Search Results (506)

Background/Objectives: Bipolar disorder affects about 40 million people worldwide, and the greatest burden of the disease is associated with depressive episodes. About 25% of patients experience drug-resistant depression, in which standard treatment turns out to be insufficient, and monotherapy often does not bring full remission. Despite the use of second-generation antipsychotics, the effectiveness of therapy in TRBD remains limited, which necessitates rational polypharmacotherapy and augmentation strategies. The paper discusses the receptor mechanisms of drug combination, current therapeutic regimens and new interventions such as ketamine acting on the glutamate anergic system. The aim was to synthetically compare the efficacy and safety of available augmentation strategies and polypharmacotherapy. Methods: The material consists of published clinical, observational and randomized trials on pharmacotherapy of drug-resistant bipolar depression, including atypical neuroleptics, ketamine, pramipexole, modafinil, lamotrigine, celecoxib and memantine. The authors analyze receptor mechanisms, neurobiological data and clinical trial results, comparing them with current definitions of TRBD according to ISBD and CINP. Biomarker data, such as the Systemic Immune-Inflammation Index, and the results of neuroimaging and metabolomic studies were also used in the work. Results: The analysis showed that atypical neuroleptics showed limited efficacy and high rates of side effects, while ketamine has the fastest and most pronounced antidepressant effect with a low risk of phase change. Pramipexole has shown promise in terms of long-term efficacy, but its use reduces the high risk of induction of mania and impulse control disorders. Celecoxib as an anti-inflammatory therapy significantly increased response and remission rates compared to escitalopram alone, and memantine showed only an early, short-term antidepressant effect. The results highlight that TRBD requires targeted polypharmacotherapy, with the most promising directions being glutamatergic modulation and anti-inflammatory therapies. Conclusions: Drug-resistant bipolar depression requires a departure from classical monotherapy in favor of rational, mechanistically justified polypharmacotherapy, targeting complex monoaminergic, glutamatergic and neuroinflammatory disorders. Available data indicate that ketamine has the greatest clinical potential among the current strategies, characterized by a rapid onset of action and a favorable safety profile compared to atypical neuroleptics or dopamine agonists. Modulation of inflammatory processes with the use of celecoxib also has promising results, which highlights the importance of biomarkers and personalization of therapy. However, further, large, and well-designed studies are needed to unambiguously determine optimal treatment strategies for TRBD and to verify the effectiveness of new pharmacological interventions. Full article

Domestic Violence affects 1 in 3 women worldwide. Empirical evidence from India suggests that women and girls experience a continuum of violence and discrimination from prenatal stages till death in families that largely continue to operate within a dominantly patriarchal framework. However, the literature on domestic violence in India suffers from problems pertaining to reductive and episodic framing, focusing on short-term prevalence, and frames the impact on survivors largely in terms of clinical constructs such as anxiety, depression, and PTSD. This work argues for a broader, thematic framing of domestic and familial violence and contends that the psychological sequelae of this kind of chronic and systemic discrimination and violence cannot be captured using rigid clinical constructs that dominate psychological literature. We propose a conceptual framework, i.e., SPECTRA (Socially and Psychologically Embedded Continuous Trauma in Relational Architecture), which is partially aligned with the propositions of complex trauma. However, we also critique the origin of complex trauma within hegemonic psychiatry and highlight the need for creating a culturally adapted expansion—to shift the emphasis from an individually rooted, diagnostic framework to a culturally contextualized continuous trauma framework. We utilize seven illustrative case studies to define the tenets of the SPECTRA model. Full article

Chronic pancreatitis (CP) is a fibro-inflammatory condition defined by permanent anatomical changes in the pancreas. The causes of CP are described by the TIGAR-O classification system: toxin-related, idiopathic, genetic mutations, autoimmune disorders, episodes of recurrent acute pancreatitis, and obstructions. Pain is multifactorial in nature, and common psychopathological consequences of CP, including depression and anxiety, complicate the clinical picture of chronic pancreatitis. As a result, the quality of life of patients with CP is decreased. This review describes the pathophysiology of pain and its relationship to underlying psychological consequences, with a focus on a long-term, holistic management approach. Strategies that combine physical and psychological management align with SDG 3 (Good Health and Well-being). CP predominantly affects patients from low socioeconomic backgrounds due to disparities in medical care, underscoring the relevance of achieving SDG 10 (Reduced Inequalities). This review emphasizes the importance of targeted research in developing a holistic care model for CP that aligns with the SDGs. Full article

Daylight Saving Time (DST) creates abrupt, externally imposed circadian disruptions that can impair sleep regulation, hormonal balance, cognitive performance, and emotional stability. Although these effects are known in the general population, individuals with chronic mental illness, whose circadian systems are often intrinsically dysregulated, may face increased neuropsychological consequences. This comprehensive review synthesizes evidence from chronobiology, psychiatry, neuroscience, and population health to examine how DST-related circadian misalignment impacts cognitive functioning, mood regulation, suicidality risk, and symptom exacerbation across psychological disorders such as depression, anxiety disorders, bipolar disorder, post-traumatic stress disorder, attention-deficit/hyperactivity disorder, and psychotic disorders. Following the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines, a search of PubMed, PsycINFO, Scopus, and Google Scholar was conducted to identify studies published from 2000–2026 examining DST, circadian rhythm disruption, neuropsychological outcomes, and chronic mental illness. Empirical, theoretical, and mechanistic studies were included to ensure comprehensive synthesis. Across conditions, DST, particularly spring forward transitions, is associated with increased sleep disturbance, impaired executive functioning, reduced attention and working memory, heightened emotional reactivity, increased depressive symptoms, elevated risk of manic episodes, and short-term increases in suicidality. Neurobiological mechanisms include altered melatonin secretion, cortisol dysregulation, Hypothalamus Pituitary Axis (HPA-axis) activation, and clock-gene desynchrony. DST may function as a modifiable negative environmental influence capable of affecting neuropsychological functioning in vulnerable populations. These findings underscore the need for clinical awareness, preventive strategies, and policy reconsiderations, including calls to eliminate seasonal time changes. Standardizing DST-related research outcomes and expanding longitudinal, multi-site studies will be essential for advancing this emerging field. Full article

Background/Objectives: A psychiatric consultation is a professional evaluation aimed at establishing a diagnosis, a prognosis, and developing a treatment plan. The objective was to assess psychiatric consultations (PCs) at the Community Mental Health Center (CMHC), Emergency Room (ER) and General Hospital (GH) to highlight differences across settings. Methods: With a retrospective design, we examined all PCs performed between 1 January 2024 and 31 December 2024 at the CMHC, ER and GH of Baggiovara in Modena. Descriptive statistical analysis and a multivariate logistic regression were performed. Results: We collected a total of 3174 PCs for 1801 patients, performed in the three settings: 52% in ER, 30% in CMHC and 18% in GH. In ER, PCs were most frequently requested for suicide risk (26%), psychomotor agitation (14%) and substance intoxication (14%). In CMHC, the most common diagnoses were depressive disorders (22%), acute anxiety (20%) and acute psychotic episodes (13%). In GH, consultations mainly addressed psychiatric symptoms associated with medical and eating disorders. The overall rate of psychiatric hospitalization after PCs was 16.2%, reaching 23.4% for consultations in ER. Discontinuation of pharmacological therapy was significantly associated with an increased risk of hospitalization (p < 0.001), which rose to 17% when therapy had been interrupted for more than one year. Conclusions: PCs at ER were the access point for most hospitalizations. Therapeutic discontinuation, acute psychosis and substance use represented the main predictors of hospitalization. Strengthening shared care pathways among CMHC, ER and GH represents an effective model of integration between hospital and community services, ensuring continuity of care. Full article

Home has been recognized as a health infrastructure through hospital-at-home, home care, and direct-to-consumer wellness and fitness products. However, the patient home environment has been largely overlooked by healthcare as a means to improve therapy outcomes for difficult-to-treat chronic conditions, such as migraine; high-impact pain; and treatment-resistant depression, anxiety, or insomnia. Growing research evidence enables the formulation of a therapeutic home environment standard consisting of three pillars: biophilic design, indoor environmental quality, and intentional self-care spaces that serve as habit cues and foster sleep hygiene, stress management, relaxation, physical activity, and social interactions. Together, these environmental and behavioral interventions can transform real-world inputs into clinical benefits through autonomic, circadian, and emotional regulation. We also highlight the converging roles of self-management, self-efficacy, self-regulation, and self-compassion in sustaining patient engagement and healing at home. The applicability of the therapeutic home environment as an adjunct is illustrated in the case of chronic migraine, a debilitating neurological condition commonly associated with comorbidities. Current challenges in achieving migraine freedom with FDA-approved pharmacotherapies, neuromodulation devices, and digital health technologies are underscored by the high prevalence of refractory, chronic, episodic, and pediatric migraine. Perspectives on developing a personalized, multimodal cure for migraine are illustrated through a hypothetical drug + digital combination therapy comprising anti-CGRP drugs and an AI-powered digital health platform that promotes daily self-care practices within the therapeutic home environments. In conclusion, achieving sustained freedom from high-morbidity conditions requires end-to-end care ecosystems that integrate pharmacological, cognitive, behavioral, and environmental interventions into real-world settings. Full article

The ambiguous evolution of the depositional system in the Pinghu Formation of Block K, Xihu Depression, East China Sea Basin, has long constrained the accuracy of reservoir prediction in this area. Based on petrological analysis, sedimentary system identification, and depositional model reconstruction, this study systematically elucidates the sedimentary evolution of the Pinghu Formation in Block K. The results indicate that the Pinghu Formation exhibits diverse lithologies and multiple types of grain-size distribution, reflecting complex hydrodynamic conditions. The early stage was dominated by tidal processes with fluvial influence, transitioning to fluvial dominance in the late stage. The depositional system evolved through a complete sequence: the early stage (E2pSQ1) was characterized by a tide-dominated delta, the middle stage (E2pSQ2) by fluvial-tidal interaction, and the late stage (E2pSQ3) by an overwhelmingly fluvial-dominated system. This evolution was controlled by the combined effects of a persistently increasing sediment supply and episodic relative sea-level fall, with the transition mechanism primarily governed by tectonic-eustatic coupling. In the lowstand systems tract of the middle-upper section, a “high-supply, high-progradation” fluvial-dominated delta developed in the Kongbei fault-step zone, whereas a “low-supply, low-progradation” minor fluvial system formed in the Kongnan fault-step zone. Here, tidal reworking was weak, and tidal flats developed only locally. In contrast, the highstand systems tract in the middle-lower section was dominated by a tide-dominated delta in the Kongnan fault-step zone, while the Kongbei fault-step zone remained a “low-supply, low-progradation” minor fluvial system. The established depositional models provide a geological basis for reservoir prediction and hydrocarbon exploration in the Pinghu Formation of Block K. Full article

Background: Sleep disturbance is a well-recognized contributor to headache burden, yet the specific sleep domains associated with disability may differ between episodic migraine (EM) and episodic cluster headache (ECH). Methods: In this prospective observational study, 20 EM patients, 21 ECH patients, and 18 age-, sex-, and BMI-matched healthy controls (HCs) were evaluated during interictal periods. None of the patients were receiving prophylactic headache treatment. Sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and Sleep Hygiene Index (SHI). Psychological status was measured with the Hospital Anxiety and Depression Scale (HADS). Headache-related disability was assessed using the Headache Impact Test-6 (HIT-6) as a continuous outcome. Separate multivariable linear regression models were constructed for each headache group. Results: Both headache groups showed significantly impaired sleep and higher anxiety and depression scores compared with controls (all p < 0.001). HIT-6 scores did not differ between EM and ECH (p = 0.770 after Bonferroni correction). In multivariable regression, excessive daytime sleepiness (ESS) independently predicted disability in EM (B = 1.633, p = 0.033; R² = 0.571). In ECH, global sleep quality (PSQI; B = 0.701, p = 0.004) and sleep hygiene (SHI; B = 0.557, p = 0.033) were independently associated with HIT-6 (R² = 0.562). No significant multicollinearity was observed (all VIF < 2.5). Conclusions: Sleep disturbance is prevalent in both EM and ECH; however, the sleep domains associated with disability differ between phenotypes. Daytime sleepiness is more relevant in EM, whereas global sleep quality and sleep hygiene are more strongly associated with disability in ECH. These findings support a phenotype-specific approach to sleep assessment in headache management. Full article

Background and objectives: Ischemic priapism is a rare but serious adverse effect of trazodone, associated with a high risk of long-term sexual dysfunction. While its urological consequences are well described, psychiatric and psychosocial outcomes remain insufficiently explored. This study assessed psychiatric and sexual sequelae following trazodone-associated ischemic priapism and compared clinical characteristics with trazodone-treated patients without priapism. Materials and Methods: In this single-center observational study, 268 adult patients receiving trazodone were analyzed, including 17 patients with ischemic priapism and 251 controls. Data on episode duration and urological management were collected. Psychiatric status and sexual functioning were evaluated through structured clinician-led interviews informed by validated psychometric frameworks during hospitalization and at 1-, 3-, and 6-month follow-up. Nonparametric analyses and Spearman rank correlations were applied. Results: Patients with priapism were significantly older than controls (44.1 ± 5.1 vs. 39.0 ± 4.4 years; p < 0.0001), while trazodone dose distribution did not differ between groups. The mean episode duration was 26.5 ± 16 h (median 24 h). Older age and longer ischemic duration were independently associated with increased treatment intensity, whereas trazodone dose was not. Persistent depressive and anxiety symptoms and impaired sexual functioning were observed in a subset of patients during follow-up. Conclusions: Trazodone-associated ischemic priapism is not only an acute urological emergency but may also lead to sustained psychiatric and sexual sequelae. Interdisciplinary follow-up should be considered to address long-term psychosocial outcomes. Full article

Objectives. The aim of our study was to track changes in ODQ scores in adolescents with depressive episodes taking sertraline, depending on CYP2C19 polymorphisms. Methods. This study included 88 adolescents (88% were female) aged 12–17 who were prescribed sertraline. Emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ) scale when the antidepressant was prescribed, after one, three, and 8 weeks, taking into account other medications used. Part 3 of the ODQ scale assessed the changes that occurred after the prescription of an antidepressant. All patients were genotyped for CYP2C19*2, *3, and *17. Based on genotypes, the phenotypes of the CYP2C19 isoenzyme were determined. Results. The ODQ score at the time of enrollment was higher (65[50;79] points) compared with after 8 weeks (38.5[32.5;56.5] points). Part 3 of the ODQ-26 questionnaire remained approximately the same for 8 weeks. Patients with higher ODQ-26 values at enrollment (73[56;83] vs. 59[44;71] points) were more likely to be prescribed antipsychotics. Differences in ODQ scores remained significant up to 3 weeks after enrollment (50.5[41.5;68] vs. 45.5[36;54] points). The comparison of ODQ scores and their dynamics did not show significant differences depending on CYP2C19*2 or *17 polymorphisms, or the type of CYP2C19 metabolism. Conclusions. There was no increase in emotional blunting according to the ODQ score among adolescents with depression who took sertraline for eight weeks. No significant correlations were found between the carrier status of CYP2C19 gene variants and the development of apathy induced by antidepressants. Full article

Background: The glymphatic system, essential for brain waste clearance and neuroimmune regulation, remains underexplored in the context of bipolar disorder (BD) among young populations. Methods: Using diffusion tensor image analysis along the perivascular space (DTI-ALPS), we compared ALPS indices derived from the conventional FSL-based (cFSL) pipeline with those from the individualized ALPS (iALPS) pipeline. A cohort of young adults comprising 77 individuals with BD and 289 healthy controls was analyzed to evaluate methodological consistency and to identify disorder-specific alterations in glymphatic function. Results: The two pipelines showed only moderate agreement (Lin’s concordance correlation coefficient = 0.52–0.60), suggesting that differences in ROI placement strategies significantly affect ALPS estimation. While the cFSL pipeline detected no group differences, the iALPS pipeline identified a trend-level reduction in ALPS index in patients with BD during depressive episodes, particularly in the right hemisphere (p = 0.036, uncorrected, FDR-adjusted p = 0.071). No significant glymphatic alterations were observed in individuals with early-stage BD. Conclusions: These findings suggest that glymphatic dysfunction in psychiatric disorders may be phase-specific on illness. The use of individualized and automated analytical strategies, such as the iALPS pipeline, appears to enhance sensitivity to subtle, state-related brain changes that conventional methods may overlook. This methodological advancement provides a more biologically informed framework for future large-scale and longitudinal studies aimed at elucidating the role of glymphatic function in the pathophysiology of psychiatric disorders. Full article

Background: Non-invasive brain stimulation (NIBS) is increasingly used as an adjunctive option in late-life depression (≥60 years), a condition frequently complicated by multimorbidity and incomplete response to standard treatments. Comparative real-world evidence between repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), particularly including functional outcomes, remains limited. Methods: We conducted a retrospective, naturalistic comparative study of 104 depressed inpatients (≥60 years), either unipolar or bipolar, treated with rTMS (n = 48) or tDCS (n = 56) as part of routine care. Depression severity was assessed with the 21-item Hamilton Depression Rating Scale (HDRS21) at baseline, 2 weeks, and 1 month; response was defined as ≥50% HDRS21 score reduction and remission as HDRS21 < 7 at 1 month. Global Assessment of Functioning (GAF) was assessed at admission and discharge (baseline and 1 month). Longitudinal changes were examined using covariate-adjusted mixed-effects models; categorical outcomes were compared using χ² tests. Propensity score matching was applied as an additional approach to reduce confounding due to the observational design. Results: At 1 month, response and remission rates were significantly higher in the rTMS group than in the tDCS group (87.5% vs. 55.4%, p < 0.001; 62.5% vs. 41.1%, p = 0.047, respectively). rTMS showed greater HDRS21 score reductions at 2 weeks and 1 month (Time × Treatment, p < 0.001). GAF scores significantly improved over time in both groups (Time effect, p < 0.001) without between-technique differences (Time × Treatment, p = 0.56), and GAF scores did not differ by response/remission status. Conclusions: In this cohort of inpatients aged ≥ 60 years with depressive episodes, rTMS was associated with greater short-term reductions in HDRS21 scores compared with tDCS, whereas both modalities showed comparable improvements in GAF from admission to discharge. Full article

Background: Elderly patients with heart failure with reduced ejection fraction (HFrEF) who experience worsening heart failure (wHF) remain at high residual risk despite optimal medical therapy (OMT), and data on cognitive function and comprehensive geriatric assessment (CGA) in this setting are lacking. This study evaluated the association between 12-month treatment with vericiguat and changes in cardiac, functional and geriatric parameters in elderly patients with recent wHF. Methods and results: In this single-center prospective observational study, 55 patients (45 men, mean age 76.4 ± 5.1 years) with HFrEF on OMT and a recent episode of wHF were treated with vericiguat and followed for 12 months. Clinical assessment, CGA and echocardiography including speckle-tracking were performed at baseline, 6, and 12 months. At 12 months, the mean vericiguat dose was 5.5 ± 2.9 mg/day. NT-proBNP levels decreased from 980 (467–2106) to 654 (274–1762) pg/mL (p < 0.0001), while left ventricular ejection fraction increased from 36.8 ± 3.1% to 43.4 ± 5.7% (p < 0.0001). Global longitudinal strain improved from −9.2 ± 1.7% to −11.5 ± 2.1% (p = 0.008), with parallel improvements in right ventricular function and pulmonary pressures. Cognitive performance improved (MMSE 25.1 ± 1.7 to 26.2 ± 2.1 points, p < 0.0001), as did depressive symptoms (GDS 7.8 ± 2.0 to 5.4 ± 1.6 points, p < 0.0001), physical performance (SPPB 6.7 ± 1.1 to 8.4 ± 0.9 points, p < 0.0001), and gait speed (0.70 ± 0.10 to 0.83 ± 0.06 m/s, p < 0.0001). Conley score decreased from 5.2 ± 2.3 to 2.4 ± 1.8 points (p < 0.0001), suggesting a lower risk of falls. Loop diuretic and MRA use were significantly reduced during follow-up. Conclusions: In this elderly HFrEF cohort with recent wHF on contemporary OMT, 12-month treatment with vericiguat was associated with consistent improvements in cardiac structure and function, biomarkers, and multidimensional geriatric status. These hypothesis-generating findings support the integration of CGA into future controlled studies of vericiguat in frail older patients with HFrEF. Given the observational design and lack of a control group, causal inference is not possible. Full article

Background/Objectives: Dialysis-induced hypotension (DIH) affects 10–30% of hemodialysis sessions and increases mortality. Sertraline may stabilize blood pressure by modulating the Bezold–Jarisch reflex. We aimed to evaluate the efficacy and safety of sertraline for preventing DIH. Methods: We searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov through December 2025. Random-effects meta-analysis was performed using standardized mean differences (SMD). Results: Nine studies (140 patients) met inclusion criteria. Sertraline significantly increased mean arterial pressure (SMD: 0.87; 95% CI: 0.52–1.22; p < 0.001), corresponding to approximately 8.5 mmHg. DIH episodes decreased by 35% (RR: 0.65; 95% CI: 0.48–0.88). Heterogeneity was moderate (I² = 42%). Among studies reporting safety data (n = 106), adverse events were mild (14%) with no serious events. No publication bias was detected (Egger’s p = 0.21). Conclusions: Sertraline significantly improves hemodynamic stability during hemodialysis with a favorable safety profile. It represents a promising option for DIH, particularly in patients with comorbid depression or contraindications to midodrine. Full article

Background: Hemophilia adversely affects several health domains and impairs the daily life of both patients and caregivers. Objectives: To assess the impact of hemophilia A without inhibitors on humanistic outcomes in adult and young patients and their caregivers in a real-life setting. Methods: This was a 12-month multicenter prospective observational study conducted in 18 Spanish hospitals. Patients who were diagnosed with hemophilia A (PWHs), without inhibitors, and who were 12 years of age or older, and their caregivers were included in the study. Results: A total of 85 PWHs (mean age: 33 years) and 12 caregivers participated in the study; 51 PWHs completed it, representing a 40% lost-to-follow-up rate. Twenty-five percent of PWHs showed maladjustment at study completion, with ‘leisure time’ and ‘work/studies’ being the most affected domains. Quality of life was particularly impaired in the sport, physical health and future areas. ‘Lying/sitting/kneeling/standing’ and ‘leisure activities and sports’ were the most impaired functions. Productivity was mainly affected by presenteeism in adult PWHs; 40 painful joint bleeding episodes were reported. Active strategies were mostly used for coping with chronic pain, and anxiety and/or depression were present in more than 10% of PWHs. Anxiety and depression were more frequently reported by caregivers. Conclusions: The study results suggest sustained impairments in adaptation to their disease, quality of life, and functionality in PWHs without inhibitors, especially related to leisure and sports activities, and a nontrivial proportion of them presented clinical levels of depression and anxiety. Overall impairment was more marked in adults than in children. In addition, due to the limited number of caregivers, their results must be considered exploratory. Full article