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Lit jest lekiem normotymicznym, stosowanym z wyboru w leczeniu profilaktycznym choroby afektywnej dwubiegunowej (ChAD). Skuteczność profilaktyczna litu może być uwarukowana czynnikami genetycznymi, związanymi częściowo z predyspozycją do choroby afektywnej dwubiegunowej. W dziedzinie genetyki w psychiatrii pierwsza dekada XXI wieku została zdominowana przez badania „genów kandydujących”. W niniejszym artykule przedstawiono badania genów kandydujących związanych z profilaktyką litem, prowadzone na Uniwersytecie Medycznym w Poznaniu w latach 2005-2018. W tym czasie badane były polimorfizmy wielu genów, z których część jest również związana z predyspozycją do choroby afektywnej dwubiegunowej. Związek ze skutecznością profilaktyczną litu stwierdzono w przypadku polimorfizmów genów 5HTT, ACP1, ARNTL, BDNF, COMT, DRD1, FKBP5, FYN, GLCC, NR3C1 i TIM. Nie stwierdzono takiego związku w odniesieniu do genów 5HT2A, 5HT2C, DRD2, DRD3, DRD3, GRIN2B, GSK-3β, MMP-9 i NTRK2. Wykazano natomiast asocjację polimorfizmu genu GSK-3β z nerkowymi działaniami niepożądanymi w przebiegu stosowania litem. Omówiona została możliwa rola tych genów zarówno w mechanizmie profilaktycznej skuteczności litu, jak i w patogenezie choroby afektywnej dwubiegunowej.

OBJECTIVE: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth.METHODS: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer.RESULTS: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001).CONCLUSION: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.

Objectives:Bipolar disorder (BD) may be connected with accelerated aging, the marker of this can be shorter telomere length (TL). Some data suggest that lithium may exert a protective effect against telomere shortening. The study aimed to compare the TL between patients with BD and control subjects. The effect of long-term lithium treatment was also assessed.Methods:The study group comprised 41 patients with BD, including 29 patients treated longitudinally with lithium (mean 16.5 years) and 20 healthy people. TL was assessed by the quantitative polymerase chain reaction (qPCR).Results:In the control group, the TL was significantly longer in males than in females. Male bipolar patients had significantly shorter TL compared with the control male group. In bipolar patients, there was no correlation between TL and duration of treatment. The TL was negatively correlated with age in male bipolar patients.Conclusions:The study did not confirm the lithium effect on TL in bipolar patients. TL showed gender differences, being shorter in BD males, compared to control males, and longer in healthy males, compared to control females.

Aims: Long-term treatment with lithium in patients with bipolar disorder (BD) exerts a significant effect on thyroid structure and function. Previously, it was found that adding to lithium other mood stabilising or antidepressant drugs can also be important. The aim of this preliminary study was to compare thyroid structure and function in patients with BD receiving long-term lithium monotherapy with monotherapy using other mood stabilising drugs, such as carbamazepine, valproates or quetiapine. Method: Forty-one BD patients were studied (13 male, 28 female) aged 28–80 years. In 15, monotherapy with lithium was given; in 10 – with carbamazepine; and in 8 – with valproate and quetiapine. In all patients, the thyroid-stimulating hormone (TSH), free thyroxine (fT3) free triiodothyronine (fT4), and the antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb) and TSH receptors (TSHRAb) were estimated. Goiter was diagnosed when the thyroid volume exceeded 18 cm3 in women and 25 cm3 in men. Results: The groups were of similar age; however, the duration of quetiapine therapy was shorter than lithium or carbamazepine. Comparing to patients on lithium monotherapy, the median of TSH concentration was lower in patients on quetiapine, and the median of TPOAB lower in patients on valproates. The highest frequency of goiter (47%) was observed in patients receiving lithium. Conclusions: The results obtained may suggest that among the studied mood stabilisers, lithium exerts the biggest goiter-inducing effect. The differences between groups as to thyroid hormones and antibodies were not significant. The limitation of the study was a small number of studied patients.

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.

This paper discusses essential issues related to long-term lithium therapy and presents a case of successful 50-year lithium treatment. Lithium is currently regarded as the drug of choice for preventing manic and depressive recurrences in bipolar disorder. In 1/3 of patients with bipolar disorder, long-term monotherapy with lithium can completely prevent recurrences of abnormal mood. Numerous clinical and psychosocial factors associated with a good response to lithium have been described. Lithium is more efficacious than other mood stabilizers, and its long-term treatment significantly exceeds them. Lithium also exerts antisuicidal, immunomodulatory, and neuroprotective effects. The main problems associated with long-term lithium treatment include kidney, thyroid, and probably cognitive issues. In this paper, a case of successful continuous lithium treatment for 50 years in a 79-year-old female patient is presented. In this patient, apart from maintaining a euthymic state, long-term lithium treatment also exerted a favorable effect on general health, especially the elimination of viral and other respiratory infections. It is concluded that ultra-long term lithium therapy can enable good professional and psychosocial functioning for many patients, and the possible somatic side effects are manageable.

Introduction The studies on the effect of lithium treatment on antithyroid antibodies showed either a higher concentration of these antibodies in patients receiving lithium compared to those lithium-naive or no difference between these groups. In lithium-treated bipolar patients, some researchers pointed to an association between antithyroid antibodies and other features of thyroid dysfunction such as hypothyroidism and decrease of glomerular filtration rate. Methods We compared antithyroid antibodies in 98 patients (30 male, 68 female) with bipolar disorder, aged 62±13 years, who received lithium for 19±10 years to 39 patients (12 male, 27 female), aged 57±10 years, who were never treated with lithium. The antibodies against thyroid peroxidase (TPOAb), against thyroglobulin (TGAb), and thyroid-stimulating hormone (TSH) receptors (TSHRAb) were estimated. Results No difference in the percentages of antibodies occurrence was found between groups, although the concentrations of TGAb were higher in patients receiving lithium. In lithium-treated patients, the presence of TPOAb was associated with lower concentrations of free triiodothyronine and the presence of TGAb, with higher concentrations of TSH. In females, the levels of TGAb were associated with lower thyroid volume. The concentrations of TPOAb correlated positively with the duration of lithium therapy in males, and those of TPOAb and TGAb negatively, with such duration, in female patients. Conclusion The results obtained showed no significant connection between long-term lithium treatment and antithyroid antibodies. In bipolar patients receiving lithium longitudinally, antithyroid antibodies can be associated with some indexes of thyroid function. However, they behave differently in male and female patients.

Objectives. The efficacy of pharmacotherapy augmentation by total sleep deprivation (TSD) with sleep phase advance (SPA) was evaluated in patients with treatment-resistant depression (TRD). The study examined the relationship between chronotype, affective temperaments and clinical improvement resulting from the treatment. Material and methods. The study group comprised of 30 persons with treatment-resistant unipolar (n = 15) or bipolar (n = 15) depression aged 52 ± 12 years (17 women and 13 men). TSD and three consecutive nights with SPA were used during pharmacotherapy. Severity of depression was determined using the Hamilton Depression Rating Scale (HDRS). All patients were assessed using the Composite Scale of Morningness (CSM) and Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A). Results. Clinical response, defined as a reduction in the severity of depression by ≥ 50% in HDRS compared to the baseline score, lasting until the end of the study (14 days), was obtained in 16 out of 30 patients with TRD. There was found no significant correlation between clinical improvement, chronotype and affective temperaments. Conclusions. TSD with SPA proved to be an effective method of pharmacotherapy augmentation in over half of the patients with TRD. The relationship between chronotype, affective temperaments and the clinical response to chronotherapy of depression requires further research.

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = −0.14; 95% confidence interval [CI]: −0.24 to −0.03; p value = 0.010) and MDD (β = −0.16; 95% CI: −0.27 to −0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34–1.93; p value = 2e−7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.

This mini-review aims to show a discrepancy between favorable data of lithium's therapeutic activity and the decreased use of the drug worldwide. The data point to lithium as the best mood stabilizer in the maintenance treatment of bipolar disorder for the prevention of manic and depressive recurrences. The second most encouraging psychiatric use of lithium is the augmentation of antidepressants in treatment-resistant depression. In addition to its mood-stabilizing properties, lithium is the most efficacious antisuicidal drug among all mood stabilizers. The drug also exerts antiviral, immunomodulatory, and neuroprotective effects which may be of major clinical value. On the other hand, the data of lithium use show that its therapeutic application in many countries has declined. A reason for this can be the introduction and heavy promotion of other mood-stabilizers, while lithium is an "orphan" drug with the minimal interest of any drug company. Probably, very important is also a perception of lithium as a "toxic drug", pointing to its side effects, mainly thyroid, renal and cognitive ones. In recent years, several proposals to turn back this anomalous association appeared, challenging a negative perception of lithium and optimizing its long-term administration. They show the data on lithium superiority over other mood stabilizers and point to the proper management of the lithium-induced side effects. This endeavor aims to allow a larger number of mood disorder patients to become beneficiaries of lithium use.

Progress in medical science has allowed the discovery of many factors affecting the pathogenesis of bipolar disorder, and among the most recent research directions are found regenerative and inflammatory processes. The role of regenerative processes remains particularly poorly explored, but available data encourage further research, which may explain the pathogenesis of bipolar disorder (BD). The aim of this study was to evaluate the mobilization of stem cells into peripheral blood, in patients with bipolar disorder during stable phase, not treated with lithium salts. The study included 30 unrelated individuals with the diagnosis of bipolar disorder, with disease duration of at least 10 years, not treated with lithium salts for at least five years prior to the study. The control group consisted of 30 healthy subjects, matched for age, sex, body mass index (BMI), origin, socio-demographic factors and nicotine use. Blood samples underwent cytometric analyses to assess concentrations of: Very Small Embryonic Like (VSEL) CD34+, VSEL AC133+, HSC CD34+, HSC AC133+. There were no significant differences in stem cell levels between patients with BD and healthy controls. However, the level of VSEL cells AC133 + was significantly higher in type I BD patients compared to healthy controls. Our results indicate a disturbance in regenerative processes in patients with bipolar disorder.

Objectives To assess the neurobiology of treatment-resistant depression (TRD), and factors connected with improvement after total sleep deprivation (TSD) with sleep phase advance (SPA), for the augmentation of pharmacotherapy. Methods The study comprised 43 patients with TRD, (15 male, 28 female), aged 48 ± 13 years, with the illness duration 12 ± 9 years, and the depressive episode 8 ± 7 months. TRD was defined as a lack of significant improvement despite at least two antidepressant treatments and the augmentation with mood-stabilisers. Clinical improvement (response) was a reduction of ≥50% of points in the Hamilton Depression Rating Scale (HDRS), and the remission criterion was ≤7 points in HDRS, lasting until the 14th day after TSD + SPA. Results TRD severity was associated with greater activity of the hypothalamic-pituitary-adrenal axis, the pro-inflammatory status of the immune system and lower reactivity of the hypothalamic-pituitary-thyroid axis. The response was achieved by 18 of 42 subjects, and connected with the later onset and shorter duration of the disease. In responders, there was a decrease in cortisol and interferon-gamma. In all subjects, a decrease in thyroid hormones was observed. Conclusions TRD can improve after augmentation of pharmacotherapy by TSD + SPA and some biological changes may be compatible with a decrease in allostatic load.

Aims: The aim of this study was to evaluate serum levels of the antineuronal antibodies anti-N-methyl-D-aspartate receptor (NMDAR) and anti-glutamic acid decarboxylase (GAD), and insulin-like growth factor 1 (IGF-1), in patients with bipolar disorder (BD), during manic and depressive episodes and in remission compared to euthymic patients receiving long-term lithium therapy. Methods: Serum levels of anti-NMDAR and anti-GAD 450/620 antibodies, as well as IGF-1, were measured using the ELISA method in 19 manic and 17 depressed patients both in an acute episode and in remission after the episode. All of the subjects were under pharmacological treatment. The control group included 18 euthymic BD patients receiving lithium for 9–44 years (mean 22 ± 11) in whom a single measurement was performed. Results: Serum levels of anti-NMDAR antibodies were higher in acute manic episodes than in lithium-treated patients. Serum levels of anti-GAD 450/620 antibodies were higher in acute manic and depressive episodes compared to remission after the respective episode. Their values in both acute manic and depressive episodes were higher than those in lithium-treated patients. Serum levels of IGF-1 were higher in acute manic episodes and in remission after mania than in lithium-treated patients. Conclusion: Higher levels of anti-NMDAR and anti-GAD antibodies during episodes may point to an abnormality in the glutamatergic system in BD. Increased levels of IGF-1 during an acute manic episode and in remission after mania may constitute a compensatory mechanism against excitotoxicity. Lower levels of anti-NMDAR, anti-GAD antibodies, and IGF-1 during long-term lithium treatment may reflect normalization of this processes, contributing to mood stabilization.

Introduction The aim was to assess the efficacy of total sleep deprivation (TSD) with sleep phase advance (SPA) in treatment-resistant depression (TRD) and associated biochemical factors. Methods We studied nine males and 12 females, aged 49±14 years, with treatment-resistant unipolar or bipolar depression, receiving antidepressant and mood-stabilizing drugs. The four-day schedule included single TSD and three consecutive nights with SPA. Biochemical markers were measured on the day before and on 1st, 7th and 14th day after the TSD. Results Ten subjects met criteria for response, defined as a reduction of ≥50% in the Hamilton Depression Rating Scale, on the 14th day. Concentrations of cortisol at baseline were lower in responders, and they decreased during therapy in both groups. In responders, there was an increase of interleukin-10 (IL-10) and IL-1β on the 14th day. Discussion Our preliminary study demonstrated the efficacy of pharmacotherapy augmentation by TSD and SPA in half of the patients with TRD. The main biochemical factors related to clinical response included status of cortisol and increase in IL-10 and IL-1β levels.

Background We investigated the effect of long-term lithium treatment on very-small embryonic-like stem cells (VSELs) and the mRNA expression of pluripotency and glial markers, in peripheral blood, in patients with bipolar disorder (BD). Methods Fifteen BD patients (aged 53 ± 7 years) not treated with lithium, with duration of illness > 10 years, 15 BD patients (aged 55 ± 6 years) treated with lithium for 8–40 years (mean 16 years) and 15 control subjects (aged 50 ± 5 years) were included. The number of VSELs was measured by flow cytometric analysis. Assessment of the mRNA levels of pluripotency markers (Oct-4, Sox 2 and Nanog) and glial markers (glial fibrillary acidic protein - GFAP, Olig1 and Olig2) was performed, using the Real-time quantitative reverse transcription PCR. Results In BD patients not taking lithium, the number of VSELs was significantly higher than in control subjects and correlated with the duration of illness. The expression of pluripotency markers was significantly higher than in the controls and correlated with the number of VSELs. The mRNA levels of the Olig1 and Olig 2 were higher than in the controls and those of the GFAP were higher than in patients receiving lithium. In lithium-treated BD patients the number of VSELs was similar to controls and correlated negatively with the duration of lithium treatment and serum lithium concentration. The mRNA levels of Oct-4, Sox-2, GFAP and Olig1 were not different from controls. The mRNA expression of Nanog was significantly higher and correlated with the number of VSELs. The mRNA expression of Olig 2 was higher than in the BD patients not taking lithium. Conclusion Long-term treatment with lithium may suppress the activation of regenerative processes by reducing the number of VSELs circulating in PB. These cells, in BD patients not treated with lithium, may provide a new potential biological marker of the illness and its clinical progress. The higher expression of peripheral mRNA markers in BD patients may involve ongoing inflammatory process, compensatory mechanisms and regenerative responses. Long-term lithium treatment may attenuate these mechanisms, especially in relation to the transcription factors Oct-4, Sox-2, GFAP and Olig1.

Objective: To assess the relationship of biological rhythms, evaluated by the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), with affective temperaments and schizotypy. Methods: The BRIAN assessment, along with the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A) and the Oxford-Liverpool Inventory for Feelings and Experiences (O-LIFE), was administered to 54 patients with remitted bipolar disorder (BD) and 54 healthy control (HC) subjects. Results: The TEMPS-A cyclothymic temperament correlated positively and the hyperthymic temperament correlated negatively with BRIAN scores in both the BD and HC groups, although the correlation was stronger in BD subjects. Depressive temperament was associated with BRIAN scores in BD but not in HC; conversely, the irritable temperament was associated with BRIAN scores in HC, but not in BD. Several positive correlations between BRIAN scores and the schizotypal dimensions of the O-LIFE were observed in both BD and HC subjects, especially with cognitive disorganization and less so with unusual experiences and impulsive nonconformity. A correlation with introversion/anhedonia was found only in BD subjects. Conclusion: Cyclothymic and depressive temperaments predispose to disturbances of biological rhythms in BD, while a hyperthymic temperament can be protective. Similar predispositions were also found for all schizotypal dimensions, mostly for cognitive disorganization.

Neuroinflammation, with microglial activation as an important element, plays a role in the pathogenesis of bipolar disorder (BD). Also, in mood disorders, pathological changes have been demonstrated in macroglial cells, such as astrocyctes and oligodendrocytes. Postmortem brain studies of BD patients to assess glial cells, such as astrocytes and oligodendrocytes and their markers such as glial fibrillary acidic protein (GFAP), Olig1 and Olig2, produced controversial results. On the other hand, investigation of these markers in the peripheral blood of such patients has not been performed so far. In this study, we examined the mRNA levels of GFAP, Olig1 and Olig2, in the peripheral blood of three groups: 15 BD subjects with a duration of illness at least 10 years (mean 20±9 years) but never treated with lithium, 15 subjects with BD treated continuously with lithium for 8-40 years (mean 16±8 years), and 15 control subjects. The groups were age-and sex-matched. Expression of mRNA markers was measured by real-time quantitative reverse transcription PCR (RQ-PCR). We observed increased mRNA levels of the Olig1 and Olig 2 glial markers studied in the BD patients not taking lithium, compared with the control subjects and increased mRNA level of GFAP, compared with lithium-treated patients. In the lithium-treated BD patients GFAP and Olig1 expression was at similar levels to that in the control group. However, Olig 2 expression was even higher than in the BD patients not taking lithium. The possible mechanisms concerning the higher expression of peripheral mRNA markers in BD patients may involve ongoing inflammatory process, compensatory mechanisms and regenerative responses. The beneficial effect of lithium may be related to its anti-inflammatory properties.

Background The aim was to evaluate the peripheral mRNA expression of pluripotency master transcriptional factors such as octamer-binding transcription factor 4 (Oct4), sex-determining region Y-box 2 (Sox2) and homeobox protein Nanog, in patients with bipolar disorder (BD), and the effect of long-term lithium treatment. Methods Fifteen BD patients (aged 53 ± 7 years) not treated with lithium, with duration of illness >10 years, 15 BD patients (aged 55 ± 6 years) treated with lithium for 8–40 years (mean 16 years) and 15 control subjects (aged 50 ± 5 years) were included. Assessment of the mRNA levels of pluripotency markers (Oct-4, Sox 2 and Nanog) was performed, using the Real-time quantitative reverse transcription PCR (RQ-PCR) procedure, and the number of CD34+ very small embryonic-like stem cells (VSELs) was measured by flow cytometric analysis. Results In those BD patients not treated with lithium the expression of all three pluripotency genes was significantly higher than that in the control subjects. Oct-4, Sox2 and Nanog also positively correlated with the number of CD34+ VSELs/[ul] in this group. In the lithium-treated patients the mRNA levels of Nanog were significantly higher than in the control individuals and correlated with the number and % of CD34+ VSELs. Conclusions The overexpression of the pluripotency master transcriptional factors in patients with a long duration of BD not treated with lithium, may contribute to the pathogenesis of the illness and make them potential biological markers of BD. Long-term lithium treatment may attenuate these excessive regenerative processes, especially in relation to the transcription factors Oct-4 and Sox2.

Objectives: To investigate the effect of long-term lithium treatment on very small embryonic-like stem cells (VSELs), haematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) circulating in peripheral blood (PB), in bipolar disorder (BD).Methods: The study included 15 BD patients (aged 55 ± 6 years) treated with lithium for 8–40 years (mean 16 years), 15 BD patients (aged 53 ± 7 years) with duration of illness >10 years, who had never received lithium, and 15 healthy controls (aged 50 ± 5 years). The VSELs, HSCs, MSCs and EPCs were measured by flow cytometric analysis.Results: In BD subjects not taking lithium the number of CD34+ VSELs was significantly higher, and MSCs and EPCs numerically higher, than in control subjects and the number of CD34+ VSELs correlated with the duration of illness. In lithium-treated patients these values were similar to controls and the number of CD34+ VSELs correlated negatively with the duration of lithium treatment and ...

Background/Aims: The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) is a novel tool allowing for a complex assessment of biological rhythms. We compared patients with bipolar disorder (BD) and healthy control subjects (HC) using the Polish version of the BRIAN scale. Method: Fifty-four remitted BD patients (17 males and 37 females aged 52 ± 13 years) and 54 healthy control subjects (25 males and 29 females aged 42 ± 14 years) were studied. In addition to the BRIAN scale, the Composite Scale of Morningness (CSM) and the Sleep-Wake Pattern Assessment Questionnaire (SWPAQ) were employed. Results: The Polish version of the BRIAN scale displayed high feasibility and consistency, showing that the patients had greater biological rhythm disturbances than the controls. After regression analysis, significant differences were obtained for the BRIAN subscales activity and predominant chronotype, and for the SWPAQ items quality of night-time sleep and ability to stay awake. We obtained positive correlations between higher BRIAN scores and morningness and eveningness, but the correlations with vigilance and the ability to stay awake (on the SWPAQ) were negative. Conclusions: Using the BRIAN scale, we confirmed the greater disturbances of biological rhythm in Polish remitted bipolar patients, compared with healthy controls. The differences between these 2 groups in sleep-awake patterns were also demonstrated by the SWPAQ scores. In contrast to other studies, we were unable to confirm an evening chronotype as a discriminating factor between remitted bipolar patients and healthy subjects. This can be explained by the older age and the use of lithium by a significant proportion of the patients.

Lithium has been used in modern psychiatry for more than 65 years, constituting a cornerstone for the long-term treatment of bipolar disorder. A number of biological properties of lithium have been discovered, including its hematological, antiviral and neuroprotective effects. In this article, a systematic review of the effect of lithium on hematopoietic, mesenchymal and neural stem cells is presented. The beneficial effects of lithium on the level of hematopoietic stem cells (HSC) and growth factors have been reported since 1970s. Lithium improves homing of stem cells, the ability to form colonies and HSC self-renewal. Lithium also exerts a favorable influence on the proliferation and maintenance of mesenchymal stem cells (MSC). Studies on the effect of lithium on neurogenesis have indicated an increased proliferation of progenitor cells in the dentate gyrus of the hippocampus and enhanced mitotic activity of Schwann cells. This may be connected with the neuroprotective and neurotrophic effects of lithium, reflected in an improvement in synaptic plasticity promoting cell survival and inhibiting apoptosis. In clinical studies, lithium treatment increases cerebral gray matter, mainly in the frontal lobes, hippocampus and amygdala. Recent findings also suggest that lithium may reduce the risk of dementia and exert a beneficial effect in neurodegenerative diseases. The most important mediators and signaling pathways of lithium action are the glycogen synthase kinase-3 and Wnt/β-catenin pathways. Recently, to study of bipolar disorder pathogenesis and the mechanism of lithium action, the induced pluripotent stem cells (iPSC) obtained from bipolar patients have been used.