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Biomedical subjects

Rulun Zhou

Publications and source records attributed to Rulun Zhou.

22 records · Page 2Linked to original sources

Family-based and case-control association studies of catechol-O-methyltransferase in attention deficit hyperactivity disorder suggest genetic sexual dimorphism.

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset behavioral disorder. Boys are more often affected than girls. Family, twin, and adoption studies have supported a strong genetic basis. Some studies show that a catechol-O-methyltransferase (COMT) polymorphism affecting enzyme activity was associated with personality characteristics and diseases, such as novelty-seeking personality, substance abuse, and heroin addiction, whose features are similar to ADHD or are associated with ADHD. These findings suggest that the COMT gene may be a candidate gene for ADHD. TDT, HHRR, and case-control association studies were conducted within a sample of 202 nuclear ADHD families, 340 ADHD cases, and 226 controls in the Han Chinese population. Diagnoses and ADHD subtypes were ascertained according to DSM-IV criteria using American Clinical Diagnostic Interviewing Scales. The HHRR analysis suggested that the low enzyme-activity COMT Met allele was preferentially transmitted to ADHD boys (160 trios, chi(2) = 3.858, P = 0.05, df = 1) but not girls. This association is particularly pronounced among male ADHD probands without any comorbidity (50 trios, HHRR: chi(2) = 5.128, P = 0.024, df = 1; TDT: chi(2) = 4.558, P = 0.033, df = 1), especially the ADHD-I subtype (32 trios, HHRR: chi(2) = 5.792, P = 0.016, df = 1; TDT: chi(2) = 5.333, P = 0.021, df = 1). The case-control study revealed that the Val allele was more frequent in females meeting ICD-10 or DSM-IV criteria for ADHD than in female controls (86 and 79.5%, respectively, chi(2) = 4.059, P = 0.044, df = 1). Although these results suggest the COMT gene exerts some influence on the risk for ADHD in the Han Chinese population, given the potential for Type I error, these findings require replication before drawing definitive conclusions.

Adolescent↗

The use of mood stabilizers as plasticity enhancers in the treatment of neuropsychiatric disorders.

Mood disorders have traditionally been conceptualized as neurochemical disorders, but there is now evidence from a variety of sources demonstrating regional reductions in central nervous system (CNS) volume, as well as reductions in the numbers and/or sizes of glia and neurons in discrete brain areas. Although the precise cellular mechanisms underlying these morphometric changes remain to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. It is thus noteworthy that lithium and valproate have recently been demonstrated to robustly increase the expression of the cytoprotective protein bcl-2 (an abbreviation for the B-cell lymphoma/leukemia-2 gene) in the CNS in vivo and in cells of human neuronal origin. Lithium and valproate also robustly activate a signaling cascade utilized by endogenous growth factors-the extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathway. Complementary human studies have shown that chronic lithium administration significantly increases gray matter content in a regionally selective manner, suggesting a reversal of illness-related atrophy and an increase in the volume of the neuropil. These unique and unexpected properties of lithium and valproate suggest that they may have broader utility as adjunctive agents in the treatment of a variety of neuropsychiatric disorders associated with cell atrophy or loss. The adjunctive use of these agents-at low doses-may provide the trophic support necessary to restore, enhance, and maintain normal synaptic connectivity, thereby allowing the chemical signal to reinstate the optimal functioning of critical circuits necessary for normal functioning.

Anticonvulsants↗

[Association studies of dopamine D4 receptor gene and dopamine transporter gene polymorphisms in Han Chinese patients with attention deficit hyperactivity disorder].

OBJECTIVE: To investigate association of the 48 bp variable number of tandem repeat (VNTR) polymorphism in the D4 receptor gene (DRD4) exon 3 and 40 bp VNTR polymorphism in the dopamine transporter gene (DAT1) 3' untranslated region with attention deficit hyperactivity disorder (ADHD) in Han Chinese children. METHODS: The study samples were comprised of 340 ADHD children, 226 unrelated controls and 202 integrated ADHD trios (included proband and biological parents). The polymorphisms consisted of 48 bp VNTR in exon 3 of DRD4, and 40 bp VNTR in the 3' untranslated region of DAT1. Associations of polymorphisms with ADHD and its subtypes were examined by: (i) comparing cases and controls; and (ii) using family-based association study in an extension of exact transmission-disequilibrium test (ETDT) and haplotype-based haplotype relative risk (HHRR). RESULTS: The repeat numbers at the DRD4 48 bp locus ranged from 2-6 repeats in the Han Chinese controls, with the most common being the 4-repeat (77%) and 2-repeat (19.4%) alleles. Neither the 7-repeat allele nor longer repeats were found. For the DAT1, the repeat numbers at the 40 bp locus ranged from 6-7 repeats and 9-11 repeats. The 10-repeat allele was the most frequent (90.7%). The long-repeat alleles of DRD4 (ranging from 4-6 repeats) and DAT1 (ranging from 11-12 repeats), were present more frequently in ADHD probands than in controls. Our primary analyses failed to replicate the associations between ADHD and 7-repeat allele of DRD4 and the 10-repeat allele of DAT1. CONCLUSION: The long-repeat alleles of DRD4 (after a stratification by gender) and DAT1 may increase the risk for ADHD in Han Chinese children.

Alleles↗

[Association of 5-HT(2A) receptor polymorphism and attention deficit hyperactivity disorder in children].

OBJECTIVE: To stude the association of 5-HT(2A) receptor polymorphism and attention deficit hyperactivity disorder (ADHD) in children. METHODS: Blood samples were taken from 323 6 approximately 17.5-year-old children with ADHD disgnosed based on the DSM-IV criteria, 182 healthy 18 approximately 49-year-old controls, and 195 pairs of parents of affected children, all of Han nationality. DNA was extracted. PCR was performed to examine the 5-hydroxytryptamine (5-HT)(2A) receptor T102C polymorphism. Transmission disequilibrium test (TDT) was used to test the association of alleles of 5-HT(2A) T102C polymorphic sites and AFDHD. RESULTS: The frequency of T102T in patients with ADHD combined subtype was lower than that in the controls (22.35 vs 33.5%, OR = 0.569, P = 0.028, 95% CI 0.344 - 0.943), and the frequency of T102C in patients with ADHD combined subtype was higher than that in the controls (64.0% vs 47.3%, OR = 1.987, P = 0.003, 95% CI 1.264 approximately 3.124). TDT showed biased transmission of the alleles of T102C polymorphism among families of girl patients with ADHD combined subtype (P = 0.031). CONCLUSION: For the ADHD combined subtype, the T102T genotype is a protective factor and the T102C genotype is a risk factor. For the girl with ADHD combined subtype, the allele C102 is a disease-predisposing gene.

Adolescent↗