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Laboratory Clinical Genetics

The laboratory was found in 1988. The Head is Golimbet Vera E. Ph.D., Dr.Sci, the author of more than 100 publications in the field of psychiatric genetics.

Scientific staff.

Margarita V. Alfimova, Ph.D., the leading researcher, conducting psychological studies.

Lubov' G. Uvarova, Ph.D., the senior researcher, conducting neurophysiological studies.

Natalia S. Demikova, Ph.D, genetic counsellor.

Laboratory scientific activity addresses a development of complex prediction criteria (clinical, psychological, neurophysiological, molecular genetic) for identifying persons-at- risk of schizophrenia for further implementing these criteria for medical-genetic counselling.

To realize this goal, families with multiple cases of psychoses as well as unrelated sample of affected individuals are investigated using the following approach. At first stage, abnormal traits that are common in patients and their healthy relatives, but rare in the general population, are being identified. At second stage, the role of both genetic and environmental factors in the variability of these traits is determined. At third stage, the inherited traits are integrated into multiple indices of hereditary predisposition by means of multivariate statistics. And at final stage, the components of phenotypic variance of the indices are determined in order to confirm their genetic nature.

The approach mentioned above is applied for studying different pathological levels.

Clinical investigation aims to study phenotypical variability of psychopathological disorders in schizophrenic families using international scales for clinical assessment and Russian formalized case-reports (more than 400 items including 300 characteristics of clinical state). Genealogical analysis of schizophrenic families, analysis of heretability of different forms of disease, analysis of clinical characteristics with risk of schizophrenia, correlations between genetically inormative clinical characteristics and multilevel markers of pathogenesis schizophrenia are conducted.

Psychological assessment of schizophrenics and their relatives involves the application of experimental and neuropsychological tests, designed to measure aspects of attention, memory, thinking, verbal and communication abilities, as well as personality inventories (MMPI, EPI, STAI, TCI, SPQ). Data obtained are analyzed using methods of behavioral genetics and multivariate statistics, namely, component portioning of phenotypic variance, estimation of phenotypic and genetic correlations, regression and cluster analyses, method of principal components etc. This approach aims at investigating a number of issues concerning a role of genetic factors in development of schizophrenia, including search for psychological markers of genetic risk for the psychosis, exploration of the latent structure of cognitive and personality deficits in schizophrenia, assessment of heritability of psychological characteristics in schizophrenic families, ect.

The aim of the neurophysiological investigation is to search for EEG and ERP markers of predisposition to schizophrenia. Computerized analysis of EEG frequency bands power at 19 derivations (10/20 system) and analysis of AERP of schizophrenics and their healthy first-degree relatives and normal controls are used. Resting EEG and task-related EEG changes for performing mental arithmetic, vebal and spatial tasks are studied as well.

Currently, a data base, including demographic, pathogenetic, clinical, psychological, neurophysiological descriptions of the 150 families with schizophrenia is available for investigation, along with a collection of DNA and blood samples, comprising over 2000 DNA's of unrelated individuals with schizophrenia and affective disorders and their first-degree relatives as well as psychiatrically well healthy controls without family history of psychiatric illness. Structured interview and ICD-10 check lists are used as standardized diagnostic tools for establishing a diagnosis. Along with DNA and demographic details information on clinical (positive and negative symptom evaluation), neurophysiological and psychological traits has been accumulated for each patient. A battery of psychological tests is administered to each healthy individual as well. The collection is being used for population based case/control and family-based association study and appears to be suitable for the QTL (quantitative trait loci) approach with regard to personality and cognitive traits.

The unique computer program has been developed by Dr. Trubnikov for genetic analysis of biological data. Genetic analysis includes multivariate statistical procedures along with techniques for calculation heritability as well as genetic correlations, and for evaluation of shared and nonshared environmental factors' impact.

Genetic consultations have been conducting in the Clinical Genetics Lab. since 1991. Counseling is based on the integral indices, including information on different stages of disease manifestation in families with schizophrenia. The main goal of the counseling is to assist a person-at-risk in making a decision regarding reproductive choices.

Publications (selected).

Reviews.

Ozerova NI., Orlova V.A, Trubnikov V.I. et al., Twins studies in psychiatry by the data of literature of last years (1989). Med Ref J: 9, 1-11.

Orlova V.A., Ozerova N.I., Demikova N.S. et al. (1992). Clinico-genealogical studies of schizophrenia in literature of last years (1985-1990). Korsakov J Neurol Psychiatr: 92(4), 100-105.

Orlova VA, Demikova NS, Ozerova NI, Alfimova MV, Trubnikov VI. (1993). Patterns of schizophrenia inheritance and development (based on findings of genealogical studies of recent five years). Social and Clinical Psychiatry (Socialnaya i klinicheskaya psichiatria): 3 (2), 113-127 .

Orlova V, Golimbet V, Uvarova L., Alfimova M., Trubnikov V. (1993). Modern aspects and persrectives of study on heredity predisposal to schizophrenia markers. Social and clinical psychiatry.(Socialnaya i klinicheskaya psichiatria): 3 (4), 119-134.

Golimbet VE., Trubnikov VI. Molecular genetics in schizophrenia.(1996). Annals of Psychiatry: 6, 123-132.

Trubnikov V, Golimbet V.(1996). Modern aspects of anticipation study on endogenic psychoses. Vestnik Rossiiskoi akademii medizinskich nauk (Reports of Russian Academy of Medical Sciences): No4, 11-14.

Alfimova M.V., Uvarova L.G., Trubnikov V.I. (1999). A method of evoked potentials in the study of cognitive processes in schizophrenia. Korsakov J Neurol Psychiatr: 99(1), 55-58.

Alfimova M.V., Uvarova L.G., Trubnikov V.I. (1999). Electroencephalography and cognitive processes in schizophrenia. Korsakov J Neurol Psychiatr: 99(1), 62-68.

Psychological, neurophysiological and computer tomography studies of schizophrenia

Ozerova NI, Alfimova MV, Iznak AF et al. (1992). A multidisciplinary approach to studying the large family with several schizophrenic patients. Korsakov J Neurol Psychiatr: 92, 121-126 .

Poliakov YuF, Alfimova MV. (1993) Problems and perspectives of a psychologist's participation in schizophrenia forecasting. Vestnik of Moscow State University, 1: 17-25.

Trubnikov V, Uvarova L, Alfimova M et al. (1993) Neurophysiological and psychological predictors of genetic risk to schizophrenia. Behavior Genetics. 23: 455-459.

Poliakov YuF, Trubnikov VI, Alfimova MV et al. (1993). Development of psychological predictors of genetic risk for schizophrenia in families at risk. Social and Clinical Psychiatry (Moscow). 3: 6-12 ( in Russ).

Trubnikov VI, Alfimova MV. (1994) Inheritance of Mental Traits in Families of Schizophrenics and Use of These Traits for Disease Risk Estimation. Genetica: 30: 695-701 ( in Russ).

Alfimova M, Trubnikov V. (1994). Psychological variables and genetic predisposition to schizophrenia. Journal of Russian & East European Psychology (USA) 32: 53-66.

Trubnikov VI, Alfimova MV, Uvarova LG, Orlova VA. (1995). Multivariate genetic analysis of data of complex investigation of predisposition to schizophrenia. Korsakov J Neurol Psychiatr: 95, 50-56.

Orlova V.A., Vavilov SB, .Belova OG. (1994). Genetic analyses of computer tomographic parameters in schizophrenia. Korsakov J Neurol Psychiatr: 94 (2), 85-90.

Uvarova LG, Alfimova MV, Trubnikov VI. (1995). Interhemispheric asymmetry of the resting EEG and its relation with psychological indices of cognitive activity in schizophrenic families. Human physiology: 21, 39-49 ( in Russ).

Alfimova MV, Trubnikov VI. (1995). Heritability of personality traits measured by MMPI in schizophrenic families. Genetica (Moscow). 31: 1010-1015 ( in Russ).

Alfimova MV, Trubnikov VI, Orlova VA. (1996). The peculiarities of extraversion and neuroticism manifestations in families of schizophrenic patients. Korsakov J Neurol Psychiatr: (Moscow). 96: 32-37 (in Russ).

Alfimova MV, Trubnikov VI, Uvarova LG, Orlova VA. (1996). Genetic aspects of neuropsychology of verbal memory in schizophrenia. Vestnik RAMN (Moscow). N 4: 39-45 ( in Russ).

Alfimova MV, Trubnikov VI. (1996). Mathematical-genetic approach to the development of prognostic criteria for psychological traits. Shkola zdorovia (Moscow). 3: 14-23 ( in Russ).

Alfimova MV, Trubnikov VI. (1999). Cognitive heterogeneity in schizophrenics and in individuals at high risk to schizophrenia. Social and Clinical Psychiatry (Moscow): 9 (2), 5-13 (in Russ).

Orlova V.A., Trubnikov V.I., Odintsova S.A. et al. (1999). Genetic analysis of morphological brain parameters determined by magnetic resonance imaging in families with schizophrenia. Genetics (Russ): 35 ( 7), 998-1004.

Orlova V.A., Savina T.D., Trubnikov V.I et al. (1998). Structural peculiarities of the brain (MRI data) and the functional connection in the families of schizophrenia patients. J Rus Psychiatr: 6, 48-56.


[Personality disorders diagnosed psychometrically in relatives of patients with schizophrenia and schizoaffective disorders]

[Article in Russian]

Alfimova MV, Trubnikov VI, Bondar' VV, Kaleda VG, Oleichik IV, Golimbet VE.

By means of MMPI test 287 healthy relatives of 159 patients with schizophrenia and schizoaffective disorders were examined. Anomalies of personality were found in 44% of 287 relatives examined, that did not differ significantly from the same index (36% of 179) in the control group of healthy individuals without any family history of mental diseases. A cluster analysis has revealed that anomalies of personality in the patients relatives can be divided into the next types: schizoid (15%), sociopathic (7%), masculine, superrational (5%) and neurotic (16%). In most of schizoid relatives anomalies of personality were reflected by the 2-7-8 profile of personality that differed them from schizoid personalities in control group. On the basis of both the results obtained and literature data it was suggested that together with the schizoid relatives, the relatives with sociopathic features should be included in the schizophrenic risk group, while anomalies of personality of both neurotic and superrational types were the reactions to the stress in families of the patients with schizophrenia.

PMID: 11552634 [PubMed - indexed for MEDLINE]


[Psychological mechanisms of communication disorders in schizophrenics and their relatives]

[Article in Russian]

Alfimova MV, Bondar' VV, Abramova LI, Kaleda VG, Golimbet VE.

The study aimed at searching for mechanisms of communicative impairments in patients with schizophrenia and their relatives. To evaluate a contribution of attention and memory to communication efficacy and to ability for understanding mental states of others, 100 patients with schizophrenia and schizoaffective psychosis, 150 their healthy relatives and 145 controls have been studied. The results confirmed a presence of communicative deviations in the patients with schizophrenia and their relatives. In these groups, communication deficit was determined by disturbance of 1 out of 4 communication principles--the principle of information quantity. Attention and memory did not exert any significant influence on communication efficacy in the patients and their relatives. Distinct deterioration of fulfilling the tasks demanding mentalizing ability was found only in the patients. However, no correlation was revealed between this deterioration and communication peculiarities.

PMID: 12789822 [PubMed - indexed for MEDLINE]

Molecular genetic studies.


Serotonin transporter polymorphism and depressive-related symptoms in schizophrenia.

Golimbet VE, Alfimova MV, Shchebatykh TV, Abramova LI, Kaleda VG, Rogaev EI.

Research Center of Mental Health, Russian Academy of Medical Sciences, Zagorodnoe sh 2/2, 113152 Moscow, Russia. golimbet@mail.ru

A role for the serotonin transporter (5-HTT) gene polymorphism in mental illnesses and anxiety-traits has been implicated. The contribution of genetic factors in personality traits and the manifestation of specific symptoms in psychiatric illnesses have yet to be elucidated. Anxious-depressive symptoms are a significant component in a pattern of schizophrenic symptoms. This study focused on the relation between 5-HTT polymorphism and clinical presentations of schizophrenia, specifically those related to the affective spectrum. Using clinical and psychological analyses, we tested the genetic association between the 5-HTTLPR polymorphism (5-HTT gene-linked polymorphic region) and anxiety- and depressive-related symptoms emerged in schizophrenia. In 260 patients with an ICD-10 diagnosis of schizophrenia (broad definition), we studied the 5-HTTLPR genotype (insertion-deletion polymorphism), the Positive and Negative Syndrome Scale (PANSS), and self-rated inventories (EPI, MMPI, STAI) scores. Patients with the "ss" genotype (deletion variant) scored significantly higher on "Guilt feelings" and "Depression" items, as compared with those of the "ll" genotype (insertion variant) (P = 0.016, 0.039, respectively). The frequency of the "ss" genotype was reduced in patients with no depression or guilt feelings, or in those patients exhibiting questionable symptoms. In contrast, the "ss" genotype carriers prevailed among the patients with mild, moderate, or severe ratings of the symptoms. The scores on all anxiety- and depression-related traits, self-rated by the patients, did not significantly differ by genotype. Our finding may contribute to understanding of molecular genetic features underlying an appearance of psychopathological symptoms emerged in schizophrenia. Copyright 2003 Wiley-Liss, Inc.

PMID: 15048639 [PubMed - in process]


[In Process Citation]

[Article in Russian]

[No authors listed]

Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, 117152 Russia. golimbet@online.ru

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.

PMID: 15042846 [PubMed - in process]

[Polymorphism of serotonin receptor gene 5-HTR2A and schizotypic traits in mentally healthy subjects]

[Article in Russian]

Mitiushina NG, Alfimova MV, Liashenko GL, Asanov AIu, Golimbet VE.

Serotonin receptor type 2 (5-HTR2A) polymorphism was consistently reported to be related to schizophrenia and some clinical presentations of the disease. The present study aimed at searching for association between 5-HTR2A polymorphism and schizotypic personality traits being considered as recognized phenotype predisposing to schizophrenia. Relationship between these features measured by SPQ-74 and two 5-HTR2A polymorphic loci has been studied in mentally healthy community sample (n = 64). Significant difference was found between AG and GG genotype carriers on No-close-friends scale (t = 2.3; p = 0.03), with GG scoring higher on this item. Also, a trend towards higher scores on this scale (p = 0.08) was observed in women, but not in men, with A2A2 genotype. To a certain extent, the results confirm a hypothesis articulated in the study of G-allele and A2-allele relation to interpersonal relationship factor of SPQ-74.

PMID: 14681967 [PubMed - indexed for MEDLINE]


[Genetics of schizophrenia]

[Article in Russian]

Golimbet VE.

Publication Types:

  • Review

  • Review, Academic


PMID: 12830510 [PubMed - indexed for MEDLINE]


[A-1438-G serotonin receptor type 2A (5-HTR2A) gene polymorphism in patients in patients with schizophrenia]

[Article in Russian]

Mitiushina NG, Abramova LI, Kaleda VG, Golimbet VE.

A-1438-G 5-HTR2A gene polymorphism is known to be related to some clinical presentations of endogenous psychoses, in particular, of schizophrenia. The present study aim was to study association between clinical appearances of schizophrenia and A-1438-G allelic polymorphism. Alleles (A and G) and genotypes (AA, AG and GG) distribution did not significantly differ between patients and control groups. No association has been found between the genotypes and clinical characteristics of the patients, such as age at disease onset, age at psychosis manifestation, as well as positive, negative and general psychopathological symptoms severity measured by PANSS.

PMID: 12830506 [PubMed - indexed for MEDLINE]


Analysis of the linkage of the Taq1A and Taq1B loci of the dopamine D2 receptor gene with schizophrenia in patients and their siblings.

Golimbet VE, Aksenova MG, Nosikov VV, Orlova VA, Kaleda VG.

Laboratory of Prophylactic Genetics, Department of Endogenous Psychoses and Affective Disorders, Mental Health Scientific Center, Russian Academy of Medical Sciences, Moscow.

The linkage of the polymorphous markers Taq1A and Taq1B of the DRD2 dopamine receptor gene, located in region 11q22-11q23 of chromosome 11, with schizophrenia was studied. The investigation involved 29 complete families containing concordant and discordant sibling pairs. Common alleles at locus Taq1A were found significantly more frequently in concordant pairs (p = 0.04), and there was a tendency to a higher frequency of transmission of the maternal allele as compared with the paternal allele (p = 0.06). No such relationships were seen in the case of the Taq1B locus. Neither locus showed any significant difference in the frequency of common alleles in discordant pairs or in the predominance of allele transmission from one of the parents. These data demonstrate a possible linkage with schizophrenia for the Taq1A marker but not for the Taq1B marker.

PMID: 12762588 [PubMed - indexed for MEDLINE]

[Gene insertion and deletion polymorphism in the serotonin transporter gene and personality traits measured by MMPI]

[Article in Russian]

Golimbet VE, Alfimova MV, Shcherbatykh TV, Rogaev EI.

Mental Research Health Center, Russian Academy of Medical Sciences, Moscow, 113152 Russia. golimbet@mail.ru

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.

PMID: 12760255 [PubMed - indexed for MEDLINE]


[Polymorphism of the serotonin receptor (5-HTR2A) gene and verbal fluency in normalcy and schizophrenia]

[Article in Russian]

Alfimova MV, Golimbet VE, Mitiushina NG.

Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, 113152 Russia.

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.

PMID: 12624948 [PubMed - indexed for MEDLINE]


Serotonin transporter gene polymorphism and schizoid personality traits in the patients with psychosis and psychiatrically well subjects.

Golimbet VE, Alfimova MV, Shcherbatikh T, Kaleda VG, Abramova LI, Rogaev EI.

The Preventive Genetics Laboratory, Research Mental Health Center, Zagorodnoe sh 2/2, 113152 Moscow, Russia. golimbet@mail.ru

BACKGROUND AND OBJECTIVES: serotonin transporter (5-HTT) gene allelic variants were shown to be associated with Neuroticism and Harm Avoidance but the results were not replicated in other studies. The current investigation was undertaken in a further attempt to study the relationship between 5-HTT polymorphism and personality traits. SUBJECTS AND METHODS: to evaluate a spectrum of personality traits, MMPI was administered to a sample including patients with affective disorders (n=114), patients with schizophrenia spectrum illnesses (n=110) and psychiatrically well controls (n=124). All groups were genotyped for VNTR-17 and functional insertion-deletion (5-HTTLPR) polymorphisms. RESULTS: an association was found between 5-HTTLPR polymorphism and scores on three MMPI scales: Psychopathic deviance, Paranoia and Schizophrenia in patients with affective disorders and S chizophrenia in normal subjects. Both affected and control individuals with 'ss' genotype exhibited lower scores on these scales. CONCLUSION: we demonstrated that functional deletion/insertion allelic variation associated with decreased expression of serotonin transporter ('s' allele or 'ss' genotype) may restrict expression of schizoid traits in normal subjects and patients with affective disorders.

PMID: 12582974 [PubMed - indexed for MEDLINE]


[Allele polymorphism of the serotonin transporter gene and clinical heterogeneity of depressive disorders]

[Article in Russian]

Golimbet VE, Alfimova MV, Shcherbatykh TV, Rogaev EI.

Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, 113152, Russia. golimbet@mail.ru

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.

PMID: 12068552 [PubMed - indexed for MEDLINE]


[Linkage sib-pair analysis of dopamine receptor D2 gene Taq1A and Taq1B polymorphism and schizophrenia]

[Article in Russian]

Golimbet VE, Aksenova MG, Nosikov VV, Orlova VA, Kaleda VG.

PMID: 12001666 [PubMed - indexed for MEDLINE]


5HTR2A gene polymorphism and personality traits in patients with major psychoses.

Golimbet VE, Alfimova MV, Manandyan KK, Mitushina NG, Abramova LI, Kaleda VG, Oleichik IV, Yurov Y, Trubnikov VI.

Laboratory of Preventive Genetics, Research Mental Health Center, Russian Academy of Medical Sciences, Zagorodnoe sh. 2/2, Moscow, Russia 113152. golimbet@mail.ru

Serotonin receptor (5HTR2A) gene polymorphism has been reported to be associated with clinical phenotypes in schizophrenia. The current study attempted to investigate a relationship between 5HTR2A 102T/C polymorphism and personality traits as well as clinical symptoms in patients with ICD-10 diagnoses of schizophrenia and affective disorders. 5HTR2A genotyping, clinical and psychological assessment were administered to 375 patients, 104 first-degree healthy relatives of the patients and 157 controls. In the patients an association was observed between the 2/2 5HTR2A genotype and scores on the Hypochondriasis scale (MMPI) (ANOVA, F = 4.56; P = 0.011) and trait anxiety (F = 4.21; P = 0.002). A significant difference between 1/1 and 2/2 genotypes has been also found for Neuroticism scores (EPI) (t = 2.18; P = 0.0031). No significant differences by 5HTR2A genotype were observed in either the control or first-degree relatives group for all scales studied. Positive, negative and psychopathological symptoms emerged higher in the 2/2 genotype patients compared to other genotype carriers. Therefore, the 2/2 genotype may contribute to produce the phenotype, with specific clinical and pathological features in common, regardless of nosologic heterogeneity of psychoses.

PMID: 11918989 [PubMed - indexed for MEDLINE]


[Dopamine receptor gene (DRD2) polymorphism in patients with endogenous psychoses with regard to their clinical heterogeneity]

[Article in Russian]

Golimbet VE, Aksenova MG, Abramova LI, Kaleda VG, Orlova VA, Brusentseva LN, Nosikov VV.

Recently an association between genetic dopamine receptor gene (DRD2) polymorphism and schizophrenia was observed in several studies. In the current investigation we attempted to undertake further study of such association using an extended sample which comprised patients with schizophrenia (n = 184), schizoaffective psychosis (n = 63), affective disorders (n = 121)); healthy control subjects (n = 117) and first-degree relatives of the patients with psychoses who show no signs of mental diseases (n = 111). The genotypes A1A1, A1A2 and A2A2 and the relationship between Taq1DRD2 variants and some clinical symptoms and pathogenetic features of the patients with schizophrenia were studied. The results did not confirm the association between DRD2 genotype and any of disorders studied. But the A2A2 genotype frequency in the schizophrenic patient's group, with illness duration above 20 years and highly expressed positive, negative and psychopathological symptoms, increased significantly as compared to control group (73.7% vs 52.9%) and patients with less illness duration (73.7% vs 42.5%). In the latter case odds ratio was calculated as 4.12. In the light of this finding, A2A2 DRD2 genotype appears to be related to chronicity of schizophrenia.

PMID: 11765615 [PubMed - indexed for MEDLINE]


[Serotonin transporter gene polymorphism in families with schizophrenia]

[Article in Russian]

Golimbet VE, Shcherbatykh TV, Abramova LI, Kaleda VG, Oleichik IV, Orlova VA, Rogaev EI.

Recently association between VNTR-17 (12 copies, allel 12) and schizophrenia has been reported. Relations between allele polymorphism of serotonin transporter gene and schizophrenia in 71 Russian families with schizophrenia (n = 253) were studied. Genotyping was made by VNTR-17 and HTTLPR loci. Allele 10 was transmitted 25 times and allele 12 was transmitted 28 times. In the case of HTTLPR polymorphism allele I was transmitted 26 times and allele s was transmitted 19 times. These differences in transmission also were statistically insignificant (p = 0.69). Therefore, our findings do not support association between 5-HTT polymorphism and susceptibility to schizophrenia.

PMID: 11712269 [PubMed - indexed for MEDLINE]


[Molecular genetic polymorphism of the genes of neurotransmitter systems in schizophrenics with early manifestation of the disease]

[Article in Russian]

Golimbet VE, Mitiushina NG, Shcherbatykh TV, Aksenova MG, Abramova LI, Kaleda VG, Nosikov VV, Iurov IuB, Rogaev EI.

Molecular-genetic polymorphism of genes-candidates was investigated: the genes of serotonin receptor--type 2a (HTR2A), dopamine receptor gene--type 2, serotonin transporter (5HTTLPR). Thirty one schizophrenic patients whose age was 12.6 +/- 3.6 years at the onset of the disease and 208 patients whose age was 23.5 +/- 6.7 years at the onset of the disease were examined. The frequencies of HTTLPR and DRD2 genotypes differed insignificantly in both groups. The distribution of 5HTR2A genotypes in the schizophrenic group with an early manifestation of the disease differed from that with a later manifestation significantly (chi 2 = 6.27; df = 2; p = 0.044). The relative risk (odds ratios) was 7.9 with 95% significance interval 1.008-61.94; p = 0.045. The severity of the disease and a positive family history were also examined in A2A2 genotype carriers. A positive family history was found in 9 (52.9%) of the 17 schizophrenics with an early manifestation and only in 15 (21.1%) of 71 patients of the similar group with a later one. Assessment of the clinical symptoms revealed that the total scores by the negative symptomatology subscale (PANSS) was higher in the patients with an early manifestation than in those with later one; but these differences did not achieve the significance level. These and earlier findings lead to the conclusion that A2A2 genotype was more frequently observed in the patients with more pronounced negative symptoms and high hereditary burden, which suggests that the A2A2 genotype is associated with an early onset.

PMID: 11490436 [PubMed - indexed for MEDLINE]


[Insertion-deletion polymorphism of the serotonin carrier gene and evaluation of neurotism as a temperament trait in patients with affective disorders and mentally healthy people]

[Article in Russian]

Golimbet VE, Alfimova VM, Shcherbatykh TV, Abramova LI, Kaleda VG, Rogaev EI.

golimbet@mail.ru

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.

PMID: 11443919 [PubMed - indexed for MEDLINE]


[Serotonin type 2a (5-HTR2A) receptor gene polymorphism and personality traits in patients with endogenous psychoses]

[Article in Russian]

Golimbet VE, Alfimova MV, Manandian KK, Abramova LI, Kaleda VG, Mitiushina NG, Oleichik IV, Iurov IuB, Trubnikov VI.

Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, 113152 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.

PMID: 11421130 [PubMed - indexed for MEDLINE]


[Polymorphism in the human serotonin transporter gene in endogenous psychoses]

[Article in Russian]

Shcherbatykh TV, Golimbet VE, Orlova VA, Kaleda VG.

Research Center of Mental Health, Russian Academy of Medical Sciences, Moscow, 115522 Russia.

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.

PMID: 11190480 [PubMed - indexed for MEDLINE]


Evaluation of the dementia carers situation in Russia.

Golimbet V, Trubnikov V.

Laboratory of Preventive Genetics, National Center for Mental Health, Zagorodnoe sh.2, k.2, Russian Academy of Medical Sciences, Moscow 113152, Russia. golimbet@mail.ru

OBJECTIVE: The objective of this study was to assess the situation of carers in Russia and to determine predictors of their quality of life and psychological morbidity. DESIGN/SETTING: Attendees of the geriatric department in a mental hospital and referrers to an out-patient geriatric unit who had a diagnosis of dementia and their principal carers formed the study group. CARERS: The total sample was 83, 15 males and 68 females, aged from 19 to 72 years. The relationships to the demented person were: daughters (52%); spouses (8%), sons (12%) and others (28%). MEASURES: Structured questionnaire, Quality of Life Questionnaire (WHOQOL BREF), and General Health Questionnaire (GHQ-12) were administered. RESULTS: The results of this study demonstrate the low level of service input most carers have been receiving. A large number of carers do not use services provided by health and social services. The most commonly received service appears to be health services (doctor visits and short-term hospital admission). Aids to daily living from social service were unknown to most carers. Female carers were found to report lower QOL mean scores in G4 (Health in general) and D1 (physical) domain and were significantly more stressed on the GHQ compared to male carers. Daughters were less dissatisfied with the QOL in G4, D1 D3 (social relationship) and D4 (environmental) domains than other relatives. CONCLUSION: The study indicated that carers, especially daughters, of dementia sufferers need more attention from social and health services. Copyright 2001 John Wiley & Sons, Ltd.

PMID: 11180492 [PubMed - indexed for MEDLINE]


[Allele polymorphism of the dopamine transporter gene in group of patients with endogenous psychotic diseases: association with pathological syndromes]

[Article in Russian]

Aksenova MG, Golimbet VE, Alfimova MV, Trubnikov VI, Ab OV, Iazykov KG, Nosikov VV.

PMID: 11042860 [PubMed - indexed for MEDLINE]


[Allelic polymorphism at the TAQIB locus of the dopamine D2 receptor gene in groups of patients with endogenous psychoses]

[Article in Russian]

Aksenova MG, Ab OV, Golimbet VE, Abramova LI, Orlova VA, Kaleda VG, Oleichik IV, Nosikov VV.

marina_aksenova@yahoo.com

PMID: 10867915 [PubMed - indexed for MEDLINE]

[Serotonin receptor gene allele polymorphism (5HTR2A) and clinical pathogenetic characteristics in patients with schizophrenia and schizophrenia spectrum disorders]

[Article in Russian]

Golimbet VE, Manandian KK, Abramova LI, Orlova VA, Kaleda VG, Oleichik IV, Iurov IuB, Trubnikov VI.

Serotonin receptor 5HTR2A gene polymorphism was reported to be associated with psychiatric disorders, in particular schizophrenia, in numerous studies. This study aimed to analyze a possible association between 5HTR2A gene polymorphism and clinical and pathogenetic characteristics in schizophrenia and schizophrenia spectrum disorders. We studied 209 individuals with schizophrenia and related disorders (107 male and 102 female, mean age 34.7 +/- 17.2 years) and 116 healthy controls (44 males, 72 females, mean age = 33.6 +/- 14.4 years). Diagnoses were made according diagnostic criteria of ICD-10. Positive and Negative Symptoms Scale (PANSS) assessed clinical symptoms. Significant difference (p < 0.01) was found for 5HTR2A genotype distribution between affected and control groups. The frequencies of genotypes A1A1, A1A2 and A2A2 for schizophrenia were 13.3%, 44.0% and 42.7%, respectively, versus 33%, 47% and 27% in controls. These results support the evidence for association between 5HTR2A A2A2 genotype and schizophrenia. Schizophrenics with A2A2 genotype were characterized by significantly higher mean values of the PANSS negative symptoms subscale than those with A1A1 genotype (22.6 vs 17.8; p < 0.05) and, consequently, by majority of deficit patients and patients with more severe forms of schizophrenia. Patients with A1A1 genotype were younger compare to those with A2A2 genotypes and had the least familial factors (35.7% vs 46.1%). In agreement with the results obtained in the study the 5HTR2A gene polymorphism appears to be considered as additional diagnostic or prognostic trait in the medical genetic studies of schizophrenia.

PMID: 10709289 [PubMed - indexed for MEDLINE]


[Association of allele polymorphism of dopamine d2 receptors with schizophrenic and affective disorders]

[Article in Russian]

Golimbet VE, Aksenova MG, Abramova LI, Kaleda VG, Orlova VA, Braga EA, Nosikov VV, Trubnikov VI.

DRD2 Taq polymorphism has been studied in the samples from 214 patients (119 males, 95 females, mean age 37.8 +/- 13.6) and of 96 controls (50 males, 46 females, mean age 40.7 +/- 20.0). The latter group comprised 75 unrelated controls and 21 healthy first degree relatives of schizophrenic patients. All the patients were diagnosed according to ICD-10 and have been divided into 4 groups: paranoid schizophrenics (n = 102), schizotypic patients (n = 25), patients with schizoaffective psychoses (n = 40) and affective disorders (n = 47). Taq1A DRD2 polymorphism was represented by 3 genotypes: A1A1, A1A2, A2A2 (allele A2 was a result of nucleotide substitution). The frequencies of genotypes in affected group didn't significantly differ from a control one. However, a frequency of A2A2 genotype (0.45) in a group of paranoid schizophrenics was significantly higher, than in the patients with schizoaffective psychoses (0.22) or in a control group (0.26), but was similar to that of the patients with schizotypic or affective disorders (0.4). A2A2 DRD2 genotype seems to be a potential genetic factor of susceptibility to schizophrenia.

PMID: 9866157 [PubMed - indexed for MEDLINE]


[Linkage analysis of schizophrenia with markers of chromosomes 2 and 11 in russian families]

[Article in Russian]

Golimbet VE, Korovaitseva GI, Trubnikov VI, Orlova VA, Shipitsina NI.

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.

PMID: 8964484 [PubMed - indexed for MEDLINE]


[Current concepts of anticipation in endogenous psychoses]

[Article in Russian]

Trubnikov VI, Golimbet VE.

It has been recently discovered that anticipation may correlate with expansion of trinucleotide repeats in human genome. Therefore some diseases that show anticipation, such as bipolar affective disorders and schizophrenia, deserve to be studied. Anticipation used to be considered as a result of the onset age hereditability that may be described as a lineal decrease of the age of manifestation in the following generation. Positive assortative matings leading to genes predisposed to schizophrenia ascertainment as well might be responsible for earlier onset and disease severity in descendants (Shakhmatova-Pavlova et al., 1979; Trubnikov et al., 1978; Gindilis, 1979). Therefore, clinical genetic data are to be used as the basis for anticipation study. To exclude statistical artifacts, it seems necessary to study three generations in families and proband parent siblings as a control group. The phenomena of anticipation can be regarded as a special case when a relationship between clinical and molecular genetic traits is found. In a common case, trinucleotide expansion study on the basis of vast experimental clinical family material suppose to be sensible to elucidate the correlations between the clinical level of disease description and molecular genetic characteristics. Another approach to the problem is to ascertain special relative groups to compare with. For example, the concordant and discordant monozygotic tween pairs study also seems to be promising because the molecular genetic characteristic of genome instability may help in the elucidation of protection mechanisms that prevent disease manifestations.

Publication Types:

  • Review

  • Review, Tutorial


PMID: 8754072 [PubMed - indexed for MEDLINE]


[The formation of a collection of DNA from patients with endogenous psychoses and the prospects for its use in molecular genetic research in psychiatry]

[Article in Russian]

Golimbet VE, Trubnikov VI, Orlova VA, Panteleeva GP, Tsutsul'kovskaia MIa.

A genetic study of psychiatric diseases meets a lot of difficulties because of incomplete penetrance, phenocopies, probable genetic heterogeneity. The progress in exploring of new effective markers and human genome mapping enables one to undertaken a systematic search for alleles confirming susceptibility to manic depressive illness and schizophrenia. It is important therefore to have in one's disposal the collection of DNA samples appropriate for different aspects of molecular genetic study. The collection of DNA samples deposited in National Centre for Mental Health of Russian Academy of Medical Sciences includes DNA of informative small-scaled families and a number of DNA from unrelated subjects with manic-depressive illness, schizophrenia, schizoaffective disorders. This collection may be used for linkage analysis, association and sib-pair studies and for detection of mutations responsible for mental diseases.

PMID: 7483933 [PubMed - indexed for MEDLINE]

Ethical issues of molecular genetic studies in psychiatry and medical genetic consulting.

Trubnikov VI. Molecular genetic research in psychiatry. (1991). In “Ethical issues of Molecular genetics in psychiatry”. Eds. Sram RL., Bulyzhenkov V., Prilipko L., Christen Y.. Springer-Velag, p.131.

Trubnikov V, Golimbet V. (1993). Ethical aspects of molecular-genetic research in psychiatry: family analysis. Social and clinical psychiatry. (Russ) (Socialnaya i klinicheskaya psichiatria): 3 (4), 48-52.

Trubnikov V, Golimbet V. (1994). Medico-genetic consultation in psychiatry: risk predictors for mental disorders. Sozialnaya i klinicheskaya psikhiatria( Social and clinical psychiatry): 4 (4), 46-50.

Golimbet V, Trubnikov V.(1996). Ethical problems of molecular-genetic diagnostics in psychiatry. Sozialnaya i klinicheskaya psichiatria (Social and clinical psychiatry): 6 (1), 109-112.

Golimbet V, Trubnikov V. (1997). Molecular genetic testing in endogenic psychoses: perspectives from the point of medical ethics. Korsakov J Neurol Psyciatr: 97 (10), 74-75.

Mail address: Zagorodnoe sh. 2/2. Moscow. Russia. 117152. Tel. (095) 952-9040. Fax: (095)952-. E-mail: golimbet@online.ru