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.

No abstract

Monocyte activation is consistently reported in patients with schizophrenia (SZ). We aimed to study the ultrastructure of monocytes and monocyte production of IL-1β in drug-free patients with SZ and controls. Monocytes from young (18-30 y.o.) healthy and SZ men in relapse were studied. Electron microscopy and morphometry were applied to estimate areas of monocytes, volume density (Vv), areas, and number of organelles. The production IL-1β by monocytes was estimated by the ELISA method. Group differences were examined using ANCOVA. Pearson's correlation coefficients were used to examine the effects of possible confounding variables. Correlation analyses were applied to detect the relationships between the parameters of monocytes measured and between the parameters measured and the IL-1β production. Area of nucleolus, Vv and area of mitochondria and lysosomes, and the number of lysosomes were significantly increased in patients as compared to controls. Area of mitochondria was correlated significantly with Vv and area of lysosomes, and the number of lysosomes was significantly correlated with area of monocyte and Vv of vacuoles only in the control group. The production of IL-1β by monocytes was higher in patients than in controls (p = 0.01) and was correlated with Vv of lysosomes (r = 0.68, p = 0.04) and area of lysosomes (r = 0.78, p = 0.013). The data provide new evidence for over activation of monocytes in SZ and disturbed metabolic relationships between lysosomes, mitochondria, and vacuoles.

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.

The MEGA-PRESS pulse sequence was used for determination of overlapping signals in the (1)H-MRS spectra of the human brain. For the first time, the balance of GABA glutamate/glutamine concentrations was estimated quantitatively in the human brain of patients with ultra-high risk of schizophrenia. It was found that GABA concentration and GABA/GLX ratios were significantly reduced in the left frontal lobe of UHR subjects.

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.

Serotonin type 2A receptors (5-HTR2A) have long been implicated in schizophrenia pathology. A decreased number of these receptors were found in postmortem brain studies of schizophrenic patients as well as in experiments using neuroimaging techniques. Molecular genetic studies revealed that the T102C polymorphism of the 5-HTR2A gene is associated with schizophrenia, with the CC genotype frequency being higher in patients compared to healthy controls. However the association was not confirmed in all studies. We carried out a replication study, which aimed at searching for association between this polymorphism and schizophrenia in a large samples of patients (n=919), their psychiatrically well first-degree relatives (n=330) and screened controls (n=500). The C allele and the CT+CC genotype frequencies were significantly higher in patients than in controls (chi2=5.1; df=1; p=0.02; OR 1.2, 95% CI 1.0-1.4) and chi2=5.4; df=1; p=0.02; OR 1.4, 95% CI 1.1-1.8 respectively). In a family-based study, the transmission disequilibrium test (TDT) and the family-based association test (FBAT) did not show a preferential transmission of any allele. In conclusion, our replication study provides further evidence for association between the 5-HTR2A receptor T102C polymorphism and schizophrenia.

No abstract