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Background: This study examines the association between the coefficient of variation (%CV) of lithium levels and episode risk and frequency in bipolar patients maintaining serum lithium levels within the therapeutic range. Methods: We retrospectively reviewed patients with bipolar disorder under care from 2018 to 2022. Inclusion criteria were at least 2 years of follow-up, a minimum of three annual lithium level measurements within the therapeutic range. Patients were categorized based on seizure status. We calculated mean lithium levels, standard deviation (SD), and %CV. Results: The study included 75 patients (patients with-without episodes, 39–36). Demographic data revealed no significant differences. While mean lithium levels showed no significant disparity between groups, SD and %CV were notably higher in patients with episodes (P <.05). ROC analysis demonstrated AUC values of 0.722 (95% CI: 0.607–0.836 P =.001) for %CV and 0.709 (95% CI: 0.593–0.826; P =.002) for SD. The optimal %CV cutoff was 17.39, with 67% sensitivity and 69% specificity. A weak correlation was found between %CV and the number of episodes (P =.001, r = 0.376). The post-hoc power analysis for this study was 0.78. Conclusions: Despite acceptable lithium levels, patients with recent episodes exhibited significant lithium level fluctuations. Integrating %CV with real-time lithium measurements during bipolar disorder follow-up may enhance clinical monitoring and seizure prediction. [ABSTRACT FROM AUTHOR]

As high-sensitivity cardiac troponin T (hs-cTnT) is making the transition from diagnostic to prognostic use, a long-term stability study of 5th generation hs-cTnT according to EFLM CRESS recommendations was set up for investigation of frozen clinical specimens (two matrices).Study samples collected in serum tubes and lithium heparin tubes with gel from patients admitted for suspected minor myocardial damage were measured directly after completion of the study (0 years), and after 3-year and 6-year storage at −80 °C, and recovery of hs-cTnT concentrations after long-term storage (%hs-cTnT concentration compared to 0-year) was calculated. Hs-cTnT changes were also compared to decisive delta changes, such as the ones proposed in the ESC NSTEMI 0 h/1 h algorithm (<3 or >5 ng/L for ruling out and ruling in suspected NSTEMI patients).Eighty-six patients were included in the study, whereof 28 both lithium heparin plasma and serum samples were collected simultaneously, in others only serum (n=30) or plasma (n=28). Multiple aliquots per patient were made, so that 479 serum and 473 plasma samples were available for analysis. Across the overall hs-cTnT measuring range, median recovery after 6 years was 105.4 % and 106.2 % for serum and plasma, respectively. Based on these decisive delta changes, serum showed consistent results upon long term storage (max 0.8 % of samples above delta threshold of >5 ng/L) as compared to heparin plasma (up to 19.2 % of samples above threshold).Over 6 years of storage at −80 °C, recovery of hs-cTnT in serum and heparin plasma was similar and within common lot-to-lot variation. Yet, when evaluating absolute delta increments around hs-cTnT clinical decision points, long-term stored sera displayed better clinical performance compared to heparin plasma samples. [ABSTRACT FROM AUTHOR]

Introduction: Bipolar disorder is a psychiatric condition commonly treated with lithium. This treatment has various biological effects on the brain; however, variability in the areas and types of changes as a result of lithium treatment has resulted in discourse over lithium's effect. As a result, a comprehensive synthesis is needed to understand lithium's true neurological effect. This review aims to identify a common result of lithium use in the neurobiology of bipolar patients, specifically in the amygdala, to determine whether volumetric changes in the amygdala are a common effect. Methods: We conducted a preliminary search to identify key search terms across electronic databases, including Google Scholar and PubMed. After screening and application of inclusion and exclusion criteria, 9 cross-sectional studies were identified. Results: The evidence from these cross-sectional studies showed either an increase or no change in amygdalar volume. While this fails to identify a definite pattern in amygdalar volume changes, it highlights a need for further research to identify sources of heterogeneity and minimize them to ascertain accurate results. Conclusions: The present review may be used to influence future work concerning neurobiological changes in the amygdala as a result of lithium treatment for bipolar patients by summarizing patterns in the current literature. [ABSTRACT FROM AUTHOR]

It is studied how the treatment of a metal lithium surface with a 1 M LiN(CF3SO2)2 solution in the 1,3-dioxolane/1,2-dimethoxyethane (2 : 1) mixture affects the resistance of the interphases formed by lithium with the polymer and nanocomposite electrolytes based on the 1-ethyl-3-methylimidazolium tetrafluoroborate ionic liquid. The liquid-phase therapy is shown to reduce the resistance at the Li/electrolyte interphase by a factor of 2.5 at room temperature and extend the working temperature range to –30°C. The introduction of TiO2 nanoparticles into the polymer electrolyte, along with the liquid-phase therapy of both the cathode and the Li-anode, provides a high and stable discharge capacity of the Li//LiFePO4 battery for 100 charge–discharge cycles. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non‐psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder.Individuals aged 15–65 with bipolar disorder were identified from Finnish national health registers in 1996–2018. Studied antipsychotics included olanzapine, risperidone, quetiapine, aripiprazole; mood stabilizers lithium, valproic acid, lamotrigine, and carbamazepine. Medication use was divided into three time‐varying dose categories: low, standard, and high. The studied outcomes were risk of psychiatric hospitalization (relapse) and the risk of non‐psychiatric hospitalization (treatment safety). Stratified Cox regression in within‐individual design was used.The cohort included 60,045 individuals (mean age 41.7 years, SD 15.8; 56.4% female). Mean follow‐up was 8.3 years (SD 5.8). Of antipsychotics, olanzapine and aripiprazole were associated with a decreased risk of relapse in low and standard doses, and risperidone in low dose. The lowest adjusted hazard ratio (aHR) was observed for standard dose aripiprazole (aHR 0.68, 95% CI 0.57–0.82). Quetiapine was not associated with a decreased risk of relapse at any dose. Mood stabilizers were associated with a decreased risk of relapse in low and standard doses; lowest aHR was observed for standard dose lithium (aHR 0.61, 95% CI 0.56–0.65). Apart from lithium, high doses of antipsychotics and mood stabilizers were associated with an increased risk of non‐psychiatric hospitalization. Lithium was associated with a decreased risk of non‐psychiatric hospitalization in low (aHR 0.88, 95% CI 0.84–0.93) and standard doses (aHR 0.81, 95% CI 0.74–0.88).Standard doses of lithium and aripiprazole were associated with the lowest risk of relapse, and standard dose of lithium with the lowest risk of non‐psychiatric hospitalization. Quetiapine was not associated with decreased risk of relapse at any dose. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to review and summarise the existing human literature on the association between lithium and hyperparathyroidism. Methods: A systematic literature search was carried out according to PRISMA guidelines (last search 27 February 2024), using MEDLINE, Web of Science, Embase and the Cochrane Library. A meta-analysis was performed to determine the prevalence of lithium-associated hypercalcemia (LAHca) in lithium-treated patients. Results: The pooled prevalence of LAHca based on total calcium and ionised calcium was comparable, at 3.17% and 4.23%, respectively. Calcium, and PTH if the patient is hypercalcaemic, is insufficiently measured in lithium-treated patients in clinical practice. Lithium use is associated with higher calcium and PTH levels, as well as a higher incidence of hyperparathyroidism. There is a high prevalence of multiglandular disease in lithium-associated hyperparathyroidism (LAH), with a pooled prevalence of 51.28%. Parathyroid surgery and cinacalcet are effective treatments for LAH. Regarding lithium discontinuation, there is anecdotal but conflicting evidence suggesting that it can result in the resolution of LAH in selected cases. Conclusions: Lithium treatment increases the risk of hyperparathyroidism, a treatable complication with a pooled prevalence of around 4%, compared to 0.5% in the healthy population. [ABSTRACT FROM AUTHOR]

The average lithium content in the Earth's crust is estimated at about 0.007%. Despite this, lithium is considered abundant and widely distributed, with significant extraction from various sources. Notably, the brines in the Salar de Atacama are highlighted for their high lithium concentration ~1800 mg/L. Lithium is currently recovered from these brines through a solar evaporation process. The brine is transferred through a series of ponds, increasing the lithium concentration from 0.2% to 6% over 18 months, while decanting other minerals like potassium, magnesium, and boron. This method is the most efficient and cost-effective globally due to the Salar de Atacama's high lithium concentration of approximately 1800 ppm and the region's intense solar radiation, which facilitates evaporation at no economic cost. This manuscript describes in detail the lithium and potassium extraction processes used in the Salar de Atacama. [ABSTRACT FROM AUTHOR]

Tumor-produced pro-inflammatory cytokines and toxic substances passing through the blood-brain barrier can cause disturbances of brain homeostasis and neuronal damage. Correction of brain homeostasis under peripheral tumor growth conditions is an important task. In the present study, a cytokine expression in the brain and ultrastructural features of the prefrontal cortex pyramidal neurons in animals with skin melanoma and after lithium carbonate treatment were detected by PCR analysis, transmission electron microscopy, and immunohistochemical staining. The low expression levels of the neurotrophic factor BDNF and an increase expression of colony-stimulating factors G-CSF and GM-CSF were noted in animals with skin melanoma. At the same time, as welling of mitochondria, inner mitochondrial membrane damage and dilated endoplasmic reticulum were revealed in the prefrontal cortex neurons. Furthermore, the predominance of autophagosomes was revealed under peripheral tumor growth conditions. Lithium carbonate administration had a corrective effect on the cytokine expression in the brain and the ultrastructure of the prefrontal cortex neurons in animals with skin melanoma. [ABSTRACT FROM AUTHOR]

Local phase transition in transition metal dichalcogenides (TMDCs) by lithium intercalation enables the fabrication of high‐quality contact interfaces in two‐dimensional (2D) electronic devices. However, controlling the intercalation of lithium is hitherto challenging in vertically stacked van der Waals heterostructures (vdWHs) due to the random diffusion of lithium ions in the hetero‐interface, which hinders their application for contact engineering of 2D vdWHs devices. Herein, a strategy to restrict the lithium intercalation pathway in vdWHs is developed by using surface‐permeation assisted intercalation while sealing all edges, based on which a high‐performance edge‐contact MoS2 vdWHs floating‐gate transistor is demonstrated. Our method avoids intercalation from edges that are prone to be random but intentionally promotes lithium intercalation from the top surface. The derived MoS2 floating‐gate transistor exhibits improved interface quality and significantly reduced subthreshold swing (SS) from >600 to 100 mV dec–1. In addition, ultrafast program/erase performance together with well‐distinguished 32 memory states are demonstrated, making it a promising candidate for low‐power artificial synapses. The study on controlling the lithium intercalation pathways in 2D vdWHs offers a viable route toward high‐performance 2D electronics for memory and neuromorphic computing purposes. [ABSTRACT FROM AUTHOR]

Agitated depression, also known as melancholia agitata, is a variant of depression characterized by severe symptoms of psychomotor agitation, inner unrest, anxiety, restlessness, prominent vegetative symptoms, and a high risk of suicide. This form of depression is reported to worsen with antidepressants and potentially improve with the use of ECT, lithium, antiepileptics, antipsychotics, and benzodiazepines. We describe a case of a 73‐year‐old female with a prior history of depression and generalized anxiety disorder who was maintained on flurazepam for 44 years and was admitted for severe depression with psychomotor agitation, prominent vegetative symptoms, thought perseveration, indecisiveness, and psychotic features that emerged following the discontinuation of flurazepam. Symptoms did not resolve with the use of alternative benzodiazepines such as nitrazepam and temazepam and further worsened with the use of several antidepressants. She finally had a complete resolution of these symptoms with a combination of alprazolam, zopiclone, and olanzapine. This case provides insight into this unique variant of depression and the role of GABA agonists in its pathology and management. [ABSTRACT FROM AUTHOR]

Lithium, a natural element, has been employed as a mental stabilizer in psychiatric treatments; however, some reports indicate it has an anticancer effect, prompting the consideration of repurposing lithium for cancer treatment. The potential anticancer use of lithium may depend on its form (salt type) and the type of cancer cells targeted. Little is known about the effects of Li2CO3 or LiCl on cancer cells, so we focused on exploring their effects on proliferation, apoptosis, migration, and cell cycle as part of the hallmarks of cancer. Firstly, we established the IC50 values on HeLa, SiHa, and HaCaT cells with LiCl and Li2CO3 and determined by crystal violet that cell proliferation was time-dependent in the three cell lines (IC50 values for LiCl were 23.43 mM for SiHa, 23.14 mM for HeLa, and 15.10 mM for HaCaT cells, while the IC50 values for Li2CO3 were 20.57 mM for SiHa, 11.52 mM for HeLa, and 10.52 mM for HaCaT cells.) Our findings indicate that Li2CO3 and LiCl induce DNA fragmentation and caspase-independent apoptosis, as shown by TUNEL, Western Blot, and Annexin V/IP assay by flow cytometry. Also, cell cycle analysis showed that LiCl and Li2CO3 arrested the cervical cancer cells at the G1 phase. Moreover, lithium salts displayed an anti-migratory effect on the three cell lines observed by the wound-healing assay. All these findings imply the viable anticancer effect of lithium salts by targeting several of the hallmarks of cancer. [ABSTRACT FROM AUTHOR]

Introduction: Lithium is a key medication for treating various neuropsychiatric disorders, with a narrow therapeutic index and significant drug interactions. Monitoring lithium blood levels is crucial. This study aims to investigate the relationship between lithium blood levels and demographic characteristics such as age and gender, as well as possible drug interactions, in patients with a history of lithium use who applied to various services and outpatient clinics. Materials & Methods: The files of 438 patients who were admitted to various services and outpatient clinics of Kırklareli Training and Research Hospital between January 1 and December 31, 2023, were retrospectively reviewed. Patients' blood lithium levels, gender, age, service/outpatient clinic they admitted to, other medications used, urea, creatinine, and eGFR values were recorded. Results: When the demographic characteristics of 438 patientswere examined, 62% were female (270), 38%weremale (168), and the average agewas 46.3 ± 14.8 years, showing a normal distribution. It was found that 192 patients (71 males, 121 females) had therapeutic lithium blood levels, while 244 patients (97 males, 147 females) had levels below 0.6 mmol/L. Two female patients had blood levels above the therapeutic range (1.23 and 1.43 mmol/L). Among the clinics and services, the four most frequented were the psychiatry clinic (314 patients), internalmedicine clinic (36 patients), emergency service (27 patients), and medical oncology clinic (17 patients). Of the 314 patients admitted to the psychiatry clinic, 168 had therapeutic drug levels; only 7 of the 36 admitted to internal medicine had therapeutic levels; 12 of the 27 patients in the emergency service had therapeutic levels; and all 17 patients in medical oncology had levels below therapeutic limits. Discussion: The data emphasize the importance of regular blood level monitoring to ensure lithium treatment's efficacy and patient safety. It is noteworthy that most patients in the psychiatry clinic had therapeutic drug levels, while those in other clinics had lower levels. Conclusion: In conclusion, this study highlights the importance of regular blood level monitoring to ensure the efficacy and safety of lithium treatment. [ABSTRACT FROM AUTHOR]

Lithium (Li+) therapy is a valuable tool in psychiatric practice that remains underutilized due to safety concerns. Excessive plasma Li+ levels are nephrotoxic and can trigger a local immune response. Our understanding of the immunomodulatory effects of Li+ in the kidney is fragmentary. Here, we studied how immune mechanisms contribute to the development of Li+-induced adverse effects in the kidneys of C57BL/6NJ mice placed on a 0.3% lithium carbonate diet for 28 days. We combined histochemical techniques, immunoblotting, flow cytometry, qPCR and proteome profiler arrays to characterize renal tissue damage, infiltrating immune cells and cytokine markers, activation of pyroptotic and apoptotic cascades in the kidneys of mice receiving Li+-containing and regular diets. We found that biomarkers of tubular damage, kidney injury marker, KIM-1, and neutrophil gelatinaseassociated lipocalin, NGAL, were elevated in the renal tissue of Li+-treated mice when compared to controls. This correlated with increased interstitial fibrosis in Li+-treated mice. Administration of Li+ did not activate the proinflammatory NLRP3 inflammasome cascade but promoted apoptosis in the renal tissue. The TUNEL-positive signal and levels of pro-apoptotic proteins, Bax, cleaved caspase-3, and caspase-8, were elevated in the kidneys of Li+- treated mice. We observed a significantly higher abundance of CD93, CCL21, and fractalkine, accumulation of F4.80+ macrophages with reduced M1/ M2 polarization ratio and decreased CD4+ levels in the renal tissue of Li+- treated mice when compared to controls. Therefore, after 28 days of treatment, Li+-induced insult to the kidney manifests in facilitated apoptotic cell death without an evident pro-inflammatory response. [ABSTRACT FROM AUTHOR]

Lithium is the superior first-line treatment for bipolar disorder (BD). Yet the percentage of patients receiving lithium is abysmally low, especially in the US. Since psychiatrists have failed to place lithium in its appropriate role, we make the case that patients with BD themselves need to be better educated about the unique characteristics and pre-eminence of the drug so that it can be used more often and appropriately. Lithium has a highly unfavorable popular reputation among would-be patients and many psychiatrists. Thus, a direct appeal to patients with BD appears appropriate to try to remediate this situation. The unique assets of lithium are underappreciated or not well known. Conversely, the side effects profile of lithium are overestimated. Here, we make the case that lithium's image needs to be revised not only with better and more accurate information but also with a wholesale renaming and rebranding of the drug. We will not only outline the unique qualities and new information about the side effects of the drug but attempt to change some of the terminology conventionally used to refer to lithium so that its use may be appropriately applied earlier and at an increased frequency for patients with BD. [ABSTRACT FROM AUTHOR]

Lithium is commonly used in the treatment of bipolar disorders (BD) and consumer electronics. It has been reported that lithium exposure is associated with mitochondrial dysfunction and oxidative stress in isolated cardiac mitochondria. Mitochondrial protection has a key role in myocardial tissue homeostasis, cardiomyocyte survival and inhibition of cardiotoxicity. Hesperidin as a flavanone and cardioprotective agent has shown high potential in antioxidant activity and restoration of mitochondrial dysfunction in different models. Therefore, we aimed to evaluate the ameliorative effects of hesperidin against lithium-induced mitochondrial toxicity in rat cardiac mitochondria. Isolated mitochondria were classified into six groups; control, lithium carbonate (125 µM), three groups of lithium + hesperidin-treated received lithium (125 µM) and hesperidin with various concentrations (10, 50, and 100 µM) and hesperidin (100 µM). Succinate dehydrogenases (SDH) activity, mitochondrial swelling, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial glutathione (GSH) and lipid peroxidation (LPO) were measured. The mitochondria received lithium showed a significant reduction of SDH activity, MMP collapse, mitochondrial swelling, induction of ROS formation and lipid peroxidation. However, we observed that the administration of hesperidin (50 and 100 µM) resulted in the increase of SDH activity, improved MMP collapse, mitochondrial swelling, and reduced ROS formation and lipid peroxidation. Also, there were no obvious changes in cardiac mitochondria received of hesperidin. These findings suggest that hesperidin could reduce lithium-induced mitochondrial dysfunction through antioxidant activities in cardiac mitochondria, may be beneficial for prevention and treatment of lithium toxicities, either as a drug to treat BD or as an environmental pollutant. [ABSTRACT FROM AUTHOR]

Lithium is an effective mood stabiliser, but its mechanism of action is incompletely defined. Even at very low doses, lithium may have neuroprotective effects, but it is not clear if these relate to brain lithium concentration in vivo. We have developed magnetic resonance imaging (7Li-MRI) methods to detect lithium in the brain following supplementation at a very low dose. Lithium orotate supplements were taken by nine healthy adult male subjects (5 mg daily) for up to 28 days, providing 2–7 % of the lithium content of a typical therapeutic lithium carbonate dose. One-dimensional 7Li-images were acquired on a 3.0 T MRI scanner. All subjects were scanned on day 14 or 28; seven were scanned on both, one at baseline and one after 7-days washout. 7Li-MR signal amplitude was broadly stable between days 14 and 28. Two subjects had notably higher 7Li-signal intensities (approximately 2–4×) compared to other study participants. Lithium adherence was self-reported by all participants without formal validation. The coarse spatial resolution necessary for detection of low concentrations of 7Li exhibits imperfect spatial separation of signal from adjacent pixels. 7Li-MRI performed using a clinical 3T scanner demonstrated detection of lithium in the brain at very low concentration, in the range of approximately 10–60 mM. The methods are suited to studies assessing low dose lithium administration in psychiatric and neurodegenerative disorders, and permit the comparison of different lithium salt preparations at a time of emerging interest in the field. • 7Li-MRI permits direct, non-invasive, longitudinal measurement of brain lithium. • Brain lithium was detected after administration of very low dose lithium orotate. • Brain 7Li-signal was stable between two- and four-weeks of supplementation. • A subset of individuals showed notably higher brain 7Li-signal intensity. [ABSTRACT FROM AUTHOR]

The contamination of F inhibits the recovery of pure Li from spent Li-ion batteries (LIBs). In this study, we extracted F from a cathode material of spent Li-ion batteries by dry and wet processes and investigated the effect on Li recovery. In the dry process, F was removed by calcination at a controlled temperature in the presence of an F-fixing agent. In the wet process, F− ions were removed by adding Ca(OH)2 as a F-fixing agent to F-containing aqueous Li solution. Through sequential calcination (500 °C) and water leaching cycles, we achieved high Li- and F-leaching efficiencies of 87 and 93%, respectively. When the second calcination temperature (500 °C) was higher than the first (350 °C), a high-purity Li solution was attained from water leaching after the second calcination, in which the F− concentration was approximately 1/10th that of the Li+ concentration. Furthermore, the wet process successfully removed 98% of F from a F-containing aqueous Li solution by adding Ca(OH)2. Thus, pure Li was successfully extracted from spent LIBs by a carbothermal process using calcium salt and water leaching treatment. The proposed acid-free process facilitates the recovery of Li from spent LIBs, which is promising for the closed-loop recycling of Li. [ABSTRACT FROM AUTHOR]