► Attention span-persistence at age 4 and later educational outcomes were examined. ► Age 4 attention span-persistence predicted math and reading achievement at age 21. ► Age 4 attention ...span-persistence predicted college completion by age 25. ► Relations were mostly direct and not fully mediated by early math or reading. ► Strong attention span-persistence predicted 49% greater odds of completing college.
This study examined relations between children's attention span-persistence in preschool and later school achievement and college completion. Children were drawn from the Colorado Adoption Project using adopted and non-adopted children (N=430). Results of structural equation modeling indicated that children's age 4 attention span-persistence significantly predicted math and reading achievement at age 21 after controlling for achievement levels at age 7, adopted status, child vocabulary skills, gender, and maternal education level. Relations between attention span-persistence and later achievement were not fully mediated by age 7 achievement levels. Logistic regressions also revealed that age 4 attention span-persistence skills significantly predicted the odds of completing college by age 25. The majority of this relationship was direct and was not significantly mediated by math or reading skills at age 7 or age 21. Specifically, children who were rated one standard deviation higher on attention span-persistence at age 4 had 48.7% greater odds of completing college by age 25. Discussion focuses on the importance of children's early attention span-persistence for later school achievement and educational attainment.
The Rubinstein-Taybi syndrome (RTS) is a well-defined complex of congenital malformations characterized by facial abnormalities, broad thumbs and big toes, and mental retardation. The breakpoint of ...two distinct reciprocal translocations occurring in patients with a clinical diagnosis of RTS was located to the same interval on chromosome 16, between the cosmids N2 and RT1, in band 16p13.3. By using two-color fluorescence in situ hybridization, the signal from RT1 was found to be missing from one chromosome 16 in 6 of 24 patients with RTS. The parents of five of these patients did not show a deletion of RT1, indicating a de novo rearrangement. RTS is caused by submicroscopic interstitial deletions within 16p13.3 in approximately 25% of the patients. The detection of microdeletions will allow the objective conformation of the clinical diagnosis in new patients and provides an excellent tool for the isolation of the gene causally related to the syndrome.
Temporal lobe epilepsy is associated with large-scale, wide-ranging changes in gene expression in the hippocampus. Epigenetic changes to DNA are attractive mechanisms to explain the sustained ...hyperexcitability of chronic epilepsy. Here, through methylation analysis of all annotated C-phosphate-G islands and promoter regions in the human genome, we report a pilot study of the methylation profiles of temporal lobe epilepsy with or without hippocampal sclerosis. Furthermore, by comparative analysis of expression and promoter methylation, we identify methylation sensitive non-coding RNA in human temporal lobe epilepsy. A total of 146 protein-coding genes exhibited altered DNA methylation in temporal lobe epilepsy hippocampus (n = 9) when compared to control (n = 5), with 81.5% of the promoters of these genes displaying hypermethylation. Unique methylation profiles were evident in temporal lobe epilepsy with or without hippocampal sclerosis, in addition to a common methylation profile regardless of pathology grade. Gene ontology terms associated with development, neuron remodelling and neuron maturation were over-represented in the methylation profile of Watson Grade 1 samples (mild hippocampal sclerosis). In addition to genes associated with neuronal, neurotransmitter/synaptic transmission and cell death functions, differential hypermethylation of genes associated with transcriptional regulation was evident in temporal lobe epilepsy, but overall few genes previously associated with epilepsy were among the differentially methylated. Finally, a panel of 13, methylation-sensitive microRNA were identified in temporal lobe epilepsy including MIR27A, miR-193a-5p (MIR193A) and miR-876-3p (MIR876), and the differential methylation of long non-coding RNA documented for the first time. The present study therefore reports select, genome-wide DNA methylation changes in human temporal lobe epilepsy that may contribute to the molecular architecture of the epileptic brain.
Family transmission of marijuana use, abuse, and dependence Hopfer, Christian J; Stallings, Michael C; Hewitt, John K ...
Journal of the American Academy of Child and Adolescent Psychiatry,
07/2003, Letnik:
42, Številka:
7
Journal Article
Recenzirano
To examine the familial aggregation of marijuana use, abuse, and dependence.
Adolescents recruited from residential and day treatment programs for youths with conduct and substance problems, matched ...controls, and all available family members were interviewed with structured research instruments. A total of 2,546 individuals from 781 families were interviewed. Risk ratios of relatives of clinical cases were calculated, compared with controls, for marijuana use, abuse, or dependence. Spousal, parent-offspring, and sibling correlations and the proportion of variance attributable to parent-offspring transmission were estimated using structural equation modeling.
For all three measures, the risk ratios were elevated in the family members of clinical probands, with estimates ranging from 1.5 to 3.3. Spousal correlations ranged from 0.33 to 0.70. Parent-offspring correlations ranged from 0.17 to 0.30. Sibling correlations ranged from 0.34 to 0.44. The proportion of variance attributable to factors transmitted from parents to children ranged between 25% and 44%.
Familial aggregation of marijuana use, abuse, and dependence is present for all three measures. The results suggest significant parent-offspring transmission of risk, sibling environmental influences, and assortative mating for all three levels of marijuana use.
Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, ...psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10(-8)) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.
This study describes results from an ongoing family study of adolescent boys and their families designed to investigate potential risk factors for substance abuse. The adolescent treatment probands ...have severe drug and alcohol related problems and were recruited through a residential rehabilitation program. To date, the sample includes 251 individuals: 39 male probands and their families and 34 control families matched for age and geographic location (zip code). Probands and participating family members are given a structured interview which assesses alcohol and drug problems, and various psychiatric symptoms. The purpose of the present study was to examine the coaggregation of depressive symptoms, antisocial behavior, and alcohol misuse. Multivariate pedigree analyses were performed using a model that allowed for the estimation of vertical familial transmission, residual sibling resemblance, and assortative mating. Spouse correlations were estimated at .57, .21, and .31 for antisocial behavior, depressive symptoms, and alcohol abuse, respectively. Residual sibling environment (i.e., sibling resemblance unaccounted for by parent-offspring transmission) was not found for alcohol problem symptoms, but did contribute to resemblance for antisocial behavior and depressive symptoms. The proportion of variance accounted for by vertical familial transmission was estimated at approximately 30 to 40%. More important, correlations among the transmissible family factors for these psychiatric syndromes ranged from .58 to .73, suggesting substantial overlap among the underlying familial antecedents for these disorders.
We describe direct immunofluorometric assays for luteinizing hormone (hLH) and follicle-stimulating hormone (hFSH) in fingerstick blood spots dried on filter paper, based on modifications of ...commercially available kits. Determinations are made from 2.5-mm-diameter discs (3 microL of dried blood) punched out from blood spot standards and samples. Sample dose detection limits of the assays (IU/L) are 0.26 for LH and 0.13 for FSH, with mean interassay CVs of 11.6% (LH) and 7.8% (FSH) at low concentrations. Analytical recoveries of added hormone averaged 100% for LH and 95% for FSH. Clinical studies showed that values for blood spots (x) and directly assayed plasma (y) are highly correlated, so that results from blood spots can be converted directly to plasma equivalents, as follows: yLH = 0.07 + 1.90 xLH, and yFSH = 0.424 + 2.207 xFSH. These gonadotropins are stable in blood spots for at least a year under refrigeration; LH for at least 8 weeks and FSH 6 weeks at 22 degrees C; and both hormones for a week at 37 degrees C. These methods thus allow self-sampling, serial sampling, and mailing of specimens.
Neuroblastoma is a paediatric cancer which originates from precursor cells of the sympathetic nervous system and accounts for 15% of childhood cancer mortalities. With regards to the role of miRNAs ...in neuroblastoma, miR-34a, mapping to a chromosome 1p36 region that is commonly deleted, has been found to act as a tumor suppressor through targeting of numerous genes associated with cell proliferation and apoptosis.
A synthetic miR-34a (or negative control) precursor molecule was transfected into NB1691luc and SK-N-ASluc neuroblastoma cells. Quantitative PCR was used to verify increased miR-34a levels in NB1691luc and SK-N-ASluc cell lines prior to in vitro and in vivo analysis. In vitro analysis of the effects of miR-34a over expression on cell growth, cell cycle and phosphoprotein activation in signal transduction pathways was performed. Neuroblastoma cells over expressing miR-34a were injected retroperitoneally into immunocompromised CB17-SCID mice and tumor burden was assessed over a 21 day period by measuring bioluminescence (photons/sec/cm²).
Over expression of miR-34a in both NB1691luc and SK-N-ASluc neuroblastoma cell lines led to a significant decrease in cell number relative to premiR-negative control treated cells over a 72 hour period. Flow cytometry results indicated that miR-34a induced cell cycle arrest and subsequent apoptosis activation. Phosphoprotein analysis highlighted key elements involved in signal transduction, whose activation was dysregulated as a result of miR-34a introduction into cells. As a potential mechanism of miR-34a action on phosphoprotein levels, we demonstrate that miR-34a over-expression results in a significant reduction of MAP3K9 mRNA and protein levels. Although MAP3K9 is a predicted target of miR-34a, direct targeting could not be validated with luciferase reporter assays. Despite this fact, any functional effects of reduced MAP3K9 expression as a result of miR-34a would be expected to be similar regardless of the mechanism involved. Most notably, in vivo studies showed that tumor growth was significantly repressed after exogenous miR-34a administration in retroperitoneal neuroblastoma tumors.
We demonstrate for the first time that miR-34a significantly reduces tumor growth in an in vivo orthotopic murine model of neuroblastoma and identified novel effects that miR-34a has on phospho-activation of key proteins involved with apoptosis.
The objective of this study was explore the relationship between pregnancy outcomes and dietary sugar intake by pregnant adolescents. From two urban, prenatal clinics in the City of Camden, NJ, a ...cohort of 594 nondiabetic, pregnant adolescents, aged 13-19 y, who delivered live, singleton newborns between 1985 and 1990, was recruited and followed through pregnancy. Registered dietitians collected up to three 24-h recalls during pregnancy. The adolescents were categorized according to total sugar in their diets, with those in the top 10th percentile defined as high sugar consumers (> or = 206 g, n = 60) and the remainder as reference consumers (< 206 g). Primary outcome measures were birth of small-for-gestational-age infants and gestational age. The cohort was 61% black, 30% Hispanic (Puerto Rican) and 9% white. The adjusted odds ratio was 2.01 (95% confidence interval 1.05-7.53) for the delivery of a small-for-gestational-age infant for adolescents consuming high sugar diets, regardless of their ethnicity. In addition, gestational age at delivery was -1.69 +/- 0.62 wk (beta +/- SE) shorter among Puerto Rican adolescents consuming high sugar diets (P = 0.007) compared with all reference sugar consumers and white adolescents consuming high sugar diets. Black adolescents consuming high sugar diets did not exhibit a shortening of gestation. Thus, adolescents consuming high sugar diets are at increased risk for delivering small-for-gestational-age infants, and for delivering infants earlier if they are of Puerto Rican ethnicity.
Ethanol-induced activation (LDA) is a measure of alcohol action on behavior and a predictor of future human alcoholism. Previous studies have shown that the long sleep (LS) and short sleep (SS) ...selected lines of mice differ in LDA and that two to five genes specify this phenotypic difference. The current study examines the genetic components of LDA in the ILS and ISS mice that are inbred derivatives of LS and SS and examines the effects of inbreeding on LDA. We provide estimates of heritability and number of loci that are consistent with those found in previous studies of the LS and SS. We conclude that LDA is a polygenic trait, specified by two to six loci, which have not been affected by inbreeding or genetic drift in the ILS and ISS populations.
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