Lithium (Li) represents a first choice mood stabilizer for bipolar disorder (BD). Despite extensive clinical use, questions regarding its mechanism of action and pathological mechanism of renal function impairment by Li remain open. The present study aimed to improve our knowledge in this area paying special attention to the relationship between the length of Li action, lipid peroxidation (LP), and Na+/K+-ATPase properties. The effects of therapeutic Li doses, administered daily to male Wistar rats for 1 (acute), 7 (short term) and 28 days (chronic), were studied. For this purpose, Na+/K+-ATPase activity measurements, [3H]ouabain binding and immunoblot analysis of α-Na+/K+-ATPase were performed. Li-induced LP was evaluated by determining the malondialdehyde concentration by HPLC. Sleep deprivation (SD) was used as an experimental approach to model the manic phase of BD. Results obtained from the kidney were compared to those obtained from erythrocytes and different brain regions in the same tested animals. Whereas treatment with therapeutic Li concentration did not bring any LP damage nor significant changes of Na+/K+-ATPase expression and [3H]ouabain binding in the kidney, it conferred strong protection against this type of damage in the forebrain cortex. Importantly, the observed changes in erythrocytes indicated changes in forebrain cortices. Thus, different resistance to SD-induced changes of LP and Na+/K+-ATPase was detected in the kidney, erythrocytes and the brain of Li-treated rats. Our study revealed the tissue-specific protective properties of Li against LP and Na+/K+-ATPase regulation.

• MeSH
• Antimanic Agents administration & dosage   pharmacology   MeSH
• Bipolar Disorder drug therapy   MeSH
• Time Factors MeSH
• Erythrocytes drug effects   metabolism   MeSH
• Rats MeSH
• Kidney drug effects   metabolism   MeSH
• Lithium Carbonate administration & dosage   pharmacology   MeSH
• Disease Models, Animal MeSH
• Brain drug effects   metabolism   MeSH
• Lipid Peroxidation drug effects   MeSH
• Rats, Wistar MeSH
• Sodium-Potassium-Exchanging ATPase metabolism   MeSH
• Sleep Deprivation psychology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

• Keywords
• sekundární nefrotický syndrom,
• MeSH
• Anti-Anxiety Agents administration & dosage   therapeutic use   MeSH
• Biomarkers blood   urine   MeSH
• Biopsy methods   utilization   MeSH
• Diuresis physiology   drug effects   MeSH
• Edema diagnosis   etiology   complications   MeSH
• Drug Therapy MeSH
• Hyperkalemia diagnosis   etiology   therapy   MeSH
• Humans MeSH
• Lithium Carbonate * administration & dosage   adverse effects   therapeutic use   MeSH
• Adolescent MeSH
• Nephrology MeSH
• Nephrotic Syndrome diagnosis   etiology   MeSH
• Drug-Related Side Effects and Adverse Reactions etiology   complications   MeSH
• Proteinuria diagnosis   etiology   complications   MeSH
• Anxiety Disorders * diagnosis   drug therapy   complications   MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Lithium (Li) is a typical mood stabilizer and the first choice for treatment of bipolar disorder (BD). Despite an extensive clinical use of Li, its mechanisms of action remain widely different and debated. In this work, we studied the time-course of the therapeutic Li effects on ouabain-sensitive Na+/K+-ATPase in forebrain cortex and hippocampus of rats exposed to 3-day sleep deprivation (SD). We also monitored lipid peroxidation as malondialdehyde (MDA) production. In samples of plasma collected from all experimental groups of animals, Li concentrations were followed by ICP-MS. The acute (1 day), short-term (7 days) and chronic (28 days) treatment of rats with Li resulted in large decrease of Na+/K+-ATPase activity in both brain parts. At the same time, SD of control, Li-untreated rats increased Na+/K+-ATPase along with increased production of MDA. The SD-induced increase of Na+/K+-ATPase and MDA was attenuated in Li-treated rats. While SD results in a positive change of Na+/K+-ATPase, the inhibitory effect of Li treatment may be interpreted as a pharmacological mechanism causing a normalization of the stress-induced shift and return the Na+/K+-ATPase back to control level. We conclude that SD alone up-regulates Na+/K+-ATPase together with increased peroxidative damage of lipids. Chronic treatment of rats with Li before SD, protects the brain tissue against this type of damage and decreases Na+/K+-ATPase level back to control level.

• MeSH
• Antimanic Agents pharmacology   therapeutic use   MeSH
• Hippocampus drug effects   metabolism   MeSH
• Binding, Competitive drug effects   MeSH
• Rats MeSH
• Lithium Carbonate pharmacology   MeSH
• Malondialdehyde metabolism   MeSH
• Ouabain metabolism   MeSH
• Lipid Peroxidation drug effects   MeSH
• Rats, Wistar MeSH
• Prosencephalon drug effects   enzymology   metabolism   MeSH
• Sodium-Potassium-Exchanging ATPase metabolism   MeSH
• Sleep Deprivation drug therapy   enzymology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Lithium is widely used in psychiatry to treat bipolar affective disorders since 1970 but little is known about the incidence, clinical course and associated factors of acute lithium intoxication. Moderate and severe cases of lithium intoxication are rare. This case reports a patient with acute lithium intoxication (serum level of 3.7 mmol/L) with neurological symptoms imitating stroke, which affects the differential diagnosis in the pre-hospital and hospital care. Patient was treated with forced diuresis and dismissed 21 days after admission.

• MeSH
• Antimanic Agents adverse effects   therapeutic use   MeSH
• Bipolar Disorder drug therapy   MeSH
• Stroke diagnosis   MeSH
• Diagnosis, Differential MeSH
• Humans MeSH
• Lithium blood   MeSH
• Lithium Carbonate adverse effects   therapeutic use   MeSH
• Drug Overdose blood   diagnosis   MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

BACKGROUND: Lithium in the form of lithium carbonate (Li2CO3) has become one of the most effective and widely prescribed drugs for mood stabilization. However, lithium has adverse effects on renal tubular functions, such as decreased concentrating function of the kidneys, and even occasional symptoms of nephrogenous diabetes insipidus occur with additional evidence of glomerular disruption in lithium-treated patients. METHODS: We assessed the kidney function of patients with bipolar disorder who are under long-term lithium treatment using novel markers of kidney damage such as plasma neutrophil gelatinase-associated lipocalin, cystatin C, albuminuria, estimated glomerular filtration rate, Chronic Kidney Disease-Epidemiology Investigation using creatinine and cystatin C, and serum and urinary osmolality, and compared the results with those of age-matched patients with bipolar disorder not treated with lithium. The study enrolled 120 patients with bipolar disorder, consisting of 80 (30 male and 50 female patients) who have been receiving lithium for 0.5 to 20 (mean, 7) years and 40 (10 male and 30 female patients) who had never been exposed to lithium treatment. RESULTS: Patients treated with lithium had significantly decreased urine osmolality (mean ± SD, 405 ± 164 vs 667 ± 174 mmol/kg) and urine-to-serum osmolality ratio (1.35 ± 0.61 vs 2.25 ± 0.96). No significant difference was found in creatinine, estimated glomerular filtration rate values calculated using the Chronic Kidney Disease-Epidemiology Investigation using creatinine and cystatin C, neutrophil gelatinase-associated lipocalin, cystatin C, and albuminuria between both groups. We found no significant difference in renal biomarkers between patients treated with lithium for 6 to 24 months and those treated for 25 to 240 months. CONCLUSIONS: We found significantly decreased kidney concentrating ability in the long-term lithium-treated patients compared with the control group. Other renal function markers did not indicate any significant signs of renal dysfunction.

• MeSH
• Antimanic Agents administration & dosage   adverse effects   MeSH
• Biomarkers metabolism   MeSH
• Bipolar Disorder drug therapy   MeSH
• Time Factors MeSH
• Adult MeSH
• Glomerular Filtration Rate MeSH
• Middle Aged MeSH
• Humans MeSH
• Lithium Carbonate administration & dosage   adverse effects   MeSH
• Kidney Diseases chemically induced   epidemiology   MeSH
• Aged MeSH
• Kidney Function Tests MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Importance: Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ). Objectives: To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association. Design, Setting, and Participants: A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36 989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017. Main Outcomes and Measures: Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained. Results: Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P < 5 × 10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines. Conclusions and Relevance: This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.

• MeSH
• Bipolar Disorder drug therapy   genetics   MeSH
• Genome-Wide Association Study * MeSH
• Adult MeSH
• Genetic Load MeSH
• Genotype MeSH
• HLA Antigens genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lithium Carbonate therapeutic use   MeSH
• Multifactorial Inheritance genetics   MeSH
• Schizophrenic Psychology MeSH
• Schizophrenia drug therapy   genetics   MeSH
• Treatment Outcome MeSH
• Inflammation genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVE: Lithium has been long used in psychiatry as an adjuvant treatment for bipolar disorder. Chronic lithium intoxication is very rare. DESIGN: We present the case of a 72-year-old female, treated with lithium for more than 10 years for bipolar disorder, who was admitted for gait impairment with weakness of limbs, myoclonus, speech impairment and memory disturbances. RESULTS: Diagnosis of lithium intoxication was based on clinical picture and determination of serum lithium levels. EEG showed severe encephalopathy with triphasic wave complexes. Sensory and motor axonal neuropathy was observed by EMG. Discontinuation of the drug leads to clinical improvement, although not to a fully neurological recovery. CONCLUSION: Lithium is still very effective drug, but requires regular monitoring of serum levels to prevent overdose and symptoms of intoxication. Neurophysiological methods, including EEG and EMG, are strongly recommended to determine the level of peripheral and/or central nervous system impairment.

• MeSH
• Antimanic Agents adverse effects   blood   therapeutic use   MeSH
• Bipolar Disorder blood   drug therapy   physiopathology   MeSH
• Electroencephalography MeSH
• Humans MeSH
• Lithium Carbonate adverse effects   blood   therapeutic use   MeSH
• Myoclonus blood   chemically induced   physiopathology   MeSH
• Brain Diseases blood   chemically induced   physiopathology   MeSH
• Memory Disorders blood   chemically induced   physiopathology   MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

• Keywords
• sekundární nefrotický syndrom,
• MeSH
• Anti-Anxiety Agents administration & dosage   therapeutic use   MeSH
• Biomarkers blood   urine   MeSH
• Biopsy methods   utilization   MeSH
• Diuresis physiology   drug effects   MeSH
• Edema diagnosis   etiology   complications   MeSH
• Drug Therapy MeSH
• Hyperkalemia diagnosis   etiology   therapy   MeSH
• Humans MeSH
• Lithium Carbonate * administration & dosage   adverse effects   therapeutic use   MeSH
• Adolescent MeSH
• Nephrology MeSH
• Nephrotic Syndrome diagnosis   etiology   MeSH
• Drug-Related Side Effects and Adverse Reactions etiology   complications   MeSH
• Proteinuria diagnosis   etiology   complications   MeSH
• Anxiety Disorders * diagnosis   drug therapy   complications   MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Acute Kidney Injury chemically induced   MeSH
• Humans MeSH
• Lithium Carbonate adverse effects   MeSH
• Adolescent MeSH
• Nephrotic Syndrome chemically induced   MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Female MeSH
• Publication type
• Letter MeSH
• Case Reports MeSH

Hlavním cílem udržovací léčby bipolární poruchy (BP) je prevence rozvoje nových epizod poruchy nálady a udržení symptomatické i funkční remise. Přestože řada farmakologických a psychosociálních intervencí prokázala účinnost v udržovací léčbě BP, dlouhodobé stabilizace onemocnění se daří dosáhnout jen u části pacientů. Existuje poměrně málo informací o účinnosti těchto postupů v běžné klinické praxi. U 121 pacientů (76 žen) s BP potvrzenou diagnostickým rozhovorem dle Schedule for Affective Disorders and Schizophrenia, průměrného věku 44,6 let a průměrné délky nemoci 13,1 let, kteří byli aspoň jeden rok léčeni monoterapií stabilizátory nálady (lithium, karbamazepin, valproat, lamotri^in a olanzapin), byla vyhodnocena odpověď na udržovací léčbu podle Treatment Response Scale (TRS). Celkového skóru > 7 („plní respondéři") dosáhlo 22 (18 %) pacientů. Pro jednotlivé stabilizátory nálady se podíl respondérů pohyboval mezi 5 a 28 %. Respondéři se od nonrespondérů nelišili věkem při začátku nemoci, délkou trvání nemoci, polaritou 1. epizody, počtem epizod před léčbou, výskytem psychotických příznaků či sebevražedných pokusů ani výskytem komorbidních poruch. Přestože je monoterapie některým ze stabilizátorů nálady doporučovanou, preferovanou a žádoucí formou udržovací léčby BP, naše výsledky naznačují, že uspokojivé odpovědi je touto strategií dosaženo jen u menšiny pacientů.

The main aim of long-term management for bipolar disorder (BD) is the prevention of new mood episodes and maintaining symptomat ic and functional remission. Although several pharmacological and psychosocial interventions have shown effectiveness in maintenan ce treatment of BP, long-term recovery is achieved only in some patients. Little is known how these treatments are effective in routine clin ical practice. 121 patients (76 women) with BD confirmed by SADS-L interview, with mean age of 44.6 and mean duration of illness of 13.1 years who were at le- ast one year on maintenance monotherapy with mood stabilizers (lithium, carabamazepine, valproate, lamotrigine and olanzapine) were asses- sed using the Treatment Response Scale (TRS). Total score  7 in TRS („full responders“) reached 22 (18 %) patients. For particular mood sta- bilizers, we found response rate from 5 to 28 %. Responders did not differ from non-responders in the length of illness, age of onset, the pola- rity of first episode, number of episodes, the occurrence of psychotic symptoms and suicide attempts, positive family history, and the presence of comorbid disorders. Although mood stabilizer monotherapies remain recommended and desirable strategies for maintenance treat ment of BD, our results show that a satisfactory response is achieved only in a minority of patients.

• Keywords
• stabilizátory nálady,
• MeSH
• Affect drug effects   MeSH
• Benzodiazepines therapeutic use   MeSH
• Bipolar Disorder drug therapy   MeSH
• Long-Term Care MeSH
• Adult MeSH
• Financing, Organized MeSH
• Carbamazepine therapeutic use   MeSH
• Valproic Acid therapeutic use   MeSH
• Lamotrigine MeSH
• Middle Aged MeSH
• Humans MeSH
• Lithium Carbonate therapeutic use   MeSH
• Treatment Failure MeSH
• Olanzapine MeSH
• Recurrence MeSH
• Secondary Prevention MeSH
• Statistics as Topic MeSH
• Triazines therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Comparative Study MeSH