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Lithium (Li) is the gold standard treatment for bipolar disorder (BD). However, its mechanisms of action remain unknown but include neurotrophic effects. We here investigated the influence of Li on cortical and local grey matter (GM) volumes in a large international sample of patients with BD and healthy controls (HC).
We analyzed high-resolution T1-weighted structural magnetic resonance imaging scans of 271 patients with BD type I (120 undergoing Li) and 316 HC. Cortical and local GM volumes were compared using voxel-wise approaches with voxel-based morphometry and SIENAX using FSL. We used multiple linear regression models to test the influence of Li on cortical and local GM volumes, taking into account potential confounding factors such as a history of alcohol misuse.
Patients taking Li had greater cortical GM volume than patients without. Patients undergoing Li had greater regional GM volumes in the right middle frontal gyrus, the right anterior cingulate gyrus, and the left fusiform gyrus in comparison with patients not taking Li.
Our results in a large multicentric sample support the hypothesis that Li could exert neurotrophic and neuroprotective effects limiting pathological GM atrophy in key brain regions associated with BD.
We discuss here the choice of solid compounds and materials which best suit various types of applications, focusing mainly on the polarized targets. These materials include hydrogen-rich glassy hydrocarbons and simple cubic crystalline ammonia and lithium hydrides. The glassy hydrocarbons can doped by dissolved stable free radicals, while crystalline materials are doped by radiolytic paramagnetic radicals. The leading application of DNP up till now has been the scattering experiments in high-energy and nuclear physics. Other applications include measurements of slow neutron cross-sections, molecular physics using slow neutrons, nuclear magnetism and other solid-state physics experiments, and spin filters. The use of polarized solids in fusion and in magnetic resonance imaging has also been discussed. The material choice evidently depends strongly not only on the application but also on the goal of the experiment or process which is considered. More recently DNP has been used for the signal enhancement in NMR studies of complex chemical and biochemical molecules. In this context DNP and other enhancement techniques are called by the term “hyperpolarization”.
Mechanical fracture of electrodes will occur during lithiation caused by large volume changes, which leads to the capacity loss of the lithium-ion battery. Herein, we present a new analytical model to investigate the effect of creep deformation on stress relaxation and fracture of the lithiated tin (Sn) electrode under the galvanostatic and potentiostatic operation. Interestingly, it is found that the presence of creep can improve fracture resistance and toughness of the Sn electrode. In addition, the surface effect has the capacity to weaken the creep deformation effectively. And the different size of the Sn electrode shows different effects for creep deformation. This conclusion explains the difference in charging conditions, and the mechanism of stress change inside the electrode is also different. Deeply, the base on our model, the stress strength factor, and critical size of the electrode have been evaluated under galvanostatic and potentiostatic operation with creep deformation effects. Finally, the safety area during lithiation is established to determine the critical size of the Sn electrode. And the presence of creep deformation may significantly increase critical dimensions of the electrode. These results will provide a valuable basis to design the durable electrodes.
Currently, the evidence for lithium as a maintenance treatment for bipolar disorder type II (BD-II) remains limited. Guidelines commonly extrapolate recommendations for BD-II from available evidence for bipolar disorder type I (BD-I). Comparing the impact of lithium discontinuation is one way of assessing effectiveness in both groups.
To compare the impact of lithium discontinuation on hospital admissions and self-harm in patients with BD-I or schizoaffective disorder (SZD) and patients with BD-II or other bipolar disorder.
Mirror-image study, examining hospital admissions within 2 years before and after lithium discontinuation in both patient groups. This study was part of a retrospective cohort study (LiSIE) into effects and side-effects of lithium for maintenance treatment of bipolar disorder as compared with other mood stabilisers.
For the whole sample, the mean number of admissions/patient/review period doubled from 0.44 to 0.95 (P<0.001) after lithium discontinuation. The mean number of bed days/patient/review period doubled from 11 to 22 (P = 0.025). This increase in admissions and bed days was exclusively attributable to patients with BD-I/SZD. Not having consulted with a doctor prior to lithium discontinuation or no treatment with an alternative mood stabiliser at the time of lithium discontinuation led to more admissions.
The higher relapse risk in patients with BD-I/SZD suggests a higher threshold for discontinuing lithium than for patients with BD-II/other bipolar disorder. In patients with BD-II/other bipolar disorder, however, judged on the impact of discontinuation alone, lithium did not appear to prevent more severe depressive episodes requiring hospital admission.
Lithium was added to the hypereutectic Mg–Ni alloy to investigate the effect of volatilization of Li on the hydrogen storage characteristics of the eutectic Mg–Ni alloy at 300 °C. After fully activated at 300 °C, Li was almost completely volatilized and the structure of Li-containing Mg82Ni18 alloy was converted to the structure of Li-free Mg82Ni18 alloy, but hydrogen absorption capacity significantly decreased. This is because volatilization of Li weakened the bonding between eutectic Mg and Mg2Ni, lowering the catalytic effect of Mg2Ni on Mg. The decrease in hydrogen absorption capacity was more obvious with increasing Li content. In addition, experimental alloy in powder form could increase surface area, causing Li to volatilize at 300 °C.
Bipolar disorder (BD) is a highly heritable mood disorder with complex genetic architecture and poorly understood etiology. Previous transcriptomic BD studies have had inconsistent findings due to issues such as small sample sizes and difficulty in adequately accounting for confounders like medication use.
We performed a differential expression analysis in a well-characterized BD case-control sample (Nsubjects = 480) by RNA sequencing of whole blood. We further performed co-expression network analysis, functional enrichment, and cell type decomposition, and integrated differentially expressed genes with genetic risk.
While we observed widespread differential gene expression patterns between affected and unaffected individuals, these effects were largely linked to lithium treatment at the time of blood draw (FDR < 0.05, Ngenes = 976) rather than BD diagnosis itself (FDR < 0.05, Ngenes = 6). These lithium-associated genes were enriched for cell signaling and immune response functional annotations, among others, and were associated with neutrophil cell-type proportions, which were elevated in lithium users. Neither genes with altered expression in cases nor in lithium users were enriched for BD, schizophrenia, and depression genetic risk based on information from genome-wide association studies, nor was gene expression associated with polygenic risk scores for BD.
These findings suggest that BD is associated with minimal changes in whole blood gene expression independent of medication use but emphasize the importance of accounting for medication use and cell type heterogeneity in psychiatric transcriptomic studies. The results of this study add to mounting evidence of lithium's cell signaling and immune-related mechanisms.
Iron sulfides have attracted much interests for their potential as anode materials in energy storage devices in view of their low costs, and environmentally benign and high theoretical capacities. Among them, Fe1−xS is relatively rarely investigated. In this work, Fe1−xS@rGO has been synthesized using a facile in situ hydrothermal method. After wrapped by rGO, the morphology of Fe1−xS particles changes from hexagonal flakes to irregular particles with much smaller sizes. As the anode material for lithium ion batteries, Fe1−xS@rGO exhibits excellent lithium storage ability. It can deliver an initial discharge capacity of 1575.5 mA h/g in the potential window of 0.005–3 V, and a reversible capacity of 907.8 mA h/g can be maintained after 200 cycles at 100 mA/g. Its improved electrochemical performance can be attributed to the effect of enhanced contact area and shortened Li+ ion transport distance because of rGO’s contribution.
Metal oxides are promising candidates as the anodes of next-generation lithium ion batteries. However, the low electronic conductivities hinder their practical applications. Herein, through a facile calcination process using ammonium bicarbonate (NH4HCO3) as the N source, the nitrogen heteroelement was introduced into the ZnO/CoO micro-/nanospheres, which greatly improves the conductivity of the composites. As the lithium-ion battery anode, the N-doped ZnO/CoO micro-/nanosphere demonstrates much enhanced electrochemical performance. It displays a high initial capacity of 911.8 mA h/g at a current density of 0.2 A/g and long-term cycling stability, with a reversible capacity of 977.8 mA h/g remained after 500 cycles at a current density of 1 A/g. Furthermore, the N-doped ZnO/CoO composite presents an outstanding rate performance, with 605 mA h/g remained even at 5 A/g. The excellent electrochemical properties make N-doped ZnO/CoO micro-/nanospheres a promising candidate as high-performance anodes for next-generation rechargeable LIBs.
Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
Electroconvulsive therapy (ECT) is effective for unipolar depression but relapse and suicide are significant challenges. Lithium could potentially lower these risks, but is used only in a minority of patients.
This study quantifies the effect of lithium on risk of suicide and readmission and identifies factors that are associate with readmission and suicide.
This population-based register study used data from the Swedish National Quality Register for ECT and other Swedish national registers. Patients who have received ECT for unipolar depression as in-patients between 2011 and 2016 were followed until death, readmission to hospital or the termination of the study at the end of 2016. Cox regression was used to estimate hazard ratios (HR) of readmission and suicide in adjusted models.
Out of 7350 patients, 56 died by suicide and 4203 were readmitted. Lithium was prescribed to 638 (9%) patients. Mean follow-up was 1.4 years. Lithium was significantly associated with lower risk of suicide (P = 0.014) and readmission (HR 0.84 95% CI 0.75–0.93). The number needed to be treated with lithium to prevent one readmission was 16. In addition, the following factors were statistically associated with suicide: male gender, being a widow, substance use disorder and a history of suicide attempts. Readmission was associated with young age, being divorced or unemployed, comorbid anxiety disorder, nonpsychotic depression, more severe symptoms before ECT, no improvement with ECT, not receiving continuation ECT or antidepressants, usage of antipsychotics, anxiolytics or benzodiazepines, severity of medication resistance and number of previous admissions.
More patients could benefit from lithium treatment.
A technique to characterize the native passivation layer (NPL) on pure lithium metal foils in a scanning electron microscope (SEM) is described in this paper. Lithium is a very reactive metal, and consequently, observing and quantifying its properties in a SEM is often compromised by rapid oxidation. In this work, a pure lithium energy-dispersive x-ray spectrum is obtained for the first time in a high vacuum SEM using a cold stage/cold trap with liquid nitrogen reservoir outside the SEM chamber. A nanomanipulator (OmniProbe 400) inside the microscope combined with x-ray microanalysis and windowless energy dispersive spectrometer is used to fully characterize the NPL of lithium metal and some of its alloys by a mechanical removal procedure. The results show that the native films of pure lithium and its alloys are composed of a thin (25 nm) outer layer that is carbon-rich and an inner layer containing a significant amount of oxygen. Differences in thickness between laminated and extruded samples are observed and vary depending on the alloy composition.
Structural variation of LiMn1.5Ni0.5O4 spinel cathode during the Li+ extraction/insertion reaction was studied using operando X-ray diffraction. It was found that the reaction in the voltage range from 3.5 to 4.9 V consisted of two consecutive two-phase reactions, where three spinel phases of LiMn1.5Ni0.5O4, Li0.5Mn1.5Ni0.5O4 and Mn1.5Ni0.5O4 were identified and the lattice volume change in the whole reaction was evaluated as 6%. The reactions were symmetric and reversible under low-current conditions, but some asymmetries were detected during high current operation. Furthermore, a two-phase reaction between cubic and tetragonal phases was observed in the low-voltage reaction at 2.1–3.5 V, where the lattice volume change was approximately 4.9%. The rate-determining step was discussed based on these operando results.
We review spectroscopic results concerning multiple stellar populations in globular clusters. The cluster initial mass is the most important parameter determining the fraction of second generation stars. The threshold for the onset of the multiple population phenomenon is 1–3×105 M⊙. Nucleosynthesis is influenced by metallicity: Na/O and Mg/Al anti-correlations are more extended in metal-poor than in metal-rich clusters. Massive clusters are more complex systems than the smaller ones, with several populations characterized by different chemical compositions. The high Li abundance observed in the intermediate second generation stars strongly favours intermediate mass AGB stars as polluters for this class of stars; however, it is well possible that the polluters of extreme second generation stars, that often do not have measurable Li, may be fast rotating massive stars or super-massive stars. The mass budget factor should be a function of the cluster mass, and needs to be large only in massive clusters.
Lithium-treated patients with polyuria are at increased risk of lithium toxicity. We aimed to describe the clinical benefits and risks of different management strategies for polyuria in community lithium-treated patients.
This is a naturalistic, observational, prospective 12-month cohort study of lithium-treated patients with polyuria attending a community mental health service in Dublin, Ireland. When polyuria was detected, management changed in one of four ways: (a) no pharmacological change; (b) lithium dose decrease; (c) lithium substitution; or (d) addition of amiloride.
Thirty-four participants were diagnosed with polyuria and completed prospective data over 12 months. Mean 24-hour urine volume decreased from 4852 to 4344 ml (p = 0.038). Mean early morning urine osmolality decreased from 343 to 338 mOsm/kg (p = 0.823). Mean 24-hour urine volume decreased with each type of intervention but did not attain statistical significance for any individual intervention group. Mean early morning urine osmolality decreased in participants with no pharmacological change and increased in participants who received a change in medication but these changes did not attain statistical significance. Only participants who discontinued lithium demonstrated potentially clinically significant changes in urine volume (mean decrease 747 ml in 24 hours) and early morning urine osmolality (mean increase 31 mOsm/kg) although this was not definitively proven, possibly owing to power issues.
Managing polyuria by decreasing lithium dose does not appear to substantially improve objective measures of renal tubular dysfunction, whereas substituting lithium may do so. Studies with larger numbers and longer follow-up would clarify these relationships.
Experimental studies indicate that lithium may facilitate neurotrophic/protective responses in the brain. Epidemiological and imaging studies in bipolar disorder, in addition to a few trials in Alzheimer's disease support the clinical translation of these findings. Nonetheless, there is limited controlled data about potential use of lithium to treat or prevent dementia.
To determine the benefits of lithium treatment in patients with amnestic mild cognitive impairment (MCI), a clinical condition associated with high risk for Alzheimer's disease.
A total of 61 community-dwelling, physically healthy, older adults with MCI were randomised to receive lithium or placebo (1:1) for 2 years (double-blind phase), and followed-up for an additional 24 months (single-blinded phase) (trial registration at clinicaltrials.gov: NCT01055392). Lithium carbonate was prescribed to yield subtherapeutic concentrations (0.25–0.5 mEq/L). Primary outcome variables were the cognitive (Alzheimer's Disease Assessment Scale – cognitive subscale) and functional (Clinical Dementia Rating – Sum of Boxes) parameters obtained at baseline and after 12 and 24 months. Secondary outcomes were neuropsychological test scores; cerebrospinal fluid (CSF) concentrations of Alzheimer's disease-related biomarkers determined at 0, 12 and 36 months; conversion rate from MCI to dementia (0–48 months).
Participants in the placebo group displayed cognitive and functional decline, whereas lithium-treated patients remained stable over 2 years. Lithium treatment was associated with better performance on memory and attention tests after 24 months, and with a significant increase in CSF amyloid-beta peptide (Aβ1−42) after 36 months.
Long-term lithium attenuates cognitive and functional decline in amnestic MCI, and modifies Alzheimer's disease-related CSF biomarkers. The present data reinforces the disease-modifying properties of lithium in the MCI–Alzheimer's disease continuum.
Research results of luminescence spectra of noble gases and Ar–Xe, Ar–Kr, and Kr–Xe mixtures under the excitation by products of nuclear reaction in the core of a stationary nuclear reactor with 0.87 × 1014 n/cm2s thermal neutron flux are described in the article. The emission spectra of noble gases are similar to the obtained spectrum under the excitation by the 40Ar+7 ion beam from the DC-60 accelerator. Bands in spectra of the binary mixtures of noble gases are connected with the radiation on heteronuclear ion molecule transitions. The appearance of the lines of alkali metal atoms at the temperature increase of gas chamber is explained by sputtering of the lithium layer via nuclear reaction products as well as ionized and excited particles of the buffer gas.
People with bipolar disorder typically require long-term pharmacological treatment to prevent episodes of depression or mania. However, evidence-based guidelines are often not followed by prescribers and, in some countries, prescribing of lithium is in decline. Polypharmacy is also common in bipolar disorder.
To employ a data linkage approach to describe and evaluate prescribing patterns in bipolar disorder in Scotland between 2009 and 2016.
By linking prescribing data to the electronic Scottish Morbidity Records, we identified a cohort of 23 135 patients with bipolar disorder who were prescribed psychotropic medication between 2009 and 2016. We examined trends in proportions of patients prescribed each of six drug categories. Random effects logistic models examined change in prescribing over years of interest.
The most common form of treatment was antidepressant monotherapy (24.96%), with only 5.90% of patients receiving lithium monotherapy. Prescribing of antipsychotics and anti-epileptics increased from 2009 to 2016 (antipsychotics: odds ratio 1.16, 95% CI 1.15–1.18; anti-epileptics: odds ratio 1.34, 95% CI 1.32–1.36), whereas prescribing of lithium decreased (odds ratio 0.83, 95% CI 0.82–0.85). Prescribing of valproate decreased from 2009–2016 in women, but increased in men (women: odds ratio 0.93, 95% CI 0.90–0.97; men: odds ratio 1.11, 95% CI 1.04–1.18).
Antidepressant monotherapy was the most common form of treatment for bipolar disorder in Scotland and prescribing of lithium has declined between 2009 and 2016. The findings are concerning and represent a gap between treatment guidelines and clinical practice.
Compared with commercial polyolefin membranes, polyacrylonitrile (PAN) membrane prepared by electrostatic spinning has higher porosity, electrolyte uptake, thermal stability, and lithium-ion conductivity, etc. However, poor mechanical performance has largely limited the application of electrospun PAN separators. In this study, PAN/polyimide (PI) composite membrane is prepared by electrostatic spinning to improve the mechanical and electrochemical performances. Scanning electron microscopy, thermal analysis method, and electrochemical methods were used for evaluation of the electrospun composite membrane. The results show that the composite membrane possesses good thermal stability and exhibits better mechanical performance than pristine PAN membrane (increasing by 1.1 times in tension strength). The addition of PI can increase porosity and fluid absorption rate obviously. In addition, the composite membrane has high ionic conductivity (18.77 × 10−4 S/cm), wide electrochemical window (about 4.0 V), and excellent cycling performance. It can retain a discharge specific capacity of 153 mA h/g even after 50 cycles at 0.5 C. The electrospun PAN/PI membrane may be a promising candidate for lithium-ion battery separators.
3D ordered bimodal mesoporous carbon (OBMC) with a high specific surface area of 1368.7 m2/g, ordered large mesopores, and small mesopores on the walls is prepared by a surfactant-free rapid method using SiO2 nanosphere arrays as templates. The resulting OBMC is then composited with sulfur to prepare S/OBMC hybrids via a simple solution infiltration method followed by a heat treatment process. In S/OBMC composite, sulfur is uniformly infiltrated inside the 3D hierarchical pores of OBMC. On the basis of this systematic design, the obtained S/OBMC cathode shows a large discharge capacity value of 1590 mA h/g at first cycle and maintains 989 mA h/g after 100 cycles at 0.2 C. Furthermore, at 1 C charge–discharge rate, a reversible discharge capacity of 733 mA h/g after 100 cycles is reached. The extraordinary electrochemical property of S/OBMC derives from the unique bimodal mesoporous structure with large mesopores and small mesopores that can facilitate the mass transfer and strict dissolution of polysulfide species into the electrolyte.
In addition to suicide prediction, neuroscience can be expected to contribute in a unique and substantial way to the treatment of suicide risk. For psychotropic drugs such as lithium and clozapine a specific antisuicidal effect has been demonstrated, independent of effects on associated psychiatric disorders. The results from studies with ketamine are promising as they indicate a rapid and sustained relief of suicidal thoughts. Neurostimulation and neuromodulation provide new approaches to treatment, with a substantial impact on suicide risk. Novel pharmacological compounds targeting the vulnerability to suicidal behavior include drugs that affect the stress-response system and neuroprotective factors.