Vergence eye movements impairments in schizophrenia and bipolar disorder.

One of the most evaluated eye tracking tasks in schizophrenia (SZ) and bipolar disorder (BD) are smooth pursuit eye movements. They rely on the maintenance of slowly moving object on the fovea. While most of the studies evaluated tracking of a target that moves in the fronto-parallel plane, only two assessed vergence eye movements (VEM), which relies on the pursuit of object that moves in depth. The aim of our study was to compare VEM performance in SZ and BD. We evaluated 28 SZ patients, 32 BD patients and 25 healthy controls (HC). Participants underwent thorough optometric examination before eye tracking task. VEM were measured with the use of infrared eye tracker and dedicated vergence stimuli generator. SZ patients showed higher mean break and recovery points of fusion and shorter correct tracking time than HC. BD individuals revealed tracking accuracy deficits and higher number of saccades than HC. Compared to BD, SZ patients showed decrease of maximal convergence and divergence. Moreover, they presented tracking accuracy deficits of non-dominant eye: altered eyes positioning error during convergence and divergence gain. Exploratory analysis revealed significant gender differences between groups in terms of binocular VEM parameters. In this study we have recognized pattern of eye movement disturbances differentiating abovementioned groups. SZ patients showed decreased vergence tracking range with shorter tracking time and impaired accuracy of non-dominant eye, while BD patients showed higher number of saccades with decreased tracking accuracy. Neuroimaging studies are necessary to identify neuronal underpinnings of VEM impairments in SZ and BD.

Vergence eye movements in bipolar disorder. / Ruchy wergencyjne w chorobie afektywnej dwubiegunowej.

OBJECTIVES: With respect to bipolar disorder (BD), previous research have demonstrated saccadic eye movements abnormalities, manifested mainly as an increase in reaction time (latency) in both prosaccadic and antisaccadic task. So far, there were no studies related to vergence eye movements in subjects with BD. Our primary aim was to evaluate vergence tracking performance in this clinical group. METHODS: 30 patients with BD in remission and 23 healthy controls were enrolled. Subjects underwent optometric examination where near point of convergence was measured by the use of Wolff Wand. Instrumented convergence measurements were performed using infrared eye tracker and dedicated vergence stimuli generator. RESULTS: BD patients presented significantly higher average error between eyes' convergence and convergence required to fixate the target and higher number of saccadic intrusions compared with healthy controls group. Principal component analysis performed on oculometric parameters revealed differences between BD patients and healthy controls. Significant correlations between the vergence disturbances and saccadic intrusions were found. CONCLUSIONS: BD patients showed the alterations of the vergence eye movements similar to the disturbances of eye movements in the fronto-parallel plane. While the abnormalities of vergence eye movements in some mental disorders have been reported, we have for the first time objectively measured this phenomenon in BD.

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

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

Kidney, thyroid and other organ functions after 40 years or more of lithium therapy: a case series of five patients.

We present the cases of five patients (two men aged 64 years and 79 years) and three women (aged 64 years, 65 years and 75 years) who have received lithium treatment for 40-45 years, with particular regard to kidney and thyroid functions, hypercalcaemia and cognition, in the context of disease course and overall functioning. Lithium was initiated in the early phase of the illness (in three patients within the first 2 years). In four patients, lithium concentration was between 0.60 and 0.65 mmol/l and in one patient, between 0.7 and 0.8 mmol/l. Four were very good lithium responders. One man had stage 3 chronic kidney disease, and the other stage 2/3 chronic kidney disease. All three women had asymptomatic stage 2 chronic kidney disease. One woman had severe thyroid dysfunction (Hashimoto's disease) with extremely high levels of antithyroid peroxidase antibodies and antithyroglobulin antibodies and was receiving thyroxine. Serum calcium levels were normal or borderline in all five patients, and most cognitive functions were comparable to healthy persons of similar gender, age and years of education. All the patients were professionally active until 55-65 years and their family and social functioning were satisfactory. It was concluded that, in good lithium responders, ultra-long-term treatment with lithium enables good professional and psychosocial functioning, and the possible somatic side effects are manageable.

Renal sonography in bipolar patients on long-term lithium treatment.

PURPOSE: The aim of the study was to analyze sonographic (US) renal findings in lithium-treated bipolar patients and to correlate them with renal function. METHODS: Renal US and renal function tests were performed on 120 patients with bipolar disorder. Ninety patients (30 males, 60 females), aged 36-82 years, had received lithium therapy for an average of 16 years, whereas 30 patients (10 males, 20 females), aged 35-85 years, who had never been exposed to lithium, served as controls. RESULTS: In the lithium-treated group, patients with macrocysts (22%) had poorer renal function with higher creatinine serum concentrations, lower estimated glomerular filtration rates, and lower urine specific gravity, compared with the patients without macrocysts. The US changes characteristic for lithium nephropathy (punctate hyperechoic foci, microcysts < 2 mm, and increased echogenicity) were seen in three patients. These patients had been treated with lithium for more than 20 years and had impaired renal function. Sixteen percent of patients in the control group had macrocysts; however, no correlation between their presence and impaired renal function was found. CONCLUSIONS: The presence of macrocysts in the kidneys of lithium-treated bipolar patients is associated with impaired renal function. The US changes characteristic for lithium nephropathy are rare, and in our study, were only found in patients treated with lithium for 20 years or more. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:354-359, 2016.

A cross-sectional study of thyroid function in 66 patients with bipolar disorder receiving lithium for 10-44 years.

OBJECTIVES: An important side effect of lithium therapy is an influence on thyroid function. It is unclear whether there is a significant association between thyroid function and duration of lithium administration. The aim of the present cross-sectional study was to measure levels of thyroid hormones and antibodies in patients with bipolar disorder receiving lithium for more than ten years. METHODS: The study was performed in 66 patients (21 males, 45 females) with bipolar mood disorder, receiving lithium for 10-44 (21 ± 9; mean ± standard deviation) years. Thyroid-stimulating hormone (TSH), free thyroxine (fT3), and free triiodothyronine (fT4) were measured by the microparticle enzyme immunoassay. Thyroid peroxidase (TPO) antibodies, thyroglobulin (TG) antibodies, and TSH receptor (TSH-R) antibodies were measured by the radioimmunoassay. RESULTS: Some features of hypothyroidism were found in ten (22%) female patients (seven received levothyroxine and three had increased TSH). No abnormality in thyroid hormones was found in male patients. A significant percentage of patients had abnormally high levels of anti-TPO, and anti-TG antibodies, which correlated with TSH and fT3 concentrations. There were no differences in thyroid function between patients receiving lithium for 10-20 years and those taking the drug for more than 20 years. CONCLUSIONS: These results confirm the greater susceptibility of female subjects for disturbances of thyroid hormones during lithium therapy, with one-fifth of them showing some features of hypothyroidism. Abnormally high levels of anti-TPO and anti-TG antibodies were shown in a significant proportion of patients. However, in contrast to the effect of lithium on kidney function, our results do not show an association between the duration of lithium therapy and thyroid dysfunction.

[The effect of lithium on thyroid function in patients with bipolar disorder]. / Wplyw stosowania litu na czynnosc gruczolu tarczowego u pacjentów z choroba afektywna dwubiegunowa.

Since 1963 lithium treatment has been the best proven long-term pharmacotherapy for bipolar disorder (BD), both in the prevention of depressive and manic episodes, along with the reduction of the suicide risk. Thyroid gland and the hypothalamic-pituitary-thyroid (HPT) axis play a role in the pathophysiology, clinical course and treatment of BD. The influence of lithium on the thyroid gland is one of the key side effects in the long-term therapy with this drug. Lithium is accumulated in the thyroid gland at 3 to 4-fold higher concentrations as compared to its plasma levels. Its administration results in the reduced production with release inhibition of thyroid hormones, altering the immune processes of this gland. The most common thyroid side effects associated with long-term lithium treatment are goiter and hypothyroidism. Hyperthyroidism is a rare complication of lithium therapy. Lithium may also induce an increase in the thyroid autoimmunity, especially if such change had been present before lithium treatment producing structural changes in this gland. This paper reviews the management of complications described above as well as recommendations for monitoring of thyroid function in patients receiving long-term lithium treatment are discussed.

The association of glycogen synthase kinase-3beta (GSK-3ß) gene polymorphism with kidney function in long-term lithium-treated bipolar patients.

BACKGROUND: Most bipolar patients experience a reduction in urinary concentrating ability within a few weeks of starting lithium treatment. This phenomenon may be connected with the effect of lithium on the glycogen synthase kinase-3beta (GSK-3ß) present in the renal tubules. The GSK-3ß gene is located on chromosome 3q13 and possesses a functional -50 C/T polymorphism. In the present study, we estimated this polymorphism in a group of long-term lithium-treated patients and assessed its association with various parameters of kidney function, including novel markers of kidney injury such as serum neutrophil gelatinase-associated lipocalin (NGAL) and urinary beta2-microglobulin (ß2-MG). METHODS: The study comprised 78 patients with bipolar mood disorder (25 males, 53 females), aged 36 to 82 (60 ± 11) years. The mean duration of bipolar illness was 6 to 50 (24 ± 10) years, and the patients have been receiving lithium for 5 to 38 (16 ± 9) years. All the patients had the following features, regarded as the phenotypes of kidney functions measured: urine examination for specific gravity evaluation, serum creatinine concentration, and estimated glomerular filtration rate (eGFR) evaluation, as well as the serum concentrations of NGAL and urinary ß2-MG. Genotyping of GSK-3ß gene -50 C/T polymorphism was done by polymerase chain reaction analysis. RESULTS AND DISCUSSION: Thirty-four patients (6 males, 28 females) had the T/T genotype, 37 patients (16 males, 21 females) had the T/C genotype, and 7 patients (3 males, 4 females) had the C/C genotype. Patients homozygous for C allele had significantly higher urine specific gravities (1.019 ± 0.008) compared to the remaining genotypes (1.013 ± 0.007) (p = 0.035), with no influence of the duration of lithium treatment. Other parameters of kidney function (serum creatinine, eGFR, serum NGAL, and urinary ß2-MG levels) were not different between genotypes and, again, were not affected by the duration of lithium treatment. There was no correlation between urine specific gravity and other kidney function parameters. The results of our study indicate that the GSK-3ß genotype may be connected with lithium-induced impairment of renal concentrating ability in long-term lithium-treated bipolar patients. Limitations of the study include small size of the sample, small number of C/C genotype patients, and a lack of multiple testing analysis of genotypic differences in various measures of kidney function.

Novel markers of kidney injury in bipolar patients on long-term lithium treatment.

OBJECTIVES: We assessed kidney function in long-term lithium-treated bipolar patients compared with age-matched patients not taking lithium, including novel markers of kidney injury such as plasma neutrophil gelatinase-associated lipocalin (NGAL) and urinary beta-2 microglobulin (ß2-MG) METHODS: The study comprised 120 patients with bipolar disorder of which 90 (30 males and 60 females) have been receiving lithium for 5-38 (mean 16) years, and 30 (10 males and 20 females) have never been exposed to lithium. RESULTS: Lithium-treated patients, both men and women, showed significantly higher plasma NGAL and urinary ß2-MG and lower urine specific gravity and estimated glomerular filtration rate (eGFR), compared with patients not taking lithium. In these patients, serum NGAL did not correlate with any clinical feature or other parameter of kidney function. Urinary ß2-MG correlated with serum creatinine and eGFR in the whole group of lithium-treated patients and in addition, in males, with duration of illness, duration of lithium treatment, and urine specific gravity. CONCLUSIONS: Lithium treatment causes an impairment of kidney function reflected also by abnormal levels of novel markers of kidney injury. Of these, urinary ß2-MG, as a marker of tubular function seems to be better predictor than serum NGAL in lithium-treated patients because it shows multiple clinical and biochemical correlations, especially in men.

[The effect of long-term lithium treatment on kidney function]. / Wplyw dlugotrwalego podawania litu na czynnosc nerek.

In 1963 it was first demonstrated that long-term lithium administration exerts a "mood-stabilising" effect, preventing recurrences of mania and depression in bipolar affective disorder. Despite the introduction of many other drugs having mood-stabilising effect, lithium still remains the first choice drug for the prophylaxis of affective episodes in mood disorder. Lithium is eliminated nearly exclusively by the kidneys: lithium clearance is proportional to creatinine clearance and is influenced by natriuretic and antinatriuretic factors. Nowadays, nearly 40-year experience with long-term lithium treatment point to a possibility of nephrotoxic effects of this ion. Impaired urinary concentrating ability, which, in a few patients can reach an intensity of diabetes insipidus, can occur after several weeks of lithium administration. Favourable results in the treatment of diabetes insipidus have been obtained with amiloride, the drug which block epithelial sodium channel. However, after 10-20 years of treatment, lithium-induced interstitial nephropathy may be demonstrated in some patients, which, in small proportion of the latter may lead to end-stage renal disease. Lithium-induced hipercalcemia and nephrotic syndrome are rare complications of lithium therapy. In patients on long-term lithium therapy periodic monitoring of kidney function by measuring serum creatinine concentration and glomerular filtration rate is necessary. In case of detecting nephropathy, a discontinuation of lithium sho uld be considered. The patient in whom lithium was discontinued due to nephropathy should remain in nephrological treatment.

Screening for the markers of kidney damage in men and women on long-term lithium treatment.

BACKGROUND: Lithium is the most effective therapeutic modality for the prevention of recurrences in bipolar disorder. An important adverse effect of lithium, especially with long-term treatment, is a possibility of a toxic effect on kidney function. Therefore, the aim of the study was to assess kidney function in a group of long-term lithium-treated patients. MATERIAL/METHODS: The study comprised 80 patients with bipolar mood disorder (26 male, 54 female), aged 60 ± 11 years. They had been receiving lithium for 5-38 (16 ± 9) years. Random urine sample was examined for albumin and creatinine excretion, and urinary albumin to creatinine ratio (UACR) was calculated. Specific gravity of the urine sample was recorded. Serum concentration of creatinine was measured and estimated glomerular filtration rate (eGFR) was calculated. Serum concentration of albumin was also measured. RESULTS: Decreased eGFR values <60 ml/min/1.73 m² were found in 23% of patients, significantly more frequently in men that in women (38% vs. 16%, p=0.04). Elevated UACR values (>30 mg/g) were found in 25% of men and 12% of women, respectively. Serum albumin concentration >52 g/l was detected in 19% of patients (17% of men and 20% of women). Specific gravity of the urine, equal to or below 1.005, was recorded in 21% of men and 14% of women. CONCLUSIONS: The results confirm the opinion that screening for the markers of kidney damage should be performed in long-term lithium-treated patients for identification of persons with impaired kidney function. Male sex seems to be the risk factor for the development of kidney damage during long-term lithium treatment.

[Long-term mood assessment in bipolar affective disorder]. / Dlugoterminowa ocena nastroju w chorobie afektywnej dwubiegunowej.

Long-term mood instability and fluctuations in mood are quintessential features of bipolar disorder; however a great majority of of mood rating scales are cross-sectional and focused on acute symptoms. NIMH Life Chart Methodology (NIMH-LCM) and ChronoRecord program on the contrary record the severity, duration and frequency of mood swings. Many bipolar patients need combined treatment and take multiple medications, which is associated with better treatment outcome but also with the increased risk of side effects. Treatment with drug combination negatively impacts the compliance of the patients. Simultaneous assessment of daily mood fluctuations and monitoring of life events and medications may help to optimize treatment and to better detect nuances of partial response. TacyJakJa.pl an Internet site, in which patients keep on-line diaries concerning their course of disease and treatment, makes this tool available to a large number of patients. Not only does it enable the patients to learn about mood disorders, but also it increases their involvement in their treatment.