Genes involved in glucocorticoid receptor signalling affect susceptibility to mood disorders.

OBJECTIVES: In mood disorders chronic stress contributes to decreased glucocorticoid receptor signalling in the brain and resistance in the periphery. We hypothesised that aberrant glucocorticoid receptor function may result from genetic predisposition and that decreased GR signalling in the brain correlates with the expression of genes regulating GR complex formation. METHODS: We performed the association analysis of 698 patients: 490 patients with bipolar disorder and 208 patients with major depressive disorder and 564 control subjects. We genotyped 11 variants using TaqMan assays. Gene expression in the brain tissue was done in male Wistar rats after chronic mild stress protocol. The SRSF5 serum concentration was performed using ELISA. Data were analysed in Statistica and GraphPad. RESULTS: We found an association of STIP1 and SRSF5 variants with major depressive disorder and BAG1 variant with bipolar disorder. Gene expression analysis in a rat model of depression confirmed significant changes in the expression of SRSF5, BAG1, and FKBP4 in the brain. For SRSF5, we observed significantly increased expression in the serum of depressed females and male rats exposed to chronic stress. CONCLUSIONS: Our results indicate the involvement of genes associated with GR function, SRSF5, BAG1, and FKBP4 with susceptibility to mood disorders.

Verbal fluency in research conducted with PET technique under conditions of extended cognitive activation with the use of 18F-fluorodeoxyglucose (FDG) tracer. / Fluencja slowna w badaniach technika PET w warunkach przedluzonej aktywizacji poznawczej z zastosowaniem znacznika 18F-fluorodeoksyglukozy (FDG).

OBJECTIVES: Functional neuroimaging of the brain is a widely used method to study cognitive functions. The aim of this study was to compare the activity of the brain during performance of the tasks of phonemic and semantic fluency with the paced-overt technique in terms of prolonged activation of the brain. METHODS: The study included 17 patients aged 20-40 years who were treated in the past for Hodgkin'slymphoma, now in remission. Due to the type of task, the subjectswere divided into two groups. Nine people performed the phonemic fluency task, and eight semantic. Due to the disease, all subjects were subject to neuropsychological diagnosis. The diagnosis of any cognitive impairment was an exclusion criterion. Neuroimaging was performed using PET technique with 18F-fluorodeoxyglucose (FDG) tracer. RESULTS: Performance of a verbal fluency test, regardless of the version of the task, was associated with greater activity of the left hemisphere of the brain. The most involved areas compared with other areas of key importance for the performance of verbal fluency tasks were frontal lobes. An increased activity of parietal structures was also shown. CONCLUSIONS: The study did not reveal differences in brain activity depending on the type of task. Performing the test in both phonemic and semantic form for a long time, in terms of increased cognitive control resulting from the test procedure, could result in significant advantage of prefrontal lobe activityin both types of tasks and made it impossible to observe the processes specific to each of them.

A systemic literature review of neuroimaging studies in women with breast cancer treated with adjuvant chemotherapy.

Chemotherapy-induced cognitive deficits in patients with breast cancer, predominantly in attention and verbal memory, have been observed in numerous studies. These neuropsychological findings are corroborated by the results of neuroimaging studies. The aim of this paper was to survey the reports on cerebral structural and functional alterations in women with breast cancer treated with chemotherapy (CTx). First, we discuss the host-related and disease-related mechanisms underlying cognitive impairment after CTx. We point out the direct and indirect neurotoxic effect of cytostatics, which may cause: a damage to neurons or glial cells, changes in neurotransmitter levels, deregulation of the immune system and/or cytokine release. Second, we focus on the results of neuroimaging studies on brain structure and function that revealed decreased: density of grey matter, integrity of white matter and volume of multiple brain regions, as well as their lower activation during cognitive task performance. Finally, we concentrate on compensatory mechanisms, which activate additional brain areas or neural connection to reach the premorbid cognitive efficiency.

Verbal fluency in breast cancer patients treated with chemotherapy.

BACKGROUND: Cognitive decline caused by chemotherapy used in the treatment of malignant diseases was reported in several studies. ICCTF recommends the diagnosis of cognitive function in patient treated with chemotherapy. One of the suggested method is Verbal Fluency Test (VFT). METHODS: Study was carried out on a group of 30 women with early breast cancer treated with adjuvant chemotherapy and 29 healthy controls. The patients underwent neuropsychological assessment using VFT at three time points: T1: before chemotherapy, T2: mid-chemotherapy and T3: post-chemotherapy. The examination in healthy controls was conducted at the same time intervals. RESULTS: In phonetic fluency task patients produced more words at T2 compared to T1 (Z = 2.02; p < 0.05) and at T3 compared to T1, both patients (Z = 2.36; p < 0.05) and controls (Z = 2.57; p < 0.01). The patients scored lower than controls (Z = -2.04; p < 0.05) as well as on average cluster size in the same task (Z = -2.38; p < 0.05) at T3, while they scored higher on the number of phonetic switches at T2 compared to T1 (Z = 2.62; p < 0.01) and at T3 compared to T1 (Z = 2.50; p < 0.01). In semantic task controls produced more words at T3 than at T1 (Z = 2.62; p < 0.01) and at T3 compared to T2 (Z = 2.89; p < 0.01) and semantic clusters at T3 compared to T2 (Z = 2.43; p < 0.05). In patients, number of clusters was smaller at T3 compared to T2 (Z = -2.85; p < 0.05), while number of semantic switches was higher at T3 than at T2 (Z = 3.05; p < 0.01). Patients scored also lower than controls on number of semantic switches at T2 (Z = -2.05; p < 0.05). CONCLUSIONS: Chemotherapy does not decrease verbal fluency, but it has a negative impact on semantic memory.

Suicide behavior as a quantitative trait and its genetic background.

INTRODUCTION: Studies have not given yet a clear answer what is the genetic background of suicidal predisposition. The associations between polymorphisms of the TPH1 and 5-HTTLPR genes and violent suicidal behavior was revealed with the least inconsistencies. METHOD: We selected 10 "strong candidate genes" and 35 SNPs, SLC6A4 and ACP1 for replication study. We searched associations between precisely described suicidal phenotype in 825 affective patients and polymorphisms of selected neurobiological pathways genes as well as their interactions that constitute suicidal risk. RESULTS: The results confirm the role of TPH1, TPH2, 5HT2A, CRHR1 and ACP1 variants in the risk of suicidal behavior. LIMITATIONS: In our study we analyzed limited number of candidate genes and only one of them is linked to lithium mechanism of action. We had no data on pharmacological treatment of investigated patients and its relation to the time of suicide attempt. CONCLUSION: Our results indicate that polymorphisms of various signaling pathways are involved in the pathogenesis of suicidal behavior. Non-genetic factors are also involved in the risk of suicidal attempts.

A Lack of Correlation between Brain-Derived Neurotrophic Factor Serum Level and Verbal Memory Performance in Healthy Polish Population.

Brain derived neurotrophic factor (BDNF) is considered to be connected with memory and learning through the processes of long term synaptic potentiation and synaptic plasticity. The aim of the study was to examine the relationship between precursor BDNF (proBNDF) and mature BDNF (mBDNF) serum levels and performance on Rey Auditory-Verbal Learning Test (RAVLT) in 150 healthy volunteers. In addition, we have verified the relationships between serum concentration of both forms of BDNF and RAVLT with sociodemographic and lifestyle factors.We found no strong evidence for the correlation of proBDNF and mBDNF serum levels with performance on RAVLT in healthy Polish population in early and middle adulthood. We observed the mBDNF serum concentration to be higher in women compared with men. Moreover, we revealed higher mBDNF level to be connected with lower body mass index (BMI). In turn, the results of RAVLT correlated with sociodemographic and lifestyle factors, such as: age, education, gender, BMI and smoking.

BDNF gene polymorphisms and haplotypes in relation to cognitive performance in Polish healthy subjects.

The brain derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in the cell survival, axonal and dendritic growth, and synaptic plasticity. BDNF gene polymorphisms, 'functional Val66Met mainly, were shown to influence human brain structure and cognition. The aim of the study was to assess the relationship between twelve BDNF gene variants and their haplotypes and cognitive performance measured using the Wisconsin Card Sorting Test (WCST), the Trail Making Test (TMT), the Stroop Test which are to a large extent connected with prefrontal cortex activity. Our sample consisted of 460 healthy participants from Polish population. We detected possible association between five BDNF polymorphisms (rs11030101, rs10835210, rs2049046, rs2030324, rs2883187) and TMT_A. Additionally, one haplotype block made from eleven BDNF variants (rs2883187, rs1401635, rs2049046, rs2030324, rs11030101, rs10835210, rs1013402, rs1401635, rs1013402), as significant linkage disequilibrium appeared. We discovered possible relationships of CACCGCGTACG and CACCGCGTACG haplotypes with TMT_A and TMT_B performance respectively. Our results confirmed the involvement of BDNF in the regulation of psychomotor speed, working memory and executive function in healthy subjects measured by a task engaging visuoperceptual abilities.

Chronotype and sleep quality as a subphenotype in association studies of clock genes in mood disorders.

Genetic background and clinical picture of mood disorders (MD) are complex and may depend on many genes and their potential interactions as well as environmental factors. Therefore, clinical variations, or endophenotypes, were suggested for association studies. The aim of the study was to investigate association between the chronotype (CH) and quality of sleep characteristics with polymorphisms CLOCK, ARNTL, TIMELESS and PER3 genes in MD. We included a total sample of 111 inpatients and 126 healthy controls. To assess CH we applied Morningness-Eveningness Questionnaire (MEQ). Additionally, we defined the quality and patterns of sleep using The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). We applied Kruskal-Wallis test to determine associations. The main positive findings refer to associations between selected polymorphisms and: 1) chronotype with the ARNTL gene (rs11824092 and rs1481892) and the CLOCK (rs1268271) 2) sleep duration with the CLOCK gene (rs3805148) and the TIM gene (rs2291739) 3) daytime dysfunction with the PER3 gene (rs228727, rs228642, rs10864315) 4) subjective sleep quality with the ARNTL gene (rs11824092, rs1982350) 5) sleep disturbances with the ARNTL gene (rs11600996) We also found the significant epistatic interactions between polymorphism of the PER3 gene (rs2640909) & the CLOCK gene (rs11932595) and following sleep quality variables: sleep duration, habitual sleep efficiency and subjective sleep quality. The present study suggests a putative role of the analyzed clock genes polymorphisms in chronotype in the control group and in sleep quality disturbances in the course of MD. The results indicate that PSQI variables can be used to refine phenotype in association studies of clock genes in MD.

Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population.

Schizophrenia has been associated with a large range of autoimmune diseases, with a history of any autoimmune disease being associated with a 45% increase in risk for the illness. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. In particular, increases or imbalance in cytokine before birth or during the early stages of life may affect neurodevelopment and produce vulnerability to the disease. A total of 27 polymorphisms of IL1N gene: rs1800587, rs17561; IL1B gene: rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627; IL1RN gene: rs419598, rs315952, rs9005, rs4251961; IL6 gene: rs1800795, rs1800797; IL6R gene: rs4537545, rs4845617, rs2228145, IL10 gene: rs1800896, rs1800871, rs1800872, rs1800890, rs6676671; IL10RA gene: rs2229113, rs3135932; TGF1B gene: rs1800469, rs1800470; each selected on the basis of molecular evidence for functionality, were investigated in this study. Analysis was performed on a group of 621 patients with diagnosis of schizophrenia and 531 healthy controls in Polish population. An association of rs4848306 in IL1B gene, rs4251961 in IL1RN gene, rs2228145 and rs4537545 in IL6R with schizophrenia have been observed. rs6676671 in IL10 was associated with early age of onset. Strong linkage disequilibrium was observed between analyzed polymorphisms in each gene, except of IL10RA. We observed that haplotypes composed of rs4537545 and rs2228145 in IL6R gene were associated with schizophrenia. Analyses with family history of schizophrenia, other psychiatric disorders and alcohol abuse/dependence did not show any positive findings. Further studies on larger groups along with correlation with circulating protein levels are needed.

Suicidal behavior in the context of disrupted rhythmicity in bipolar disorder--data from an association study of suicide attempts with clock genes.

Suicidal behavior exhibits both circadian and annual rhythms. We were seeking an association between selected candidate clock genes and suicidal behavior in bipolar patients. The study included 441 bipolar patients and 422 controls and we genotyped 41 SNPs of the CLOCK, ARNTL, TIMELESS, PER3 genes. The main positive findings built up associations between selected polymorphisms and.

Clock gene variants differentiate mood disorders.

Genetic variations in clock-related genes were hypothesized to be involved to in the susceptibility of mood disorders MD (both unipolar (UPD) and bipolar (BPD) disorders). In our work we investigated role of gene variants form four core period proteins: CLOCK, ARNTL, TIM and PER3. The total sample comprised from 744 mood disorders inpatients (UPD = 229, BPD = 515) and 635 healthy voluntary controls. The 42 SNPs from four genes of interest were genotyped. We used single polymorphisms, haplotypes, SNPs interactions and prediction analysis using classical statistical and machine learning methods. We observed association between two polymorphisms of CLOCK (rs1801260 and rs11932595) with BPDII and two polymorphisms of TIM (rs2291739, rs11171856) with UPD. We also detected ARNTL haplotype variant (rs1160996C/rs11022779G/rs1122780T) to be associated with increased risk of MD, BPD (both types). We established significant epistatic interaction between PER3 (rs2172563) and ARNTL (rs4146388 and rs7107287) in case of BPD. Additionally relation between PER3 (rs2172563) and CLOCK (rs1268271 and rs3805148) appeared in case of UPD. Classification and Regression Trees (C and RT) showed significant predictive value for 10 polymorphisms in all analyzed genes. However we failed to obtain model with sufficient predictive power. During analyses of sleep disturbances sample, we found carriers of homozygote variants (ARNTL: rs11022778 TT, rs1562438 TT, rs1982350 AA and PER3: rs836755 CC) showing more frequent falling asleep difficulties when compare to other genotypes carriers. Our study suggested a putative role of the CLOCK, TIM, ARNTL and PER3 and polymorphisms in MD susceptibility. In our analyses we showed association of specific gene variants with particular types of MD. We also confirmed necessity of performing separate analyzes for BPD and UPD patients. Comprehensive statistical approach is required even with individual symptoms analyses.

FKBP5 polymorphism is associated with major depression but not with bipolar disorder.

BACKGROUND: Altered activity of hypothalamus-pituitary-adrenal glands (HPA) axis in response to stress underlies the pathogenesis of mood disorders such as depression and bipolar disorder. Chaperone proteins regulate sensitivity of glucocorticoid receptor (GR) to steroids. We hypothesized that genetic variants within the FKBP5 - gene encoding co-chaperone protein essential in GR signaling - may influence the susceptibility to major depressive disorder and bipolar disorder. METHODS: In the study participated 528 bipolar patients, 218 patients with major depressive disorder and 742 subjects from control group. Genotypes for eight FKBP5 polymorphisms (rs1360780, rs755658, rs9470080, rs4713916, rs7748266, rs9296158, rs9394309, rs3800373) were established by TagMan SNP Genotyping Assays (Applied Biosystems). Linkage disequilibrium analysis for FKBP5 gene was done in Haploview. Gene-gene interactions between FKBP5 and NR3C1 polymorphisms (reported previously) were analyzed using the multidimensionality-reduction method (MDR). RESULTS: We have observed an association between five FKBP5 polymorphisms (rs1360780, rs9470080, rs4713916, rs9296158 and rs9394309) and major depressive disorder (p=0.011; p=0.007, p=0.038; p=0.030; p=0.018, respectively), but not bipolar disorder. In linkage disequilibrium analysis we found that seven FKBP5 polymorphisms build haplotype block (rs3800373, rs755658, rs9296158, rs7748266, rs1360780, rs9394309, rs9470080, respectively). We observed that two haplotype combinations (ACATTGT and CCACTAT) were significantly more frequent in the MDD patients than in controls (p=0.014 and p=0.043). We have not observed such an association for BD patients. We have found that interaction between rs9470080 of FKBP5 and rs6198 of NR3C1 influences MDD risk. LIMITATIONS: The main limitations of this study include low power and limited sample size of MDD patients. CONCLUSIONS: Single markers and haplotypes of FKBP5 gene and the interaction with glucocorticoid receptor gene (NR3C1) may influence MDD predisposition.

Epistatic interaction between CRHR1 and AVPR1b variants as a predictor of major depressive disorder.

OBJECTIVE: Genes involved in the regulation of the hypothalamus-pituitary-adrenal axis are responsible for altered susceptibility to mood disorders. The aim of this study was to analyze the possible association of CRHR1 and AVPR1b gene variants with bipolar disorder and major depressive disorder (MDD). METHODS: In the study, we included 486 patients with bipolar disorder and 215 patients with MDD. Consensus diagnosis was made according to Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria, using the Structured Clinical Interview for DSM Disorders. The control group consisted of 712 healthy participants. Genotyping of CRHR1 and AVPR1b polymorphisms was performed using TaqMan single nucleotide polymorphism genotyping assays. Linkage disequilibrium analysis was carried out on Haploview. Gene-gene interactions were analyzed using the multifactor dimensionality reduction method. RESULTS: By single marker analysis we have found an association of rs28536160 of AVPR1b and rs4076452 and rs16940655 of CRHR1 with mood disorders (P=0.036, 0.0013, and 0.003, respectively). We observed strong linkage disequilibrium between seven CRHR1 polymorphisms grouped in two haplotype blocks; however, none of them showed an association with MDD or bipolar disorder. Similarly, no association was found for three of four strongly linked AVPR1b polymorphisms. Gene-gene interaction analysis revealed a significant epistatic interaction between AVPR1b and CRHR1 genes in susceptibility to MDD (P=0.017). CONCLUSION: Polymorphisms of CRHR1 and AVPR1b may modify susceptibility to mood disorders.

[The assessment of metabolism of bone tissue as changes in concentration of biochemical markers of bone turnover in inpatient alcohol dependent women]. / Ocena metabolizmu tkanki kostnej u kobiet uzaleznionych od alkoholu z zastosowaniem markerów obrotu kostnego - osteokalcyny i ctx.

AIM: The aim of this study was the assessment to of metabolism of bone tissue as changes in concentration of biochemical markers of bone turnover in inpatient alcohol dependent women. METHODS: The studied group consisted of 50 alcohol dependent female patients who were divided in two groups: one with an activity ofAST or ALT above referential values and level of bilirubin and the second one with the activity oftransaminases and level ofbilirubin within referential values. The level of sex hormones and markers of bone turnover such as osteocalcin and collagen cross laps (ctx) were indicated. RESULTS: In the group with an AST, ALT or BIL above referential values, the concentration of FSH in the ovulation phase and luteal phase as well as LH in luteal phase was significantly higher, while ctx and osteocalcin was lower compared to the group with AST, ALT or BIL within referential values. The mean concentrations ofFSH in follicular phase and luteal phase as well as LH in the luteal phase and progesterone in the follicular phase were increased in the group of patients with AST, ALT or BIL above referential values. The positive correlation between levels ofctx and osteocalcin was found which suggests a balance between processes. of bone formation and bone resorption in the whole group while a lack of such correlation was observed in patients with AST, ALT or BIL above referential values. CONCLUSIONS: The results obtained indicate the multidirectional and mutual relations between the alcohol abuse, liver function, bone turnover and activity of endocrine system.

[Prospective memory - concepts, methods of assessment, neuroanatomical bases and its deficits in mental disorders]. / Pamiec prospektywna - pojecia, metody badania, podloze neuroanatomiczne oraz jej deficyty w chorobach psychicznych.

In the last two decades of the last century there has been a shift in the studies on memory. In psychology of memory the criticism of the laboratory approach resulted in development of the ecological approach. One of the effects of this change was to initiate researches on memory that includes plans for the future, which has resulted in the distinction of the concept of prospective memory. Prospective memory is used in many aspects of everyday life. It deals with remembering intentions and plans, it is connected with remembering about specific task or activity in the future. There are three types of PM: event-based prospective memory, time-based prospective memory and activity-based prospective memory. Current research in this field have already established its own paradigm and tools measuring PM and there is still increasing scientific interest in this issue. Prospective memory assessment may be carried out in various ways. Among them, the most frequently used are: a) questionnaires, b) psychological tests, c) experimental procedures. Within the latter, the additional distinction can be introduced for: the experiments conducted under natural conditions and the laboratory procedures. In Polish literature, there are only a few articles on PM. The aim of this work is to review studies on assessment methods of PM. Its neuroanatomical bases and its functioning in different mental disorders are analyzed. The work is aimed to focus clinicians attention on prospective memory as an area which is important for complex diagnosis of cognitive processes.

Glucocorticoid receptor polymorphism is associated with major depression and predominance of depression in the course of bipolar disorder.

BACKGROUND: A strong association has been found between dysregulation of hypothalamic-pituitary-adrenal (HPA) axis and depression and bipolar disorder. Glucocorticoid receptor is one of the involved receptors and its gene has been recognized as a candidate gene for major depressive disorder and bipolar disorder. Therefore, we investigated if polymorphism of the glucocorticoid receptor gene (NR3C1), involved in the regulation of HPA axis, may alter susceptibility as well as the course of major depressive disorder and bipolar disorder. METHODS: In the study we included 514 patients with bipolar disorder and 193 patients with major depressive disorder. Consensus diagnosis by at least two psychiatrists was made, according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) criteria, using SCID (Structured Clinical Interview for DSM Disorders). Control group consisted of 732 healthy subjects. Genotyping for eight NR3C1 polymorphisms was done with use of TaqMan SNP (single nucleotide polymorphism) Genotyping Assays. Linkage disequilibrium analysis was done in Haploview. RESULTS: We have found three polymorphisms (rs6198, rs6191 and rs33388) to be associated with major depressive disorder (MDD) and the same polymorphisms were associated with the predominance of depressive symptoms in the course of bipolar disorder. In linkage disequilibrium analysis we observed two haplotype blocks, however, none of those shows involvement in susceptibility to MDD or bipolar disorder. LIMITATIONS: The main limitation of this study is relatively small sample size of MDD patients group. CONCLUSIONS: Polymorphisms of NR3C1 gene analyzed in this study may modify susceptibility to major depressive disorder and seem to influence the course of bipolar disorder.

Influence of dopaminergic and serotoninergic genes on working memory in healthy subjects.

Working memory is an ability to keep information in short-term memory and manipulate them 'on line'. Working memory is also involved in complex frontal executive functions. The role of dopaminergic system in modulating working memory processes in prefrontal cortex is well established. Also the role of serotoninergic receptors is postulated. The purpose of this study was to assess the association between the polymorphisms of dopaminergic (DRD1, DRD3, DRD4, COMT) and serotoninergic (SERT--serotonin transporter, 5HT2A, 5HT2C) genes' polymorphisms and performance on WCST in 200 volunteers from the Polish population. We found the association between DRD1, DRD4, COMT and SERT genes polymorphisms and the performance on WCST. The results obtained in the study indicate that dopaminergic and serotoninergic genes may play a role in modulating the executive function and working memory processes in healthy subjects. The pattern of this influence may be different in males and females. Moreover, the relationship between the efficacy of prefrontal cognitive function and genes polymorphisms may differ between healthy subjects and schizophrenic patients.

FYN kinase gene: another glutamatergic gene associated with bipolar disorder?

Several genes of the glutamatergic system have been implicated in both schizophrenia and bipolar disorder. The Src family tyrosine kinase FYN plays a key role in the interaction between brain-derived neurotrophic factor and glutamatergic receptor N-methyl-D-aspartate. Although no association between FYN gene polymorphisms and schizophrenia has been demonstrated, in our previous paper we found an association between FYN polymorphisms and cognitive test performance in schizophrenic patients. The aim of this study was to find a possible association of three polymorphisms of the FYN gene with bipolar disorder. We analyzed 425 bipolar patients and 518 control subjects. Genotypes of three analyzed polymorphisms, i.e. rs706895 (-93A/G in the 5'-flanking region), rs6916861 (Ex12+894T/G in the 3'-UTR) and rs3730353 (IVS10+37T/C in intron 10) were established by PCR-RFLP. A significant association was found between rs6916861 T/G and rs3730353 T/C polymorphisms of the FYN gene and bipolar disorder. These results were also significant in the subgroups of bipolar I and early-onset (<18 years) bipolar disorder patients. No association with -93 A/G polymorphism was found. Haplotype analysis revealed that rs6916861 T/G and rs3730353 T/C polymorphisms are in linkage disequilibrium (r(2) = 0.86, D' = 0.93 with 95% CI = 0.9-0.97). The results suggest that the glutamatergic FYN gene may be associated with bipolar disorder, particularly with type I illness and early age of onset.

The modified Color Density Spectral Array--an alternative method for sleep presentation.

The modified Color Density Spectral Array (CDSA) method used for graphical representation of sleep patterns is described in this article. CDSA was presented for the first time in 1987 by M. Salinsky and coauthors. This method was adapted to display frequency course and voltage of EEG signal during sleep. The overnight sleep records of 35 healthy volunteers of both sexes (23 women, 12 men; aged 19-26) were analyzed in order to verify the modification of CDSA method. We propose to use combining the hypnogram and CDSA method significantly increases the informative value of data and results in enhanced quality of sleep analysis.

Association analysis of tyrosine kinase FYN gene polymorphisms in asthmatic children.

BACKGROUND: FYN is nonreceptor tyrosine kinase that represents the earliest detectable signaling response after antigen-activated inflammatory cells. Studies in animal models of allergic asthma have shown that inhibitors of tyrosine kinases exert an anti-inflammatory effect. In the FYN gene, several polymorphisms have been described. There have, however, been no studies analyzing the impact of FYN gene polymorphisms on the course and severity of asthma. The aim of this study was to analyze the possible relationship between three polymorphisms (-93A/G, Intron10+37C/T and Ex12+894T/G) in the FYN gene and asthma. METHODS: We analyzed 120 pediatric asthmatic patients aged from 6 to 18 years. The diagnosis of allergic asthma was based on clinical manifestation, lung function test and positive skin prick tests and/or an increased IgE level. The control group consisted of 187 healthy subjects. The polymorphisms were genotyped with use of the PCR-RFLP method. RESULTS: We observed an association of the -93A/G polymorphism and the presence of asthma (p = 0.014 for genotypes and p = 0.019 for alleles) and in the subgroup of 55 patients with severe asthma (p = 0.042 for genotypes and p = 0.021 for alleles). We also found an association of the Ex12+894T/G polymorphism in the whole group analyzed (p = 0.067 for genotypes and p = 0.024 for alleles), but not in the subgroup with severe asthma. For the Intron10+37T/C polymorphism, we did not find a significant difference between the whole group of asthmatic patients and the control group nor between the subgroup with severe asthma and the control group. In the linkage disequilibrium analysis, we observed a modest linkage between -93A/G and Intron10+37T/C polymorphisms (lod = 18.7, D' = 0.62, 95% CI: 0.51-0.71, r2 = 0.29); however, it was not strong enough to generate any haplotypes. CONCLUSIONS: The results may suggest a relationship between the FYN polymorphisms and allergic asthma.