Lithium Exposure Research Articles

Association between duration of lithium exposure and hippocampus/amygdala volumes in type I bipolar disorder

BackgroundPrior studies on the effects of lithium on limbic and subcortical gray matter volumes are mixed. It is possible that discrepant findings may be explained by the duration of lithium exposure. We investigated this issue in individuals with type I bipolar disorder (BP-I). MethodsLimbic and subcortical gray matter volume was measured using FreeSurfer in 60 subjects: 15 with BP-I without prior lithium exposure [no-exposure group (NE)]; 15 with BP-I and lithium exposure < 24 months [short-exposure group (SE)]; 15 with BP-I and lithium exposure > 24 months [long-exposure group (LE)]; and 15 healthy controls (HC). ResultsNo differences in limbic and subcortical gray matter volumes were found between LE and HC. Hippocampal and amygdalar volumes were larger bilaterally in both LE and HC when compared to NE. Amygdalar volumes were larger bilaterally in SE when compared to NE but did not differ from LE. Hippocampal volumes were smaller bilaterally in SE when compared to LE and HC but did not differ from NE. No between-group differences on subcortical gray matter or other limbic structure volumes were observed. LimitationsCross-sectional design and concurrent treatment with other medications limit attribution of between-group differences to lithium exposure alone. ConclusionsThe effect of lithium exposure on limbic and subcortical gray matter volumes appears to be time-dependent and relatively specific to the hippocampus and the amygdala, with short-term effects on the amygdala and long-term effects on both structures. These results support the clinical importance of long-term lithium treatment in BP-I.

Snapshots of the Hydrolysis of Lithium 4,5-Dicyanoimidazolate–Glyme Solvates. Impact of Water Molecules on Aggregation Processes in Lithium-Ion Battery Electrolytes

Despite that 4,5-dicyano-2-(trifluoromethyl)imidazole lithium salt (LiTDI) exhibits several interesting features in aprotic solvents such as glymes or carbonate esters, little is known about its structural rearrangement after exposure to water. Since the LiTDI salt has been verified as an effective moisture scavenger able to suppress degradation of the LiPF6-based electrolyte, comprehensive knowledge of coordination modes in the LiTDI–H2O system, as well as information about the structure of formed hydrates, is desirable. In the present study, we report the impact of water on the LiTDI glyme-based electrolytes investigated by means of the single-crystal X-ray diffraction technique and Raman spectroscopy. We have found that the exposure of lithium 4,5-dicyanoimidazolate–glyme solvates to humid air gives rise to the hydrolysis products arising from stepwise addition of water molecules to the lithium coordination sphere. Several structural motifs have been distinguished as preferred coordination modes in the...

Amiloride modifies the progression of lithium-induced renal interstitial fibrosis.

Long-term administration of lithium has been associated with the development of a chronic interstitial fibrosis in addition to nephrogenic diabetes insipidus (NDI). Earlier studies have demonstrated that amiloride, by blocking the epithelial sodium channel ENaC and thus preventing lithium uptake into the principal cells of the collecting ducts, can partially reverse lithium-induced NDI. However, there are no long-term studies examining whether or not amiloride also modifies the progressive chronic interstitial fibrosis and tubular atrophy often evident with long-term lithium exposure. Using an established animal model of lithium-induced chronic interstitial fibrosis, rats were treated with amiloride and lithium for 5months following 1month of exposure to lithium alone and compared with control animals and those given only lithium. In this study, the 5months of amiloride therapy partially mitigated the lithium-induced NDI and limited the further progression of lithium-induced kidney fibrosis. This improvement was associated with decreased expression of the pro-fibrotic connective tissue growth factor (CTGF), along with reduced myofibroblast infiltration and decreased collagen deposition around the distended cortical collecting ducts. This may, in part, be mediated by modifying lithium-induced alterations in β-catenin activity through its effects on GSK-3β.

Maternal mood disorders and lithium exposure in utero were not associated with poor cognitive development during childhood.

This study evaluated whether maternal mood disorders (MMD), particularly bipolar disorder, and lithium treatment during pregnancy influenced the neonatal health and cognition of children born from 2006 to 2010. Our study at Karolinska University Hospital, Stockholm, Sweden, focused on women with and without mood disorders and their children. Information on pharmacotherapy, mental health, delivery and neonatal complications was retrospectively collected from electronic patient records. Children were tested in a blinded manner at four to five years of age with the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition. Maternal health, child health and social situations were evaluated. Of the 39 children, 20 were exposed to lithium and MMD during pregnancy, eight were exposed to MMD but not lithium and 11 were not exposed to MMD or lithium. The children's full scale intelligence quotient (IQ), performance IQ and verbal IQ results did not differ significantly between the groups. The processing speed quotient was significantly lower in children exposed to mood disorders, but there was a high level of missing data for this subtest. This small, clinical cohort showed no significant association between mothers' prenatal exposure to lithium or mood disorders and their offspring's IQ.

Prophylactic mood stabilization: What is the evidence for lithium exposure in drinking water?

Large-scale population registers and databases have great potential for use in hypothesis-generating epidemiological research. Utilising such data, cross-sectional and ecological studies are relatively inexpensive and time-efficient observational studies that can identify correlations between exposures and outcomes. In the field of lithium research, this has generated interest in exploring the effect of exposure to micro-levels of lithium levels in drinking water. The studies carried out so far have predominantly examined associations between lithium exposure and rates of suicide and violence and only a paucity looked at associations between lithium exposure and mood. This is interesting considering that, for therapeutic levels of lithium in bipolar disorder, the evidence first supported its efficacy on mood and it only recently demonstrated an independent effect of lithium on suicidality, which may be specific and not secondary to the improvement of affective symptoms.1 Ecological studies have reported associations between geographical differences in lithium levels in the drinking supply and rates of suicide, suggesting that exposure to microlevels of lithium may have a prophylactic effect.2 One important limitation of such population studies, which rely on anonymised datasets, is their inability to link individual exposures to outcomes. This is overcome when all national datasets and registers use a common identifier, as is done in Denmark through the use of unique personal identification numbers, thereby allowing exposures to be linked to outcomes at an individual level. Kessing et al. have utilised this added strength of Danish population datasets to explore the link between exposure to microlevels of lithium in drinking water and incidence of bipolar disorder.3 The study estimates individual average lithium exposure by combining longitudinal data on areas of residence with data from drinking water lithium levels in the various municipalities. Comparing average lithium exposure in individuals with a hospital diagnosis of bipolar disorder to matched controls over a 13 year period, it found no association between higher long-term lithium exposure and reduced incidence of bipolar disorder.

Higher Levels of Lithium in Drinking Water May Lower Dementia Risk

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessHigher Levels of Lithium in Drinking Water May Lower Dementia RiskJoAnn BlakeJoAnn BlakeSearch for more papers by this authorPublished Online:5 Oct 2017https://doi.org/10.1176/appi.pn.2017.10a17AbstractA large population study explores the impact of lithium in groundwater for preventing dementia.A study published in JAMA Psychiatry in August attempts to answer the question, “Could lithium, a naturally occurring element in drinking water, reduce the incidence of dementia?” iStock/diane39Without a cure or treatment that slows or stops the progression of dementia, researchers have been looking to prevention—such as targeted interventions and modifiable risk factors associated with dementia. The mood stabilizer lithium has been considered as a potential treatment for Alzheimer’s disease (AD). Positive evidence in several small clinical trials has suggested that low-dose lithium may improve cognition. Lithium blocks an enzyme crucial to the development of AD’s plaques and tangles and has been shown to prevent AD in mice.“The prospect that a relatively safe, simple, and cheap intervention (i.e., optimizing lithium concentrations in drinking water) could lead to the primary prevention of dementia is a tantalizing prospect,” wrote John J. McGrath, M.D., Ph.D., of the Queensland Centre for Mental Health Research in Australia, in an accompanying editorial.In the current study, Lars Vedel Kessing, M.D., D.M.Sc., of the University of Copenhagen and colleagues found that higher concentrations of lithium in the drinking water in areas of Denmark were associated with a lower risk of developing dementia. The researchers measured lithium in drinking water from 151 communities around Denmark and mapped where people with dementia and age- and sex-matched controls lived from 1986 to 2013. They collected longitudinal, individual geographic data on municipality of residence and data from drinking water measurements combined with time-specific data from all patients aged 50 to 90 with a hospital contract and with a diagnosis of dementia from January 1, 1970, through December 31, 2013. The mean lithium exposure in drinking water since 1986 was estimated for all study individuals. A total of 73,731 patients with dementia and 733,653 controls were included in the study. The researchers found that higher long-term exposure to lithium in drinking water was associated with a lower incidence of dementia, but this association was nonlinear. Compared with people exposed to the lowest levels of lithium (up to 5 μg/L), people exposed to 5.1 to 10 μg/L had a 22 percent higher risk of dementia, people exposed to 10.1 to 15 μg/L had about the same risk of dementia, and people exposed to 15 μg/L or more had a 17 percent lower risk of dementia.The study’s authors do not suggest increasing lithium in the water supply; it is unclear how much lithium would be safe and effective to use. “There is strong epidemiological evidence in animal and human studies that certain low levels of lithium are neuroprotective,” Anna Fels, M.D., a practicing psychiatrist in New York City and a clinical professor of psychiatry at Weill Cornell Medical College, told Psychiatric News. “More studies should be done, and if they continue to find benefits, there should be ways the public could access water with lithium in tablets or another form that is measured and pharmaceutical grade.” “If the findings of Kessing and colleagues are supported in future studies, even a marginal reduction in the incidence of dementia could result in major societal and economic gains,” wrote McGrath. ■“Association of Lithium in Drinking Water With the Incidence of Dementia” can be accessed here. The related editorial, “Could Lithium in Drinking Water Reduce the Incidence of Dementia?,” is available here. ISSUES NewArchived

Li-intercalated graphene on SiC(0001): An STM study

We present a systematical study via scanning tunneling microscopy (STM) and low-energy electron diffraction (LEED) on the effect of the exposure of Lithium (Li) on graphene on silicon carbide (SiC). We have investigated Li deposition both on epitaxial monolayer graphene and on buffer layer surfaces on the Si-face of SiC. At room temperature, Li immediately intercalates at the interface between the SiC substrate and the buffer layer and transforms the buffer layer into a quasi-free-standing graphene. This conclusion is substantiated by LEED and STM evidence. We show that intercalation occurs through the SiC step sites or graphene defects. We obtain a good quantitative agreement between the number of Li atoms deposited and the number of available Si bonds at the surface of the SiC crystal. Through STM analysis, we are able to determine the interlayer distance induced by Li-intercalation at the interface between the SiC substrate and the buffer layer.

Association of Lithium in Drinking Water With the Incidence of Dementia

Results from animal and human studies suggest that lithium in therapeutic doses may improve learning and memory and modify the risk of developing dementia. Additional preliminary studies suggest that subtherapeutic levels, including microlevels of lithium, may influence human cognition. To investigate whether the incidence of dementia in the general population covaries with long-term exposure to microlevels of lithium in drinking water. This Danish nationwide, population-based, nested case-control study examined longitudinal, individual geographic data on municipality of residence and data from drinking water measurements combined with time-specific data from all patients aged 50 to 90 years with a hospital contact with a diagnosis of dementia from January 1, 1970, through December 31, 2013, and 10 age- and sex-matched control individuals from the Danish population. The mean lithium exposure in drinking water since 1986 was estimated for all study individuals. Data analysis was performed from January 1, 1995, through December 31, 2013. A diagnosis of dementia in a hospital inpatient or outpatient contact. Diagnoses of Alzheimer disease and vascular dementia were secondary outcome measures. In primary analyses, distribution of lithium exposure was compared between patients with dementia and controls. A total of 73 731 patients with dementia and 733 653 controls (median age, 80.3 years; interquartile range, 74.9-84.6 years; 44 760 female [60.7%] and 28 971 male [39.3%]) were included in the study. Lithium exposure was statistically significantly different between patients with a diagnosis of dementia (median, 11.5 µg/L; interquartile range, 6.5-14.9 µg/L) and controls (median, 12.2 µg/L; interquartile range, 7.3-16.0 µg/L; P < .001). A nonlinear association was observed. Compared with individuals exposed to 2.0 to 5.0 µg/L, the incidence rate ratio (IRR) of dementia was decreased in those exposed to more than 15.0 µg/L (IRR, 0.83; 95% CI, 0.81-0.85; P < .001) and 10.1 to 15.0 µg/L (IRR, 0.98; 95% CI, 0.96-1.01; P = .17) and increased with 5.1 to 10.0 µg/L (IRR, 1.22; 95% CI, 1.19-1.25; P < .001). Similar patterns were found with Alzheimer disease and vascular dementia as outcomes. Long-term increased lithium exposure in drinking water may be associated with a lower incidence of dementia in a nonlinear way; however, confounding from other factors associated with municipality of residence cannot be excluded.

Long-term lithium treatment in bipolar disorder: effects on glomerular filtration rate and other metabolic parameters

BackgroundConcerns about potential adverse effects of long-term exposure to lithium as a mood-stabilizing treatment notably include altered renal function. However, the incidence of severe renal dysfunction; rate of decline over time; effects of lithium dose, serum concentration, and duration of treatment; relative effects of lithium exposure vs. aging; and contributions of sex and other factors all remain unclear.MethodsAccordingly, we acquired data from 12 collaborating international sites and 312 bipolar disorder patients (6142 person-years, 2669 assays) treated with lithium carbonate for 8–48 (mean 18) years and aged 20–89 (mean 56) years. We evaluated changes of estimated glomerular filtration rate (eGFR) as well as serum creatinine, urea–nitrogen, and glucose concentrations, white blood cell count, and body-mass index, and tested associations of eGFR with selected factors, using standard bivariate contrasts and regression modeling.ResultsOverall, 29.5% of subjects experienced at least one low value of eGFR (<60 mL/min/1.73 m2), most after ≥15 years of treatment and age > 55; risk of ≥2 low values was 18.1%; none experienced end-stage renal failure. eGFR declined by 0.71%/year of age and 0.92%/year of treatment, both by 19% more among women than men. Mean serum creatinine increased from 0.87 to 1.17 mg/dL, BUN from 23.7 to 33.1 mg/dL, glucose from 88 to 122 mg/dL, and BMI from 25.9 to 26.6 kg/m2. By multivariate regression, risk factors for declining eGFR ranked: longer lithium treatment, lower lithium dose, higher serum lithium concentration, older age, and medical comorbidity. Later low eGFR was also predicted by lower initial eGFR, and starting lithium at age ≥ 40 years.LimitationsControl data for age-matched subjects not exposed to lithium were lacking.ConclusionsLong-term lithium treatment was associated with gradual decline of renal functioning (eGFR) by about 30% more than that was associated with aging alone. Risk of subnormal eGFR was from 18.1% (≥2 low values) to 29.5% (≥1 low value), requiring about 30 years of exposure. Additional risk factors for low eGFR were higher serum lithium level, longer lithium treatment, lower initial eGFR, and medical comorbidity, as well as older age.

Re-analysis of the association of temperature or sunshine with hyperthymic temperament using lithium levels of drinking water

BackgroundThe Japanese archipelago stretches over 4000km from north to south and has four large islands: Hokkaido, Honshu, Shikoku, and Kyushu. Previously, using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire version (TEMPS-A), we compared the hyperthymic scores of residents in Sapporo, Obihiro, Takaoka, Koshigaya, and Oita cities (which are located at latitudes of 43°N, 42°N, 36°N, 36°N and 33°N with various combinations of ambient temperament and sunshine in Japan, respectively). We found that latitude predicted significant variance in hyperthymic temperament, and that ambient temperature, but not sunshine, significantly affected hyperthymic temperament scores. However, the analysis failed to consider the effects of naturally occurring low-dose lithium on temperament. MethodsIn addition to the TEMPS-A data previously collected, we measured lithium levels of the five cities. The effect of temperature, sunshine, and lithium levels on hyperthymic temperament was analyzed for the five cities. ResultsA stepwise multiple regression analysis revealed that lithium levels as well as latitude, but not temperature or sunshine, predicted significant variance in hyperthymic temperament scores. Hyperthymic temperament scores were significantly and positively associated with lithium levels whereas they were significantly and negatively associated with latitude. LimitationsThe light, temperature, lithium exposure that residents actually received was not measured. The number of regions studied was limited. The findings might not be generalized to residents across Japan or other countries. ConclusionsThe present findings suggest that lithium in drinking water may positively maintain hyperthymic temperament, and that latitude may negatively maintain it.

Lithium in drinking water and the incidence of bipolar disorder: A nation-wide population-based study.

Animal data suggest that subtherapeutic doses, including micro doses, of lithium may influence mood, and lithium levels in drinking water have been found to correlate with the rate of suicide. It has never been investigated whether consumption of lithium may prevent the development of bipolar disorder (primary prophylaxis). In a nation-wide population-based study, we investigated whether long-term exposure to micro levels of lithium in drinking water correlates with the incidence of bipolar disorder in the general population, hypothesizing an inverse association in which higher long-term lithium exposure is associated with lower incidences of bipolar disorder. We included longitudinal individual geographical data on municipality of residence, data from drinking water lithium measurements and time-specific data from all cases with a hospital contact with a diagnosis of mania/bipolar disorder from 1995 to 2013 (N=14820) and 10 age- and gender-matched controls from the Danish population (N= 140311). Average drinking water lithium exposure was estimated for all study individuals. The median of the average lithium exposure did not differ between cases with a diagnosis of mania/bipolar disorder (12.7μg/L; interquartile range [IQR]: 7.9-15.5 μg/L) and controls (12.5μg/L; IQR: 7.6-15.7 μg/L; P=.2). Further, the incidence rate ratio of mania/bipolar disorder did not decrease with higher long-term lithium exposure, overall, or within age categories (0-40, 41-60 and 61-100years of age). Higher long-term lithium exposure from drinking water was not associated with a lower incidence of bipolar disorder. The association should be investigated in areas with higher lithium levels than in Denmark.

Association between Lithium Use and Melanoma Risk and Mortality: A Population-Based Study

Laboratory studies show that lithium, an activator of the Wnt/ß-catenin signaling pathway, slows melanoma progression, but to our knowledge no published epidemiologic studies have explored this association. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n=2,213,848) from 1997-2012 to examine the association between lithium use and melanoma risk. Lithium exposure (n= 11,317) was assessed from pharmacy databases, serum lithium levels were obtained from electronic laboratory databases, and incident cutaneous melanomas (n= 14,056) were identified from an established cancer registry. In addition to examining melanoma incidence, melanoma hazard ratios and 95% confidence intervals for lithium exposure were estimated using Cox proportional hazards models, adjusted for potential confounders. Melanoma incidence per 100,000 person-years among lithium-exposed individuals was 67.4, compared with 92.5 in unexposed individuals (P= 0.027). Lithium-exposed individuals had a 32% lower risk of melanoma (hazard ratio= 0.68, 95% confidence interval= 0.51-0.90) in unadjusted analysis, but the estimate was attenuated and nonsignificant in adjusted analysis (adjusted hazard ratio= 0.77, 95% confidence interval= 0.58-1.02). No lithium-exposed individuals presented with thick (>4 mm) or advanced-stage melanoma at diagnosis. Among melanoma patients, lithium-exposed individuals were less likely to suffer melanoma-associated mortality (rate= 4.68/1,000 person-years) compared with the unexposed (rate= 7.21/1,000 person-years). Our findings suggest that lithium may reduce melanoma risk and associated mortality.

Lithium exposure during pregnancy: outcomes for women who attended a specialist antenatal clinic

Introduction: Lithium treatment in pregnancy represents a significant dilemma for women and treating health professionals alike. The complexity of risk-benefit analysis is impacted by limited information.Methods: A cohort study of 33 women with severe mental illness, who were prescribed lithium at any time during the pregnancy, and gave birth between December 2007 and January 2015 at a specialist antenatal clinic in Western Australia. A descriptive comparison for women who continued lithium throughout pregnancy, and those who ceased on discovery of pregnancy was undertaken examining demographic, obstetric, neonatal and psychiatric variables.Results: Women who were prescribed lithium, irrespective of whether they continued or discontinued the medication represented a high risk group obstetrically, with high rates of smoking overall (33%) medical comorbidities (54%) and antenatal complications (88%). Preconception counseling occurred in 33% of the cohort but increased the likelihood of continuing lithium in pregnancy (p = .007). Compared to those who ceased lithium, women who remained on lithium through the pregnancy had increased rates of fetal ultrasound abnormalities such as abdominal circumference >90th % (p = .005). Psychiatric relapses through the antenatal and immediate postpartum period appeared to be due to a combination of factors.Discussion: Pregnant women with severe mood disorders treated with lithium are a vulnerable, high-risk obstetric population who would benefit from preconception counseling, regular antenatal care in a tertiary center, delivery with neonatal pediatric support and experienced psychiatric management.

Lithium in Drinking Water and Incidence of Suicide: A Nationwide Individual-Level Cohort Study with 22 Years of Follow-Up.

Suicide is a major public health concern. High-dose lithium is used to stabilize mood and prevent suicide in patients with affective disorders. Lithium occurs naturally in drinking water worldwide in much lower doses, but with large geographical variation. Several studies conducted at an aggregate level have suggested an association between lithium in drinking water and a reduced risk of suicide; however, a causal relation is uncertain. Individual-level register-based data on the entire Danish adult population (3.7 million individuals) from 1991 to 2012 were linked with a moving five-year time-weighted average (TWA) lithium exposure level from drinking water hypothesizing an inverse relationship. The mean lithium level was 11.6 μg/L ranging from 0.6 to 30.7 μg/L. The suicide rate decreased from 29.7 per 100,000 person-years at risk in 1991 to 18.4 per 100,000 person-years in 2012. We found no significant indication of an association between increasing five-year TWA lithium exposure level and decreasing suicide rate. The comprehensiveness of using individual-level data and spatial analyses with 22 years of follow-up makes a pronounced contribution to previous findings. Our findings demonstrate that there does not seem to be a protective effect of exposure to lithium on the incidence of suicide with levels below 31 μg/L in drinking water.

Interfacial instability of amorphous LiPON against lithium: A combined Density Functional Theory and spectroscopic study

The chemical instability of the glassy solid electrolyte LiPON against metallic lithium and the occurrence of side reactions at their interface is investigated by combining a surface science approach and quantum-mechanical calculations. Using an evolutionary structure search followed by a melt-quenching protocol, a model for the disordered structure of LiPON is generated and put into contact with lithium. Even the static optimization of a simple model interface suggests that the diffusion of lithium into LiPON is driven by a considerable driving force that could easily take place under experimental conditions. Calculated reaction energies indicate that the reduction and decomposition of LiPON is thermodynamically favorable. By monitoring the evolution of the LiPON core levels as a function of lithium exposure, the disruption of the LiPON network alongside the occurrence of new phases is observed. The direct comparison between UV photoelectron spectroscopy measurements and calculated electronic densities of states for increasing stages of lithiation univocally identifies the new phases as Li_2O, Li_3P and Li_3N. These products are stable against Li metal and form a passivation layer which shields the electrolyte from further decomposition while allowing for the diffusion of Li ions. Interfacial instability of amorphous LiPON against lithium: A combined Density Functional Theory and spectroscopic study. Available from: https://www.researchgate.net/publication/316112203_Interfacial_instability_of_amorphous_LiPON_against_lithium_A_combined_Density_Functional_Theory_and_spectroscopic_study [accessed May 16, 2017].

Neurobehavioral effects of lithium in the rat: Investigation of the effect/concentration relationships and the contribution of the poisoning pattern

Severity of lithium poisoning depends on the ingested dose, previous treatment duration and renal function. No animal study has investigated neurobehavioral differences in relation to the lithium poisoning pattern observed in humans, while differences in lithium pharmacokinetics have been reported in lithium-pretreated rats mimicking chronic poisonings with enhanced brain accumulation in rats with renal failure. Our objectives were: 1)-to investigate lithium-related effects in overdose on locomotor activity, anxiety-like behavior, spatial recognition memory and anhedonia in the rat; 2)-to model the relationships between lithium-induced effects on locomotion and plasma, erythrocyte, cerebrospinal fluid and brain concentrations previously obtained according to the poisoning pattern. Open-field, elevated plus-maze, Y-maze and sucrose consumption tests were used. In acutely lithium-poisoned rats, we observed horizontal (p<0.001) and vertical hypolocomotion (p<0.0001), increased anxiety-like behavior (p<0.05) and impaired memory (p<0.01) but no altered hedonic status. Horizontal (p<0.01) and vertical (p<0.001) hypolocomotion peaked more markedly 24h after lithium injection and was more prolonged in acute-on-chronically vs. acutely lithium-poisoned rats. Hypolocomotion in chronically lithium-poisoned rats with impaired renal function did not differ from acutely poisoned rats 24h after the last injection. Interestingly, hypolocomotion/concentration relationships best fitted a sigmoidal Emax model in acute poisoning and a linear regression model linked to brain lithium in acute-on-chronic poisoning. In conclusion, lithium overdose alters rat behavior and consistently induces hypolocomotion which is more marked and prolonged in repeatedly lithium-treated rats. Our data suggest that differences between poisoning patterns regarding lithium-induced hypolocomotion are better explained by the duration of lithium exposure than by its brain accumulation.

Exploring potential biomarker responses to lithium in Daphnia magna from the perspectives of function and signaling networks

Intensive usage of electronic appliances containing lithium batteries causes an accumulation of e-trash. Environmental exposure to lithium batteries contaminates ecosystems. In air and water, the batteries form lithium hydroxide (LiOH) on their surfaces. LiOH enters the aquatic environment and contaminates the aquatic ecosystem by being absorbed into biological organisms. In this study, in order to identify meaningful potential biomarkers that appear in response to lithium, we measured significantly up- and down-regulated genes after LiOH exposure by conducting a microarray. In addition, we explored the functions of differentially expressed daphnia genes, and we conducted a comparative analysis in other species, Daphnia spp. to humans, then analyzed the signaling pathways using the human gene set derived from daphnia sequences that are differentially expressed in response to LiOH using the NCBI-BLAST tool and Pathway studio. As a result, we identified signaling pathways and suggested several potential biomarkers that are up- or down-regulated in response to lithium. This study may contribute to the development of a biomonitoring system which can detect the ecotoxicity of lithium. Furthermore, lithium toxicity in humans can be predicted, so the study may also provide potential biomarkers of lithium exposure in humans.

Lithium rechallenge after renal transplant.

Mrs B is a 65-year-old, married, white woman with long-standing history of bipolar disorder type I who achieved mood stability with chronic lithium treatment. She developed end-stage renal disease, which was suspected to be the result of chronic lithium exposure in the context of medical comorbidity, and subsequently required renal transplantation. Following transplantation and discontinuation of lithium, Mrs B was unable to achieve mood stability with multiple medication trials and required more than 40 medical and psychiatric hospitalizations with eventual transition to skilled nursing care. After much discussion among the psychiatric treatment team, the patient, and her husband, primary care provider, nephrologist, and renal transplant surgeon, the decision was made to restart the patient on lithium given her previous treatment success. The purpose of this case report is to discuss the use of lithium following renal transplantation. In this case, a multidisciplinary approach was used to assist the patient in carefully weighing the risks and benefits of her treatment decisions. The consensus of the patient, her husband, and her providers was that the benefit of mood stabilization outweighed the potential risks of renal toxicity. Although treatment with lithium after renal transplant is not a first-line treatment option, this case illustrates that lithium could be considered in certain cases.

Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study.

Lithium inhibits glycogen synthase kinase-3, which is an enzyme involved in the pathogenesis of cancer. To investigate the association between lithium and cancer risk in patients with bipolar disorder. A retrospective cohort study was designed using the National Health Insurance Research Database (NHIRD) in Taiwan. Patients using lithium comprised the index drug group and patients using anticonvulsants only comprised the control group. Time-dependent Cox regression was used to evaluate the hazard ratios (HRs) for risk of cancer. Compared with anticonvulsant-only exposure, lithium exposure was associated with significantly lower cancer risk (HR = 0.735, 95% CI 0.554-0.974). The hazard ratios for the first, second and third tertiles of the cumulative defined daily dose were 0.762 (95% CI 0.516-1.125), 0.919 (95% CI 0.640-1.318) and 0.552 (95% CI 0.367-0.831), respectively. Lithium is associated with reduced overall cancer risk in patients with bipolar disorder. A dose-response relationship for cancer risk reduction was observed.

Exposure of liquid lithium confined in a capillary structure to high plasma fluxes in PILOT-PSI—Influence of temperature on D retention

Experiments on deuterium retention on liquid lithium confined in a capillary structure followed by ex-situ thermal desorption spectrometry (TDS) at high plasma fluxes (∼1023m2s−1) and high temperatures (440°C and 580°C) have been performed. Deuterium plasmas were generated at the PILOT-PSI linear plasma device and the targets were a 30mm diameter stainless steel disc, 5mm thick, covered with a porous mesh and filled with lithium. The settings (current) of the plasma source were varied in order to get different sample surface temperatures during irradiation. The targets were kept at floating potential during the exposure. Hydrogen and Li emission signals were monitored during the plasma exposure and TDS analysis was made afterwards in a separated system.Decreased retention at high exposure temperatures was deduced from the analysis of the hydrogen emission signals. Nevertheless, the results from TDS signal analysis were not conclusive.