Association of Val66Met polymorphism of brain-derived neurotrophic factor gene with cognitive impairment and clinical symptoms in first episode schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of cognitive impairment and clinical symptoms in first-episode schizophrenia with the Val66Met (rs6265) polymorphism of brain-derived neurotrophic factor (BDNF) gene.</p><p><b>METHODS</b>For 87 patients with first-episode schizophrenia and 76 healthy controls, the Val66Met polymorphism was determined with a Taqman Assay-on-Demand method. Wechsler intelligence test was carried out for all participants. Correlation of cognitive impairment with clinical severity was also analyzed.</p><p><b>RESULTS</b>The patients were significantly lower in total IQ, verbal IQ and performance IQ compared to the controls. The lower total IQ (F=4.59, P= 0.01) and verbal IQ (F=4.44, P=0.01) were influenced by genetic factors and diagnostic interaction. The vertal IQ of Val/Val patients was significantly lower than those of Val/Met and Met/Met carriers. For the control group, the verbal IQ of Met/Met carriers was lower than that of Val/Met carriers, and the total IQ of Met/Met carriers was lower than those of Val/Met and Val/Val carriers. For the patient group, the total IQ of Val/Val carriers was negatively correlated with positive symptoms (r=-0.65, P=0.03) and thought disorders (r=-0.61, P=0.02).</p><p><b>CONCLUSION</b>Cognitive impairment in first-episode schizophrenic patients is associated with the Val66Met polymorphism of the BDNF gene, and has an important clinical relevance.</p>

Pathway-focused correlation study of genome-wide methylation status with visual memory / 中华医学遗传学杂志

OBJECTIVE To explore the biological processes and pathways associated with memory function which may be regulated by gene promoter methylation. METHODS The genome-wide promoter methylation statuses in 9 healthy individuals were analyzed with a Multiplex HG18 CpG Promoter chip. Genes with promoter methylation statuses strongly correlated with both immediate and delayed visual memory function were preceded for pathway and physical interactions analysis. RESULTS Sixty nine genes have been correlated with both immediate and delayed visual memory functions. Twenty two pathways, with a Q-value of < 0.05, were identified by the pathway and physical interactions analysis, which included energy metabolism, axon guidance, tyrosine kinase activity, anterograde synaptic vesicle transport, and leukocyte migration and differentiation. CONCLUSION Pathways related with memory function may be regulated by DNA methylation.

Association of gender, age, education and polymorphism of DRD4 gene with cognitive functions in adults / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of cognitive functions with gender, age, education and polymorphism of dopamine receptor D4 (DRD4) gene in healthy adults.</p><p><b>METHODS</b>Four hundred and fifty-five healthy participants have completed 3 cognitive function tests including Tower of Hanoi (TOH), Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT). Peripheral blood samples were collected from all participants, and genomic DNA was extracted according to a standard phenol-chloroform procedure. Rs3758653 in the promoter region of the DRD4 gene was genotyped using Illumina GoldenGate genotyping assay.</p><p><b>RESULTS</b>Males have performed better than females in terms of TOH executive time and TOH total score, but did worse in TOH planning time. Most of the measured cognitive domains were affected by age and education. Cognitive ability has decreased along with increased age and decline of educational years. The polymorphism of rs3758653 has mainly correlated with the TOH executive time. Compared with A allele carriers, G allele carriers did worse in TOH executive time.</p><p><b>CONCLUSION</b>Gender, age, education and the rs3758653 polymorphism of the DRD4 gene play an important role in cognitive functions in healthy adults.</p>

Lack of association of COMT Val158Met polymorphism with attention and executive function in patients with schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the association of a functional polymorphism Val158Met of COMT gene and attention and executive function in first-episode treatment-naive patients with schizophrenia and healthy controls.</p><p><b>METHODS</b>Trail making test (TMT) and clinical performances were evaluated in 103 first-episode treatment-naive patients with schizophrenia and 99 healthy controls. Polymorphism of COMT Val158Met was analyzed using polymerase chain reaction-restriction fragment length polymorphism method. A general linear model was used to investigate the effect of genotype subgroups on the attention and executive function.</p><p><b>RESULTS</b>There was a significant difference between control subjects and patients with schizophrenia on the TMT-A and B. However, no significant difference among Val/Val, Val/Met and Met/Met on the TMT-A and B in control subjects and patients with schizophrenia was detected.</p><p><b>CONCLUSION</b>The association among COMT Met variant and trail making testing (attention and executive function) has been replicated. However, no association of COMT Met variant with disruption of dopaminergic influence on neurocognitive function was detected. This may be due to the heterogeneity of population.</p>

Regulation of PI3K-Akt-GSK3β signaling pathway in U251 cells by risperidone / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the effect of risperidone, an antipsychotic drug, on the Akt-GSK3β pathway and the role of PI3K in dopamine D2 receptor (DRD2) expression and Akt-GSK3β signal pathway.</p><p><b>METHODS</b>Human glioma cells (U251) were cultured in vitro. Cells without any treatment as control, Western blotting was used for measuring the expression of Akt (Thr308 and Ser473) and GSK3β (Ser9) protein phosphorylation by risperidone and LY294002 in U251 cell, and real-time PCR was used for detecting the expression of DRD2 mRNA.</p><p><b>RESULTS</b>Risperidone has significantly enhanced the expression of phosphorylated Akt and phosphorylated GSK3β (P< 0.05), but did not alter the mRNA expression of DRD2. LY294002 could reduce the phosphorylation of Akt and GSK3β (P< 0.01, P< 0.05), and also decrease the DRD2 mRNA (P<0 .05).</p><p><b>CONCLUSION</b>Risperidone can activate the Akt-GSK3β signaling pathway in the U251 cells, and PI3K is a common regulatory site in Akt-GSK3β signaling and D2 receptor gene expression.</p>