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There is a decrease in the expression of the reelin gene (RELN) in the brain of schizophrenia patients, which can underlie observed cognitive abnormalities. It is suggested that this decrease is caused by the hypermethylation of the RELN promoter. The aim of the study was to investigate methylation of the RELN promoter in the peripheral blood of schizophrenia patients and its association with their cognitive deficits. A modified SMRT-BS (single-molecule real-time bisulfite sequencing) was used. We determined the methylation rate of 170 CpG sites within a 1465 bp DNA region containing the entire CpG island in the RELN promoter in 51 schizophrenia patients and 52 healthy controls. All subjects completed a battery of neuropsychological tests. There were no DNA methylation changes associated with schizophrenia. Most CpGs sites were unmethylated in both groups. At the same time, there was a variability in the methylation level of different regions within the promoter. The methylation level in the area from -258 to -151 bp relative to RELN transcription start site was a significant predictor of the index of patients' cognitive functioning if sex, age, smoking, education, and polymorphism rsl858815 had been considered. The positive correlation between the methylation rate in this region and cognitive index suggests that the hypomethylation of the RELN promoter could contribute to the development of cognitive deficits in schizophrenia.

There is growing evidence that serum levels of various inflammation markers are associated with personality traits. However, only few studies investigated the link between genetic variants of cytokine encoding genes and psychological characteristics. In this study, we examined genotypes in 297 individuals to assess the association between common variants of interleukin 4 (IL-4) and interleukin 10 (IL-10) genes and basic personality traits of extraversion and neuroticism, measured using the Eysenck Personality Questionnaire (EPQ). We found that, in homozygous female carriers of high expression alleles Т (IL-4 C-589T) and G (IL-10 G-1082A), neuroticism scores were higher (p = 0.045 and p = 0.08, respectively). In turn, extraversion scores were significantly higher in both male and female carriers of heterozygous variants CT and GA (p = 0.01). Our results are in accordance with the behavioral immune system hypothesis, and the general paradigm on the role of personality traits in health and longevity.

The present study searched for associations between gene GRIN2B (glutamate receptor, ionotropic, N-methyl-D-aspartate, subunit 2B) and component processes of verbal episodic memory in schizophrenic patients. The Rey Auditory Verbal Learning Test (RAVLT) as a part of a large neuropsychological battery was administered to 302 patients with schizophrenic spectrum disorders (sample PI). Also, 285 patients (sample P2) and 243 healthy controls (sample C2) performed the “10 words” test that measures short-term memory. The GRIN2B rs7301328 (C366G) polymorphism was genotyped for each subject. There were no associations between the polymorphism and any measure of the RAVLT either in the whole PI sample or in a subsample of patients with a severe cognitive deficit. The GRIN2B influenced immediate recall and proactive interference in the “10 words” test in the control group: homozygotes CC recalled fewer words and showed a lower effect of proactive interference than carriers of other genotypes. The results suggest that the C366G polymorphism could influence verbal episodic memory in the general population, but this influence is absent in schizophrenic patients.

The purpose of this work was to search for associations between the serotonin receptor 2C gene (HTR2C) and the peculiarities of social behavior and social cognition in schizophrenia. To do this, patients with schizophrenia spectrum disorders and healthy control subjects were genotyped for the Cys23Ser HTR2C marker and underwent psychological examination, including assessment of Machiavellianism, recognition of emotions in facial expression, and theory of mind. In addition, we estimated the trait anxiety level as a potential factor affecting the relationship between the gene HTR2C and social behavior. We found a significant association between the Ser allele and a reduction of estimates on the Mach-LV Machiavellianism scale in the total sample of patients (n = 182) and control subjects (n = 189), which did not reach the confidence level in either of the groups. A tendency towards a HTR2C gene influence on the trait anxiety level was also revealed. The association between HTR2C and Machiavellianism was retained if the anxiety level was taken into account. The results suggest a pleiotropic effect of HTR2Con anxiety and Machiavellianism.

Neurotoxic products produced during tryptophan metabolism via the kynurenine pathway could be involved in schizophrenia pathogenesis. It has been shown that kynurenine-3-monooxygenase (KMO) is indirectly involved in these products' formation. KMO polymorphic loci rs2275163 (C/T) and rs1053230 (A/G) were examined in 187 schizophrenia patients and 229 healthy subjects. A genetic combination of allele T and genotype GG was observed more often in a patient group compared with healthy controls (p = 0.003, OR 2.0 (95% CI 1.2-2.9). In the latter group, this combination was associated with schizophrenia endophenotype (p = 0.04), which manifested in a higher expression of schizotypal personality traits assessed using the MMPI test.

The brain-derived neurotrophic factor (BDNF) gene is a prominent candidate gene for schizophrenia. The BDNFVal66Met polymorphism has been extensively studied for association to this disease. There is accumulating evidence that the polymorphism is associated with clinical presentations of schizophrenia and not with the disease itself. We compared the allele and genotype distribution in patients (n=1785) and healthy controls (n = 1092) and did not find association of the Va166Met polymorphism with schizophrenia. No association was found with affective syndromes. At the same time, the ValVal genotype was associated with the higher anxiety level assessed with the PANSS in male patients. We studied personality characteristics using personality questionnaires EPI, MMPI, STAI (n=363) and cognitive functions (attention (n=227) and verbal fluency (n=392). Patients with the ValVal genotype demonstrated higher levels of anxiety assessed by the MMPI and better performance on the neurocognitive tests. The interaction effect of genotype and trait anxiety, measured with the STAI, on cognitive functions was identified. In patients with higher anxiety, the performance on cognitive tests did not depend on the genotype, while in patients with lower levels of anxiety the ValVal gen- otype was associated with the better performance. This effect should be taken into account when studying the association of the Val66Met polymorphism with cognitive functions in patients with schizophrenia.

Active search for candidate genes whose polymorphisms are associated with human cognitive functions has been in progress in the past years. The study focused on the role that the insulin-like growth factor II (IGF2) gene may play in the variation of cognitive processes related to executive functions. The ApaI polymorphism of the IGF2 gene was tested for association with selective attention during visual search, working memory/mental control, and semantic verbal fluency in a group of 182 healthy individuals. The ApaI polymorphism was associated with the general cognitive index and selective attention measure. Carriers of genotype AA displayed higher values of the two parameters than carriers of genotype GG. It was assumed that the ApaI polymorphism of the IGF2 gene influences the human cognitive functions, acting possibly via modulation of the IGF-II level in the central nervous system.

Blood serotonin concentration is thought to regulate behavior and may be implicated in the development of psychopathological symptoms as well. Serotonin transporter regulates the levels of serotonin by the reuptake of this neurotransmitter from the synaptic cleft. In this study we compare the platelet serotonin concentration and constant V(max) value in patients with schizophrenia and healthy controls with different 5-HTTLPR genotypes. The study included 60 patients and 62 controls. Biochemical parameters mentioned above were associated with a 5-HTTLPR genotype. Carriers of the LL genotype had lower serotonin blood concentration and V(max) compared to genotypes containing one or two copies of an S allele both in patients and controls. The results obtained suggest that the genetic variant may contribute to the state of serotoninergic system.

Tryptophan hydroxylase is one of the key enzymes involved in serotonergic metabolism. In many studies, an association between the TPH gene and human mentality, as well as mental disorder was demonstrated. This study was designed to analyze the association between three TPH gene polymorphisms (A218C, T3792A, and (CT)n(CA)n(CT)n) and endogenous psychoses. The patients included into investigation were represented by those with manic-depressive psychosis (93 individuals) and those with the schizophrenia spectrum disorders (307 individuals). An association between the A218C polymorphism with the disorders of the schizophrenia spectrum was demonstrated. These findings confirmed the data obtained earlier for other populations. In addition, an association between the (CT)n(CA)n(CT)n microsatellite repeats and bipolar disease was shown for the first time.

Cognitive deficit is a key feature of schizophrenia. Genetic factors are thought to contribute to cognitive disturbances in schizophrenia patients. However the role of specific-genes in the development of cognitive deficit remains unclear. The article aims at reviewing the current studies devoted to association between gene polymorphisms and cognitive dysfunctions in schizophrenic patients. Main attention is drawn to the association between the Val158Met polymorphism of the COMT gene and cognitive traits that has been consistently replicated and has a biological and neuropsychological support. The association studies on the genes for dopamine and serotonin receptors, brain-derived neurotrophic factor, dysbindin, DISC1, D-amino acid oxidase and D-amino acid oxidase activator are reviewed as well.

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 dopamine receptor gene D4 is a highly polymorphic gene, which, according to a number of studies, is associated with the personality traits characterizing human activity. Earlier, a VNTR polymorphic marker in exon 3 and single-nucleotide polymorphism in the promoter region were shown to be associated with novelty seeking. However, these results were not supported by all subsequent studies, which suggest a possible effect of other polymorphic regions of this gene. The aim of the present work was studying the effect of gene DRD4 on activity-related human personality traits in Russians, using in association analysis three polymorphic markers of this gene (-809 G/A, -616 C/G, and -521 C/T) and psychological traits assessed by various tests. Genotyping and psychological examination were conducted in 220 mentally healthy subjects (131 individuals lacking hereditary load of psychic diseases and 89 relatives of patients with psychoses). In Russians, allele frequencies of all markers proved to have no significant difference from the corresponding estimates for European populations. The markers examined were in linkage equilibrium. We have found a significant contribution of genotypes -521 C/T and -809 G/A to the expression of extraversion (Eysenck Personality Inventory (EPI), P = 0.0016) and variation of scores of the Social Introversion scale (Minnesota Multiphase Personality Inventory (MMPI), P = 0.0085). Genotypes -521 C/T and -616 C/G had a joint effect on scores on the Hypomania scale (P = 0.04), while their effect on extraversion was recorded as a trend (P = 0.054). Thus, the results of this study in general support the evidence by other authors showing association of polymorphism at the DRD4 gene promoter to personality traits. We have shown that the traits in question were mainly related to social activity. A reduction in social activity is associated largely with the T(-521 C/T) allele, characterized by low transcription rate.

The interindividual variation of temperament features (such as anxiety, neuroticism, harm avoidance) is determined, in particular, by allele polymorphism of genes involved in serotonin metabolism and has earlier been associated with the insertion/deletion polymorphism of the serotonin transporter gene. Polymorphic alleles of the serotonin 2A receptor gene (5HTR2A) were tested for association with personality traits assessed with several tests. The T102C and A1438G polymorphisms were associated with a variation in emotionality, activity, and sociability, which are integral characteristics of temperament. With each polymorphism, differences were significant only between heterozygotes and homozygotes. Carriers of T102C genotype A1/A2 displayed a lower level of anxiety-related traits, a higher score on scale Hypomania, and a lower score on scale Social Introversion and were assumed to have higher activity and sociability. Carriers of A1428G genotype A/G differed from homozygotes G/G in having a lower level of social introversion and a lower score on scale No close friends, which testified to higher sociability of heterozygotes. Thus, the polymorphic alleles of SHTR2A proved to be associated with personality traits in mentally healthy people.

The review considers the most interesting data on the molecular genetic basis of mental disorders and personality traits, which were obtained within the framework of the Russian program Human Genome. Polymorphic markers Taq1A of the dopamine receptor gene and T102C of the serotonin receptor type 2A gene were associated with schizophrenia, in particular, chronic forms with poor prognosis. In mentally healthy people, the insertion/deletion polymorphism of the serotonin transporter gene was associated with schizoid traits.

Polymorphisms of the serotonin transporter gene are known to be associated with some personality traits measured by means of various psychological inventories. In the present work we attempted to find an association between genetic variants of serotonin transporter (loci VNTR-17 and 5-HTTLPR) and psychological traits scored by the MMPI inventory in 125 mentally healthy donors. No statistically significant differences in personality traits were found between carriers of different VNTR-17 genotypes. At locus 5-HTTLPR, significant between-genotype differences were revealed on the Schizophrenia scale (F = 3.49; P = 0.034) and on the validity scale F (F = 3.24; P = 0.042). The ss genotype carriers had the lowest scores on these scales. The score on the Psychopathic Deviate scale was significantly lower in the carriers of the ss genotype than in the combined group of the carriers of genotypes ll and ls (t = 2.07; P = 0.041). The differences on the validity scale K between the carriers of the ll and ss genotypes were also statistically significant (t = 2.49; P = 0.015). These results suggest that polymorphism of the serotonin transporter gene may be associated with the expression of schizoid traits (namely, social introversion, internal tension, weird thoughts and actions) in mentally healthy individuals. In the context of social adaptation, the personality profile configuration and data of statistical analysis indicate that the carriers of the ss genotype are more inclined to observe social norms than the carriers of the ll and ls genotypes.

To study the effect of the serotonergic brain system on verbal fluency (i.e., the ability to rapidly extract necessary words from the vocabulary), the T102C polymorphism of the serotonin receptor type 2A (5-HTR2A) gene was tested for association with verbal fluency in 108 patients with schizophrenia or schizotypic disorders and 97 mentally healthy individuals. A significant association was observed only in male schizophrenics (N = 67), with homozygotes A2A2 having lower verbal fluency. The results did not support the association between the 5-HTR2A polymorphism and verbal fluency in normalcy, and agree with the assumed contribution of genotype A2A2 to the severity of schizophrenia.

Depression disorders are a clinically heterogeneous disease group. Their development is to a substantial extent underlain by dysfunction of the serotonin system, in particular, disturbed serotonin transport. The heterogeneity of depressions is associated, among other factors, with the age at disease onset. Allele polymorphism of the serotonin transporter (5-HTT) gene was tested for association with age at disease onset, clinical signs, and anxiety-related traits of depression patients. A sample included 77 patients (mean age 61.2 +/- 8.8 years) with late-onset depression (LOD, mean age at onset 56.58 +/- 9.7 years) and 74 patients (mean age 31.0 +/- 11.8 years) with early-onset depression (EOD, mean age at onset 23.9 +/- 7.4 years). In genotype frequency distribution of two 5-HTT gene polymorphism, the LOD and EOD groups did not differ from each other (chi 2 = 0.33, P = 0.85 for VNTR-17; chi 2 = 3.33, P = 0.19 for HTTLPR) and from a control group (chi 2 = 0.34, P = 0.84 for VNTR-17; chi 2 = 2.1, P = 0.35 for HTTLPR). In either group, patients differing in VNTR-17 and HTTLPR genotypes did not differ in psychological traits and, in particular, in anxiety-related traits. In the case of the HTTLPR polymorphism, LOD patients with genotype ss tended to display less severe neuroticism (t = 2.03, P = 0.0507) and scored significantly less on the Hamilton depression scale (t = 2.19, P = 0.039). Thus, the 5-HTT gene polymorphisms do not affect the risk of depression but is possibly associated with specific clinical signs of the disease, at least in elderly patients.

Some studies associate the insertion/deletion polymorphism of the serotonin transporter (5-HTT) gene with anxiety-related personality traits in mentally healthy people, the short (s) allele being associated with a higher neuroticism score. The 5-HTT genotype and neuroticism score were established for 114 affective patients, 87 healthy relatives of endogenous psychosis patients, and for 156 mentally healthy people without familial psychiatric history. The effects of sex and age on the association between the two parameters was studied. Neuroticism proved to be not associated with the 5-HTT genotype.

Allele epsilon 4 of the apolipoprotein E (APOE) gene is associated with higher risk of Alzheimer's disease (AD) in many, though not all, ethnic groups. The APOE allele and genotype frequency distributions were studied in 207 AD patients without cerebrovascular disorders, 62 AD patients with cerebrovascular disorders (combined AD), and 206 control individuals (ethnic Russians from the Russian population). The frequency of allele epsilon 4 in patients with early-onset and late-onset AD was three times higher than in control individuals (p < 0.000001). Compared with control people, patients with cerebrovascular disorders displayed a twofold higher frequency of allele epsilon 4; the difference between the two groups was significant (p = 0.0019). Relative risk of AD in carriers of allele epsilon 4 was five times higher than in carriers of alleles epsilon 2 and epsilon 3 (p < 0.000001). Allele epsilon 2 had a protective effect with respect to AD onset until 65 years of age (p = 0.015). Thus, APOE allele epsilon 4 proved to be a universal factor of early-onset, late-onset, and combined AD in ethnic Russians from Russia.

Genetic polymorphism of the serotonin receptor (5-HTR2A) gene has been reported to be associated with the expression of clinical signs characteristic of major psychoses, including schizophrenia and affective disorders. In this study, personality traits of patients with these diseases and the associations of these traits with 5-HTR2A allelic polymorphisms were studied. It was demonstrated that schizophrenic and affective patients with the 2/2 genotype of serotonin receptor had lower scores on the anxiety scale and on the anxiety-related hypochondriasis and neuroticism scales than subjects with the 1/1 and 1/2 genotypes.

Associations of the VNTR-17 and 5-HTTLPR polymorphisms of the serotonin transporter gene with affective disorders, including depression, have been found. These polymorphisms were analyzed in two groups of Russian probands: patients with endogenous psychoses and control individuals without mental disorders (423 and 277 persons, respectively). No associations were found between VNTR-17 genotypes or alleles and the diseases. However, the frequency of 10/10 (VNTR-17) homozygotes increased with age in both patients and healthy persons. The results of the analysis of the 5-HTTLPR polymorphism suggest an association of the short (s) allele of the 5-HTTLPR polymorphism with schizophrenia and schizoaffective psychoses, but not with affective disorders.

Two molecular-genetic markers-H-ras and YNH24 (chromosome 2)-were tested for genetic linkage with schizophrenia in eight Russian families with different forms of the disease. Thirty-nine subjects, including 13 affected ones, were examined. Five alleles represented as DNA fragments from 2.4 to 4.0 kb in size were detected in DNA samples from probands and other family members when the H-ras probe and TagI restriction endonuclease were used. Eleven alleles were identified in hybridization experiments with YNH24 as a probe. Linkage tests between marker alleles and the schizophrenia predisposition gene were performed by means of the sib-pair method. Statistically significant evidence (5% significance level) for linkage between allele 2 of H-ras and the gene controlling predisposition to schizophrenia was found.

Water petroleum oxidizing bacteria of Arthrobacter ceroformans as well as their lipid composition are described. On a medium containing hexadecane, all the strains produce wax in large amounts (upto 70% of total free lipids) consisting by 95% of cetyl palmitate. Fatty acids are represented mainly by palmitic acid but comprise also unsaturated C16:1 and C18:1 acids. Mycolic acids have not been detected. The significance of lipid composition for the identification of arthrobacteria is discussed.