[Genetic variations associated with premorbid personality in patients with schizophrenia]. / Geneticheskie polimorfizmy, assotsiirovannye s razlichnoi stepen'iu vyrazhennosti premorbidnykh lichnostnykh anomalii u bol'nykh shizofreniei.

AIM: To search for genetic variants associated with premorbid personality in patients with schizophrenia. MATERIAL AND METHODS: The sample included 272 men diagnosed with schizophrenia or schizoaffective disorder. Patients were divided into 3 groups based on premorbid personality difficulties: mild (group 1, n=110), moderate (group 2, n=113), marked (group 3, n=49). The following polymorphisms were genotyped: 5-HTR2A (T102C), 5-HTTLPR, BDNF (Val66Met), CRP (-717A>G). RESULTS: A significant increase in the frequency of the CC (5-HTR2A T102C), LL (5-HTTLPR) and Met/Met (BDNF Val66Met) genotypes was identified in group 3 compared to group 1. Frequencies of CC and LL genotypes were significantly higher in group 2 compared to group 1 as well. The differences between group 2 and group 3 were found only for the Met/Met genotype. There were no between-group differences in the frequencies of CRP (-717A>G) genotypes. CONCLUSION: 5-HTR2A (T102C), 5-HTTLPR, BDNF (Val66Met) polymorphisms previously reported to modify schizophrenia course are also associated with premorbid personality in schizophrenic patients.

[Association of inflammatory genes with neuroticism, anxiety and depression in male patients with coronary heart disease]. / Sviaz' genov vospalitel'nykh faktorov s nevrotizmom, trevozhnost'iu i depressiei u muzhchin s ishemicheskoi bolezn'iu serdtsa.

AIM: To explore the relationship of depression and its endophenotypes (neuroticism and trait anxiety) with inflammatory genes in patients with coronary heart disease (CHD). MATERIAL AND METHODS: A sample consisted of 78 male CHD patients with depression, 91 CHD patients without depression and 127 healthy men. Polymorphisms of the genes encoding interleukine-4 (IL-4 -589 C/T), interleukine-6 (IL-6 -174 G/C), tumor-necrosis factor alpha (TNF-α -308 G/A) and C-reactive protein (CRP -717A/G) were studied. RESULTS: There was the association between the IL-6 -174 G/C and depression comorbid to CHD (р=0.01; OR=2.3 CI 95% 1.2-4.3). The frequency of the 'high expression' allele G in this group was higher compared to controls. The association between IL-4 -589 C/T and CHD was found. Compared to the control group, the frequency of the IL-4 -589CC genotype was higher in patients regardless of whether they had symptoms of depression (р=0.007; OR=2.1 CI 95% 1.2-3.4). No association between the TNF-α -308G/A and the CRP -717A/G with depression in CHD was observed. There were no differences between neuroticism and anxiety scores in patients with different IL-4 -589 C/T, IL-6 -174 G/C, TNF-α -308 G/A, CRP -717A/G genotypes. CONCLUSION: The finding of the association between the IL-6 -174G/C and depression, comorbid to CHD, is in line with literature on a role of IL-6 in the development of depression in patients with CHD.

[A study of the effect of the genes of inflammatory proteins on basic personality dimensions]. / Issledovanie effekta genov vospalitel'nykh faktorov na bazovye cherty lichnosti.

AIM: The present research examines the association between two basic dimensions of personality and genes of inflammatory cytokines and mediators reported to be elevated in schizophrenia and affective disorders. Genes of interleukin-1B (IL-1B), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP) and alpha 1-antitrypsin (A1AT) were studied. MATERIAL AND METHODS: A total of 639 healthy subjects, aged from 17 to 69 years, participated in the study. The following polymorphisms were genotyped: IL-1B С-511Т (rs16944) and С3954Т (rs1143634), IL-6 G-174C (rs1800795), TNF-α G-308A (rs1800629), CRP (rs279452), A1AT 374G/A (rs709932). Basic personality dimensions Extraversion and Neuroticism were assessed using the Eysenck Personality Inventory. RESULTS AND CONCLUSION: The levels of Extraversion and Neuroticism were not associated with IL-1B, IL-6, TNF-α G and CRP polymorphisms. The association between the A1AT 374G/A polymorphism and Extraversion (р=0.036) was shown. There was a trend towards the association between the A1AT 374G/A polymorphism and Neuroticism (p=0,05) in women. Because this is the first study of the effect of IL-1B, IL-6, TNF-α and A1AT on personality dimensions, the results should be considered as preliminary and need to be replicated.

[Anxiety and polymorphism Val66Met of BDNF gene--predictors of depression severity in ischemic heart disease].

In a framework of search for early predictors of depression in patients with ischemic heart disease (IHD) we studied effect of molecular-genetic factors (polymorphism of brain-derived neirotrophic factor--BDNF), personality traits (anxiety, neuroticism), IHD severity, and psychosocial stressors on manifestations of depression in men with verified diagnosis of IHD. Severity of depression was assessed by Hamilton Depression Rating Scale 21-item (HAMD 21), anxiety and neuroticism were evaluated by the Spielberger State-Trait Anxiety Inventory and "Big Five" questionnaire, respectively. It wa shown that personal anxiety and ValVal genotype of BDNF gene appeared to be predictors of moderate and severe depression.

[Anxiety and Polymorphism Val66Met of BDNF gene Predictors of Depression Severity in Ischemic Heart Disease].

In a framework of search for early predictors of depression in patients with ischemic heart disease (IHD) we studied effect of molecular- genetic factors (polymorphism of brain-derived neirotrophic factor - BDNF), personality traits (anxiety, neuroticism), IHD severity, and psychosocial stressors on manifestations of depression in men with verified diagnosis of IHD. Severity of depression was assessed by Hamilton Depression Rating Scale 21-Item (HAMD 21), anxiety and neuroticism were evaluated by the Spielberger State-Trait Anxiety Inventory and "Big Five" questionnaire, respectively. It was shown that personal anxiety and ValVal genotype of BDNF gene appeared to be predictors of moderate and severe depression.

[A study of IL-1Β and IDO gene polymorphisms in patients with schizophrenia].

OBJECTIVE: Neurotoxic metabolites of the kynurenine pathway are thought to be implicated in the pathogenesis of schizophrenia. The enzyme indoleamine 2,3-dioxygenase (IDO) catalyzes the initial step of the kynurenine pathway that converts tryptophan to kynurenine metabolites. IDO is induced by proinflammatory cytokines. We studied IL-1Β T-511C (rs16944), IL-1Β C3954T (rs1143634), IDO VNTR and IDO rs9657182 polymorphisms in patients with schizophrenia and controls. MATERIAL AND METHODS: Genotyping was performed in 296 patients with schizophrenia (ICD-10 F20.0) and 355 healthy controls. RESULTS: The multiple dimension reduction (MDR) analysis revealed a combination included alleles С (T-511C), Т (C3954T), V1 (VNTR) and С (rs9657182), which was associated with schizophrenia (OR 3,3 CI 95% 2,3-4,8). CONCLUSION: This is the first report of the interaction between IL-1Β and IDO genes. Further research into genes of the kynurenine pathway is needed.

[The association study of interleukin-1beta and interleukin-1 receptor antagonist and clinical symptoms of schizophrenia].

Growing evidence suggest that interleukin-1beta (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) are involved in the pathogenesis of schizophrenia. The objective of this study was to test the association of the functional promoter polymorphism 511T>C of the IL-1B gene and the VNTR polymorphism of the IL-1RN gene with clinical symptoms of schizophrenia. We studied 758 patients, 415 men and 343 women, with the ICD-10 diagnosis of schizophrenia. Symptoms of schizophrenia were measured using the Positive and Negative Symptome Scale (PANSS). The sample was stratified by gender and type of schizophrenia (chronic or episodic). We found the association between the VNTR IL-1RN polymorphism and PANSS negative symptoms (p = 0.02) in men. Male patients with the genotype 2*2 had lower scores than those with 1*2 and 1*1 genotypes. The genotype 2*2 was associated with a more severe illness course (shorter illness duration and smaller number of hospitalizations) as well. The results suggest that the VNTR polymorphism in the IL-1RN gene may be a predictor of outcome of schizophrenia in men.

[Molecular-genetic study of early-onset schizophrenia].

Schizophrenia with early onset is a relatively rear form of the disease which characterized by severe chronic course and poor outcome. In the present paper, we studied several genes possibly involved in the pathogenesis of this form. These are genes for brain-derived neurotrophic factor (Val66Met polymorphism), serotonin transporter (5-HTTLPR), serotonin receptor type 2A (T102C) and dopamine receptor D2 (Taq1A). Sixty-five patients (age at onset before 15 years) and 111 healthy controls were included in the study. Out of all genes tested, the association was found only for the Val66Met BDNF polymorphism. Frequency of the ValVal genotype was higher in the group of patients (p=0.03; OR 2.1 CI 1.1-4.0) compared to the controls. These results were consistent with our previous study which was carried out on the sample of schizophrenic patients with later age of disease onset. In this study, the frequency of the ValVal genotype was higher only in the group of patients with chronic schizophrenia compared to the controls. It is concluded that the ValVal BDNF genotype may be considered as a marker of schizophrenia with more severe course.

[Association between the Val66Met polymorphism of brain-derived neurotrophic factor gene and schizophrenia in Russians].

Recent studies have demonstrated a role of the brain-derived neurotrophic factor (BDNF) in schizophrenia. An association between the Val66Met BDNF polymorphism has been reported but the results of different studies are inconsistent. An aim of the present article is to study the allele and genotype distribution in patients with schizophrenia (783) and mentally healthy controls (633). No statistically significant between-group differences have been found. When the group of patients has been stratified by sex and form of schizophrenia, the higher frequency of the Val/Val genotype is observed in the subgroup of men with continuous (chronic) schizophrenia as compared to men with attack-like form (p = 0.047). Clinical symptoms assessed with the PANSS were more severe in male patients with the Val/Val genotype. The Val66Met polymorphism was not associated with forms of schizophrenia or clinical symptoms in female patients. The results obtained suggest that the association between the BDNF gene and schizophrenia may be related to sex and clinical heterogeneity of disease. The Val/Val genotype is associated with severer form of schizophrenia in men.

[The molecular-genetic study of juvenile endogenous attack-like psychoses].

Polymorphisms of the following genes (dopamine receptors D2 (Taq1A), D3 (Ser/Glu), D4 (VNTR, -521T/C, -616 G/C, -809A/G), catechol-O-methyltransferase, serotonin receptor type 2A (T102C), serotonin transporter (5-HTTLPR small i, Cyrillic VNTR) and brain-derived neurotrophic factor) have been studied in 260 men with juvenile endogenous attack-like psychoses and 145 age- and sex-matched controls. Type of psychopathological syndrome, PANSS scores and cognitive traits have been assessed. Only the T102C 5-HTR2A polymorphism was associated with some changes in the progress of this type of psychosis. As compared to the TT genotype, patients with 1 or 2 copies of the C allele were characterized by the absence of or less pronounced affective symptoms and more cognitive impairment that implies severity of illness. Moreover, the higher frequency of the C allele was found in the group of patients with chronic course of disease. In conclusion, the T102C polymorphism can be taken into account in prediction of juvenile endogenous attack-like psychosis.

[Dopamine receptor DRD4 gene polymorphism and its association with schizophrenia spectrum disorders and personality traits of patients].

A vast body of associative studies reported a role of highly polymorphic dopamine receptor DRD4 gene in regulation of emotional processes and development of mental disorders. The present study addresses allele, genotype and haplotype distribution of 3 polymorphic DRD4 markers (-809G/A, -616G/C N -521C/T) in Russian patients with schizophrenia spectrum disorders and their relation to the disease and personality traits. A sample included 151 patients with iCD-10 diagnosis of schizophrenia, schizoaffective psychosis and schizotypal personality disorders, 89 their first-degree non-psychotic relatives and 131 mentally healthy individuals. No differences in allele and genotype frequency was found between the patients and the controls. Transmission disiquilibrium test (TDT) did not reveal a preferential transmission of either allele from parents to proband. The 521C/T N -616G/C markers were linked to the disease when the EH program has been used in the analysis. Patients with the GG (-809G/A) and GG (-616G/C) genotypes had higher scores on the Hypomania scale (MMPI) comparing to the GA(-809G/A)+AA(-809G/A) and GC(-616G/C)+CC(-616G/C) genotypes but the association did not reach a level of significance (p = 0.06). The results confirmed the literature reports on the relation of the DRD4 gene to schizophrenia and personality traits related to social activity.