To review the pharmacology, pharmacokinetics, efficacy, safety, and clinical role of milsaperidone (Bysanti), a newly approved atypical antipsychotic for schizophrenia and acute bipolar I disorder. A comprehensive literature search was conducted using PubMed, Embase, and Google Scholar from database inception through April 2026. Additional data were obtained from Food and Drug Administration prescribing information and pharmacologic references using key terms including milsaperidone, Bysanti, iloperidone, atypical antipsychotics, schizophrenia, and bipolar I disorder. English-language studies evaluating milsaperidone or its parent compound, iloperidone, were included, focusing on pharmacologic properties, clinical efficacy, and safety outcomes. Key trials, reviews, and regulatory data were abstracted and synthesized. Milsaperidone, the active metabolite of iloperidone, exerts its effects through dopamine D₂ and serotonin 5-HT₂A receptor antagonism, with additional α₁-adrenergic blockade contributing to its safety profile. Clinical evidence demonstrates efficacy in reducing symptoms of schizophrenia and bipolar mania, with low rates of extrapyramidal symptoms and akathisia. However, tolerability concerns include orthostatic hypotension, QTc prolongation, sedation, and weight gain. Pharmacokinetic variability associated with CYP2D6 metabolism and gradual titration remain key considerations.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:Milsaperidone expands available atypical antipsychotic options, offering a potentially favorable tolerability profile for patients with prior intolerance or sensitivity to movement-related adverse effects. Careful patient selection and monitoring are essential. Milsaperidone represents an incremental yet meaningful addition to antipsychotic therapy, supporting individualized strategies in schizophrenia and bipolar I disorder while balancing efficacy and tolerability.
Physicians aim to identify the lowest effective dose for maintenance pharmacotherapy in bipolar disorder, but evidence remains limited. We aimed to investigate the association between maintenance doses of mood stabilizers and antipsychotics and relapse risk in patients with first-episode bipolar disorder. Using the Korean National Health Insurance Database, we identified patients aged 19-60 years with a first admission for bipolar disorder between 2002 and 2022. After discharge from the first admission (acute phase), maintenance doses of mood stabilizers and antipsychotics were assessed as absolute doses (defined daily doses [DDDs]/day) and relative doses (percentages of the acute-phase dose) during follow-up. The outcome was readmission for mood disorders. Hazard ratios (HRs) and 95% confidence intervals (CIs) for readmission according to time-varying maintenance doses were estimated using time-dependent Cox regression. A negative dose-response relationship between mood stabilizer dose and readmission was observed below 0.4 DDDs/day (absolute) and 80% (relative) in both the continuous and categorical analyses. For antipsychotics, a progressively higher risk of readmission was observed below 0.5 DDDs/day and 50%, with a near plateau above these levels. Joint dose-category analyses suggested that increased readmission risk associated with low-dose mood stabilizers or antipsychotics was attenuated when the other class was used above the observed dose threshold. In time-stratified analyses, these associations were significant after three years of follow-up. This study found that maintenance doses of mood stabilizers and antipsychotics below specific levels were associated with increased readmission risk in first-episode bipolar disorder, which may help inform clinically cautious dose reduction strategies.
Higher time in sedentary behavior and insufficient physical activity are very common in bipolar disorder (BD). Whereas physical activity and exercise offer significant benefits across mental health, brain health, and heart health in BD. The International Society for Bipolar Disorders Nutrition and Exercise Task Force (NExT) synthesized evidence to evaluate the impacts of sedentary behavior, physical activity, and exercise on illness course, physical health, and treatment outcomes. A best-evidence synthesis was conducted using a question-and-answer format. We searched PsycINFO, SPORTDiscus, Embase, PubMed, and Web of Science from inception to March 1st, 2026, supplemented by reference lists and existing guidelines. Search terms included combinations of physical activity, exercise, sedentary behavior, and bipolar disorder-related terms. Observational studies show that individuals with BD exhibit significantly higher sedentary behavior and lower physical activity compared to the general population, with notable discrepancies between self-reported and objective measurements. Evidence on physical activity's protective role against BD onset is mixed, with some prospective and Mendelian randomization studies suggesting reduced risk, while others report bidirectional or null associations. Preliminary findings from clinical trials indicate that exercise improves overall functioning, reduces mood episode frequency and hospitalizations, and alleviates depressive symptoms, with one pilot study showing an 82% antidepressant response rate. Exercise also shows potential to reduce anxiety and improve sleep, though robust data are limited. Despite limited high-quality evidence, physical activity and exercise demonstrate promising physical and mental health benefits for individuals with BD. Future research should prioritize multicenter randomized controlled trials, enhanced assessment tools, and accessible, tailored programs to integrate physical activity into routine BD management.
Acute bipolar mania carries negative social and economic consequences. We investigated the comparative efficacy/response/acceptability of pharmacological interventions for acute bipolar mania, considering dose effects across different age groups. We conducted a network meta-analysis (NMA) to search for randomized controlled trials (RCTs) comparing pharmacological interventions with one another or placebo in acute bipolar mania patients, indexed in PubMed/MEDLINE, Embase, Web of Science, and Scopus (from inception through 2025.12.24). Co-primary outcomes were change in manic symptoms/response/and acceptability. Tolerability/remission and rate of adverse events were secondary outcomes. Confidence-In-Network-Meta-Analysis was likewise appraised. 113 RCTs, encompassing 49 distinct treatment combinations, included 20,666 participants. Sensitivity analysis retaining only low-risk-of-bias studies and excluding outliers for possible effect modifiers indicated that risperidone 3 mg/day(SMD = -7.57;95%C.I. = -8.25;-5.85); tamoxifen 160 mg/day(SMD = -1.73;95%C.I. = -2.32;-1.13); rivastigmine 3 mg/day(SMD = -1.13;95%C.I. = -1.06;-0.58); haloperidol 30 mg/day(SMD = -0.96;95%C.I. = -1.25;-0.75); valproate 750 mg/day(SMD = -0.76;95%C.I. = -1.48;-0.58); tamoxifen 40 mg/day(SMD = -0.75;95%C.I. = -1.41;-0.59); celecoxib 400 mg/day(SMD = -0.74;95%C.I. = -1.20;-0.38); paliperidone extended-release 12 mg/day(SMD = -0.62; 95%C.I. = -0.91;-0.32); olanzapine 15 mg/day(SMD = -0.59;95%C.I. = -0.60;-0.38); olanzapine 20 mg/day(SMD = -0.52;95%C.I. = -0.66;-0.38); risperidone 4 mg/day(SMD = -0.53;95%C.I. = -0.76;-0.29); allopurinol 600 mg/day(SMD = -0.54;95%C.I. = -0.67;-0.22); cariprazine 12 mg/day(SMD = -0.49;95%C.I. = -0.66;-0.33); risperidone 4.2 mg/day(SMD = -0.46;95%C.I. = -0.75;-0.17); lithium 1500 mg/day(SMD = -0.42;95%C.I. = -0.57;-0.28); ziprasidone 160 mg/day(SMD = -0.49;95%C.I. = -0.68;-0.31); asenapine 20 mg/day(SMD = -0.38;95%C.I. = -0.53;-0.22); haloperidol 8 mg/day(SMD = -0.34;95%C.I. = -0.63;-0.05); aripiprazole 15 mg/day(SMD = -0.33;95%C.I. = -0.61;-0.06) outperformed placebo. Ziprasidone 160 mg/day, celecoxib 200 mg/day, asenapine 20 mg/day, and asenapine 10 mg/day proved more efficacious than placebo in children. No statistically significant differences were reported between treatments and placebo for response/remission/acceptability/tolerability, and manic/hypomanic switch. A meta-regression of efficacy effect sizes against the adapted AMSTAR-Plus content scores showed that larger SMDs were associated with lower AMSTAR scores, indicating lower study quality, warranting further caution for such large efficacy estimates. Our findings are consistent with previous NMAs and current guidelines, expanding the current knowledge base while concurrently appraising different drugs, doses, and age groups.
Lithium remains a first-line treatment for bipolar disorder but its use is declining owing to the need for intensive monitoring and concerns about tolerability. Digital decision-support tools that combine model-informed precision dosing, Bayesian therapeutic-drug-monitoring, and adherence support may facilitate safer, more effective lithium therapy and improve long-term adherence. We aimed to evaluate whether adding a mobile application with precision-dosing, monitoring reminders and medication-support functions («PharmOracle») to standard care reduces a composite measure of non-adherence and adverse outcomes over 12 months, compared with standard care alone. We planning an open-label, multicenter, randomized (1:1) superiority trial enrolling adults (≥18 years) with ICD-10 bipolar I/II or schizoaffective disorder who are initiating lithium carbonate. Planned sample size is 210 participants (105 per arm). The primary endpoint is time to first occurrence of a composite outcome: lithium discontinuation for any reason, hospitalization for lithium toxicity (serum lithium ≥1.2 mmol/L with symptoms), or unplanned psychiatric hospitalization/emergency visit for mood relapse assessed continuously and verified at 3, 6 and 12 months. Key secondary endpoints include changes in the Integral Diagnostic Index for Bipolar Disorder composite index for assessing symptoms of depression (HDRS), mania (YMRS), psychosocial functioning (PSP), and quality of life (WHOQOL), self-reported medication adherence (10-item Medication Adherence Report), adherence to recommended laboratory/instrumental monitoring, proportion of patients achieving therapeutic serum lithium (0.6-1.0 mmol/L), and safety outcomes. The intervention comprises a mobile/web platform performing model-informed individualized dose prediction, Bayesian dose refinement from measured troughs, automated monitoring reminders, adverse-event self-reporting, and clinician dashboards. Analyses will follow intention-to-treat principles using survival methods (Kaplan-Meier, log-rank, Cox regression) for the primary outcome and mixed models or appropriate nonparametric tests for longitudinal secondary outcomes. We anticipate that using of mobile application with precision-dosing, monitoring reminders and medication-support functions will reduce the incidence of the composite outcome by improving adherence and accelerating attainment of therapeutic lithium concentrations, while maintaining an acceptable safety profile.
Conversion of a failed bipolar hemiarthroplasty to total hip replacement (THR) is technically demanding because of acetabular erosion, scarred soft tissues, compromised bone stock and instability risk. Superadded culture-positive infection further complicates implant selection, antibiotic strategy and follow-up surveillance. A 35-year-old male with previous tuberculous meningitis and bilateral avascular necrosis underwent right bipolar hemiarthroplasty in 2016 and left THR in 2019. He later presented with persistent right hip pain and restricted movement. He underwent conversion of the failed right bipolar hemiarthroplasty to THR. Early recurrent instability required a second revision using a long uncemented revision stem, cerclage fixation for an intraoperative proximal femoral fracture and a dual mobility construct. During the infection/revision course, intraoperative culture was positive for Klebsiella pneumoniae. The patient received 6 weeks of intravenous ceftazidime-avibactam and aztreonam. Serial CRP/high-sensitivity c-reactive protein values were 2.92, 239.79, 150.25, 379.13 and 24.43 mg/L, while erythrocyte sedimentation rate values were 6, 103, 103, 75, and 22 mm/h on June 19, 2025, June 25, 2025, June 30, 2025, July 04, 2025 and July 29, 2025, respectively. This case highlights the layered challenges of conversion THR in a young patient: acetabular reconstruction, instability control, intraoperative femoral fracture management, culture-positive Gram-negative infection and biochemical monitoring after debridement and targeted antibiotics. RésuméLa conversion d’une hémiarthroplastie bipolaire échouée en remplacement total de la hanche (RTH) est techniquement exigeante en raison de l’érosion acétabulaire, des tissus mous cicatriciels, du stock osseux compromis et du risque d’instabilité. Une infection surajoutée à culture positive complique davantage le choix de l’implant, la stratégie antibiotique et la surveillance du suivi. Un homme de 35 ans, ayant des antécédents de méningite tuberculeuse et de nécrose avasculaire bilatérale, a bénéficié d’une hémiarthroplastie bipolaire droite en 2016 et d’un RTH gauche en 2019. Il a ensuite présenté une douleur persistante de la hanche droite avec limitation des mouvements. Il a subi une conversion de l’hémiarthroplastie bipolaire droite échouée en RTH. Une instabilité précoce récidivante a nécessité une seconde révision avec une longue tige de révision non cimentée, une fixation par cerclage pour une fracture fémorale proximale peropératoire et une construction à double mobilité. Au cours de l’évolution infectieuse/de révision, la culture peropératoire était positive pour Klebsiella pneumoniae. Le patient a reçu six semaines de ceftazidime-avibactam et d’aztréonam par voie intraveineuse. Les valeurs sériées de CRP/protéine C-réactive hypersensible étaient de 2,92, 239,79, 150,25, 379,13 et 24,43 mg/L, tandis que les valeurs de vitesse de sédimentation érythrocytaire étaient de 6, 103, 103, 75 et 22 mm/h les 19 juin 2025, 25 juin 2025, 30 juin 2025, 4 juillet 2025 et 29 juillet 2025, respectivement. Ce cas souligne les défis multiples de la conversion en RTH chez un jeune patient : reconstruction acétabulaire, contrôle de l’instabilité, prise en charge d’une fracture fémorale peropératoire, infection à bacille Gram négatif à culture positive et surveillance biologique après débridement et antibiothérapie ciblée.
Bipolar membranes (BPMs), owing to their unique structure enabling efficient water dissociation and acid-base compartmentalization, have garnered significant attention in clean energy technologies such as fuel cells, water electrolysis for hydrogen production, and electrochemical CO2 reduction. The interfacial layer, serving as the core region for water dissociation, is critically governed by the intrinsic performance of embedded catalysts, which directly impacts the overall voltage efficiency and long-term stability of BPMs. This review summarizes the research progress on BPM interfacial water dissociation catalysts over the past decade. It begins by elucidating the mechanistic models of water dissociation within BPMs and analyzes the key factors affecting catalyst activity and stability. Subsequently, a comprehensive classification and in-depth analysis are presented on state-of-the-art developments of inorganic, organic, and composite catalyst materials. This work further categorizes and introduces common catalyst optimization strategies, including intrinsic material modulation, structural design and interface engineering. Finally, the remaining critical challenges and promising future research directions are outlined, with the aim of providing insightful guidance for the development of high-performance bipolar membranes.
Functional impairment often persists in bipolar disorder despite symptomatic remission. Cognitive reserve (CR) has been proposed as a protective factor that may influence recovery. This cross-sectional study examined the association between CR and functional outcome among euthymic individuals with Bipolar I Disorder (BD-I). Eighty-four outpatients with DSM-5 BD-I attending a tertiary-care teaching hospital in Puducherry, India, were assessed using the Lifetime of Experiences Questionnaire (LEQ) and the Functioning Assessment Short Test (FAST). Higher CR was significantly associated with better psychosocial functioning (rho = -0.27, p = 0.011), and the association remained modestly significant after controlling for age, education, duration of illness, and age at onset (partial rho = -0.26, p = 0.022). Women and participants from middle socioeconomic groups demonstrated higher CR scores. Although CR showed a significant association with functional outcome in multivariable analysis, the modest explanatory power of the model suggests that functional outcome is influenced by multiple factors. These findings support a potential role for cognitive reserve in functional outcome among individuals with bipolar disorder.
Reverse shoulder arthroplasty (RSA) is commonly performed for complex proximal humeral fractures in older adults when fixation or anatomic reconstruction is unlikely to provide reliable outcomes. Recurrent instability following RSA remains a devastating complication, particularly in medically frail patients with poor bone quality and compromised soft tissue balance. Salvage strategies after repeated failed revisions are limited and often associated with poor functional outcomes. A 75-year-old man with severe chronic obstructive pulmonary disease, hypertension, hypercholesterolaemia, transitional cell carcinoma, rectal polyposis, active smoking history, and frailty sustained a comminuted, displaced left proximal humeral fracture with subglenoid humeral head dislocation following a mechanical fall. He underwent hybrid reverse-polarity total shoulder replacement. One week postoperatively, the shoulder developed anterior instability requiring closed manipulation under anaesthesia. Despite a temporary reduction, recurrent instability persisted during rehabilitation, necessitating two subsequent open revision procedures, including liner exchange with adjustment of implant inclination and later glenosphere cup modification. Persistent instability led to referral and multidisciplinary review at a tertiary shoulder centre. The failed RSA was ultimately converted to a large-head bipolar hemiarthroplasty as a salvage procedure. The hemiarthroplasty later dislocated anteriorly, with migration of the prosthetic head into the anterior deltopectoral/coracoid region and severe upper-limb dysfunction suggestive of brachial plexus neuropraxia. Given the patient's significant comorbidities and elevated operative risk, further reconstruction was deemed unsuitable after shared decision-making, and conservative management was pursued. The patient subsequently developed septic arthritis of the contralateral shoulder, further worsening overall functional status. Serial imaging through 2025 demonstrated persistence of the dislocated bipolar implant without evidence of implant fracture or gross stem loosening. This case illustrates the catastrophic progression of recurrent instability following fracture-related RSA in a medically frail patient with compromised bone and soft tissue conditions. It underscores the importance of careful patient selection, accurate restoration of implant positioning and soft tissue tension, prompt tertiary multidisciplinary involvement after failed stabilisation, and realistic counselling regarding the limited salvage potential and persistent complications associated with hemiarthroplasty conversion after failed RSA. This case highlights that, in medically frail patients with multiple risk factors for instability, early recognition of recurrent dislocation and timely referral to specialist shoulder centres may help guide management decisions, optimise patient expectations, and avoid repeated interventions with diminishing likelihood of durable success.
Bipolar membranes (BPMs) are enabling materials for electrochemical conversion technologies such as water electrolysis, fuel cells, CO2 electrolysis, and electrodialysis (ED) for direct air/ocean capture of CO2. However, current BPM durability can suffer from chemical, mechanical, and performance degradation when operated at high current density (ion flux) and physical scale. Therefore, this limits its adoption in a wider applications space. BPMs have several known degradation mechanisms, including chemical breakdown of ion-exchange polymers, loss of junction adhesion, or physical breakdown due to shearing force and pressure swings in an electrodialysis cell. To assess the electrochemical stability and mechanical durability of BPMs under operational conditions, we investigated how fabrication conditions (including preconditioning, hot-pressing temperature and pressure, and catalyst loading) impact the adhesion of custom-made BPMs. T-peel studies were performed ex situ to quantify adhesive forces of BPMs, and bipolar membrane electrodialysis (BPMED) experiments were performed to assess the electrochemical performance of the corresponding BPMs. The results of this systematic comparison indicate that hydration and heated pressing create improved adhesion during the fabrication of BPMs, and BPMED testing shows that these fabrication techniques are not detrimental to the electrochemical performance of the BPMs.
Bipolar disorder is a chronic, episodic mood illness characterized by recurrent oscillations between mania, depression, and euthymia, affecting an estimated 2.4% of the global population. This pictorial review explores its pathophysiology through the case of a young individual presenting with a first manic episode with psychotic features. We examine the convergence of genetic loading (∼70-90% heritability), neurodevelopmental vulnerability, and environmental precipitants-including sleep restriction and antidepressant exposure-in unmasking this individual's illness. We review interconnected pathophysiological mechanisms underlying bipolar disorder, including fronto-limbic, reward, and cognitive control circuit dysfunction; opposing catecholaminergic-cholinergic imbalances driving mania vs depression; peripheral and central neuroinflammation; BDNF-mediated synaptic plasticity disruption; hypothalamic-pituitary-adrenal, thyroid, and gonadal axis dysregulation; and circadian rhythm disturbance. Recurrent episodes may drive progressive, heterogeneous brain changes that are potentially modifiable, reinforcing early intervention and adherence. Emerging biomarkers and phase-specific pharmacotherapy reflect progress toward personalized, multimodal treatment integrating mood stabilization with chronobiological and psychosocial optimization.
Bipolar disorder (BD) is a chronic psychiatric illness. Thyroid hormones play a crucial role in maintaining normal brain function and have a significant impact on mood regulation and neuroendocrine activity. Increasing evidence suggests that thyroid dysfunction is closely related to the onset, progression, and severity of BD. A systematic bibliometric analysis of this field is important for understanding its research trajectory and identifying emerging hotspots. Literature on BD and thyroid hormones published between 1998 and 2022 was retrieved from the Web of Science Core Collection. Data were analyzed and visualized using VOSviewer and CiteSpace software to explore publication trends, major contributing countries and institutions, authors, journals, and keyword characteristics. A total of 452 relevant publications were identified, covering 229 journals, 2318 authors, 1443 institutions, and 188 countries. The United States, China, and Germany were the most active countries in this field. Major contributing institutions included the University of California, Los Angeles, the University of Toronto, and the Technical University of Dresden. Leading scholars were Bauer M, Whybrow PC, and Rybakowski JK. The Journal of Affective Disorders published the most relevant papers. Keyword analysis revealed that research hotspots mainly focused on BD, thyroid function, and depression, particularly around themes such as "risk," "affective illness," and "bipolar affective disorder." The relationship between thyroid hormones and BD has become an important research focus in recent years, providing new directions for future studies in this field. This study systematically reveals the research landscape and developmental trends from 1998 to 2022, offering valuable references and guidance for future research and clinical practice.
Cognitive impairment is a frequent feature of bipolar disorder (BD), often persisting during euthymic phases and affecting multiple cognitive domains. These deficits impair functional recovery and quality of life. Pharmacological treatments have shown limited efficacy in ameliorating cognitive dysfunction in BD. Cognitive remediation (CR) has emerged as a promising nonpharmacological alternative. However, reviews of its efficacy in BD have reported inconsistent findings. One major limitation highlighted in past reviews is the heterogeneity of study samples, due to the inclusion of participants without cognitive impairment, potentially introducing a ceiling effect that may obscure treatment benefits. This review addresses this gap by examining only studies that selected participants through objective or structured subjective cognitive screening. A systematic search of PubMed and Web of Science (finalized 27 January 2026) identified interventional studies of CR in adults with BD requiring objective or subjective cognitive impairment for inclusion. Of 2662 records retrieved, 128 full texts were reviewed, and 6 studies met eligibility criteria; 2 secondary analyses derived from 2 of these studies were also retained for synthesis. Four studies were randomized controlled trials, one was non-randomized with a control group, and one was uncontrolled. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Given methodological variability, results were synthesized narratively. Six studies met inclusion criteria. Findings were inconsistent: three reported significant cognitive improvements following CR or related interventions, whereas three randomized trials found no significant cognitive effects. Variability in screening methods, intervention formats, and outcome selection precluded meta-analysis. Evidence is constrained by the small number of eligible studies, methodological heterogeneity, and variable risk of bias. Current evidence from enriched samples suggests that CR may improve specific cognitive domains in BD, but overall results remain inconclusive. Future trials should employ rigorous cognitive screening, harmonized outcome measures, and more individualized interventions to clarify efficacy. PROSPERO registration ID: CRD42025642423.
Lumbar microdiscectomy is an established treatment for symptomatic lumbar disc herniation; however, persistent pain and functional limitation may occur, particularly in patients with annular defects. Is adjunctive external bipolar thermal annuloplasty (EBTA) associated with improved outcomes after lumbar microdiscectomy in patients with Carragee Type I and III annular defects? This retrospective single-center matched cohort study included 60 patients with symptomatic single-level lumbar disc herniation and intraoperatively confirmed Carragee Type I or III annular defects. Thirty patients underwent microdiscectomy with adjunctive EBTA and were matched 1:1 with 30 patients treated with microdiscectomy alone based on age, sex, operated level, Carragee classification, baseline VAS-leg, VAS-back, and Oswestry Disability Index (ODI) scores. Outcomes were assessed preoperatively and at 6 and 12 months. Exploratory clinical relevance was assessed using MCID thresholds of ≥4.7 points for VAS-leg and >20 points for ODI. Both groups improved significantly in VAS-leg, VAS-back, and ODI scores (p < 0.001). Compared with controls, the EBTA group had significantly lower VAS-leg, VAS-back, and ODI scores at both follow-ups. VAS-back decreased from 5.84 ± 1.17 to 1.20 ± 0.49 at 12 months in the EBTA group and from 5.96 ± 1.08 to 2.06 ± 0.72 in controls. EBTA was also associated with earlier return to work and higher satisfaction, without increased complications. Mean ODI improvement exceeded the MCID threshold in both groups, whereas VAS-leg exceeded the threshold at both follow-ups only in the EBTA group. Adjunctive EBTA was associated with greater improvements in leg pain, back pain, and disability without increased perioperative morbidity. These exploratory findings require confirmation in larger prospective studies.
Bipolar Disorder (BD) is a chronic, debilitating mood disorder, yet its structural neurobiology remains incompletely understood. Although prior studies have identified regional brain volumetric differences, many rely on outdated diagnostic criteria, and more recent evidence has not been systematically synthesized. Herein, we aim to meta-analytically synthesize evidence on brain structural alterations in adults with BD using DSM-IV to DSM-5-TR criteria. Systematic search of PubMed and OVID databases was conducted from inception to February 20, 2026. Eligible studies examined structural or volumetric brain differences in adults with BD. A systematic review and meta-analysis were conducted to estimate standardized mean differences, and variability was assessed. Effect sizes were pooled using a multivariate random-effects meta-analysis. Risk of bias and heterogeneity were assessed using established methods. BD was associated with significantly greater cerebrospinal fluid (CSF), intracranial, and right lateral ventricle volumes compared with controls, which may reflect altered intracranial composition and potential reductions in brain parenchymal volume. Variability analyses demonstrated significantly greater variability in CSF and intracranial volumes among individuals with BD, while other regions showed no significant differences. Moderate between-study heterogeneity was observed (I² ≈ 51%), and there was no significant evidence of publication bias. These findings suggest that specific structural alterations, particularly increased CSF and ventricular volumes which may reflect underlying brain tissue loss, may characterize BD; however, substantial variability exists across individuals and brain regions. This heterogeneity highlights the complexity of BD neurobiology and underscores the need for larger, methodologically consistent studies to better characterize structural changes and their clinical implications.
With limited evidence-based options, treatment of depressive episodes in bipolar disorder (BD-DE) remains challenging. This study examines the trajectories of psychotropic drug use and polypsychopharmacy in psychiatric inpatients with acute BD-DE. Using data from the German pharmacovigilance program "Arzneimittelsicherheit in der Psychiatrie" (AMSP), the pharmacological treatment of 1,902 psychiatric inpatients with BD-DE between 2007-2024 was analyzed. Temporal changes in drug use between early (T1: 2007-2010) and late (T2: 2021-2024) periods were calculated using prevalence ratios (PR) with 95% confidence intervals (CI) and Welch's t-test. Overall, 98.5% of inpatients with acute BD-DE were treated with psychotropic drugs. Antipsychotic drugs (APD) were the most used psychotropic drug group (76.2%), followed by antidepressant (ADD; 70.3%) and antiepileptic drugs (AED; 44.3%) during the entire study period. Over time, APD use increased from 70.1% in T1 to 80.7% in T2 (PR 1.15, CI 1.06-1.25), attributable to the increased use of second-generation APD (PR 1.19, CI 1.07-1.32), especially quetiapine and aripiprazole. ADD (T1: 78.1% vs T2: 67.6%; PR 0.87, CI 0.79-0.95) and AED (T1: 56.7% vs T2: 34.6%; PR 0.61, CI 0.51-0.73) use significantly declined, while lithium use remained stable (31.7% from 2007-2024). Although the mean number of psychotropic drugs per patient decreased (T1: 3.85 vs T2: 3.34, p < 0.001, d=-0.30), complex polypsychopharmacy consisting of ≥3 psychotropic drugs remained prevalent (66.1% of patients during the entire study period). Combination strategies involving APD, especially use of two APD, significantly increased (T1: 15.6% vs T2: 31.5%; PR 2.01, CI 1.51-2.69). Pharmacological treatment of BD-DE has shifted towards an increased use of second-generation APD while AED are less utilized. ADD use and complex polypsychopharmacy continue to be prevalent, indicating a persistent gap between guideline recommendations and real-world practice.
Bipolar disorder (BD) is a highly complex, chronic psychiatric illness marked by episodic disturbances of mood. While historically conceptualized as a disorder of neurotransmitter imbalance, converging evidence suggests it is better understood as a disorder of dynamic dysregulation across multiple interacting systems, including genetic and epigenetic vulnerability, HPA axis dysregulation, mitochondrial/metabolic dysfunction, immune activation, circadian disruption, and gut-brain axis disturbances. These systems comprise a hierarchically organized, bidirectionally coupled feedback network that is responsible for the oscillatory mood states that define the disorder. Here, it's proposed that a specific, testable, integrative model in which genetic/epigenetic vulnerabilities lead to destabilization of HPA axis regulation, which then leads to mitochondrial bioenergetic dysfunction (the central integrative node of the cascade), which then, through its interaction with immune activation and gut-brain signaling, causes the excitation-inhibition imbalance underlying the clinical presentation of mood-state transitions. From this model, three empirically tractable predictions are made: that co-occurring inflammatory/metabolic/circadian dysregulation will constitute a biological subtype with earlier onset, more rapid cycling, and a more negative response to lithium; that neuroendocrine/metabolic disturbances will prospectively precede rather than simply co-occur with mood-state transitions; and that interventions targeting the metabolic-inflammatory interface will produce mood-stabilizing effects whose magnitude correlates with baseline biological severity rather than symptom severity. Throughout, the importance of state-dependence, trait-level features, and medication confounds is discussed. Finally, translational implications for metabolic stratification, circadian-focused intervention, and gut-brain modulation are outlined.
Cardiac troponin I (cTnI) is widely recognized as a critical biomarker for the early diagnosis of acute myocardial infarction (AMI). Consequently, the precise and sensitive detection of cTnI during the initial phases of AMI is vital. In this study, we propose the development of an advanced bipolar electrochemiluminescence (ECL)-based miniaturized, cost-effective, and optimized biosensor incorporating novel nanostructures such as MXene (Ti₃C₂Tx-TiO2) and Ce-MOF without using luminol's co-reactant (H2O2). The conjugation of Ce-MOF with MXene enhances ECL intensity due to increase in surface area and electron conductivity, respectively. Using a camera as the detection device, cTnI can be quantified within a wide range of 0.01 to 100 ng/mL. The proposed approach integrates principles of biotechnology and nanotechnology, enabling rapid and accurate quantification of this biomarker even at low concentrations and can be used for clinical diagnostics.
Identifying reproducible neural markers of bipolar disorder(BD) risk is critical for early detection and differentiation from unipolar/major depression. We previously demonstrated that inter-amygdala functional connectivity(FC) and bilateral-ventrolateral-right-dorsolateral-prefrontal-cortex(vlPFC-dlPFC)-FC were positively associated with both mania/hypomania and depression risk and mania/hypomania risk, respectively, as measured by the Mood Spectrum Self-Report(MOODS-SR) 'mood' subdomains, replicated in three independent samples. We tested whether these neural markers also generalized to the MOODS-SR 'cognition' and 'energy' subdomains and whether they are elevated in individuals with BD versus those at-risk. Three independent young adult samples without BD(n=299/ages 18-30) completed an fMRI approach emotion-processing task(Discovery n=114/age=21.60±1.91; Test sample-1 n=103/21.57±2.09; Test sample-2 n=82/23.43±2.86), and a fourth sample with BD(n=32/25.11±3.73) completed the same protocol. Poisson loglinear models tested whether previously identified neural markers of MOODS-SR mood subdomains were also associated with manic and depressive cognition and energy subdomains. One-way ANOVAs compared neural variables showing significant relationships with subdomain scores between low-risk, high-risk, and BD groups. Across all risk samples, inter-amygdala-FC was positively associated with manic and depressive mood and cognition subdomains(qFDRs<0.001-0.01); vlPFC-dlPFC-FC was positively associated with manic mood and cognition subdomains(qFDRs<0.001-0.048). Inter-amygdala-FC differed significantly across groups(F2,328=3.56, P=0.03) and was higher in BD versus low-risk and in high-risk versus low-risk groups(Ps=0.033). Inter-amygdala-FC emerged as a robust, cross-dimensional correlate of BD risk, linking subsyndromal risk to syndromal BD, whereas vlPFC-dlPFC-FC was specific to mania risk. Findings support a multidimensional, circuit-based model of BD risk supporting early identification and prevention.
Bipolar membrane electrodialysis (BPMED) is a promising technology for recovering dissolved ammonia (NH3) from concentrated wastewater streams, such as scrubber effluents. To date, most research remains laboratory-scale, while existing pilot-scale studies operate at effluent concentrations of 2 g-N/L, membrane areas below 3.5 m², and current densities under 150 A/m². In this study, a pilot-scale BPMED system with an active membrane area of 21.3 m² was operated in a sequential batch mode. Real scrubber effluents (18-22 g-N/L) were treated to simultaneously recover dissolved NH₃ and regenerate citric acid. For the first time, the influence of non-ideal phenomena including proton (H⁺) competition, NH₃ back diffusion, electro-osmotic and osmotic water fluxes on NH3 recovery, was systematically investigated at current densities beyond typical laboratory values. At feed pH below 3, decreasing current efficiency and a sharply increasing energy consumption established an operating window for the pilot-scale BP-C system, irrespective of the applied current density. NH₃ concentrations in the base compartment increased with increasing current density, reaching 48 g-N/L at 500 A/m² and corresponding to treatment capacities of up to 1.8 kg-N/m²d. At 150 A/m², NH₃ recovery was limited by cyclic NH₄⁺ transport associated with NH₃ back diffusion, coinciding with increased electro-osmotic water flux. At higher current densities, NH₃ recovery was instead limited by electro-osmotic and osmotic water flux driven by current density and osmotic pressure gradients across the membrane. Despite comparable energy consumption (7-9 kWh/kg-N recovered) to previous pilot-scale studies, this work achieved higher NH3 concentrations and treatment capacities while advancing mechanistic understanding of transport limitations in BPMED systems.