Venlafaxine and sertraline does not affect the expression of genes regulating stress response in female MDD patients. / Wenlafaksyna i sertralina nie wplywaja na ekspresje genów regulujacych poziom kortyzolu u kobiet chorych na depresje.

OBJECTIVES: The aim of this study was to analyze the expression of 3 genes involved in the regulation of HPA axis: GR, HSP90 and FKBP5, in patients with major depressive disorder (MDD) before antidepressant treatment and after 8 weeks of pharmacotherapy. Additionally, we analyzed the level of glucocorticoid receptor isoforms before and after treatment. METHODS: The study included 30 female patients (aged 18-60 years), with major depres- sive disorder diagnosed on the basis of the Structured Clinical Interview for DSM-IV (SCID). Antidepressant treatment included use of sertraline or venlafaxine. The assessment of patients' mental state (severity of depression) was checked by the Hamilton Depression Rating Scale (HDRS). After 8 weeks of treatment, the same clinical and molecular tests were performed. All of the patients underwent dexamethasone suppression test (DST). MRNA was isolated from the peripheral blood to evaluate the expression of the studied genes using real-time PCR with TaqMan probes. The concentration of GR isoforms (α and ß) in serum was also determined using ELISA. Statistical analysis was performed using Statistica v.12.0 software. RESULTS: The abnormal cortisol level was only seen in 20% of patients. Dysregulation on HPA axis was observed in 10% of patients. We observed significant clinical improvement after 8 weeks of pharmacotherapy in all patients. Almost the whole group of patients (except one patient) showed full remission of symptoms. We observed significant moderate correlation between cortisol level after DST before treatment and after 8 weeks of pharmacotherapy (r2 = 0.44). The results showed no significant difference in the expression of 3 analyzed genes compared before and after 8 weeks of therapy. The results of ELISA showed decreased level of α isoform after pharmacotherapy, independent of drug. CONCLUSIONS: The results showed no significant changes in the expression of genes involved in the stress axis activity during antidepressant therapy.

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.

Can Psychological, Social and Demographical Factors Predict Clinical Characteristics Symptomatology of Bipolar Affective Disorder and Schizophrenia?

Schizophrenia (SCH) is a complex, psychiatric disorder affecting 1 % of population. Its clinical phenotype is heterogeneous with delusions, hallucinations, depression, disorganized behaviour and negative symptoms. Bipolar affective disorder (BD) refers to periodic changes in mood and activity from depression to mania. It affects 0.5-1.5 % of population. Two types of disorder (type I and type II) are distinguished by severity of mania episodes. In our analysis, we aimed to check if clinical and demographical characteristics of the sample are predictors of symptom dimensions occurrence in BD and SCH cases. We included total sample of 443 bipolar and 439 schizophrenia patients. Diagnosis was based on DSM-IV criteria using Structured Clinical Interview for DSM-IV. We applied regression models to analyse associations between clinical and demographical traits from OPCRIT and symptom dimensions. We used previously computed dimensions of schizophrenia and bipolar affective disorder as quantitative traits for regression models. Male gender seemed protective factor for depression dimension in schizophrenia and bipolar disorder sample. Presence of definite psychosocial stressor prior disease seemed risk factor for depressive and suicidal domain in BD and SCH. OPCRIT items describing premorbid functioning seemed related with depression, positive and disorganised dimensions in schizophrenia and psychotic in BD. We proved clinical and demographical characteristics of the sample are predictors of symptom dimensions of schizophrenia and bipolar disorder. We also saw relation between clinical dimensions and course of disorder and impairment during disorder.

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.

Analysis of genetic association and epistasis interactions between circadian clock genes and symptom dimensions of bipolar affective disorder.

Bipolar affective disorder (BD) is a severe psychiatric disorder characterized by periodic changes in mood from depression to mania. Disruptions of biological rhythms increase risk of mood disorders. Because clinical representation of disease is heterogeneous, homogenous sets of patients are suggested to use in the association analyses. In our study, we aimed to apply previously computed structure of bipolar disorder symptom dimension for analyses of genetic association. We based quantitative trait on: main depression, sleep disturbances, appetite disturbances, excitement and psychotic dimensions consisted of OPCRIT checklist items. We genotyped 42 polymorphisms from circadian clock genes: PER3, ARNTL, CLOCK and TIMELSSS from 511 patients BD (n = 292 women and n = 219 men). As quantitative trait we used clinical dimensions, described above. Genetic associations between alleles and quantitative trait were performed using applied regression models applied in PLINK. In addition, we used the Kruskal-Wallis test to look for associations between genotypes and quantitative trait. During second stage of our analyses, we used multidimensional scaling (multifactor dimensionality reduction) for quantitative trait to compute pairwise epistatic interactions between circadian gene variants. We found association between ARNTL variant rs11022778 main depression (p = 0.00047) and appetite disturbances (p = 0.004). In epistatic interaction analyses, we observed two locus interactions between sleep disturbances (p = 0.007; rs11824092 of ARNTL and rs11932595 of CLOCK) as well as interactions of subdimension in main depression and ARNTL variants (p = 0.0011; rs3789327, rs10766075) and appetite disturbances in depression and ARNTL polymorphism (p = 7 × 10(-4); rs11022778, rs156243).

Possible association between haplotypes of the FKBP5 gene and suicidal bipolar disorder, but not with melancholic depression and psychotic features, in the course of bipolar disorder.

We aimed to analyzed the association between polymorphisms of the FKBP5 (FK506 binding protein 5) gene and subtypes of bipolar disorder. In the study, we included 195 bipolar disorder patients with psychotic features, 129 bipolar patients with melancholic depression, and 156 bipolar patients with a history of suicidal attempts. We found weak association between the haplotypes of the FKBP5 gene and bipolar patients with suicidal attempts. We did not find an association between polymorphisms of the FKBP5 gene and bipolar disorder with psychotic features, nor with bipolar disorder with melancholic depression. Limitations of our study are the absence of data about previous trauma exposure and the small sample size of patients, which of course can lead to false-positive results, so further validation and replication of the present findings are still needed.

Association between OPCRIT dimensions and polymorphisms of HPA axis genes in bipolar disorder.

The aim of the study was to investigate the possible association between polymorphisms of HPA axis genes-CRHR1 (corticotrophin-releasing hormone receptor), NR3C1 (glucocorticoid receptor) and AVPR1B (arginine vasopressin receptor) and dimensions of bipolar disorder assessed by OPCRIT. We examined 560 patients with diagnosis of bipolar disorder (n=457) and unipolar disorder (n=103). Diagnosis was established by SCID and OPCRIT. We found association between polymorphisms of AVPR1b gene and psychotic dimension and CRHR1 polymorphisms and excitement and psychotic dimension. Our results suggest possible involvement of the AVPR1b and CRHR1 genes in the ethiology of psychotic features in the course of affective disorders, and possible involvement of CRHR1 gene in the ethiology of bipolar disorder.

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.

Suicide attempts and clinical risk factors in patients with bipolar and unipolar affective disorders.

BACKGROUND: Suicide is an important clinical problem in psychiatric patients. The highest risk of suicide attempts is noted in affective disorders. OBJECTIVE: The aim of the study was to look for suicide risk factors among sociodemographic and clinical factors, family history and stressful life events in patients with diagnosis of unipolar and bipolar affective disorder (597 patients, 563 controls). METHOD: In the study, the Structured Clinical Interview for DSM-IV Axis I Disorders and the Operational Criteria Diagnostic Checklist questionnaires, a questionnaire of family history, and a questionnaire of personality disorders and life events were used. RESULTS: In the bipolar and unipolar affective disorders sample, we observed an association between suicidal attempts and the following: family history of psychiatric disorders, affective disorders and psychoactive substance abuse/dependence; inappropriate guilt in depression; chronic insomnia and early onset of unipolar disorder. The risk of suicide attempt differs in separate age brackets (it is greater in patients under 45 years old). No difference in family history of suicide and suicide attempts; marital status; offspring; living with family; psychotic symptoms and irritability; and coexistence of personality disorder, anxiety disorder or substance abuse/dependence with affective disorder was observed in the groups of patients with and without suicide attempt in lifetime history.

Suicide attempts and psychological risk factors in patients with bipolar and unipolar affective disorder.

Suicide is an important clinical problem in psychiatric patients. The highest risk of suicide attempts is noted in affective disorders. The aim of the study was looking for suicide risk factors among personality dimensions and value system in patients with diagnosis of unipolar and bipolar affective disorder (n=189 patients, n=101 controls). To establish the diagnosis, we used SCID (Structured clinical interview for diagnostic and statistical manual of mental disorders, fourth edition) questionnaire, TCI (Temperament and Character Inventory) questionnaire and Value Survey--to assess the personality. The main limitations of the study are number of participants, lack of data about stressful life events and treatment with lithium. Novelty seeking and harm avoidance dimensions constituted suicide attempt risk factors in the group of patients with affective disorders. Protective role of cooperativeness was discovered. Patients with and without suicide attempt in lifetime history varied in self-esteem position in Value Survey.

No association between polymorphisms and haplotypes of the AVPR1b, CRHR1 and NR3C1 genes and depression with melancholic features in the course of bipolar disorder.

The present study included 130 patients with melancholic depression in the course of bipolar disorder and 732 healthy controls. No association was found for alleles, genotypes, or haplotype analysis for NR3C1, AVPR1b, and CRHR1 genes and melancholic depression.

[No association of glucocorticoid receptor gene polymorphism (rs6190) with unipolar and bipolar disorder]. / Brak zwiazku polimorfizmu (rs6190) genu receptora glikokortykoidowego z choroba afektywna jedno- i dwubiegunowa.

AIM: Functional polymorphism ER22/23EK glucocorticoid receptor leads to reduction of its resistance and to increase in its sensitivity to the glucocorticoid that regulate the functioning of the axis hypothalamus - pituitary - adrenal glands. Disturbances in the regulation of this axis are observed in patients with psychiatric disorders. The aim of this study was to demonstrate the association ER22/23EK polymorphism with bipolar disorder and major depressive disorders. METHODS: In the study 144 patients with unipolar disorders and 479 patients with bipolar disorder were included. Patients were diagnosed by two psychiatrists on the basis of medical records and interview based on SCID criteria (Structured Clinical Interview for DSM Disorders). The control group comprised 595 healthy subjects. As the research material peripheral blood was used, from which DNA was obtained. Genotyping was performed using PCR - RFLP method. RESULTS: No association of ER22/23EK polymorphism with unipolar disorder or with bipolar disorder was found. GA genotype was not observed in any of the subjects. CONCLUSION: ER22/23EK functional polymorphism of the glucocorticoid receptor gene is not associated with unipolar and bipolar disorder.

Association, haplotype, and gene-gene interactions of the HPA axis genes with suicidal behaviour in affective disorders.

Family twin and adoption studies have noted the heritability of specific biological factors that influence suicidal behaviour. Exposure to stress is one of the factors that strongly contribute to suicide attempts. The biological response to stress involves the hypothalamic-pituitary-adrenal axis (HPA). Therefore, we found it interesting to study polymorphisms of genes involved in the HPA axis (CRHR1, NR3C1, and AVPBR1). The study was performed on 597 patients, 225 of whom had a history of suicide attempts. We did not observe any significant differences in the studied polymorphisms between the group of patients with a history of suicide attempts and the control subjects. Our haplotype analysis of the AVPR1b gene revealed an association between the GCA haplotype and suicide attempts; however, this association was not significant after correcting for multiple testing. We did not observe any other association in haplotype and MDR analysis. We report here a comprehensive analysis of the HPA axis genes and a lack of association for genetic variations regarding the risk of suicide attempts in affective disorder patients. Nonetheless, the inconsistencies with the previously published results indicate the importance of the further investigation of these polymorphisms with respect to the risk of suicide attempts.

Analysis of OPCRIT results indicate the presence of a novel 'social functioning' domain and complex structure of other dimensions in the Wielkopolska (Poland) population.

OBJECTIVE: The main goal of our study was to examine factor structure of schizophrenia and bipolar affective disorder in the Wielkopolska population, using dimension reduction techniques. METHODS: Schizophrenia (n=443) and bipolar affective disorder (n=499) patients were assessed using Operational Criteria Checklist (OPCRIT). Principal component analysis and Maximum Likelihood Factor analysis were carried out to obtain factor structure with significance level for the factor loadings exceeding 0.4. Varimax and promax rotations were used to identify the meaningful factors. RESULTS: Rotated solution indicated multidimensional structure for depression and excitement as well as positive domains in the schizophrenia sample. Negative and disorganized dimensions existed as single factors, with item composition similar to that already described. Additionally, a new "social functioning" dimension was identified. In bipolar affective disorder sample, the interpretable dimensions included: depression, psychotic, atypical depression, negative, substance use, excitement and "social functioning". Factor structure of the combined sample consisted of depression, excitement, disorganization, delusions, substance use, negative and social functioning factors. CONCLUSIONS: Our results indicated multidimensional and hierarchical structures for some of the previously described dimensions. Additional use of items not exactly related to disease symptoms lead to discovery of "substance use" and "social functioning" dimensions.

Association between functional polymorphism of the AVPR1b gene and polymorphism rs1293651 of the CRHR1 gene and bipolar disorder with psychotic features.

BACKGROUND: An association between HPA-axis disturbances and susceptibility towards depression with psychotic features has been reported. NR3C1, CRHR1 and AVPR1b are the key components of this system. We investigated the possible involvement of the polymorphisms of those genes with the susceptibility to psychotic features in the course of BP I disorder. METHODS: The study was conducted on 194 patients with psychotic features in the course of BPI. Control group consisted of 732 healthy subjects. Genotyping for NR3C1, AVPR1b and CRHR1 polymorphisms was done with use of TagMan SNP Genotyping Assays. RESULTS: The association of polymorphisms rs28536160 genotype TT of the AVPR1b gene and polymorphisms rs1293651 of CRHR1 gene with psychotic features in the course of BPI. LIMITATIONS: The main limitation of our study is the small sample size of the group of patients with psychotic features. CONCLUSIONS: The results of our study suggest that the studied polymorphisms may increase susceptibility for obtaining psychotic features in the course of BP I.

Clinical and pathogenic aspects of candidate genes for lithium prophylactic efficacy.

A number of candidate genes for lithium prophylactic efficacy have been proposed, some of them being also associated with a predisposition to bipolar illness. The aim of the present study was to investigate a possible association between polymorphisms of 14 common genes with the quality of prophylactic lithium response in patients with bipolar mood disorder, in relation to the putative role of these genes in the pathogenesis of this disorder. Some association with lithium prophylactic efficacy was found for the polymorphisms of 5HTT, DRD1, COMT, BDNF and FYN genes, but not for 5HT2A, 5HT2C, DRD2, DRD3, DRD4, GSK-3, NTRK2, GRIN2B and MMP-9. Possible aspects of these genes with regard to the mechanism of lithium activity and pathogenesis of bipolar mood disorder are discussed.

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.