Prediction of lithium response using clinical data.

OBJECTIVE: Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers. METHOD: Our data are the largest existing sample of direct interview-based clinical data from lithium-treated patients (n = 1266, 34.7% responders), collected across seven sites, internationally. We trained a random forest model to classify LR-as defined by the previously validated Alda scale-against 180 clinical predictors. RESULTS: Under appropriate cross-validation procedures, LR was predictable in the pooled sample with an area under the receiver operating characteristic curve of 0.80 (95% CI 0.78-0.82) and a Cohen kappa of 0.46 (0.4-0.51). The model demonstrated a particularly low false-positive rate (specificity 0.91 [0.88-0.92]). Features related to clinical course and the absence of rapid cycling appeared consistently informative. CONCLUSION: Clinical data can inform out-of-sample LR prediction to a potentially clinically relevant degree. Despite the relevance of clinical course and the absence of rapid cycling, there was substantial between-site heterogeneity with respect to feature importance. Future work must focus on improving classification of true positives, better characterizing between- and within-site heterogeneity, and further testing such models on new external datasets.

Neuroprotective effect of lithium on hippocampal volumes in bipolar disorder independent of long-term treatment response.

BACKGROUND: Neuroimaging studies have demonstrated an association between lithium (Li) treatment and brain structure in human subjects. A crucial unresolved question is whether this association reflects direct neurochemical effects of Li or indirect effects secondary to treatment or prevention of episodes of bipolar disorder (BD). METHOD: To address this knowledge gap, we compared manually traced hippocampal volumes in 37 BD patients with at least 2 years of Li treatment (Li group), 19 BD patients with <3 months of lifetime Li exposure over 2 years ago (non-Li group) and 50 healthy controls. All BD participants were followed prospectively and had at least 10 years of illness and a minimum of five episodes. We established illness course and long-term treatment response to Li using National Institute of Mental Health (NIMH) life charts. RESULTS: The non-Li group had smaller hippocampal volumes than the controls or the Li group (F 2,102 = 4.97, p = 0.009). However, the time spent in a mood episode on the current mood stabilizer was more than three times longer in the Li than in the non-Li group (t(51) = 2.00, p = 0.05). Even Li-treated patients with BD episodes while on Li had hippocampal volumes comparable to healthy controls and significantly larger than non-Li patients (t(43) = 2.62, corrected p = 0.02). CONCLUSIONS: Our findings support the neuroprotective effects of Li. The association between Li treatment and hippocampal volume seems to be independent of long-term treatment response and occurred even in subjects with episodes of BD while on Li. Consequently, these effects of Li on brain structure may generalize to patients with neuropsychiatric illnesses other than BD.

Serum brain-derived neurotrophic factor in euthymic bipolar patients on prophylactic lithium therapy.

AIM: The aim of the study was to evaluate serum brain-derived neurotrophic factor (BDNF) levels in a group of euthymic bipolar patients on long-term prophylactic lithium treatment and to delineate putative relationships between lithium efficacy and BDNF concentrations. METHODS: 141 euthymic bipolar patients (51 male, 90 female) on long-term lithium treatment were studied. Three categories of prophylactic lithium response were delineated: excellent lithium responders (ER; 30 patients), partial lithium responders (PR; 61 patients) and lithium nonresponders (NR; 50 patients). The control group consisted of 75 age- and gender-matched healthy subjects. RESULTS: The lithium-treated patients as a whole group had lower BDNF levels compared to the healthy controls. However, after breaking down the patients into ER, PR and NR, it appeared that only NR had significantly lower BDNF levels compared with the healthy control subjects. No association between the age of the patients, duration of bipolar illness, and serum lithium and BDNF levels was found. CONCLUSION: The results point to a relationship between lithium prophylactic efficacy and plasma BDNF levels in euthymic bipolar patients where lithium NR had reduced BDNF levels. These findings suggest that serum BDNF is associated with lithium efficacy in bipolar disorder.

Diet quality and eating patterns in euthymic bipolar patients.

OBJECTIVE: As mood disorders and obesity are interrelated, and both are linked to increased morbidity and mortality, risk factors for obesity should be identified and closely monitored in patients with bipolar disorder (BD). The aim of this study was to determine the diet quality of BD patients and to investigate its putative associations with comorbid obesity and disorders of carbohydrate metabolism, as well as the relationship between diet and clinical features of BD. PATIENTS AND METHODS: Eating patterns in 113 euthymic BD patients and 160 healthy control subjects were assessed using data obtained from a food frequency questionnaire. Associations of diet quality with subjects' weight, waist circumference (WC), insulin resistance index and clinical features of BD were also analyzed. RESULTS: BD patients had lower Mediterranean Diet Score than controls. Using principal analysis, four dietary patterns were revealed in the BD group (western-type, pro-healthy carbohydrates, unhealthy snacks, and meats and potatoes). Over 70% of patients with BD had Body Mass Index above 25kg/m2. The values of Fasting Triglycerides Glucose Index and WC were significantly higher in BD patients than in the control group. No significant association between diet quality indices and the clinical course of BD was found. CONCLUSIONS: In our work, euthymic bipolar patients showed unhealthy dietary patterns and had lower adherence to the Mediterranean diet than the controls. Increased values of insulin resistance indicators in the BD group point to the necessity of monitoring glucose and triglycerides levels and measurement of waist circumference in bipolar patients in the routine clinical practice. The cooperation between psychiatrists, dieticians and other medical professionals are necessary to develop dietary recommendations for patients with bipolar disorder.

Do antidepressants influence mood patterns? A naturalistic study in bipolar disorder.

This prospective, longitudinal study compared the frequency and pattern of mood changes between outpatients receiving usual care for bipolar disorder who were either taking or not taking antidepressants. One hundred and eighty-two patients with bipolar disorder self-reported mood and psychiatric medications for 4 months using a computerized system (ChronoRecord) and returned 22,626 days of data. One hundred and four patients took antidepressants, 78 did not. Of the antidepressants taken, 95% were selective serotonin or norepinephrine reuptake inhibitors, or second-generation antidepressants. Of the patients taking an antidepressant, 91.3% were concurrently taking a mood stabilizer. The use of antidepressants did not influence the daily rate of switching from depression to mania or the rate of rapid cycling, independent of diagnosis of bipolar I or II. The primary difference in mood pattern was the time spent normal or depressed. Patients taking antidepressants frequently remained in a subsyndromal depression. In this naturalistic study using self-reported data, patients with bipolar disorder who were taking antidepressants--overwhelmingly not tricyclics and with a concurrent mood stabilizer--did not experience an increase in the rate of switches to mania or rapid cycling compared to those not taking antidepressants. Antidepressants had little impact on the mood patterns of bipolar patients taking mood stabilizers.

Health status correlates of malnutrition in the polish elderly population - Results of the Polsenior Study.

OBJECTIVE: The aim of the study was to analyze health-related factors associated with poor nutritional status (PNS) of a representative group of Polish older people, based on data from the PolSenior project (the first nation-wide study of Polish senior citizens). PATIENTS AND METHODS: Nutritional status was assessed in 3751 community-dwelling older people (1770 females, mean age: 77.4±8.0 years) using the Mini Nutritional Assessment - Short Form. Elements of comprehensive geriatric assessment (cognitive and mood screening), selected medical data were analyzed in relation to the nutritional status. These were: the number of medications, the number of chronic diseases, selected diseases potentially related to malnutrition (anaemia, stroke, peptic ulcer, Parkinson's disease, cancer - past or present), total edentulism, use of dentures, and chronic pain. RESULTS: PNS was observed in 44.2% of participants. Female sex [OR 1.72, 95% Cl (1.45-2.04)], advanced age [OR 2.16 (1.80-2.58)], symptoms of depression [OR 11.52 (9.24-14.38)], cognitive impairment [OR 1.52 (1.20-1.93], multimorbidity [OR 1.27 (1.04-1.57)], anaemia [OR 1.80 (1.41-2.29)] and total edentulism [OR 1.26 (1.06-1.49)] were independently correlated with PNS. CONCLUSIONS: PNS in Polish elderly population is strongly related to the occurrence of symptoms of depression. People in advanced age with symptoms of depression, cognitive impairment, multimorbidity, anaemia and total edentulism should be screened and monitored for early symptoms of malnutrition.

Seasonality of food groups and total energy intake: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: The aim of this systematic review and meta-analysis was to assess the effect of season on food intake from selected food groups and on energy intake in adults. SUBJECTS/METHODS: The search process was based on selecting publications listed in the following: Medline, Scopus, Web of Science, Embase and Agris. Food frequency questionnaires, 24-h dietary recalls and food records as methods for assessment of dietary intake were used to assess changes in the consumption of 11 food groups and of energy intake across seasons. A meta-analysis was performed. RESULTS: Twenty-six studies were included. Articles were divided into those reporting data on four seasons (winter, spring, summer and autumn) or on two seasons (pre-and post-harvest). Four of the studies could be utilized for meta-analysis describing changes in food consumption across four season scheme: from winter to spring fruits decreased, whereas vegetables, eggs and alcoholic beverages increased; from spring to summer vegetable consumption further increased and cereals decreased; from summer to autumn fruits and cereals increased and vegetables, meat, eggs and alcoholic beverages decreased; from autumn to winter cereals decreased. A significant association was also found between energy intake and season, for 13 studies reporting energy intake across four seasons (favors winter) and for eight studies across pre- and post-harvest seasons (favors post-harvest). CONCLUSIONS: The winter or the post-harvest season is associated with increased energy intake. The intake of fruits, vegetables, eggs, meat, cereals and alcoholic beverages is following a seasonal consumption pattern and at least for these foods season is determinant of intake.

Psychosocial functioning in relation to symptomatic remission: A longitudinal study of first episode schizophrenia.

OBJECTIVES: The aims of the study were: (1) to evaluate longitudinally symptomatic remission in first-episode (FE) schizophrenia, (2) to describe symptoms, social functioning and quality of life (Qol) in relation to remission status, and (3) to determine the long-term outcome of schizophrenia and its early predictors. METHODS: Sixty-four patients were assessed 1 month after a first hospitalization (T1), 12 months (T2), 4-6 years (T3), and 7-11 years (T4) after T1. The patients were allocated to three remission groups according to their remission status over the whole observation period, e.g. stable remission (SR), unstable remission (UR) and non-remission (NR). The PANSS, Social Functioning Scale and WHOQoL were used to evaluate the patients' psychosocial functioning levels, symptomatic and functional remissions and satisfying QoL. A good outcome was defined as meeting, simultaneously, the criteria of symptomatic and functional remissions and satisfying QoL at T4, while failure to meet all of these criteria was defined as a poor outcome. RESULTS: Among them, 17.2% patients were in stable remission, 57.8% in unstable remission and 25.0% were unremitted at all time points. The SR group had lower levels of psychopathological symptoms and reported better social functioning and QoL than the NR group. During the follow-up, the symptoms increased, social functioning slightly improved and QoL did not change. At T4, 53% of the sample had a poor outcome, which was independently predicted by the longer duration of untreated psychosis and a lack of satisfying QoL at T1. CONCLUSIONS: Our results demonstrate that: (1) the long-term course in schizophrenia is heterogeneous and that three illness trajectories exist, (2) social functioning and QoL are only partially connected with symptomatic remission (3), the risk of a poor outcome may potentially be reduced by appropriate interventions at an early stage of the illness.

Factors contributing to cognitive deficits in elderly residents of rural areas.

OBJECTIVE: Due to the growing aging of societies an increasingly large group of people suffers from age-related impairment of cognitive functions and thus reducing the quality of life of the elderly. The purpose of the study was to evaluate the efficiency of cognitive functions in a group of aging residents of rural areas. PATIENTS AND METHODS: The inhabitants of a rural area were recruited and assessed: cognitive function as well as intellectual and physical activity, number of years of education, presence of diseases, using stimulants, diet, sources of living, marital status and family situation Subjects were divided into two groups: persons above 65 and older, constituting the studied group and persons between 40 and 64 years of age, constituting the control group. Both groups did not significantly differ in terms of sex or years of education. RESULTS: Statistically significant differences (p < 0.05) were found in the results of the tests concerning such functions as the sight recognition memory and spatial recognition memory, spatial operating memory both on the strategy level and on the level of committed errors. An analysis of the results obtained in the group of elderly people did not indicate any major differences between men and women as regards the analyzed cognitive functions, no statistically significant differences were found in cognitive testing depending on the number of years of education. The studied persons included in the physically active group scored better in the visual memory and learning tests. CONCLUSIONS: The conducted studies elucidated the dependence of the level of cognitive functions on age, a positive impact of physical activity on some cognitive functions, however we could not find differences between the efficiency of those functions and education, sex, presence of somatic diseases and activity of persons aged > 65.

[Biological mechanisms of drug-resistant depression]. / Biologiczne mechanizmy lekoopornosci depresji.

The authors review recent findings concerning biological mechanisms of drug-resistant depression. Treatment-resistant depression may result from the inability of antidepressants to normalize serotonergic transmission. Efficacy of therapeutic strategies enhancing serotonergic function such as potentiation of tricyclic antidepressants with lithium or fluoxetine as well as effectiveness of selective serotonin reuptake inhibitors in drug-resistant depression may support this hypothesis. Limbic-hypothalamic-pituitary-adrenal axis hyperactivity may be also an important factor of the persistence of depression, and so treatment with inhibitors of steroid biosynthesis may bring about readjustment of this axis and remission of depression in some cases of drug-resistant depression with hypercortisolemia. Another subtype of drug-resistant depression may be related to a dysfunction of hypothyroidism. Some evidence suggests also a relationship between drug resistance in depression and changes in the immune system. Research on biological mechanisms of drug-resistant depression may help clinicians to decide on the most appropriate treatment strategy in resistant depression as well as to shed light on the pathomechanism of depression.

[The influence of mood-normalizing agents on cognitive functions]. / Wplyw leków normotymicznych na czynnosci poznawcze.

The influence of lithium, carbamazepine or valproate treatment on the cognitive functions is presented.

[Psychiatric disorders in thyroid and adrenal gland diseases]. / Zaburzenia psychiczne w chorobach tarczycy i nadnerczy.

Clinical picture of psychiatric disturbances occurring in dysfunctions of thyroid or adrenal axes is presented.

[Cognitive deficits in the bipolar affective disorder]. / Zaburzenia czynnosci poznawczych w chorobie afektywnej dwubiegunowej.

Cognitive deficits have been viewed as being characteristic features of schizophrenia. Neuropsychological impairment has been also identified in depression and mania. Recent studies have suggested that patients with bipolar disorder do not make full recovery between episodes of illness and that neuropsychological dysfunction may persist beyond these episodes. Remitted bipolar patients performed worse on Wisconsin Card Sorting Test, Verbal fluency and Stroop Test than healthy controls, the results of the patients with affective disorders with psychotic features were comparable with those of schizophrenics. Some studies suggest an association between the course of illness and the intensity of cognitive deficits, this link was not confirmed in other reports. Imaging studies have shown the presence of white matter lesions and other abnormalities in the brains of bipolar patients. The relative reduction in cerebral tissue may contribute to neuropsychological impairment in subgroup of bipolar patients. Results of studies on the role of white matter lesions are inconsistent. Recent studies point to an association between decreased prefrontal cortex volume and cognitive disturbances. Attention is focused on hippocampus volume as well, since it is associated with cognitive deficits in bipolar disorder. Further studies are needed to elucidate whether a severe course of illness is associated with more pronounced cognitive disorders and whether presence of psychotic symptoms during the acute phase of the illness is a predictor of the occurrence of cognitive deficits in patients with bipolar affective disorder.

[Usefulness of Widlöcher scale in assessment of psychomotor activity disorders in endogenous depression]. / Przydatnosc skali Widlöchera dla oceny zaburzen aktywnosci psychoruchowej w depresjach endogennych.

A group of 50 patients with a diagnosis of affective disease was examined. Dependence between the intensification of depression psychomotor activity measured according to Widlöcher scale was established. Neurophysiological factors (such as thinking productivity, letter drafting, tapping test, simple reaction time) correlated with the intensification of psychomotor activation disorders.

Eating patterns are associated with cognitive function in the elderly at risk of metabolic syndrome from rural areas.

OBJECTIVE: The Mediterranean diet (MedDiet) represents a promising approach in the prevention of cognitive decline, but the evidence for such beneficial effect, especially among elderly populations in non-Mediterranean regions, is at present inconsistent. This study investigated the relationship between adherence to MedDiet and cognitive function (CF), along with selected sociodemographic (SD) and clinical indices, in Polish elderly people > 60 years of age, with high risk of metabolic syndrome (MS), living in rural area. SUBJECTS AND METHODS: Complete SD and lifestyle information was collected. The dietary outcome was recorded as a MedDiet score with the frequencies of consumption of the main food groups in the a MedDiet pyramid. Parameters identifying MS and body weight status were determined, and 11 psychological test results were examined in four domains: visual memory, executive function, attention, and global cognition. RESULTS: The lower MedDiet score was more often connected with living without children and with CF impairment. The MedDiet score was linked with global cognition; frequency of consumption of vegetable, fish, olive and rapeseed oil with visual memory, attention, executive function respectively. The consumption of full-fat dairy products and red meat and meat products was negatively related to executive and global CF. Also, insufficient physical activity, low educational status, female gender, living without children, and the existence of MS were factors of risk of CF impairment. CONCLUSIONS: Greater adherence to MedDiet and frequency of consumption of some foods were associated with better scores in several CF tests in elderly individuals with high risk of MS living in a rural community. However, lifestyle, clinical, and SD factors should also be considered.

Obesity itself does not influence BDNF serum levels in adults.

OBJECTIVE: In European countries more than 50% of the population are overweight, 30% with obesity. In Poland overweight was present in 41% of men and 28.7% of women (obesity 15.7% and 19.9%). It was examined whether obesity affects serum levels of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6), which may lead to the consequences of obesity, such as type 2 diabetes, hypertension, and finally the metabolic syndrome. We aimed to examine whether obesity affects the serum levels of BDNF and IL-6. PATIENTS AND METHODS: The study involved 144 people aged 45 to 86 years, 80 subjects with diagnosed obesity and 64 with normal body weight, ≤ 65 years old (n = 45) and > 65 years old (n = 99). All patients underwent tests of glucose, total cholesterol, HDL, LDL, triglycerides levels, using routine laboratory methods. A test of the concentration of IL-6 and BDNF was carried out. The declared level of physical activity (gymnastics, cycling or walking) was considered. RESULTS: It was shown that in women ≤ 65 years old, obesity was associated with higher levels of interleukin-6. When the test group, divided into the above categories, was analyzed for the diagnosis of hypertension, heart failure or diabetes mellitus, no statistically significant differences in the investigated parameters were detected. The concentration of brain-derived neurotrophic factor did not differ in the investigated subjects, regardless of sex, age, obesity, or the declared physical activity. CONCLUSIONS: The concentration of interleukin-6 in younger people, including those with normal body weight, correlated with total cholesterol and triglyceride levels, and it was significantly higher in obese women compared to those with normal body weight.

Association of cognitive performance with the physical activity and body mass index in middle-aged and older rural inhabitants.

OBJECTIVE: Last few decades have witnessed rapid ageing of the population. The prevalence of mild cognitive impairment and dementia is significantly higher in people aged 60 and over than in younger. The aim of the study was the assessment of the putative associations between physical activity and cognitive functioning in elderly inhabitants of a rural area. PATIENTS AND METHODS: The participants underwent physical assessment, physical activity, cognitive functions, depression were assessed. RESULTS: Highly active participants had better results in tests assessing psychomotor speed and in measuring attention and its flexibility comparing to groups of medium and low physical activity. Active people made fewer errors in the test measuring visual memory and new learning, and had significantly better results in the spatial-recognition memory test. Persons with symptoms of depression performed worse in visuospatial memory and working memory tests. Associations between physical activity and cognitive test results as well as association between body mass index and blood pressure and cognitive performance were observed. CONCLUSIONS: The results of the study suggest an association between higher physical activity and better cognitive functioning in the field of working memory and visual and spatial-recognition, attention and attention flexibility. Symptoms of depression, hypertension and increased BMI may adversely affect cognitive performance in elderly.

Dopamine D1 receptor gene polymorphism is associated with prophylactic lithium response in bipolar disorder.

BACKGROUND: Previously, we have found an association between the -48 A/G polymorphism of the dopamine receptor D1 (DRD1) gene and bipolar disorder. The aim of the present study was to investigate a possible association of this polymorphism with the quality of the prophylactic lithium response in bipolar patients. METHODS: Ninety-two patients (39 male, 53 female), aged 30-77 (mean: 54 years) were studied. They have received lithium for prophylactic purposes for 5-27 years (mean: 15 years). Twenty-four patients were identified as excellent lithium responders (ER), 48 patients as partial responders (PR), and 20 patients were non-responders (NR). They all were genotyped for -48 A/G polymorphism of the DRD1 gene. RESULTS: The frequency of G/G genotype in ER, PR, and NR patients was 21%, 48%, and 60%, respectively, and the frequency of G allele was 58%, 76%, and 80%, respectively. DISCUSSION: The results obtained suggest that the higher frequency of G allele, and G/G genotype, which has been associated with a predisposition to bipolar illness, is also connected with a poorer prophylactic effect of lithium.

Quality of life, depressive symptoms and anxiety in hyperthyroid patients.

PURPOSE: The aim of the study was to evaluate quality of life and to assess frequency and severity of depressive and anxiety symptoms in hyperthyroid patients. MATERIAL AND METHODS: Forty-seven hyperthyroid patients (38 female, 9 male, mean age 51.4 +/- 13.0; 25-Graves disease, 22 - nodular goitre) and fifty-eight sex- and age-matched controls (40 female, 18 male, mean age 49.6 +/- 16.0) were studied. Quality of life was assessed by means of WHO QuoL Questionnaire. Psychometric evaluation included assessment of depressive symptoms (Hamilton Depression Rating Scale and Beck Depression Inventory) and anxiety level (State and Trait Anxiety Inventory--STAI). RESULTS: Patients presented significantly decreased perception of quality of life and health state, and scored worse in physical domain and global score of WHO QuoL. Nineteen patients showed depressive symptoms, remaining 28 were euthymic. Level of anxiety did not differ significantly between the patients group and controls. Free thyroxine plasma level correlated with psychological domain of QuoL. Depression severity correlated with anxiety (STAI 2). Anxiety as a state marker influenced psychological and environmental domains and global score of quality of life questionnaire. CONCLUSIONS: The influence of hyperthyroidism on the quality of life was observed. Depressive symptoms are frequent in hyperthyroidism, occurring in 40% hyperthyroid patients. We found also the association between the anxiety level and the quality of life.

Prophylactic lithium response and polymorphism of the brain-derived neurotrophic factor gene.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) has been involved in the pathogenesis of bipolar mood disorder and in the mechanism of mood-normalizing action of lithium. The aim of this study was to find a possible association between lithium prophylactic effect in bipolar patients and two polymorphisms of BDNF gene. METHODS: Eighty-eight patients (35 males, 53 females) with bipolar illness were studied. Duration of lithium prophylaxis ranged between 5-27 years (mean 15 years). Three categories of prophylactic lithium response were delineated: excellent responders (ER), partial responders (PR) and non-responders (NR). All patients were genotyped for two polymorphisms of BDNF gene: Val66Met and -270C/T. RESULTS: The Val/Met genotype of Val66Met polymorphism occurred more frequently (p = 0.037) and there was a trend for a higher incidence of Met allele (p = 0.076), in ER than in NR. A trend for C/T genotype and T allele of -270C/T polymorphism was observed to occur more frequently in ER than in NR (p = 0.057 and p = 0.065, respectively). CONCLUSION: The data obtained suggest that polymorphism of BDNF gene may be connected with a quality of lithium prophylaxis.