve (AUC) of 0.863 for distinguishing FES. The combination of LHR, NLR, and platelet count is significantly elevated in antipsychotic-naïve FES patients compared with healthy controls. These findings highlight immune-metabolic dysregulation in acute-phase FES, but do not establish diagnostic specificity. Comparative studies with other acute psychiatric disorders are needed.
Psychotic-like experiences (PLEs) are associated with subjective loneliness, as well as social isolation. However, few studies have examined how different combinations of loneliness and social isolation relate to overall PLEs and specific psychotic symptom domains. The aim of this study was to examine the associations between combinations of loneliness and social isolation and PLEs in a population-based sample in Japan. Data were derived from the 2025 wave of the Japan Society and New Tobacco Internet Survey (JASTIS), including 25,424 adults aged 15–84 years. PLEs were assessed using the Japanese version of the PRIME Screen–Revised (PS-R). Loneliness was measured using the University of California, Los Angeles Loneliness Scale version 3, Short Form 3-item (UCLA-LS3-SF3), and social isolation was assessed using the Lubben Social Network Scale (LSNS-6). Logistic regression analyses with inverse probability weighting were conducted to examine associations between four categories of loneliness/social isolation and overall PLEs as well as six psychotic symptom domains. The weighted prevalence of PLEs was 4.3
Abstract Background The aripiprazole once-monthly 400 mg two-injection start (AOM 400-TIS) enables treatment initiation at a single clinic visit, without the need for 14 days of concurrent oral aripiprazole supplementation. Previously, results from a survey outlined the views and experiences of healthcare professionals (HCPs) with the AOM 400-TIS in a real-world setting in Europe. The current work extends these findings to include a broader pool of participants from more European countries. Methods This was a non-interventional, cross-sectional survey of HCPs from Germany, Italy, the United Kingdom, Denmark, and Sweden. Participants were licensed nurses/physicians with experience prescribing and/or administering the AOM 400-TIS to patients diagnosed with schizophrenia. Two waves of survey data were pooled and analysed using descriptive methods. Results Data from 229 HCPs were evaluated. Poor treatment adherence (88.6%), relapse (51.1%), and patient preference (47.6%) were common reasons for using the AOM 400-TIS, while patients not wanting two injections at the same time (52.4%) and concerns about safety (34.1%) and tolerability (33.6%) were common barriers. Among HCPs, 86.0% agreed/strongly agreed they were satisfied with outcomes of patients treated with the AOM 400-TIS, with most agreeing/strongly agreeing that patients appeared satisfied in general (73.4%) and with sustained quality of life and functioning (66.4%). Conclusions This survey provides a pan-European account of HCPs’ views and experiences with the AOM 400-TIS in adults diagnosed with schizophrenia. Initiatives to overcome barriers to AOM 400-TIS use include providing clearer evidence and education on its efficacy and safety and consideration of how the regimen is presented in patient−provider discussions.
Abstract Objective This systematic review and meta-analysis aimed to evaluate the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) in patients with anorexia nervosa (AN) and bulimia nervosa (BN), focusing on its impact on psychological, psychopathological, neurocognitive, and behavioral outcomes. Methods A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Cochrane CENTRAL from inception to May 2025. Eligible studies included clinical trials involving adult patients with AN or BN treated with rTMS. Data were pooled using fixed or random-effects models depending on heterogeneity. Mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated. Risk of bias was assessed using Cochrane RoB 2.0 and NIH tools. Results Thirteen studies were included, yielding a total of n = 195 active rTMS treatments and n = 132 sham treatments. Compared to sham, rTMS did not significantly improve BMI in AN patients (MD: 0.19; 95% CI: -0.50, 0.88; P = 0.59). A significant moderate reduction in eating disorder severity was found in single-arm analysis (31 patients, SMD: -0.50, 95% CI [-0.90, -0.10], p = 0.01). Depression improved with rTMS over sham (105 patients, SMD: -0.41, 95% CI [-0.81, -0.02], p = 0.04), while anxiety, binge frequency, and vomiting frequency did not. Urge to eat increased in AN (30 patients, MD: 1.20, 95% CI [0.20, 2.21], p = 0.02) and decreased in BN (25 patients, MD: -10.25, 95% CI [-15.88, -4.62], p = 0.0004). No serious adverse events were reported. Conclusions rTMS shows potential in improving eating disorder severity and depressive symptoms in AN, with disorder-specific modulation of food-related urges. Its effects on BMI and behavioral symptoms remain inconclusive. rTMS was well tolerated.
Following Italy’s psychiatric reform, national inpatient numbers declined, but how the age at admission has changed across sex, diagnostic, and admission-type subgroups remains unclear. This study examined 17 consecutive years (2006–2022) of psychiatric admissions to the sole ward serving L’Aquila, assessing temporal trends in age at admission by diagnosis, sex, and admission status (voluntary vs. compulsory). All adult admissions (≥ 18 years) were extracted from hospital discharge records (Schede di Dimissione Ospedaliera, SDO). Analyses were conducted at the admission-episode level. Primary diagnoses were grouped into four ICD-9 categories: schizophrenia spectrum, major depressive disorder, bipolar disorder, and alcohol/substance use disorder. Multiple linear models tested time-related changes in mean age at admission, including interactions for time × diagnosis × sex × admission type. Across 5,207 admission episodes, the Trimester × Diagnosis interaction showed a marked decline in age at admission for major depression (B = − 0.20 per trimester, p < 0.001) and bipolar disorder (B = − 0.09, p = 0.03), equivalent to approximately − 0.80 and − 0.36 years per year, yielding total reductions of 13.6 and 6.1 years over 2006–2022. The Trimester × Diagnosis × Sex interaction indicated that the decline in depression was driven by men (B = − 0.32, p < 0.001; ≈ −1.28 years/year; −21.76 over 17 years), while in bipolar disorder it was driven by women (B = − 0.14, p = 0.03; ≈ −0.56 years/year; −9.52 over 17 years). The Trimester × Admission type interaction showed the reduction was specific to voluntary admissions (B = − 0.10, p < 0.001; ≈ −0.40 years/year), while compulsory admissions were stable (B = − 0.01, p = 0.87). No significant age change occurred in schizophrenia spectrum disorders or in alcohol/substance use disorders. Between 2006 and 2022, we observed a progressive rejuvenation of voluntary and affective-disorder inpatient admissions, with the clearest subgroup-specific reductions detected in men with major depression and women with bipolar disorder, while remaining stable in schizophrenia spectrum, alcohol/substance use disorder, and compulsory admissions. These findings underscore the need to balance youth-focused outreach with adequate capacity for chronic psychosis and substance use disorder.
Abstract Background Nonadherence is a major cause of relapse in patients with schizophrenia, schizoaffective disorder, or bipolar disorder who have achieved remission. However, it is also a significant challenge during manic episodes. Risperidone in-situ microimplant (ISM) releases the drug early and in a sustained manner once a month, eliminating the need for daily administration, which can be difficult during a manic episode. In this study, we described symptom trajectories and tolerability of a brief oral risperidone lead-in followed off-label initiation of risperidone ISM within multimodal inpatient care in nonadherent inpatients with schizoaffective disorder experiencing a manic episode with psychotic symptoms. Methods This retrospective, observational, single-centre study included 50 consecutive adults admitted after discontinuation/marked non-adherence and with prior response to risperidone who received ≥ 6 days of oral risperidone to confirm tolerability, then risperidone ISM (75 or 100 mg) and were followed for 6 weeks. Mania severity was assessed with the Young Mania Rating Scale (YMRS). Results Fifty patients were included; most received concomitant mood stabilisers and benzodiazepines. Median YMRS decreased from 32 at admission (Tx) to 26 at the first injection (T0, after the oral lead-in), 8 by day 8, and remained low at day 28 (5) and day 42 (6). Activation/behavioural items improved earlier, whereas psychotic thought content improved more gradually, predominantly between days 8 and 28. Side-effect burden at weeks 4 and 6 was minimal, and no discontinuations due to adverse events occurred. Conclusions In this exploratory uncontrolled cohort, an oral risperidone lead-in plus monthly risperidone ISM within multimodal inpatient care was associated with with rapid and sustained improvement in symptom trajectories and favourable short-term tolerability. Findings reflect multimodal inpatient care and cannot be attributed to ISM alone. Prospective, controlled studies are warranted.
