[MRI-parameters of frontal lobes in schizophrenia: correlations with the level of autoantibodies to nerve growth factor in the blood serum].

The relationship between MRI-parameters of frontal lobes and levels of autoantibodies to nerve growth factor (Aab-NGF) in the blood serum of patients with schizophrenia and their relatives was studied. The negative correlation between the Aab-NGF level and the total volume of frontal lobes (r= -0,59; p<0,01) was found in the group of patients. No significant correlations were found in the control groups of healthy subjects without family history of schizophrenia and relatives of patients. The authors concede that Aab-NGF may play a substantial role in the development of neuromorphological changes in schizophrenia.

[Memory peculiarities in patients with schizophrenia and their first-degree relatives].

Eighty-four families with schizophrenia: 84 patients (probands) and 73 their first-degree unaffected relatives as well as 37 normals and their relatives have been studied using pathopsychological (pictogram) and Luria's neuropsychological tests. The most prominent abnormalities both in patients and relatives were global characteristics of auditory-speech memory predominantly related to left subcortical and left temporal regions. Abnormalities of immediate recall of short logic story (SLS) were connected with dysfunction of the same brain regions. Less prominent delayed recall abnormalities of SLS were revealed only in patients and connected with left subcortical, left subcortical-frontal and left subcortical-temporal zones. This abnormality was absent in relatives and age-matched controls. The span of mediated retention was decreased in patients and, to a less degree, in relatives. A quantitative psychological analysis has demonstrated the disintegration ("schizys") between semantic conception and image memory structure in patients and, to a less degree, in relatives. Data obtained show primary memory abnormalities in families with schizophrenia related to the impairment of decoding information process in the subcortical structures, the left-side dysfunction of brain structures being predominantly typical.

MicroRNA in schizophrenia: genetic and expression analysis of miR-130b (22q11).

MicroRNAs (miRNAs) are a class of small regulatory RNAs that control a level of expression of protein encoding genes. Their role in brain pathologies is unknown. We made a first attempt to carry out a genetic study coupled with gene expression analysis of microRNA in human neuropsychiatric pathology. Presumably, at least one third of known miRNA genes are expressed in the brain. Mutations disrupting MECP2 protein lead to abnormal development of the brain and resulting behavior. MiR-130b expressed in the brain and potentially targeting MECP2 is located in the susceptibility locus for schizophrenia (22q11). We performed a comparative analysis of the expression of miR-130b in 24 brain neocortex samples from schizophrenic and normal individuals. The stability and effective detection of mature microRNA in postmortem tissues using Real-time PCR have been shown. Screening for mutations has identified a population polymorphism in the 5 -upstream miR-130b gene region containing DNA elements for putative transcription factors. Genetic association analysis of 300 schizophrenia and 316 normal control individuals revealed no statistically significant association of any of the miR-130b allelic variants with schizophrenia. The data demonstrated feasibility and perspective of convergent genetic and expression analysis of human microRNA genes in testing their role in human diseases.

[Relation between immunological and neurophysiologic markers during exacerbation of schizophrenic process].

Relation between leukocyte elastase (LE) activity of peripheral blood and temporal parameters of late cognitive component of event-related potentials (ERP) was studied in 36 patients with different types of schizophrenia and 28 healthy controls. Both P300 latency and amplitude correlated with LE activity in patients, but not in controls. The results suggest a relationship between innate immunity activation and pathophysiologic processes underlying cognitive impairment in schizophrenia. Possible mechanisms of the correlations revealed are analyzed.

[Peculiarities of attention in families with schizophrenia: correlation between psychological and neurophysiological characteristics].

A relationship between neurophysiological and psychological characteristics of attention was studied in 18 patients with schizophrenia and their 34 mentally healthy relatives: parents and siblings (20 subjects) and children (14 subjects). In patients, a decrease of P300 auditory evoked potentials significantly correlated with disturbances of attention stability and volume as well as characteristics of involuntary attention. At the same time, in the groups of relatives the anomalies of attention stability and attention in conditions of prolonged concentration were positively related to P300 latency.

[Bioelectrical activity of the brain in parents of schizophrenics]. / Bioélektricheskaia aktivnost' golovnogo mozga u roditelei bol'nykh shizofreniei.

The peculiarities of brain electric activity in mentally normal parents of schizophrenics (52 subjects) as compared to the control group of mentally normal subjects without family history of manifest psychosis (22 subjects). In both groups, EEG spectral densities and auditory evoked potentials (AEP) characteristics were compared. The parents of schizophrenics appeared to differ from controls by decrease of N1 amplitude and prolongation of N2, P3 which was similar to that observed in patients with schizophrenia. The findings are discussed as evidence of heritability of deviations in cognitive processes.

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

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.

[Genetic determination of mental activity parameters in the families of schizophrenic patients]. / Geneticheskaia determinatsiia priznakov psikhicheskoi aktivnosti v sem'iakh bol'nykh shizofreniei.

Psychological parameters of mental activity (30 in total) and their genetic determination were studied in 67 families of schizophrenia patients (67 patients, 107 parent, and 30 sibs). Abnormalities of most of the examined characteristics were found in both the patients and their healthy relatives. Parameters of attention shifting and emotionality exhibited the largest genetic component (25-75 and 17-98%, respectively) in all analyzed groups of relatives (probands-affected sibs, probands-healthy sibs, healthy parents-healthy children, affected parents-affected children). Significant impact of genetic factors was also found in parameters "steadiness of attention under conditions of continuous concentration," "mediated retention span" "productivity of arbitrary retention by reproduction data," "personal anxiety level," "reflection of unusual social groups," and "self-assessment." The relationships among the characteristics examined in the system of mental activity were established by means of cluster analysis. The results of this study can be used in medical genetic counseling for identifying persons at high risk for schizophrenia.

[Rigidity of psyche processes and factors predisposing to schizophrenia]. / Rigidnost' psikhicheskikh protsessov v sisteme faktorov predraspolozhennosti k shizofrenii.

To evaluate the rigidity of psychic processes (RPP) as a factor predisposing (vulnerability) to schizophrenia and to study interactions between RPP and other susceptibility factors, psychological characteristics and magnetic resonance tomography data have been studied in 26 families with schizophrenia. Correlation, cluster and regression analyses and trait phenotypic variance decomposing into genetic and environmental components for heritability estimation were used. RPP indices in patients with schizophrenia and their relatives differed significantly from those in the control group of healthy subjects without positive family history of schizophrenia. The RPP heritability was estimated as high (58%). In RPP patients, RPP clustered with parameters of attention, memory, dynamic and intellectual activity; in the siblings--with attention, dynamic and intellectual activity and the width of anterior horns of left and right lateral ventricules next to genum, in the parents--with motivation, attention, memory, dynamic and intellectual activity. In the siblings, heritability for parameters of frontal horn lateral ventricules was estimated as high (66%) for the right ventricles and moderate (30%) for the left ones. Both morphological parameters are among morphological predictors for prognosis of negative symptoms in the patients with schizophrenia. The authors regarded RPP as a factor predisposing to schizophrenia.

[Serotonin transporter gene polymorphism in families with schizophrenia]. / Polimorfizm gena-perenoschika serotonina v otiagoshchennykh shizofreniei semi'iakh.

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.

[Dopamine receptor gene (DRD2) polymorphism in patients with endogenous psychoses with regard to their clinical heterogeneity]. / Polimorfizm gena dofaminovogo retseptora vtorogo tipa u bol'nykh s éndogennymi psikhozami s uchetom ikh klinicheskoi geterogennosti.

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.

[Serotonin receptor gene allele polymorphism (5HTR2A) and clinical pathogenetic characteristics in patients with schizophrenia and schizophrenia spectrum disorders]. / Allel'nyi poliforfizm gena serotoninovogo retseptora (5HTR2A) i kliniko-patogeneticheskie osobennosti bol'nykh shizofreniei i rasstroistvami shizofrenicheskogo spektra.

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.

[Polymorphism in the human serotonin transporter gene in endogenous psychoses]. / Polimorfizm v gene serotoninovogo transportera cheloveka pri éndogennykh psikhozakh.

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.