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Rulun Zhou

Publications and source records attributed to Rulun Zhou.

At least 19 recordsLinked to original sources
PubMed2007

Evaluation of potential gene-gene interactions for attention deficit hyperactivity disorder in the Han Chinese population.

Several lines of evidence suggest that attention-deficit/hyperactivity disorder (ADHD) is a polygenic disorder produced by the interaction of several genes with minor effects. To explore potential gene-gene interactions among candidate genes for ADHD, we studied the dopamine D2 receptor (DRD2), dopamine D4 receptor (DRD4), dopamine transporter (DAT1), and catechol-O-methyltransferase (COMT) genes in the Han Chinese population. A sample of 340 children with ADHD was diagnosed according to the DSM-IV criteria. We also recruited 226 unrelated controls. Identified polymorphisms included a 48-base-pair-repeat in Exon 3 of DRD4, a 40-base-pair-repeat in the 3' untranslated region of DAT1, a restriction-fragment-length polymorphism at codon 158 of COMT, and a -241A > G transition in the promoter of DRD2. Associations of polymorphisms with ADHD and its subtypes were examined by comparing allele frequencies between probands and controls. Binary logistic regression analysis was used to examine the potential gene-gene interactions. Binary logistic regression analysis with the sample of refined phenotypes showed that male gender and long-repeat genotypes of DRD4 and DAT1 were independent risk factors for ADHD. We found no evidence for gene-gene interactions among the candidate genes studied. The present study suggests that dopamine candidate genes are associated with increased vulnerability to ADHD in the Han Chinese population.

Adolescent↗
PubMed2007

Association between polymorphisms in serotonin transporter gene and attention deficit hyperactivity disorder in Chinese Han subjects.

Prior work has shown reduced serotonin transmission to be associated with impulsivity and behavioral problems. The current study assessed the association between ADHD and two variants of the serotonin transporter gene: the 44-bp deletion/insertion polymorphism (5-HTTLPR) and the 17 bp-repeat polymorphism in intron 2 (STin2.VNTR). We hypothesized that ADHD phenotypes associated with impulsivity would show an association with these variants. Two-hundred and ninety-three ADHD trios were genotyped and analyzed using transmission disequilibrium test (TDT) analysis and haplotype analysis. We found no association between the STin2.VNTR and ADHD, but did find preferential transmission of the S allele of the 5-HTTLPR polymorphism (chi(2) = 5.751, P = 0.016) to probands with ADHD. Haplotype analysis found the L/10 haplotype was over-transmitted (chi(2) = 6.172, P = 0.013), while L/12 was under-transmitted to probands with ADHD (chi(2) = 4.866, P = 0.027).

Alleles↗
PubMed2006

The serotonin 5-HT1D receptor gene and attention-deficit hyperactivity disorder in Chinese Han subjects.

Attention-deficit/hyperactivity disorder (ADHD) is a heritable disease. Serotonin is one of the neurotransmitters involved in the etiology of ADHD. Serotonin-1D receptors are autoreceptors which can regulate the release of serotonin in brain, so the HTR1D gene may be predisposing. The current study genotyped two variants of HTR1D gene in 272 ADHD trios of Chinese ethnicity, that is 1350T > C in the coding region and 1236A > G in 3'-UTR by the use of transmission disequilibrium test (TDT). The A allele of the 1236A > G polymorphism exhibited both a trend toward preferential transmission to ADHD probands (chi2 = 3.815, P = 0.051) and a significant preferential transmission to probands of ADHDC (chi2 = 4.198, P = 0.040). Additional polymorphisms in this gene need to be studied further.

Asian People↗
PubMed2006

Association between polymorphisms in serotonin 2C receptor gene and attention-deficit/hyperactivity disorder in Han Chinese subjects.

Attention deficit hyperactivity disorder (ADHD) is much more frequent in males than females, so several genes on the X chromosome (e.g., MAOA and MAOB) have been pursued as candidates for influencing risk for the disorder. HTR2C is also located on the X chromosome. In the current study, we examined the relationship between the C-759T and G-697C polymorphisms of HTR2C and ADHD in 488 Han Chinese families. Transmission Disequilibrium Test (TDT) analysis showed that the -759C allele, the -697G allele, and haplotype -759C/-697G were significantly over-transmitted to affected probands, while haplotypes -759C/-697C and -759T/-697C were under-transmitted. When families were divided into three subtypes according to the diagnosis of probands, the -697G allele and haplotype -759C/-697G were significantly over transmitted to ADHD-C probands, while haplotype -759T/-697C was under-transmitted to these individuals; however, no biased transmission of any allele or haplotype was observed for probands with ADHD-I, suggesting that different subtypes of ADHD have different genetic influences. Our findings highlight the need to explore the role of 5-HT2C receptor dysfunction in the pathogenesis of ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

Contribution of 5-HT2A receptor gene -1438A>G polymorphism to outcome of attention-deficit/hyperactivity disorder in adolescents.

Attention-deficit/hyperactivity disorder (ADHD) typically emerges before 7 years of age and may persist into adolescence or adulthood. The adolescent outcome can be classified into four types, including non-remission, syndromatic remission, symptomatic remission, and functional remission. Genetic factors are believed to contribute to symptom stability and change across development, so adolescent outcome may be a sub-phenotype for molecular genetic studies of ADHD. Serotonin system genes are prime candidates for this sub-phenotype, since the development of this neurotransmitter system parallels the course of ADHD. The current study examined the association between adolescent outcome in ADHD and serotonin system genes, including the -1438A>G polymorphism of the serotonin 2A receptor gene (HTR2A) and the -759C>T polymorphism of the serotonin 2C receptor gene (HTR2C). The -1438A>G polymorphism was found to be related to remission in ADHD, especially functional remission (P = 0.029). Due to potential phenotypic and etiologic heterogeneity in ADHD, the results of this study must be replicated in additional samples before they can be generalized to other populations.

Adolescent↗
PubMed2006

No association of attention-deficit/hyperactivity disorder with genes of the serotonergic pathway in Han Chinese subjects.

Attention-deficit/hyperactivity disorder (ADHD) is a complex psychiatric syndrome with cardinal symptoms of inattention, hyperactivity and impulsivity, and is a significant risk factor for poor health outcomes in both adolescence and adulthood. Etiology is clearly multifactoral, with probable contributions from both genetic and environmental factors. The genetic contribution is prominent, with estimated heritability at about 0.80. Although effects in dopamine metabolism have long been implicated in the etiology of ADHD, the role for serotonin has gained more attention in recent years. The current study examined five variants in three serotonin genes [those that code for serotonin receptors 2A (HTR2A), 5A (HTR5A) and 6 (HTR6)] in a relatively large sample of ADHD nuclear families. The transmission disequilibrium test (TDT) and the extended transmission disequilibrium test (ETDT) were performed to test for evidence of distorted transmission of alleles or haplotypes. No significant biased transmission was observed. These results do not support a substantial role of these serotonin gene in ADHD, however, additional work may be warranted before this association is definitively discounted.

Asian People↗
PubMed2006

Association of attention-deficit/hyperactivity disorder with serotonin 4 receptor gene polymorphisms in Han Chinese subjects.

Attention-deficit/hyperactivity disorder (ADHD) is an important public health problem. Although serotonin is believed to be an important neurotransmitter in the etiology of this disorder, it remains unclear which specific 5-HT receptors are involved in regulating the symptoms of ADHD. Previous studies have provided favorable evidence for the association of ADHD with both the serotonin transporter gene and serotonin 1B receptor gene. To further investigate the role of other genes of the serotonergic pathway in ADHD, the current study examined variants of the serotonin 4 receptor gene in a relatively large sample of ADHD nuclear families. The T allele of the 83097 C>T polymorphism of HTR4 showed a tendency of preferential transmission to probands with ADHD (chi(2)=2.699, P=0.100). When haplotype TDT analysis of HTR4 was performed, we further found that the C/G haplotype of the 83097 C>T and 83198 A>G polymorphisms (chi(2)=8.783, P=0.003) and the C/G/C haplotype of these and the -36 C>T polymorphism (chi(2)=5.762, P=0.016) were under-transmitted to probands with ADHD. These results suggest that the HTR4 gene may play a role in the genetic predisposition to ADHD.

Asian People↗
PubMed2006

Possible association of the alpha-2A adrenergic receptor gene (ADRA2A) with symptoms of attention-deficit/hyperactivity disorder.

A dysfunction of the central noradrenergic system has long been suggested to be involved in attention-deficit/hyperactivity disorder (ADHD). Pharmacological evidence from animal studies and clinical practice has identified the alpha-2A adrenergic receptor gene (ADRA2A) as a candidate gene in ADHD. Some findings from Caucasian populations seem to support a role for this gene in ADHD. The current study first examined the association of the ADRA2A MspI and DraI polymorphisms with ADHD in the Han Chinese population, which differs quite substantially from the Caucasian population in the frequencies of alleles at these polymorphisms. No biased transmission of alleles of either polymorphism was observed using transmission disequilibrium test (TDT) analysis in a sample of 268 nuclear families with an ADHD proband; however, haplotype analysis only identified a trend toward over-transmission of the M/C haplotype to probands with the combined subtype of ADHD (chi(2) = 3.233, P = 0.072). The mm genotype of the MspI polymorphism was also marginally related (P = 0.051) to lower ADHD symptom scores in a sample of 559 Chinese children with ADHD, which is inconsistent with data from Caucasian samples. Our results provide weak evidence for a possible role of ADRA2A in ADHD symptom expression.

Adolescent↗
PubMed2006

Association between tryptophan hydroxylase gene polymorphisms and attention deficit hyperactivity disorder in Chinese Han population.

Attention deficit hyperactivity disorder (ADHD) is a severe behavioral disorder in children known to have a substantial genetic component. Prior studies have implicated serotonin genes in the etiology of ADHD but have not examined tryptophan hydroxylase (TPH), which is a rate-limiting enzyme in serotonin biosynthesis. The current study examined the relationship between the A218C and A-6526G polymorphisms of the TPH gene and ADHD. Three hundred sixty-two unrelated ADHD probands and their biological parents were recruited to participate in this study. No biased transmission of any allele of the two polymorphisms was observed using TDT analysis. However, haplotype analyses found that the rare 218A/-6526G haplotype was significantly not transmitted to probands with ADHD (chi(2) = 4.4995, P = 0.034), regardless of subtype. Although this finding for ADHD in the Chinese Han population.

Adolescent↗
PubMed2006

Possible role of potassium channel, big K in etiology of schizophrenia.

Schizophrenia (SZ), a common severe mental disorder, affecting about 1% of the world population. However, the etiology of SZ is still largely unknown. It is believed that molecules that are in an association with the etiology and pathology of SZ are neurotransmitters including dopamine, 5-HT and gamma-aminobutyric acid (GABA). But several lines of evidences indicate that potassium large conductance calcium-activated channel, known as BK channel, is likely to be included. BK channel belongs to a group of ion channels that plays an important role in regulating neuronal excitability and transmitter releasing. Its involvement in SZ emerges as a great interest. For example, commonly used neuroleptics, in clinical therapeutic concentrations, alter calcium-activated potassium conductance in central neurons. Diazoxide, a potassium channel opener/activator, showed a significant superiority over haloperidol alone in the treatment of positive and general psychopathology symptoms in SZ. Additionally, estrogen, which regulates the activity of BK channel, modulates dopaminergic D2 receptor and has an antipsychotic-like effect. Therefore, we hypothesize that BK channel may play a role in SZ and those agents, which can target either BK channel functions or its expression may contribute to the therapeutic actions of SZ treatment.

Animals↗
PubMed2006

Stress-induced change of mitochondria membrane potential regulated by genomic and non-genomic GR signaling: a possible mechanism for hippocampus atrophy in PTSD.

Posttraumatic stress disorder (PTSD) is a common psychiatric disorder often accompanied by morphologic changes in the hippocampus. Brain imaging studies have demonstrated a strong relationship between PTSD and a reduction in the volume of the hippocampus; however, the mechanisms that cause such atrophy are not well understood. In an attempt to expand our knowledge of these mechanisms, our theory has focused on the role of mitochondria in cell death, which may be associated with atrophy of the hippocampus. In addition to their function in respiration, mitochondria play an important role in the regulation of cytochrome c, an apoptotic signaling element. Normally, cytochrome c resides in the intermembrane space of mitochondria, where membrane potential exists-negative inside of about 180-200mV. In response to a variety of apoptotic stimuli, mitochondria membrane potential can be changed by genomic and non-genomic cortisol action. For the non-genomic action, stress increases cortisol levels, which activates the glucocorticoid receptor (GR). Stress-activated GR directly binds to mitochondrial membranes to regulate membrane potential. The GR will also produce a genomic action, in which GR, in interacting with several other molecules (such as heat shock proteins 90/70/40, etc.), translocates into the nucleus of the cell, where it binds to DNA and exerts transcriptional action. As one of the downstream modulaters of GR activation, Bax can be up regulated and translocated to the mitochondria, where it binds to modulator of apoptosis-1 (MAP-1), a mitochondrial effector of BAX to cause change Deltapsi. These non-genomic and genomic cortisol-induced changes of the mitochondrial membrane potential can result in the release of cytochrome c from the mitochondria to the cytoplasm where the cytochrome c promotes of the action of caspases which leads to apoptosis. Therefore, we hypothesis that stress-induced changes of mitochondrial membrane potential are regulated by non-genomic and genomic actions of cortisol in hippocampal neurons. Understanding the molecular mechanism for stress-induced cell death in the hippocampus may shed a new light on developing a mitochondrial membrane potential related therapeutic drug and/or diagnostic tool for PTSD.

Animals↗
PubMed2005

Identification of gene markers based on well validated and subcategorized stressed animals for potential clinical applications in PTSD.

Post-traumatic stress disorder (PTSD) is a complex mental disorder that can develop in response to traumatic experiences. The molecular mechanisms underlying the pathology of PTSD are poorly understood, and this lack of knowledge hampers our ability to find superior therapeutic approaches to the treatment of this disorder. There are two main reasons for our lack of study in this area: here is no sufficiently validated animal model and lack of large-scale studies for the search of underlying molecular mechanisms. Thus, to promote research on PTSD (especially its molecular mechanisms) and to set molecular basis for searching novel medications of this disorder, large-scale, genome-wide interrogation of a significant amount of genes based upon a well validated animal model is demanded. We hypothesize that a significant number of genes are involved in PTSD. It is only with a large number of these genes identified in specific samples of PTSD-related population, and then it is possible for a sufficient understanding of the pathology at the molecular level of a PTSD, as well as for enhancing the PTSD's therapeutic and preventative strategies. Two prerequisites are needed for testing this hypothesis: (1) relative pure samples from a well validated animal model; and (2) genome-wide screening of PTSD molecular targets. For the animal model, we suggest to use the predator-exposure paradigm, in which rats are exposed to a predator, this model has previously been evaluated behaviorally well emulated the clinical symptoms of PTSD. For a better stringency, three criteria can be used to further validate this animal model: analogous (similarity of behavior), predictive (predictability of drug response) and biological mechanism (e.g., electrophysiological and pathological change in amygdala). For large-scale molecular target screening, the new microarray technology, which can profile expression of tens of thousands genes simultaneously, is the method of choice. The validity and practicability of this hypothesis and the strategy for its testing have been supported by our preliminary laboratory data.

Animals↗
PubMed2005

Stepholidine protects against H2O2 neurotoxicity in rat cortical neurons by activation of Akt.

The fundamental pathological process(es) associated with schizophrenia (SZ) remain(s) uncertain, but multiple lines of evidence suggest that this condition is associated with excessive stimulation of striatal dopamine (DA) D2 receptors, deficient stimulation of medial prefrontal cortex (mPFC) D1 receptors as well as neuronal apoptosis. Unlike typical antipsychotics, stepholidine (SPD), which is isolated from the Chinese herb stephania, has D1 and D2 dual properties and regulates neuronal cell differentiation and proliferation. It is unknown, however, whether it possesses a neuroprotective property. Here, we report that SPD prevented neuronal cell death from H2O2 exposure and increased the levels of phosphorylated Akt (pAkt), a serine/threonine protein kinase. The SPD-induced neuroprotection and activation of Akt were blocked by LY294002, a PI3-K inhibitor, suggesting that the anti-apoptotic action of SPD is mediated via the PI3-K/Akt signaling pathway. Thus, as a survival or anti-apoptotic factor for neuronal cells, SPD may contribute to the therapeutic action of SPD in SZ treatment.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2005

The anti-apoptotic, glucocorticoid receptor cochaperone protein BAG-1 is a long-term target for the actions of mood stabilizers.

Increasing data suggest that impairments of cellular plasticity/resilience underlie the pathophysiology of bipolar disorder. A series of microarray studies with validating criteria have recently revealed a common, novel target for the long-term actions of the structurally highly dissimilar mood stabilizers lithium and valproate: BAG-1 [BCL-2 (B-cell CLL/lymphoma 2)-associated athanogene]. Because BAG-1 attenuates glucocorticoid receptor (GR) nuclear translocation, activates ERK (extracellular signal-regulated kinase) MAP (mitogen-activated protein) kinases, and potentiates anti-apoptotic functions of BCL-2, extensive additional studies were undertaken. Chronic administration of both agents at therapeutic doses increased the expression of BAG-1 in rat hippocampus. Furthermore, these findings were validated at the protein level, and the effects were seen in a time frame consistent with therapeutic effects and were specific for mood stabilizers. Functional studies showed that either lithium or valproate, at therapeutically relevant levels, inhibited dexamethasone-induced GR nuclear translocation and inhibited GR transcriptional activity. Furthermore, small interfering RNA studies showed that these inhibitory effects on GR activity were mediated, at least in part, through BAG-1. The observation that BAG-1 inhibits glucocorticoid activation suggests that mood stabilizers may counteract the deleterious effects of hypercortisolemia seen in bipolar disorder by upregulating BAG-1. Additionally, these studies suggest that regulation of GR-mediated plasticity may play a role in the treatment of bipolar disorder and raise the possibility that agents affecting BAG-1 more directly may represent novel therapies for this devastating illness.

Alkaline Phosphatase↗
PubMed2005

Serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder in Chinese Han subjects.

Serotonin is an endogenous neurotransmitter that regulates aggressive and impulsive behavior and may be involved in the development of attention deficit hyperactivity disorder (ADHD). 5-HT1B knockout mice display hyperactivity, increased exploratory activity and aggression, reduced anxiety, increased vulnerability to cocaine self-administration, and elevated alcohol consumption. Many of these same behaviors are seen in patients with ADHD. Prior studies reported excess transmission of the 861G allele of 5-HT1B to ADHD offspring. We used the transmission disequilibrium test (TDT) and haplotype analysis to investigate the A-161T and G861C polymorphisms in the 5-HT1B receptor gene in ADHD trios from the Chinese Han population. We found no association with ADHD but did find a tendency for excess transmission of the 861G allele (chi(2) = 3.766, P = 0.052) and the G/A haplotype (chi(2) = 2.925, df = 1, P = 0.087), and under-transmission of C/A haplotype (chi(2) = 3.707, df = 1, P = 0.054) to offspring with inattentive ADHD.

Alleles↗
PubMed2004

Family-based and case-control association studies of DRD4 and DAT1 polymorphisms in Chinese attention deficit hyperactivity disorder patients suggest long repeats contribute to genetic risk for the disorder.

Molecular genetic studies of attention deficit hyperactivity disorder (ADHD) have implicated the variable number of tandem repeat (VNTR) polymorphisms of two candidate genes, the dopamine D4 receptor (DRD4) and the dopamine transporter (DAT1). We sought to determine if these genes were relevant to the etiology of ADHD in China by using both family-based (N = 202 nuclear ADHD families) and case-control (N = 340 ADHD cases, and 226 controls) association study designs. Diagnoses and subtypes were ascertained according to Clinical Diagnostic Interview Scales (CDIS) using DSM-IV criteria. The repeat numbers at the DRD4 VNTR ranged from 2 to 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 VNTR, the repeat numbers ranged from 6 to 7 repeats and 9 to 11 repeats. The 10-repeat allele was the most frequent (90.7%). The long-repeat alleles of DRD4 (ranging from 4 to 6 repeats) and DAT1 (ranging from 11 to 12 repeats), were present more frequently in ADHD probands than controls (P < 0.05), although there was no significant allelic association when the alleles were analyzed separately from each other and there findings were not supported by within family tests of association. An exploratory stratification by gender suggests that long-repeat alleles of DRD4 and DAT1 may increase the risk for ADHD in Han Chinese children.

Adolescent↗