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

Abstract Background Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II. [ABSTRACT FROM AUTHOR]

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

Background: Bipolar disorder (BD) is a serious chronic disease with a high frequency of suicide attempts (SA) and suicides. There are few long-term studies concerning characteristics of SA in BD, especially what characterizes early from late SA. Methods: A long-term study of 51 BD patients (DSM-IV) with SA were collected from lithium dispensaries in northern Sweden. Patients were divided into early SA (the first five years) after age of onset (AOO) or late SA. Results: Patients with early SA were younger (p = 0.036), met BD earlier (p = 0.005), had less repeated depressions before SA (p = 0.002), often performed SA at first episode (p < 0.001) and before initiating of lithium (p = 0.002). Before first SA they had, fewer but more frequent episodes/year (p < 0.001), fewer depressive (p < 0.001) but more frequent depressive episodes/year (p < 0.001), lower frequency of hypomanic (p = 0.016) or manic episodes (p = 0.006). They had a higher frequency of episodes/year off (p = 0.047) and on (p = 0.042) lithium. Twenty percent of all patients performed SA at first episode, 47 % early SA and 65 % first ten years after AOO.Early SA was associated with a family history of first- and/or second-degree relative of affective disorder (AD) (p = 0.005), first-degree relative of AD (p = 0.031) and first-degree relative of BD (p = 0.049). All patients with early SA had a family history of AD. Conclusions: Patients with early SA have a more severe form of BD. Family history of AD among first- and/or second-degree relatives is significantly associated with especially early SA which implies a special psychiatric treatment and care for this BD group.

Aim: In order to avoid side effects of lithium doses in some patients, some commonly cultivated mushroom species including A. bisporus have been successfully lithiated, with the potential to provide more acceptable sources of Li. This study assessed the in vitro release (potential bioaccessibility) and possible intake of Li using the action of artificial gastrointestinal juices on lithiated and nonlithiated (control) button mushrooms (Agaricus bisporus) that were subjected to certain modes of culinary processing. Methods: In the in vitro release study, mushrooms were processed using a number of routinely used domestic treatments including rehydrating dried mushrooms, blanching and blanching followed by pickling of fresh or frozen mushrooms. The in vitro digestion procedure used artificial gastrointestinal juices in a two‐stage methodology that was adapted from 'The Bioaccessibility Research Group of Europe' method. The Li concentrations were determined using an inductively coupled argon plasma–dynamic reactive cell–mass spectrometer. Results: Lithium was found to be more bioaccessible from caps of lithiated mushrooms compared with nonlithiated. Releases from the caps and stipes of blanched or blanched and then pickled mushrooms through gastric digestion ranged from 32 ± 2 to 50 ± 1% relative to the dried product and was lower for gastrointestinal digestion, which ranged from 16 ± 1 to 20 ± 1%. Conclusion: Losses of Li sustained through blanching or blanching followed by pickling of fresh mushrooms (41–87% wet weight) combined with limited accessibility during gastrointestinal release (16–55%) result in much lower bioavailability of the dose from lithiated products. A 300‐g meal would provide <5% of the Li (6 mg) required for potential preventative treatments, such as reducing suicide rates and lowering dementia risk. [ABSTRACT FROM AUTHOR]

Lithium has been the treatment of choice for patients with bipolar disorder. However, lithium overdose happens more frequently since it has a very narrow therapeutic range in blood, necessitating investigation of its adverse effects on blood cells. The possible changes that lithium exposure may have on functional and morphological characteristics of human red blood cells (RBCs) have been studied ex vivo using single-cell Raman spectroscopy, optical trapping, and membrane fluorescent probe. The Raman spectroscopy was performed with excitation at 532 nm light, which also results in simultaneous photoreduction of intracellular hemoglobin (Hb). The level of photoreduction of lithium-exposed RBCs was observed to decline with lithium concentration, indicating irreversible oxygenation of intracellular Hb from lithium exposure. The lithium exposure may also have an effect on RBC membrane, which was investigated via optical stretching in a laser trap and the results suggest lower membrane fluidity for the lithium-exposed RBCs. The membrane fluidity of RBCs was further studied using the Prodan generalized polarization method and the results verify the reduction of membrane fluidity upon lithium exposure. [ABSTRACT FROM AUTHOR]

Background and Objectives: There is no biomarker to predict lithium response. This study used CellPrint™ enhanced flow cytometry to study 28 proteins representing a spectrum of cellular pathways in monocytes and CD4+ lymphocytes before and after lithium treatment in patients with bipolar disorder (BD). Materials and Methods: Symptomatic patients with BD type I or II received lithium (serum level ≥ 0.6 mEq/L) for 16 weeks. Patients were assessed with standard rating scales and divided into two groups, responders (≥50% improvement from baseline) and non-responders. Twenty-eight intracellular proteins in CD4+ lymphocytes and monocytes were analyzed with CellPrint™, an enhanced flow cytometry procedure. Data were analyzed for differences in protein expression levels. Results: The intent-to-treat sample included 13 lithium-responders (12 blood samples before treatment and 9 after treatment) and 11 lithium-non-responders (11 blood samples before treatment and 4 after treatment). No significant differences in expression between the groups was observed prior to lithium treatment. After treatment, the majority of analytes increased expression in responders and decreased expression in non-responders. Significant increases were seen for PDEB4 and NR3C1 in responders. A significant decrease was seen for NR3C1 in non-responders. Conclusions: Lithium induced divergent directionality of protein expression depending on the whether the patient was a responder or non-responder, elucidating molecular characteristics of lithium responsiveness. A subsequent study with a larger sample size is warranted. [ABSTRACT FROM AUTHOR]

Background: Time to a new episode of bipolar disorder (BD) is shorter after discontinuing lithium rapidly. We now address this and other factors associated with the risk of early illness after discontinuing lithium. Methods: We compared factors for association with recurrences of BD within 12 months of discontinuing long‐term lithium treatment, using bivariate and multivariable analyses, as well as survival analysis to evaluate latency to new episodes versus rate of lithium‐discontinuation and prior treatment duration. Results: Among 227 BD subjects who received lithium for 4.47 [CI: 3.89–5.04] years and then discontinued, rapid treatment‐discontinuation, and stopping for medical reasons were strongly associated with new illness‐episodes within 12 months, as were diagnosis (BD‐I > BD‐II), greater morbidity during lithium‐treatment, and less education, but neither longer treatment nor serum lithium concentrations. Discontinuation rate was strongly associated with shorter median latency to a new episode (rapid: 3.50; gradual [≥2 weeks]: 10.6 months), even with very early recurrences excluded to avoid potential contributions of emerging illness to treatment‐discontinuation. Early recurrence was not associated with treatment‐duration of ≥2 or ≥5 years or less. In multivariable logistic regression, rapid discontinuation, stopping for medical reasons, and BD‐I diagnosis remained significantly, independently associated with early illness after lithium‐discontinuation, with no effect of treatment duration. Conclusions: Early recurrence risk was again much greater after rapid discontinuation of lithium and discontinuing for medical reasons, somewhat greater with BD‐I than BD‐II, and following greater morbidity during lithium‐treatment, but not related to dose or duration of preceding treatment exposure. [ABSTRACT FROM AUTHOR]

Lithiated products such as button mushrooms that are cultivated in substrates fortified with lithium (Li) salts, have the potential to provide accessible and safe Li dosing as a treatment for some neurological disorders. However, Li losses sustained during culinary processing are not known. This study of commonly used culinary treatments including various combinations of drying, maceration, blanching (of fresh, deep-frozen and re-hydrated mushrooms) and pickling (of fresh and deep-frozen mushrooms) shows that Li is lost from the edible flesh at varying rates depending on the treatment. Blanching of fresh lithiated mushrooms resulted in a 40% loss, increasing to 77–87% when blanching was followed by pickling. Corresponding losses were similar (47–72%) for non-lithiated mushrooms. Higher losses through the combined treatment relative to just blanching appear to be due to chelating and acidifying effects of the vinegar used. This finding has important dose implications for potential future use of lithiated products.

Introduction Suicide risk is 20-30 fold higher in bipolar disorder(BD) than general population. A positive family history of suicide, early-onset bipolar disorder, rapid cycling, and drug/alcohol addiction have been identified as risk factors for non-fatal suicidal behavior. Lithium is the only mood stabilizer known to have a suicide-reducing effect in patients with BD. Less than half of the bipolar patients respond lithium well. Even though mechanism of action on suicide behavior is not clearly known, it is thought that lithium significantly reduces “impulsive-aggressive” behavior via serotonergic system which might also be related with treatment response in BD. Objectives The aim of this study is to evaluate the relationship between lithium response and history of suicide. Methods Those who scored 7 points or more from the Alda total score were considered good responders. Patients were divided into those who responded well to lithium treatment and those who did not. History of suicide attemptbetween these two groups was compared. Results 65.3% of the patients were female (n:49). The mean age of the patients was 36.82±13.35 years. 25 patients responded well to lithium treatment. Among the good responders, 32% of the patients and 25% of the non-responders had a history of suicide attempts. This difference was not statistically significant. (p=0.46 x²=0.13) Conclusions The insufficient number of data in the study was considered as a limitation of this study. In addition, there is a need for more studies as there are many factors that cause suicide attempts. Disclosure No significant relationships.

Background and Objectives: There is no biomarker to predict lithium response. This study used CellPrint™ enhanced flow cytometry to study 28 proteins representing a spectrum of cellular pathways in monocytes and CD4+ lymphocytes before and after lithium treatment in patients with bipolar disorder (BD). Materials and Methods: Symptomatic patients with BD type I or II received lithium (serum level ≥ 0.6 mEq/L) for 16 weeks. Patients were assessed with standard rating scales and divided into two groups, responders (≥50% improvement from baseline) and non-responders. Twenty-eight intracellular proteins in CD4+ lymphocytes and monocytes were analyzed with CellPrint™, an enhanced flow cytometry procedure. Data were analyzed for differences in protein expression levels. Results: The intent-to-treat sample included 13 lithium-responders (12 blood samples before treatment and 9 after treatment) and 11 lithium-non-responders (11 blood samples before treatment and 4 after treatment). No significant differences in expression between the groups was observed prior to lithium treatment. After treatment, the majority of analytes increased expression in responders and decreased expression in non-responders. Significant increases were seen for PDEB4 and NR3C1 in responders. A significant decrease was seen for NR3C1 in non-responders. Conclusions: Lithium induced divergent directionality of protein expression depending on the whether the patient was a responder or non-responder, elucidating molecular characteristics of lithium responsiveness. A subsequent study with a larger sample size is warranted.

Lithium is one of the most widely used medications for the treatment of bipolar disorder (BD). It also has some side effects on thyroid functions. We aimed to investigate the role of oxidative stress, trace elements, and hemorheological parameters on the pathophysiology of thyroid dysfunctions developed by lithium treatment in patients with BD. Patients with BD were divided into three groups: patients that non-lithium-treated, lithium-treated patients for 4-6 weeks, and lithium-treated patients for 40-68 weeks. Blood samples for analysis were taken before and after the treatment period. After analysis, patients were divided into six groups: non-treatment BD group (Group 1); short-term lithium-treatment group that did not develop thyroid dysfunctions (Group 2); short-term lithium-treatment group that developed hyperthyroidism (Group 3); long-term lithium treatment group that developed hypothyroidism (Group 4), long-term lithium-treatment group that developed hyperthyroidism (Group 5), and long-term lithium-treatment group that did not develop thyroid dysfunctions (Group 6). Plasma and whole blood viscosity levels were significantly increased in Groups 4 and 6 compared to Groups 1, 2, and 3. Hemoglobin levels were lower in Group 4 than in Groups 1, 2, and 5. Fibrinogen values were higher in Groups 4 and 5 than Group 1. Plasma and erythrocyte malondialdehyde levels were higher in Group 4 than In Groups 1, 2, 3, and 5. Also, they were increased in Group 6 in comparison with Groups 2 and 3. Erythrocyte glutathione levels were lower in Groups 4 and 6 than Groups 1, 2, 3 and 5. Plasma protein carbonyls levels were higher in Group 4 than in Group 1, or in Group 5 than in Groups 1, 2, and 3, as well as in Group 6 than Groups 1, and 2. Serum zinc levels were higher in Groups 2, 3 and 6 than in Group1. Serum copper levels increased in Groups 2, 4 and 6 in comparison with Group1. The results of this study indicate that oxidative stress increased with treatment time in lithium-induced thyroid dysfunctions. Also, whole blood viscosity, plasma viscosity, fibrinogen, zinc, and copper levels were affected by lithium treatment and treatment duration induced thyroid dysfunctions. [ABSTRACT FROM AUTHOR]

Despite unlimited access to therapeutic drug monitoring lithium poisoning is still a common and potentially life-threatening but in most cases preventable complication of lithium treatment; however, it is still considered to be the gold standard in the treatment of affective disorders. The necessity of drug monitoring and potential lithium toxicity substantiate the skepticism of many therapists with respect to this often very effective treatment. This therefore limits the use of lithium although the unique therapeutic effects and high efficiency are well known. This retrospective data analysis of risk factors and etiology of lithium poisoning cases identified 58 cases of lithium poisoning, which were treated internally in this hospital between 2010 and 2014. Of the patients 67.2% were female and the majority were classified as chronic poisoning (66.1%). The most relevant patient-related risk factor seemed to be insufficient self-management as 26% of cases of lithium poisoning occurred during febrile infections or exsiccosis. Regarding practitioner-related risk factors, an insufficient consideration of drug interactions, insufficient therapeutic drug monitoring after dose increase and a paucity of experience and knowledge concerning lithium treatment were most relevant. This study illustrates the most important risk factors for lithium poisoning and their frequencies and contributes to raise awareness for this highly relevant topic. These data can help to prevent further cases of lithium poisoning. Furthermore, the results enable a comparison between the actual treatment reality and currently available evidence for the treatment of lithium poisoning. [ABSTRACT FROM AUTHOR]

Lithium, which is still the gold standard in the treatment of bipolar disorder, has been proposed to inhibit inositol monophosphatase (IMPase) and is hypothesized to exert its therapeutic effects by attenuating phosphatidylinositol (PI) cell signalling. Drug‐discovery efforts have focused on small‐molecule lithium mimetics that would specifically inhibit IMPase without exhibiting the undesired side effects of lithium. L‐690,330 is a potent bisphosphonate substrate‐based inhibitor developed by Merck Sharp & Dohme. To aid future structure‐based inhibitor design, determination of the exact binding mechanism of L‐690,330 to IMPase was of interest. Here, the high‐resolution X‐ray structure of human IMPase in complex with L690,330 and manganese ions determined at 1.39 Å resolution is reported. [ABSTRACT FROM AUTHOR]

Introduction There is a resurgence of interest in lithium treatment of bipolar disorders in part related to its unique anti-suicidal and neuroprotective effects. Methods This is a narrative review of key studies pertaining to the effectiveness and tolerability of lithium treatment in pediatric populations. Results Evidence supports that lithium is an effective and generally well-tolerated acute treatment for pediatric mania compared to placebo. Lithium may be less effective than risperidone for treating chronic mixed/manic symptoms in young children but comparable to anticonvulsants. However, in comparison, risperidone was associated with higher weight gain and prolactin levels. There is a lack of evidence inform maintenance treatment in children who benefit from lithium. Other indications that require further study include treatment of refractory or recurrent major depression in children at confirmed familial risk of bipolar disorder, as well as the treatment of acute suicidal ideation/behavior and refractory aggression. Discussion There is inadequate data about the full variety of benefit and tolerability of lithium treatment in pediatric patients. However, given the potential for protection against suicide and neurotoxic effects of illness, further studies should be a priority. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether response to lithium treatment in pediatric bipolar disorder can be predicted by changes in white matter microstructure in key cortico-limbic tracts involved in emotion regulation. Methods Eighteen clinically referred lithium-naive patients (mean age 15.5 years) were administered clinical rating scales and diffusion tensor imaging ( DTI) examinations at baseline and following 4 weeks of lithium treatment. Clinical ratings were repeated following 8 weeks of treatment. Patients with Clinical Global Impressions ( CGI) ratings of 1 ('very much improved') or 2 ('much improved') were classified as responders. Ten healthy volunteers received baseline and follow-up DTI examinations. Using the ENIGMA pipeline, we investigated the relationship between changes in fractional anisotropy ( FA) in the cingulum hippocampus (CGH) and clinical response to lithium. Results Patients demonstrated significantly lower FA compared to healthy volunteers in the left and right CGH white matter at baseline. Following 4 weeks of lithium treatment, FA in the left CGH increased in patients, but no significant changes in FA were observed among the untreated healthy volunteers. Lithium responders had a significantly greater increase in FA compared to non-responders. Moreover, baseline (pre-treatment) FA in the left CGH white matter significantly predicted week 8 overall CGI severity score, with post hoc analyses indicating that these effects were evident for both severity of depression and mania. Conclusions Our findings suggest that response to lithium treatment in pediatric bipolar disorder is associated with normalization of white matter microstructure in regions associated with emotion processing. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence points to the pathophysiological relevance between immune dysfunction and mood disorders. High rates of thyroid dysfunction have been found in patients with bipolar disorder (BD), compared to the general population. A systematic review of the relationship between BD and thyroid autoimmunity was performed.Methods: Pubmed, EMBASE and PsycINFO databases were searched up till January 28th, 2017. This review has been conducted according to the PRISMA statements. Observational studies clearly reporting data among BD patients and the frequency of autoimmune thyroid pathologies were included.Results: 11 original studies met inclusion criteria out of 340 titles first returned from the global search. There is evidence of increased prevalence of circulating thyroid autoantibodies in depressed and mixed BD patients, while there is no evidence showing a positive relationship between BD and specific autoimmune thyroid diseases. There is a controversy about the influence of lithium exposure on circulating thyroid autoantibodies, even if most of studies seem not to support this association. A study conducted on bipolar twins suggests that autoimmune thyroiditis is related to the genetic vulnerability to develop BD rather than to the disease process itself. Females are more likely to develop thyroid autoimmunity.Limitations: The samples, study design and outcomes were heterogeneous.Conclusion: Thyroid autoimmunity has been suggested to be an independent risk factor for bipolar disorder with no clear association with lithium exposure and it might serve as an endophenotype for BD. [ABSTRACT FROM AUTHOR]

Prion diseases are a group of infectious neurodegenerative diseases characterized by multiple neuropathological hallmarks, including accumulation of PrP Sc , synaptic damage, and neuronal death. We previously reported that the repressor element 1-silencing transcription factor (REST), a novel neuroprotective marker in neurodegeneration, protects neurons against neurotoxic peptide (PrP106-126)-induced neurotoxicity, but fails to maintain survival following prolonged exposure to PrP106-126. Because Wnt signaling partially induces REST and is activated by lithium, we investigated the effects of lithium on REST in prion diseases. Lithium restores nuclear expression of REST, which is essential for regulating survival proteins. Lithium also mimics neuroprotective functions when REST is blocked, and these beneficial effects are additive with REST overexpression under physiological conditions. Reciprocally, under PrP106-126-stimulated pathological conditions, REST plays a critical role in the neuroprotective mechanisms of lithium treatment. Although lithium recovers Wnt signaling by inhibiting glycogen synthase kinase-3β and stabilizing β-catenin, restores survival associated proteins after exposure to PrP106-126 in primary cortical neurons. Knockdown of REST significantly suppresses the neuroprotective function of lithium. Conversely, overexpression of REST partially recovers its actions. Notably, lithium directly alleviates PrP106-126-induced synaptic damage and neuronal cell death by preventing changes in presynaptic and postsynaptic marker proteins and promoting survival pathways also partially via the expression of REST. Our results suggest that REST acts as a novel and important nuclear target for lithium. We hypothesize that PrP106-126-stimulated neurotoxicity induces Wnt signaling dysfunction and lithium mimics this signaling cascade, suggesting that lithium should be considered as a potential therapeutic agent against prion diseases. [ABSTRACT FROM AUTHOR]

The mechanism of lithium's therapeutic action remains obscure, hindering the discovery of safer treatments for bipolar disorder. Lithium can act as an inhibitor of the kinase GSK3α/β, which in turn negatively regulates β-catenin, a co-activator of LEF1/TCF transcription factors. However, unclear is whether therapeutic levels of lithium activate β-catenin in the brain, and whether this activation could have a therapeutic significance. To address this issue we chronically treated mice with lithium. Although the level of non-phospho-β-catenin increased in all of the brain areas examined, β-catenin translocated into cellular nuclei only in the thalamus. Similar results were obtained when thalamic and cortical neurons were treated with a therapeutically relevant concentration of lithium in vitro . We tested if TCF7L2, a member of LEF1/TCF family that is highly expressed in the thalamus, facilitated the activation of β-catenin. Silencing of Tcf7l2 in thalamic neurons prevented β-catenin from entering the nucleus, even when the cells were treated with lithium. Conversely, when Tcf7l2 was ectopically expressed in cortical neurons, β-catenin shifted to the nucleus, and lithium augmented this process. Lastly, we silenced tcf7l2 in zebrafish and exposed them to lithium for 3 days, to evaluate whether TCF7L2 is involved in the behavioral response. Lithium decreased the dark-induced activity of control zebrafish, whereas the activity of zebrafish with tcf7l2 knockdown was unaltered. We conclude that therapeutic levels of lithium activate β-catenin selectively in thalamic neurons. This effect is determined by the presence of TCF7L2, and potentially contributes to the therapeutic response. [ABSTRACT FROM AUTHOR]