[Association of the insulin-like growth factor II (IGF2) gene with human cognitive functions].

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.

Association between a synaptosomal protein (SNAP-25) gene polymorphism and verbal memory and attention in patients with endogenous psychoses and mentally healthy subjects.

Synaptosomal protein SNAP-25 is involved in the process of transmitting nerve spikes in the CNS and in the consolidation of memory traces in the hippocampus. Two independent studies have demonstrated associations between SNAP-25 gene polymorphisms and intellectual functions in a group of mentally healthy subjects and patients with schizophrenia. The aim of the present work was to perform a comparative study of the association between the MnlI polymorphism of SNAP-25 and cognitive functions (verbal memory, attention/executive functions) in 66 patients with endogenous psychoses, 75 of their mentally healthy relatives, and 136 healthy control subjects. Statistical analysis showed that the effectiveness of performing cognitive tests was significantly affected by group assignment (p = 0.00001) and genotype (p = 0.012). The interaction between genotype and group assignment also had an influence (p = 0.02). In all groups, carriers of the TT genotype had worse measures than carriers of other genotypes. The similar nature of the influences of the MnlI polymorphism on variations in measures in all groups indicates that this gene is related to overall intellect.

[The association of the SNAP-25 gene polymorphism with verbal memory and attention in patients with major psychosis and healthy people].

The synaptosomal-associated protein (SNAP-25) plays an integral role in synaptic transmission and in memory consolidation in the hippocampus. Recently an association between SNAP-25 gene polymorphism and cognitive ability has been reported in two independent studies of healthy people and patients with schizophrenia. Authors carried out an association study of MnlI SNAP-25 polymorphism and performance on neurocognitive tests measuring verbal memory, attention/executive functions in 66 patients with major psychosis, 75 their relatives and 136 controls. MANCOVA revealed a significant effect of group (small er, Cyrillic=0,00001) and genotype (small er, Cyrillic=0,012) as well as an interaction effect between group and genotype (small er, Cyrillic=0,02) on the performance on neurocognitive tests. Carriers of the TT genotype performed worse on the most tasks compared to other genotypes. The similar character of the MnlI SNAP-25 polymorphism effect on the variability of neurocognitive traits in all groups suggests the relationship between this gene and general cognitive ability.

Association of dopamine receptor D5 gene polymorphism with peculiarities of voluntary attention in schizophrenic patients and their relatives.

We studied the relationship between DRD5 gene polymorphism presented by microsatellites with cognitive signs in 152 schizophrenic patients, 81 mentally healthy relatives, and 125 mentally healthy control individuals. An association was found between DRD5 polymorphism with efficiency of visual voluntary attention in patients (p = 0.02) and their relatives (p = 0.006). Carriers of two copies of the 148-b.p. allele were characterized by low efficiency of attention.

Interaction of dopamine system genes and cognitive functions in patients with schizophrenia and their relatives and in healthy subjects from the general population.

Linkage between the DRD4 and COMT genes and cognitive measures characterizing verbal memory, executive functions, and associative processes was studied in 150 patients with schizophrenia, 83 of their relatives, and 118 mentally healthy subjects without any family history of psychoses, with the aim of detecting the main effects of the polymorphic markers -809G/A and -521C/T (DRD4) and Val158Met (COMT) when present individually and together. The group of patients showed a main effect for polymorphism -521C/T on verbal fluency and an effect of the interaction of this polymorphism and the COMT gene on this cognitive trait. The highest level of verbal fluency was seen among carriers of the Val/Val+CC and Met/Met+TT genotypes. In the combined group of unaffected individuals, the interaction of the COMT and DRD4 -521C/TT genotypes had an effect on the standardness of speech associations due to a decrease in the standardness of associations in carriers of the Met/Met+CC genotype. Finally, both patients and unaffected individuals showed an effect for the interaction between the COMT and DRD4 -809G/A genotypes on working memory. Patients and healthy subjects showed similar features: the highest values were seen in subjects homozygous for the Val and G alleles, while the lowest values were seen in homozygotes for the Met and A alleles. These data provide evidence for a relationship between the DRD4 and COMT genes and different aspects of executive functions and the absence of such a relationship in relation to verbal memory.

Relationship between dopamine system genes and extraversion and novelty seeking.

Dopamine transmission is known to play an important role in the reinforcement system of the brain. Studies have identified dopamine system genes whose polymorphic variants have been linked with the intensity of psychological traits reflecting the tendency to form behaviors characterized by impulsivity and the need for additional stimulation. The aim of the present work was to seek associations between polymorphisms in the catechol-O-methyltransferase (COMT) and D4 dopamine receptor (DRD4) genes and personality traits in the Russian population. Studies of 130 subjects showed that carriers of the Met/Met genotype of the COMT gene had a greater intensity of the novelty-seeking trait than carriers of the Val/Val and Val/Met genotypes, though this association was seen only in women. In addition, the presence of the C allele of the DRD4 gene in carriers of the Met/Met genotype showed high levels of extraversion and hypomania. These results are consistent with current theoretical concepts of the regulation of dopamine transmission in the brain.

[Dopamine system genes and personality traits of extraversion and novelty seeking].

Dopamine neurotransmissin is thought to play a relevant role in behavioral reinforcement system. Polymorphism of the genes involved in dopamine system has been reported for association with psychological traits related to impulsive and sensation seeking behaviors. The study was aimed at a search for association of catechol-O-metyltransferase (COMT) and dopamine receptor D4 (DRD4) gene polymorphism with personality traits in Russian population. A sample comprised 130 subjects. It was found that carriers of the Met/Met COMT genotype had higher scores of novelty seeking as compared to those with the Val/Val and Met/Met genotypes. The association was observed in women only. In the presence of the C allele of the DRD4 gene, females with the Met/Met genotype demonstrated higher scores on extraversion and hypomania. The results are consistent with the current theoretical concepts on the regulation of dopamine neurotransmission in the brain.

[Dopamine system genes interaction and neurocognitive traits in patients with schizophrenia, their relatives and healthy controls from general population].

To elucidate main effects of dopamine receptor D4 (DRD4) and cathecol-O-methyltransferase (COMT) genes as well as their interaction effect on neurocognitive traits, DRD4 gene polymorphisms (-809G/A, -521C/T) and the COMT gene Val158Met polymorphism, along with characteristics of verbal memory, executive functions and peculiarities of associative processes, have been studied in 150 patients with schizophrenia, 83 their relatives and 118 mentally healthy subjects without positive family history of psychosis. A main effect of -521C/T polymorphism and DRD4 (-521C/T).Vall58Met polymorphisms interaction were found for verbal fluency, carriers of the Val/Val+CC and the Met/Met+TT genotypes performing better on this task as compared to other genotypes. An interaction DRD4 (-521C/T).Val158Met effect on originality of speech associations was observed in the combined group of unaffected individuals (relatives and controls), with lower scores of the trait in those with the Met/Met+CC genotype. The COMT-DRD4 (-809G/A) interaction effect on working memory was demonstrated for patients and unaffected individuals, homozygotes for the Val and the G alleles having the best results and homozygotes for the Met and the A alleles--the worst ones. The data obtained suggest the relationship of DRD4 and COMT genes with different characteristics of executive functions but not with verbal memory.

[A study of some genes related to serotoninergic and dopaminergic systems and auditory evoked-potentials (P300) in patients with schizophrenia and spectrum disorders and their first-degree relatives].

The changes of P300 parameters (lower amplitude and increased latency) are thought to be the most prominent phenomena of schizophrenia. A role of gene polymorphism in P300 generation was supported by several associative studies in psychiatrically well subjects and patients with mental disorders. We studied P300 parameters and the following polymorphisms: T102C for the serotonin receptor type 2A (5-HTR2A) gene, the 5-HTTLPR for the serotonin transporter gene, -809G/A, -616G/C N -52C/T SNPs in the promoter region of the dopamine D4 receptor (DRD4) gene and the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) in 74 patients with schizophrenia and spectrum disorders and 71 their first-degree relatives. No association was found between serotonergic system genes and P300. The -809G/A DRD4 gene polymorphism was related to amplitude in all frontal leads (p=0,01) in patients. In relatives, an association was observed between -521C/T DRD4 variants and latency (p=0,005) as well as between the COMT gene polymorphism and P300 amplitude (p=0,004) at the central lead. Thus, the genes involved in dopaminergic system play a role in P300 generation both in patients with schizophrenia and spectrum disorders and their relatives.

[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.

[Polymorphic markers of the dopamine D4 receptor gene promoter region and personality traits in mentally healthy individuals from the Russian population].

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.