Plasma Lithium Levels Research Articles

The interaction between plasma polymetals and lifestyle on cognitive dysfunction in occupational aluminum exposed workers: A cross-sectional study in China

ObjectiveTo investigate the interaction between plasma polymetallic exposure and lifestyle factors on cognitive function abnormalities in occupational aluminum workers. The aim is to develop a new occupational health management model that integrates lifestyle behaviors with occupational activities to comprehensively protect the health of these workers. Method476 Participants were recruited from an aluminum factory in Shanxi, China. Cognitive functioning was assessed using the Montreal Cognitive Assessment Scale (MoCA). Plasma polymetallic levels were measured using ICP-MS. Logistic regression analyzed the relationship between nine plasma metals, lifestyle factors, and cognitive abnormalities. A 3D model validated the interaction between metals and analyzed the combined effects of plasma metals and lifestyle on MoCA scores. The Chi-squared Automatic Interaction Detector (CHAID) decision tree was used to identify factors influencing cognitive dysfunction. ResultsHigh blood aluminum concentration (>47.85 μg/L), high blood lithium concentration(>3.15 μg/L), as well as sleep time(≤7 h and > 8 h), smoking, alcohol consumption, and length of mobile phone use(≥2 h) were risk factors for abnormal cognitive functioning. In addition aluminum and lithium have a multiplicative interaction on cognitive function(OR=1.86,95 %CI:1.14,3.050). There was an interaction between high plasma levels of aluminum and lithium and smoking on cognitive function in workers, and an interaction between high plasma levels of aluminum and lithium and sleep duration ≤7 or >8 h on cognitive function in workers. ConclusionThe levels of blood metal elements aluminum and lithium, as well as sleep time, smoking, drinking, and length of mobile phone use, are risk factors for cognitive dysfunction in occupational aluminum workers. There are the synergetic effect to increase the risk of cognitive dysfunction between blood aluminum concentration ≥50.59μg/L and blood lithium concentration ≥3.44μg/L, sleep duration ≤7h& >8 h, smoking, drinking, mobile phone use ≥2 h.

Recién nacida con litemia en rango tóxico. ¿Debemos retirar la lactancia materna?

Lithium is a common part of the treatment for bipolar disorder. It is excreted through breast milk, and traditionally, mothers undergoing this treatment were advised to discontinue breastfeeding due to the potential serious adverse effects of this medication on the infant. More recently, it has been demonstrated that plasma lithium levels in exposed children are generally low and well tolerated, so, in selected cases, breastfeeding can be maintained, and close clinical and analytical monitoring of the child can be conducted, including measurement of thyroid and renal function, and serial lithium levels. We present a clinical case of a full-term newborn, born to a mother with bipolar disorder receiving lithium treatment, exclusively breastfed on demand, who in the second week of life showed toxic levels of lithium in plasma with no symptoms. Careful investigation of the case revealed that the elevated lithium levels were falsely elevated due to incorrect collection of the blood sample in a container containing lithium-heparin as an anticoagulant. The circumstances of the case will be reviewed as well as current recommendations on lithium intake by mothers and breastfeeding of their children.

Low exposition to lithium prevents nephrogenic diabetes insipidus but not microcystic dilations of the collecting ducts in long-term rat model.

Lithium induces nephrogenic diabetes insipidus (NDI) and microcystic chronic kidney disease (CKD). As previous clinical studies suggest that NDI is dose-dependent and CKD is time-dependent, we investigated the effect of low exposition to lithium in a long-term experimental rat model. Rats were fed with a normal diet (control group),with the addition of lithium (Li+ group), or with lithium and amiloride (Li+/Ami group) for 6 months, allowing obtaining low plasma lithium concentrations (0.25 ± 0.06 and 0.43 ± 0.16 mmol/L, respectively). Exposition to low concentrations of plasma lithium levels prevented NDI but not microcystic dilations of kidney tubules, which were identified as collecting ducts (CDs) on immunofluorescent staining. Both hypertrophy, characterized by an increase in the ratio of nuclei per tubular area, and microcystic dilations were observed. The ratio between principal cells and intercalated cells was higher in microcystic than in hypertrophied tubules. There was no correlation between AQP2 messenger RNA levels and cellular remodeling of the CD. Additional amiloride treatment in the Li+/Ami group did not allow consistent morphometric and cellular composition changes compared to the Li+ group. Low exposition to lithium prevented overt NDI but not microcystic dilations of the CD, with differential cellular composition in hypertrophied and microcystic CDs, suggesting different underlying cellular mechanisms.

Understanding Lithium intoxication in Bipolar Disorder: a comparative analysis and clinical implications

IntroductionLithium treatment is a proven method for bipolar disorder management, but its narrow therapeutic range and the risk of severe side effects, including lithium intoxication, pose significant clinical hurdles. Lithium intoxication, a potentially life-threatening complication, can occur during treatment, raising ongoing questions about its clinical factors, risk elements, and best practices for management.ObjectivesOur objective is a comparative analysis between patients who have experienced lithium intoxication and those who have not, aiming to identify influencing factors and enhance clinical care.MethodsWe collected demographic data, age at lithium treatment initiation, treatment duration, therapeutic adherence, Mental Health consultations, and lithium level monitoring from 14 individuals requiring clinical attention due to lithium intoxication and 14 patients with similar gender, age, and diagnosis with lithium treatment but without intoxication during four years of follow-up.ResultsRegarding the results, the age of onset of lithium treatment in patients with lithium intoxication was 30.2 years (SD=8), and the duration of lithium treatment averaged 11.1 years (SD=8.8), which did not significantly differ from the control group with ages of onset at 38.1 years (SD=15.1) and treatment duration of 9.27 years (SD=8.8), respectively. Lithium intoxication patients developed severe complications, including hospitalizations in medical-surgical units, the necessity for dialysis, and death, one fatal case. Although therapeutic adherence to lithium, measured through pharmaceutical dispensation, exceeded 90% and was comparable in both groups, patients affected by lithium intoxication exhibited a significantly higher treatment discontinuation rate (OR 32.5; 95% CI, 3.1 to 337.8) during the follow-up period. Patients who experienced lithium intoxication had an average of psychiatric consultations every 11.2 months (SD=13.4), with 35.7% not attending at least once a year, while the control group had an appointment every 5.31 months (SD=2.7) (p > 0.05). Lastly, despite both groups having a similar frequency of plasma lithium level monitoring, occurring approximately every 5.5 months (SD=2.6) and 7.8 months (SD=4.8), respectively, in 28.5% of those who suffered from lithium intoxication did not undergo any monitoring for periods exceeding 18 months (p < 0.05).ConclusionsOur research highlights the significance of delivering thorough clinical care and continuous monitoring to patients receiving lithium treatment for bipolar disorder. Ensuring effectiveness therapeutic adherence and maintaining strict monitoring of lithium levels are critical factors that significantly enhance treatment safety. Appropriate management has the potential to improve the quality and safety of care for people with bipolar disorder who are dependent on lithium therapy.Disclosure of InterestNone Declared

Exploring the clinical factors affecting lithium dose and plasma level and the effect of brand.

Optimal use of lithium involves adjustment of the dose, to keep the plasma level within the narrow, recommended range. Brand-specific prescribing has long been considered critical to achieving this aim, but this is a convention based on very limited data. To explore the effect of selected demographic and clinical factors on the relationship between lithium dose and plasma level and determine whether there is an independent effect of lithium brand. Analysis of clinical audit data collected in 2023 as part of a quality improvement programme addressing the use of lithium, conducted by the Prescribing Observatory for Mental Health. Data were collected from clinical records using a bespoke proforma, submitted online and analysed using SPSS. Data were submitted for 4405 patients who had been prescribed solid-dosage formulations of lithium for more than a year. Priadel® was prescribed for 3722 (84%) of these patients, Camcolit® for 112 (2.5%) and the prescription was written generically for 554 (12.5%). Compared with Priadel, where Camcolit was prescribed, the mean daily dose was 10% higher and the mean plasma lithium level was 11% higher. A multivariable analysis was conducted to explore the relationship between selected clinical variables and maintenance lithium dose. This found that in 4213 patients whose most recent plasma lithium level was between 0.3 and 1.19 mmol/L, the variables age, sex, ethnicity, psychiatric diagnosis and the severity of chronic kidney disease were independently associated with dose while the brand of lithium prescribed was not. Our findings replicate those of previous studies with respect to the demographic and clinical variables that can be expected to influence lithium dosage in routine clinical practice. This reinforces the need to titrate the dosage for each individual patient, to achieve and maintain the target plasma level. However, the findings suggest that the Priadel and Camcolit brands of lithium are essentially interchangeable.

Lithium Cholesterol Sulfate: A Novel and Potential Drug for Treating Alzheimer's Disease and Autism Spectrum Disorder.

Recent studies have shown that lithium treatment can reduce symptoms of Alzheimer's disease (AD) and Autism Spectrum Disorder (ASD). However, the present lithium salts clinically available have serious short-term and long-term side effects, requiring frequent monitoring of blood chemistry and plasma lithium levels to avoid toxicity. Consequently, there is a demand for a safer and more effective lithium formulation to treat these diseases. Hence, we firstly synthesized lithium cholesterol sulfate (LiCS) and compared its pharmacological effects with that of lithium chloride (LiCl) and sodium cholesterol sulfate (NaCS) on markers of neurodegenerative disease in cell cultures. LiCS was more potent than LiCl in increasing inhibitory GSK3β (Ser9) phosphorylation (pGSK3β) in both CHO and SH-SY5Y cells. These agents dose-dependently increased pGSK3β, starting at 10 μM for LiCS and 60 μM for LiCl and maximally by approximately 100% at 60 μM for LiCS and 1.25 mM for LiCl, without altering total GSK3β levels. In HEK293/tau cells, LiCS reduced tau (Thr231) phosphorylation (ptau) starting at 10 μM and maximally by 63% at 40 μM without altering total tau levels, but ptau levels were not altered by LiCl at any dose between 60 μM and 1.25 mM. In BV2 cells, LiCS and LiCl decreased LPS-induced TNFα levels, starting at 20 μM for LiCS and 5 mM for LiCl, and maximally by approximately 30% at 80 μM for LiCS and 20 mM for LiCl. NaCS at any dose between 5 and 90 μM did not alter pGSK3β, ptau or LPS-induced TNFα. LiCS may become a new drug with good pharmacological potential for the treatment of neurodegenerative disorders, such as AD and ASD, by allowing lithium to more readily access intracellular pathological processes.

B-313 Aberrant Lithium Results After HDL Assay on Roche Cobas c503 Instrument

Abstract Background Lithium is prescribed clinically to manage mania in patients with bipolar disorder. However, blood levels higher than 1.5 mmol/L (12 h post administration) indicate toxicity accompanied by severe nausea and vomiting, severe hand tremors, confusion, and vision changes. If neglected, lithium toxicity can lead to coma, brain damage, or even death. Diligent monitoring of blood lithium levels periodically is critical to preventing lithium toxicity. Case Presentation: A 37 y/o female with schizophrenia and bipolar disorder on lithium since 2019 visited the outpatient clinic for her routing biannual lithium check. The patient’s plasma lithium levels were detected at 3.9 mmol/L (previously 0.4 mmol/L; Therapeutic range: 0.60–1.20 mmol/L; Toxic: >2.00 mmol/L). The cause for elevated lithium level was unclear; EKG and vital sign were unremarkable and patient was asymptomatic for toxicity. Nevertheless, patient was then managed with IV infusions and admitted to emergency room for follow up. A redrawn lithium sample ∼22 h later was 0.3 mmol/L, suggesting no toxicity. We then investigated the discrepancy in lithium levels reported by the laboratory. Retesting of the original sample detected lithium at 0.5 mmol/L, a value significantly less than the previously reported 3.9 mmol/L. Our laboratory had recently introduced the Roche Cobas® pro integrated solutions into the lab and chemistry testing (including Lithium) are performed on the Roche Cobas c503 analyzers (an arm of the Roche pro integrated solutions). Our goal was to investigate the observed phenomenon and find potential solutions, especially as it had significant implications to patient care. Method We reviewed all high lithium levels recently tested our new instrument within a week of this incident. Seven samples (lithium values >1.2 mmol/L) were identified and lithium measurements repeated. We also investigated and ruled out the possibility of carry over contamination by rerunning a low lithium sample before and after a high lithium sample. Results Retesting all seven samples resulted in lower lithium level with an average % change of 365%. Further investigations and discussions with manufacturers alluded to interference after HDL testing on the same instrument. To investigate this hypothesis, we reran two previously reported low samples (0.3 and 0.6 mmol/L) immediately after running the HDL cholesterol assay on the Roche Cobas c503 analyzer. Retesting resulted in lithium levels of 7.32 and 1.36 mmol/L (2313.3% and 126.7% change) respectively. Conclusion Our investigation suggests that running the HDL cholesterol assay prior to the lithium assay on the Roche Cobas c503 analyzer results in positive interference. As oppose to other Roche chemistry analyzers (such as the Roche c501), the Roche Cobas c503 analyzer has no wash step between the HDL cholesterol and the lithium assays. Detergents in buffers and reactive byproducts (like peroxide) of the HDL cholesterol assay, may leave behind salts in the instrument probe that can interfere with the lithium assay. We are currently working on adding a wash step between the HDL cholesterol and lithium assays. In the interim, we are repeating lithium testing on high lithium samples.

Optical determination of lithium therapeutic levels in micro-volumes of interstitial fluid.

Long-term management of bipolar disorder (BD), characterized by mood fluctuating between episodes of mania and depression, involves the regular taking of lithium preparations as the most reliable mood stabilizer for bipolar patients. However, despite its effectiveness in preventing and reducing mood swings and suicidality, lithium has a very narrow therapeutic index and it is crucial to carefully monitor lithium plasma levels as concentrations >1.2 mmol/L are potentially toxic and can be fatal. Current methods of lithium therapeutic monitoring involve frequent blood tests, which have several drawbacks related to the invasiveness of the technique, comfort, cost and reliability. Dermal interstitial fluid (ISF) is an accessible and information-rich biofluid, and correlations have been found between blood and ISF levels of lithium medication. In the current study, we sought to investigate the optical determination of lithium therapeutic concentrations in samples of ISF extracted from porcine skin utilizing a microneedle-based approach. Monitoring of lithium levels in porcine ISF was achieved by employing a spectrophotometric method based on the reaction between the chromogenic agent Quinizarin and lithium. The resulting spectra show spectral variations which relate to lithium concentrations of lithium in samples of porcine ISF with a coefficient of determination (R2 ) of 0.9. This study has demonstrated successfully that therapeutic levels of lithium in micro-volumes of porcine ISF can be measured with a high level of accuracy utilizing spectroscopic techniques. The results support the future development of a miniaturized and minimally-invasive device for lithium monitoring in bipolar patients.

A paper-based colorimetric method for monitoring of lithium therapeutic levels.

Lithium remains the "gold standard" for both acute and maintenance treatment of bipolar disorder (BD), a serious life-long condition characterised by recurrent episodes of depressed and manic mood states. However, lithium has a very narrow therapeutic range (0.4-1.2 mmol L-1) and despite its effectiveness in preventing and reducing mood swings and suicidality, it is a potentially hazardous drug. While it is crucial to carefully monitor lithium plasma levels, the current techniques of lithium monitoring are cumbersome and require frequent blood tests with the consequent discomfort which results in patients evading treatment. Therefore, development of low-cost and facile lithium detection techniques that can be translated into point-of-care devices for personal monitoring will be a major advance in the management of BD. In the current study, we present colorimetric determination of lithium therapeutic levels utilizing test paper strips, based on its reaction with the chromogenic agent Quinizarin. Exposure of Quinizarin-dipped test papers to samples of interstitial fluid (ISF) or dH2O spiked with therapeutic concentrations of lithium resulted in colour changes that were monitored using optical spectroscopy. The acquired spectra from the test papers show spectral variations which are related to lithium concentrations in spiked samples of dh2O and artificial ISF with a coefficient of determination (R2) of 0.9 and 0.8, respectively. Altogether, the spectrophotometric and colorimetric analyses demonstrated strong correlations between the observed colour changes and the concentrations of lithium present in the sample. Therefore, this study has demonstrated that Quinizarin-treated cellulose-based papers are suitable for the precise detection of changes in lithium therapeutic levels. This method is simple and very convenient and serves as a foundation for the future development of a paper-based colorimetric sensor for monitoring of lithium therapeutic levels in ISF and other non-invasive biological fluids.

Plus ça change? Switching lithium preparations.

A supply disruption alert in 2020, now rescinded, notified UK prescribers of the planned discontinuation of Priadel® (lithium carbonate) tablets. This service evaluation explored lithium dose and plasma levels before and after the switching of lithium brands, in order to determine the interchangeability of different brands of lithium from a pharmacokinetic perspective. Data on the treatment of 37 patients switched from Priadel® tablets were analysed. Switching to Camcolit® controlled-release tablets at the same dose did not result in meaningful differences in plasma lithium levels. Dose adjustment and known or suspected poor medication adherence were associated with greater variability in plasma lithium levels on switching brands. For comparable pre- and post-switch doses in adherent patients, the most common brands of lithium carbonate appear to produce similar plasma lithium levels. British National Formulary guidance relating to switching lithium brands may be unnecessarily complex.

Advances in Therapeutic Monitoring of Lithium in the Management of Bipolar Disorder.

Since the mid-20th century, lithium continues to be prescribed as a first-line mood stabilizer for the management of bipolar disorder (BD). However, lithium has a very narrow therapeutic index, and it is crucial to carefully monitor lithium plasma levels as concentrations greater than 1.2 mmol/L are potentially toxic and can be fatal. The quantification of lithium in clinical laboratories is performed by atomic absorption spectrometry, flame emission photometry, or conventional ion-selective electrodes. All these techniques are cumbersome and require frequent blood tests with consequent discomfort which results in patients evading treatment. Furthermore, the current techniques for lithium monitoring require highly qualified personnel and expensive equipment; hence, it is crucial to develop low-cost and easy-to-use devices for decentralized monitoring of lithium. The current paper seeks to review the pertinent literature rigorously and critically with a focus on different lithium-monitoring techniques which could lead towards the development of automatic and point-of-care analytical devices for lithium determination.

Optical Determination of Lithium Levels in Artificial Interstitial Fluid for Treatment Management of Bipolar Disorder.

Bipolar Disorder (BD), characterized by mood fluctuating between episodes of mood elevation and depression, is a leading cause of disability worldwide. Lithium continues to be prescribed as a first-line mood stabilizer for the management of BD. However, lithium has a very narrow therapeutic index and it is crucial to carefully monitor lithium plasma levels as concentrations greater than 1.2 mmol/L are potentially toxic and can be fatal. The current techniques of lithium monitoring are cumbersome and require frequent blood tests with the consequent discomfort which results in patients evading treatment. Dermal interstitial fluid (ISF), an underutilized information-rich biofluid, can be a proxy for direct blood sampling and allow lithium drug monitoring as its lithium concentration is proportional to the concentrations in blood. Therefore, in this study we seek to investigate the measurement of lithium therapeutic concentrations in artificial ISF. Our study employs a colorimetric method, based on the reaction between chromogenic agent Quinizarin and Li+ ion which can be detected using optical spectroscopy in the visible region (400-800 nm), to determine lithium levels in artificial ISF. The resulting spectra of our experiments show spectral variations which are related to lithium concentrations in spiked samples of artificial ISF, with a correlation coefficient (R) of 0.9. Future work will focus on investigating the feasibility of utilizing ISF for real-time and minimally-invasive lithium drug monitoring.

Treatment adherence and tolerability of immediate- and prolonged-release lithium formulations in a sample of bipolar patients: a prospective naturalistic study.

The aim of this study was to compare treatment adherence and tolerability of different lithium formulations in 70 bipolar patients receiving lithium therapy for the first time. During the 1-year follow-up, information was collected regarding patient's clinical course, therapeutic adherence, side effects of the treatment and serum levels of lithium, creatinine and thyroid-stimulating hormone. At baseline, 30 patients (43%) were on prolonged-release lithium formulations and 40 (57%) on immediate-release formulations. At the final evaluation, 37 patients (53%) were considered lost to follow-up. Both prolonged- and immediate-release patients showed significant improvement in the Functioning Assessment Short Test and in the Clinical Global Impressions for Bipolar Disorder scores during the follow-up. At the first follow-up visit, the mean plasma lithium level of prolonged-release patients was higher than immediate-release patients (0.61 vs. 0.47, respectively; P = 0.063), as well as the therapeutic adherence (85 vs. 64%, respectively; P = 0.089). Fine tremor and gastrointestinal symptoms were more frequent in immediate-release patients than in prolonged-release patients at each follow-up visit, with the sole exception of gastrointestinal symptoms at the last evaluation. Prolonged-release lithium therapy could provide potential advantages over immediate-release formulations. Future naturalistic studies and clinical trials with a longer follow-up duration are needed.

Decrease in Serum Lithium Levels Induced by Ursodeoxycholic Acid: A Case Report.

Lithium is a leading therapeutic option for bipolar patients in the treatment of acute and maintenance phases of illness. Lithium levels should be closely monitored due to its narrow therapeutic index. Combination of other treatment regimens with lithium may increase or decrease lithium levels that may cause intoxication symptoms or recurrence of mood episodes. Therefore, clinicians should be aware of the drugs recommended by other medical specialties that may change lithium plasma levels. Nonsteroidal anti-inflammatory drugs, thiazide diuretics, and angiotensin-converting enzyme inhibitors are the best known potential medicines for drug interactions with lithium. In this article, we aimed to present a case report of a patient who was taking lithium for recurrent depression more than 3 years with stable serum levels, but lithium levels decreased fastly after the prescription of ursodeoxycholic acid. The possible mechanism of interaction between lithium and ursodeoxycholic acid was discussed with the current literature.

A reappraisal of the role of fever in the occurrence of neurological sequelae following lithium intoxication: a systematic review

ABSTRACT Introduction We aimed to review cases of Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) characterized by neurological sequelae following acute lithium toxicity and to explore whether cerebellar sequelae are more frequent in cases presenting with fever and/or infection. Areas covered Case reports were identified from: (i) 6 reviews published up to 2005; (ii) MEDLINE, Web of Sciences, Cochrane Library and PsycINFO search. Expert opinion We identified 123 SILENT cases published from 1965 to 2019, in which cerebellar sequelae were observed in an overwhelming proportion (79%). SILENT may occur at any time during lithium treatment. This complication is most frequently observed during routine lithium treatment, with fewer than 10% of cases occurring after accidental or intentional overdoses. SILENT may occur even when lithium plasma levels are within the therapeutic range: 63% of cases had lithium plasma level <2.5 mEq/l (low/mild toxicity). Fever and/or infection were reported in nearly half of the patients (48%). The likelihood of presenting with cerebellar vs. other neurological sequelae was independently increased by elevated plasma lithium level (≥ 2.5 mEq/l) and by a history of fever and/or infection. Lithium users should be warned of the need to consult in case of fever to adjust their lithium dosage.

Treatment resistant manic episode with commorbidity with borderline personality disorder (BPD)

IntroductionA 47 y.o. female patient was admitted to the female PICU with a manic episode. Upon admission she presented with mood elation, psychosis, pressured speech, lack of sleep and agitation.ObjectivesTo investigate negative prognostic factors such as the co-morbidity with a personality disorder in patients presenting with severe mania.MethodsThe patient was assessed regularly by the psychiatric team consisting of a CT doctor and one General Adult Consultant. Appropriate psychological assessments for mania and laboratory investigations took place.ResultsThe patient initially scored above 45 in the Young Mania Rating Scale (YMRS), establishing a diagnosis of severe mania. She was treated with Olanzapine titrated up to 20mg OD and augmentation with Lithium treatment. Lithium plasma levels were at 0,6. Due to the treatment resistant manic presentation a second antipsychotic agent was administered and the patient was also treated with Zuclopenthixol depot 400mg every two weeks. Clinical improvement was observed after 16 days from admission.ConclusionsThe clinical team wondered about the clinical challenges of the case. According to the literature having a Personality Disorder diagnosis is a negative prognostic factor for patients with mania and this is relevant to this case as well.DisclosureNo significant relationships.

Increased aluminum and lithium and decreased zinc levels in plasma is related to cognitive impairment in workers at an aluminum factory in China: A cross-sectional study

BackgroundPrevious studies have shown that multiple imbalances of metal ions in the brain are closely associated with the neurodegenerative disorders. Our studies have shown that long-term working exposure to aluminum induces increased plasma aluminum levels and causes cognitive impairment in workers at aluminum factories. ObjectiveTo explore the levels of nine metals in plasma and the effect on cognitive function among in-service workers. MethodsIn this cross-sectional study, cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), which included seven subitems: executive/visuospatial abilities; naming; attention and calculation; language; abstract; recall; and orientation. The plasma levels of nine kinds of metals were measured by inductively coupled plasma-mass spectrometry (ICP-MS). A multivariate generalized linear regression model and Bayesian kernel machine regression (BKMR) were selected to estimate the relationship between metal plasma level and MoCA scores with adjustment for confounders. ResultsOne hundred and eighty-seven workers participated in this study. In the multivariable generalized linear model, among these nine metals studied, five were related to the MoCA score: aluminum, lithium, cobalt, zinc and chromium. In the BKMR model, a significantly negative correlation between the plasma aluminum, lithium and the total MoCA score was observed. Moreover, for subitems on the MoCA scale, the plasma levels of lithium, aluminum, and zinc had a significant correlation with the executive/visuospatial abilities, naming, and orientation abilities, respectively. The log-transformation concentrations of plasma aluminum and lithium were negatively correlated with the executive/visuospatial abilities and naming abilities, respectively. The log-transformation plasma zinc concentration was positively correlated with orientation abilities. ConclusionBased on the results, we determined that increased aluminum and lithium and decreased zinc levels in plasma were associated with the incidence of mild cognitive impairment (MCI) in workers at a Chinese aluminum plant.

Plasma Lithium Levels in a General Population: A Cross-Sectional Analysis of Metabolic and Dietary Correlates.

Initial evidence suggests that lithium might affect life expectancy and the risk for different disease conditions, but most studies were conducted in patients on lithium medication. Little is known about the association of blood lithium levels within the physiological range with cardiometabolic risk factors and diet. We measured plasma lithium in a community-based sample from Northern Germany (samples taken between 2010 and 2012). All participants (aged 25–82 years) underwent standardized examinations and completed a semi-quantitative food frequency questionnaire. Of several variables tested, the estimated glomerular filtration rate (eGFR) was statistically significantly (inversely) associated with lithium levels, mainly in individuals with slightly impaired renal function (eGFR < 75 mL/min/1.73 m2). Besides, lithium levels were positively associated with age and alcohol intake. Using reduced rank regression, we identified a dietary pattern explaining 8.63% variation in plasma lithium levels. Higher lithium levels were associated with higher intakes of potatoes, leafy vegetables, root vegetables, fruits, tea, beer, wine and dietetic products and lower intakes of pasta, rice, pork, chocolate, sweets, soft drinks, other alcoholic beverages, sauces and snacks. Our observations suggest that plasma lithium levels are associated inversely with kidney function, particularly in individuals with slightly impaired renal function, and positively with age and alcohol intake. Lithium at physiological levels was moderately related to an exploratory dietary pattern.

Revisiting the role of therapeutic drug monitoring in optimizing treatment outcomes in patients of bipolar affective disorders receiving lithium therapy: a prospective observational study

Background: Lithium continues to be considered first-line therapy for treatment of acute mania, acute mixed bipolar disease and long-term prophylaxis of bipolar disorder. Present study was done to study the pattern of drug therapy in bipolar affective disorder patients with special reference to lithium in the routine psychiatric outpatients care setting of a tertiary care teaching hospital as well as to understand the prospect of therapeutic drug monitoring in optimization of lithium therapy based on outcome.Methods: It was a prospective, non-randomized, observational study of a cohort of subjects who are suffering from bipolar affective disorders and on lithium therapy. Patients were prospectively followed up three monthly for three visits with therapeutic drug monitoring of their plasma lithium level, as and when advised by the treating physician, and pre-formed questionnaires.Results: Results revealed there was significant improvement in symptoms of patients who were monitored with therapeutic drug monitoring and prescribed lithium therapy in accordance with clinical pharmacological consultation for optimal dosing resulting in optimal benefit to patients.Conclusions: With regular therapeutic monitoring, optimal target serum lithium levels can be achieved with dosage modifications thereby reducing the risk of toxicity with improved drug compliance. Thus, individualization of dosing and optimization of treatment can be achieved by dependable analytical laboratory services, better psycho-education, family support and overall a disease-based management team approach with the involvement of clinical Pharmacologist to meet the complexities of lithium therapy.

Effects of chronic lithium exposure in a modified rodent ketamine-induced hyperactivity model of mania

Bipolar illness is characterized by periods of “mania” — high energy, irritability, and increased psychomotor activation. While the neurobiological investigation of mania has been limited by the lack of reliable animal models, researchers have recently reported that daily subanesthetic doses of ketamine produce a lithium-reversible increase in rodent locomotor activity. Such studies have typically employed short-term (2 week) exposure to daily intraperitoneal-injected lithium and extremely brief (i.e., 5-min) open-field tests of hyperactivity. To increase the translational utility of the model, the effects of 70-days of orally administered lithium were examined on ketamine-induced hyperlocomotion during 30-min test sessions. Rats consumed 2.0 mEq/kg lithium chloride (LiCl) presented daily in a high incentive food (10 g of peanut butter). Control animals ingested peanut butter infused with an equimolar concentration of sodium chloride (NaCl). After 60 days of treatment, a 30-min baseline revealed no differences in the locomotor activity of LiCl and NaCl animals. During the next 10 days, animals received single daily supplemental injections of 25 mg/kg IP ketamine. A subset of animals was injected daily with saline and served as non-ketamine controls. Behavioral testing on the final two days of treatment confirmed that ketamine administration produced a profound increase in locomotor activity that was significantly attenuated in the LiCl group. Additionally, blood plasma levels of lithium were found to be comparable to low-moderate human therapeutic levels. These data confirm the viability and utility of ketamine-induced hyperlocomotion as a rodent model of mania.