Kaleda Vg

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.

Serotonin transporter polymorphism and depressive-related symptoms in schizophrenia

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.