Stephen V. Faraone

Bio: Stephen V. Faraone is an academic researcher from State University of New York Upstate Medical University. The author has contributed to research in topics: Attention deficit hyperactivity disorder & Bipolar disorder. The author has an hindex of 188, co-authored 1427 publications receiving 140298 citations. Previous affiliations of Stephen V. Faraone include University of Bergen & National Institute for Health Research.

Time reproduction in children with ADHD and their nonaffected siblings.

Abstract: Objective: Time reproduction is deficient in children with attention-deficit/hyperactivity disorder (ADHD). Whether this deficit is familial and could therefore serve as a candidate endophenotype has not been previously investigated. It is unknown whether timing deficits are also measurable in adolescent children with ADHD and nonaffected siblings. Method: These issues were investigated in 226 children with ADHD, 188 nonaffected siblings, and 162 normal controls ages 5 to 19. Children participated in a visual and auditory time reproduction task. They reproduced interval lengths of 4, 8, 12, 16, and 20 seconds. Results: Children with ADHD and their nonaffected siblings were less precise than controls, particularly when task difficulty was systematically increased. Time reproduction skills were familial. Time reproduction deficits were more pronounced in younger children with ADHD than in older children. Children with ADHD could be clearly dissociated from control children until the age of 9. After this age, group differences were somewhat attenuated, but were still present. Differences between nonaffected siblings and controls were constant across the age range studied. Deficits were unaffected by modality. Conclusions: Time reproduction may serve as a candidate endophenotype for ADHD, predominantly in younger children with (a genetic risk for) ADHD.

Comorbidity of parental anxiety disorders as risk for childhood-onset anxiety in inhibited children.

Abstract: Objective Previous work suggested that children of parents with panic disorder and agoraphobia were likely to be classified as behaviorally inhibited and that behaviorally inhibited children were likely to develop anxiety disorders However, the factors determining which inhibited children were at risk for childhood onset of anxiety disorders remained unknown The authors of this study hypothesized that greater anxiety loading in parents would increase the risk for anxiety disorders in children with behavioral inhibition Method Using DSM-III structured interviews, the authors examined patterns of aggregation of anxiety disorders in parents of two existing cohorts of children, one cross-sectional and clinically derived (31 children, 60 parents) and the other epidemiologically derived and longitudinal (40 children, 75 parents) Within each cohort, parents were stratified into three groups based on the presence (behavioral inhibition and anxiety) or absence (behavioral inhibition only, no behavioral inhibition and no anxiety) of behavioral inhibition and two or more anxiety disorders in their child Results Parents of children with behavioral inhibition and anxiety, from both the clinical and nonclinical cohorts, had significantly higher rates of two or more anxiety disorders than did parents of children with behavioral inhibition only and parents of children with no behavioral inhibition and no anxiety Conclusions These results indicate that the presence of parental loading for anxiety disorders may help to identify the subgroup of inhibited children at very high risk for developing childhood-onset anxiety disorders

Evidence for genetic association of RORB with bipolar disorder

Abstract: Background: Bipolar disorder, particularly in children, is characterized by rapid cycling and switching, making circadian clock genes plausible molecular underpinnings for bipolar disorder. We previously reported work establishing mice lacking the clock gene D-box binding protein (DBP) as a stress-reactive genetic animal model of bipolar disorder. Microarray studies revealed that expression of two closely related clock genes, RAR-related orphan receptors alpha (RORA) and beta (RORB), was altered in these mice. These retinoid-related receptors are involved in a number of pathways including neurogenesis, stress response, and modulation of circadian rhythms. Here we report association studies between bipolar disorder and single-nucleotide polymorphisms (SNPs) in RORA and RORB. Methods: We genotyped 355 RORA and RORB SNPs in a pediatric cohort consisting of a family-based sample of 153 trios and an independent, non-overlapping case-control sample of 152 cases and 140 controls. Bipolar disorder in children and adolescents is characterized by increased stress reactivity and frequent episodes of shorter duration; thus our cohort provides a potentially enriched sample for identifying genes involved in cycling and switching. Results: We report that four intronic RORB SNPs showed positive associations with the pediatric bipolar phenotype that survived Bonferroni correction for multiple comparisons in the case-control sample. Three RORB haplotype blocks implicating an additional 11 SNPs were also associated with the disease in the case-control sample. However, these significant associations were not replicated in the sample of trios. There was no evidence for association between pediatric bipolar disorder and any RORA SNPs or haplotype blocks after multiple-test correction. In addition, we found no strong evidence for association between the age-at-onset of bipolar disorder with any RORA or RORB SNPs. Conclusion: Our findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder.

Neuropsychological risk indicators for schizophrenia: a preliminary study of female relatives of schizophrenic and bipolar probands.

Abstract: Evidence of subtle neuropsychological deficits in relatives of schizophrenic probands (REL-SZs) suggests that these are risk indicators for schizophrenia, but little is known about whether neuropsychological performance in REL-SZs differs from that in other groups of relatives. We compared neuropsychological function in female REL-SZs (n = 39), relatives of primarily psychotic bipolar disorder probands (REL-BPs; n = 15), and a normal control group (n = 44). After adjustment for expected intellectual ability (based on reading recognition), REL-SZs showed deficits in verbal and visual memory (Wechsler Memory Scale-Revised logical memories, visual reproductions), and auditory attention (dichotic digits) compared with either REL-BPs or control subjects. Memory, but not dichotic listening differences remained significant after adjusting for current IQ; however, average effect sizes after controlling for either reading or IQ were roughly comparable for these three parameters (d = 0.80, 0.71, and 0.69, respectively). REL-BPs and control subjects showed little difference. Although both schizophrenic and bipolar patients often manifest neuropsychological dysfunction, these preliminary findings indicate subtle neuropsychological deficits only in REL-SZs. Such differences suggest different underlying processes; neuropsychological impairment may, in part, reflect an expression of genetic liability to schizophrenia but not bipolar disorder. Replication with a larger REL-BP sample and with male relatives is needed to evaluate the generalizability of the results.

Neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder.

Abstract: The goal of this study was to assess neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder (ADHD). Participants were 156 siblings of ADHD probands with (N = 40) and without (N = 116) ADHD (according to criteria of the Diagnostic and Statistical Manual of Mental Disorders (3rd edition, revised; American Psychiatric Association, 1987) and 118 siblings of non-ADHD normal controls of similar age, IQ, and grade level. Information on attention, executive, and memory functions was obtained in a standardized manner without knowledge of clinical status. Compared with siblings of controls, siblings with ADHD were significantly impaired on the Stroop test and on verbal learning and memory. In contrast, siblings without ADHD were similar to controls on virtually all measures. These data suggest that some executive, attention, and verbal learning deficits are found in nonreferred individuals with ADHD but that neuropsychological deficits are unlikely to constitute an endophenotype to ADHD.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Using Multivariate Statistics

Abstract: Thank you for downloading using multivariate statistics. As you may know, people have look hundreds times for their favorite novels like this using multivariate statistics, but end up in infectious downloads. Rather than reading a good book with a cup of tea in the afternoon, instead they juggled with some harmful bugs inside their laptop. using multivariate statistics is available in our digital library an online access to it is set as public so you can download it instantly. Our books collection saves in multiple locations, allowing you to get the most less latency time to download any of our books like this one. Merely said, the using multivariate statistics is universally compatible with any devices to read.

Human biochemical genetics

Abstract: So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Abstract: There is increasing evidence that genome-wide association ( GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study ( using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined similar to 2,000 individuals for each of 7 major diseases and a shared set of similar to 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 X 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals ( including 58 loci with single-point P values between 10(-5) and 5 X 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.