Correlation between altered levels of neurotransmitters in the frontal lobe and hippocampus and behavioral abnormalities in a Clock mutant mice modeling bipolar manic disorder / 中华医学遗传学杂志

OBJECTIVE@#To explore the correlation between altered levels of neurotransmitters in the frontal lobe and hippocampus and behavioral abnormalities in a Clock variant mice modeling bipolar disorder manic disorder.@*METHODS@#Open field test and Elevated plus-maze test were carried out on the Clock mutant and wild-type control groups. The frontal lobe and hippocampus of Clock mutant mice and controls were dissected, and neurotransmitters in tissue extracts were analyzed by high-performance liquid chromatography and mass spectrometry. The concentration of neurotransmitters and behavioral indicators were assessed by t test and Pearson correlation analysis using SPSS 22.0.@*RESULTS@#The Clock mutant mice showed a significant increase in activity, albeit with no difference in the level of anxiety from the wild-type controls, which suggested that the Clock mutant mice can be used as a model for manic attack of bipolar disorder. Altered neurotransmitter levels were detected in the frontal and hippocampal regions, including elevated histamine in the left hippocampus, reduced histamine in the right hippocampus, reduced gamma-aminobutyric acid (GABA) in bilateral hippocampus, elevated dihydroxyphenylalanine (DOPA) in the left frontal lobe and reduced DOPA in the right hippocampus, and decreased glutamine in bilateral frontal lobes. The reduced glutamine in the left frontal lobe and GABA in the right hippocampus correlated with the increased activity of Clock mutant mice.@*CONCLUSION@#Clock mutant mice showed abnormal behavior with increased activity. Reduced glutamine in the left frontal lobe and GABA in the right hippocampus were correlated with increased activity.

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>

Risperidone regulates dopamine D2-like receptors expression in rat brain in a time-dependent manner

Background and Objectives: Antipsychotics can elicit dopamine super sensitivity by up-regulation of D2-like receptors (DRD2, DRD3, and DRD4) expression. Nevertheless, the expression profile of dopamine D2-like receptors in different brain regions and peripheral blood mononuclear cells (PBMCs), and changes following risperidone administration were still unclear. In this study, we would investigate the expression of D2-like receptors mRNA in different brain regions and the peripheral blood mononuclear cells (PBMCs) in rats after 2, 6 weeks risperidone administration. Methods: The experimental rats were given risperidone (0.25mg/kg/day, i.p.), and the control rats were given 0.9% NaCl. The rats were sacrificed at 0 week, 2 weeks and 6 weeks after the drug administration. Expression of the dopamine D2-like receptors was quantified by Real-time PCR method. Results: Dopamine D2-like receptors expressed in all the examined regions of rat brain. Their expression significantly increased 2weeks after risperidone administration in different brain regions. However, the changed expression of DRD2 and DRD3 turned back to the basal level 6weeks later, while the increased DRD4 expression remained in left parietal cortex. Meanwhile, DRD2 and DRD3 but not DRD4 expressed in PBMCs, however, the risperidone could not affect their expression. Conclusions: The risperidone could change the dopamine D2-like receptors expression in a time-dependent manner in different brain regions, which might guide the clinical use in the near future (AU)

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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>