Rulun Zhou

Bio: Rulun Zhou is an academic researcher from Peking University. The author has contributed to research in topics: Attention deficit hyperactivity disorder & Haplotype. The author has an hindex of 15, co-authored 23 publications receiving 962 citations.

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

Abstract: 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.

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

Abstract: 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.

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.

Abstract: 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.

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

Abstract: 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).

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

Abstract: 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 (χ2 = 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. © 2006 Wiley-Liss, Inc.

From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression

Abstract: Major life stressors, especially those involving interpersonal stress and social rejection, are among the strongest proximal risk factors for depression. In this review, we propose a biologically plausible, multilevel theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis. Central to this social signal transduction theory of depression is the hypothesis that experiences of social threat and adversity up-regulate components of the immune system involved in inflammation. The key mediators of this response, called proinflammatory cytokines, can in turn elicit profound changes in behavior, which include the initiation of depressive symptoms such as sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. This highly conserved biological response to adversity is critical for survival during times of actual physical threat or injury. However, this response can also be activated by modern-day social, symbolic, or imagined threats, leading to an increasingly proinflammatory phenotype that may be a key phenomenon driving depression pathogenesis and recurrence, as well as the overlap of depression with several somatic conditions including asthma, rheumatoid arthritis, chronic pain, metabolic syndrome, cardiovascular disease, obesity, and neurodegeneration. Insights from this theory may thus shed light on several important questions including how depression develops, why it frequently recurs, why it is strongly predicted by early life stress, and why it often co-occurs with symptoms of anxiety and with certain physical disease conditions. This work may also suggest new opportunities for preventing and treating depression by targeting inflammation.

A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes.

Abstract: Attention-deficit/hyperactivity disorder (ADHD) is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Inattentiveness, overactivity, and impulsiveness are presently regarded as the main clinical symptoms. The dynamic developmental behavioral theory is based on the hypothesis that altered dopaminergic function plays a pivotal role by failing to modulate nondopaminergic (primarily glutamate and GABA) signal transmission appropriately. A hypofunctioning mesolimbic dopamine branch produces altered reinforcement of behavior and deficient extinction of previously reinforced behavior. This gives rise to delay aversion, development of hyperactivity in novel situations, impulsiveness, deficient sustained attention, increased behavioral variability, and failure to "inhibit" responses ("disinhibition"). A hypofunctioning mesocortical dopamine branch will cause attention response deficiencies (deficient orienting responses, impaired saccadic eye movements, and poorer attention responses toward a target) and poor behavioral planning (poor executive functions). A hypofunctioning nigrostriatal dopamine branch will cause impaired modulation of motor functions and deficient nondeclarative habit learning and memory. These impairments will give rise to apparent developmental delay, clumsiness, neurological "soft signs," and a "failure to inhibit" responses when quick reactions are required. Hypofunctioning dopamine branches represent the main individual predispositions in the present theory. The theory predicts that behavior and symptoms in ADHD result from the interplay between individual predispositions and the surroundings. The exact ADHD symptoms at a particular time in life will vary and be influenced by factors having positive or negative effects on symptom development. Altered or deficient learning and motor functions will produce special needs for optimal parenting and societal styles. Medication will to some degree normalize the underlying dopamine dysfunction and reduce the special needs of these children. The theory describes how individual predispositions interact with these conditions to produce behavioral, emotional, and cognitive effects that can turn into relatively stable behavioral patterns.