Sample records for hyperactive inteins peripheral

  1. Dynamics differentiate between active and inactive inteins

    PubMed Central

    Cronin, Melissa; Coolbaugh, Michael J; Nellis, David; Zhu, Jianwei; Wood, David W.; Nussinov, Ruth; Ma, Buyong

    2014-01-01

    The balance between stability and dynamics for active enzymes can be somewhat quantified by studies of intein splicing and cleaving reactions. Inteins catalyze the ligation of flanking host exteins while excising themselves. The potential for applications led to engineering of a mini-intein splicing domain, where the homing endonuclease domain of the Mycobacterium tuberculosis RecA (Mtu recA) intein was removed. The remaining domains were linked by several short peptides, but splicing activity in all was substantially lower than the full-length intein. Native splicing activity was restored in some cases by a V67L mutation. Using computations and experiments, we examine the impact of this mutation on the stability and conformational dynamics of the mini-intein splicing domain. Molecular dynamics simulations were used to delineate the factors that determine the active state, including the V67L mini-intein mutant, and peptide linker. We found that (1) the V67L mutation lowers the global fluctuations in all modeled mini-inteins, stabilizing the mini-intein constructs; (2) the connecting linker length affects intein dynamics; and (3) the flexibilities of the linker and intein core are higher in the active structure. We have observed that the interaction of the linker region and a turn region around residues 35-41 provides the pathway for the allostery interaction. Our experiments reveal that intein catalysis is characterized by non-linear Arrhenius plot, confirming the significant contribution of protein conformational dynamics to intein function. We conclude that while the V67L mutation stabilizes the global structure, cooperative dynamics of all intein regions appear more important for intein function than high stability. Our studies suggest that effectively quenching the conformational dynamics of an intein through engineered allosteric interactions could deactivate intein splicing or cleaving. PMID:25087201

  2. Mechanism of protein splicing of the Pyrococcus abyssi lon protease intein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    O'Brien, Kevin M.; Schufreider, Ann K.; McGill, Melissa A.

    2010-12-17

    Research highlights: {yields} The Pyrococcus abyssi lon protease intein promotes efficient protein splicing. {yields} Inteins with mutations that interfere with individual steps of splicing do not promote unproductive side reactions. {yields} The intein splices with Lys in place of the highly conserved penultimate His. {yields} The intein is flanked by a Gly-rich region at its C terminus that may increase the efficiency of the third step of splicing, Asn cyclization coupled to peptide bond cleavage. -- Abstract: Protein splicing is a post-translational process by which an intervening polypeptide, the intein, excises itself from the flanking polypeptides, the exteins, coupled tomore » ligation of the exteins. The lon protease of Pyrococcus abyssi (Pab) is interrupted by an intein. When over-expressed as a fusion protein in Escherichia coli, the Pab lon protease intein can promote efficient protein splicing. Mutations that block individual steps of splicing generally do not lead to unproductive side reactions, suggesting that the intein tightly coordinates the splicing process. The intein can splice, although it has Lys in place of the highly conserved penultimate His, and mutants of the intein in the C-terminal region lead to the accumulation of stable branched-ester intermediate.« less

  3. An intein with genetically selectable markers provides a new approach to internally label proteins with GFP.

    PubMed

    Ramsden, Richard; Arms, Luther; Davis, Trisha N; Muller, Eric G D

    2011-06-27

    Inteins are proteins that catalyze their own removal from within larger precursor proteins. In the process they splice the flanking protein sequences, termed the N-and C-terminal exteins. Large inteins frequently have a homing endonuclease that is involved in maintaining the intein in the host. Splicing and nuclease activity are independent and distinct domains in the folded structure. We show here that other biochemical activities can be incorporated into an intein in place of the endonuclease without affecting splicing and that these activities can provide genetic selection for the intein. We have coupled such a genetically marked intein with GFP as the N-terminal extein to create a cassette to introduce GFP within the interior of a targeted protein. The Pch PRP8 mini-intein of Penicillium chrysogenum was modified to include: 1) aminoglycoside phosphotransferase; 2) imidazoleglycerol-phosphate dehydratase, His5 from S. pombe ; 3) hygromycin B phosphotransferase; and 4) the transcriptional activator LexA-VP16. The proteins were inserted at the site of the lost endonuclease. When expressed in E. coli, all of the modified inteins spliced at high efficiency. Splicing efficiency was also greater than 96% when expressed from a plasmid in S. cerevisiae. In addition the inteins conferred either G418 or hygromycin resistance, or histidine or leucine prototropy, depending on the inserted marker and the yeast genetic background. DNA encoding the marked inteins coupled to GFP as the N-terminal extein was PCR amplified with ends homologous to an internal site in the yeast calmodulin gene CMD1. The DNA was transformed into yeast and integrants obtained by direct selection for the intein's marker. The His5-marked intein yielded a fully functional calmodulin that was tagged with GFP within its central linker. Inteins continue to show their flexibility as tools in molecular biology. The Pch PRP8 intein can successfully tolerate a variety of genetic markers and still retain high splicing efficiency. We have shown that a genetically marked intein can be used to insert GFP in one-step within a target protein in vivo.

  4. Traceless splicing enabled by substrate-induced activation of the Nostoc punctiforme Npu DnaE intein after mutation of a catalytic cysteine to serine.

    PubMed

    Cheriyan, Manoj; Chan, Siu-Hong; Perler, Francine

    2014-12-12

    Inteins self-catalytically cleave out of precursor proteins while ligating the surrounding extein fragments with a native peptide bond. Much attention has been lavished on these molecular marvels with the hope of understanding and harnessing their chemistry for novel biochemical transformations including coupling peptides from synthetic or biological origins and controlling protein function. Despite an abundance of powerful applications, the use of inteins is still hampered by limitations in our understanding of their specificity (defined as flanking sequences that permit splicing) and the challenge of inserting inteins into target proteins. We examined the frequently used Nostoc punctiforme Npu DnaE intein after the C-extein cysteine nucleophile (Cys+1) was mutated to serine or threonine. Previous studies demonstrated reduced rates and/or splicing yields with the Npu DnaE intein after mutation of Cys+1 to Ser+1. In this study, genetic selection identified extein sequences with Ser+1 that enabled the Npu DnaE intein to splice with only a 5-fold reduction in rate compared to the wild-type Cys+1 intein and without mutation of the intein itself to activate Ser+1 as a nucleophile. Three different proteins spliced efficiently after insertion of the intein flanked by the selected sequences. We then used this selected specificity to achieve traceless splicing in a targeted enzyme at a location predicted by primary sequence similarity to only the selected C-extein sequence. This study highlights the latent catalytic potential of the Npu DnaE intein to splice with an alternative nucleophile and enables broader intein utility by increasing insertion site choices. Copyright © 2014. Published by Elsevier Ltd.

  5. Regulation of protein activity with small-molecule-controlled inteins

    PubMed Central

    Skretas, Georgios; Wood, David W.

    2005-01-01

    Inteins are the protein analogs of self-splicing RNA introns, as they post-translationally excise themselves from a variety of protein hosts. Intein insertion abolishes, in general, the activity of its host protein, which is subsequently restored upon intein excision. These protein elements therefore have the potential to be used as general molecular “switches” for the control of arbitrary target proteins. Based on rational design, an intein-based protein switch has been constructed whose splicing activity is conditionally triggered in vivo by the presence of thyroid hormone or synthetic analogs. This modified intein was used in Escherichia coli to demonstrate that a number of different proteins can be inactivated by intein insertion and then reactivated by the addition of thyroid hormone via ligand-induced splicing. This conditional activation was also found to occur in a dose-dependent manner. Rational protein engineering was then combined with genetic selection to evolve an additional intein whose activity is controlled by the presence of synthetic estrogen ligands. The ability to regulate protein function post-translationally through the use of ligand-controlled intein splicing will most likely find applications in metabolic engineering, drug discovery and delivery, biosensing, molecular computation, as well as many additional areas of biotechnology. PMID:15632292

  6. Conditional Toxin Splicing Using a Split Intein System.

    PubMed

    Alford, Spencer C; O'Sullivan, Connor; Howard, Perry L

    2017-01-01

    Protein toxin splicing mediated by split inteins can be used as a strategy for conditional cell ablation. The approach requires artificial fragmentation of a potent protein toxin and tethering each toxin fragment to a split intein fragment. The toxin-intein fragments are, in turn, fused to dimerization domains, such that addition of a dimerizing agent reconstitutes the split intein. These chimeric toxin-intein fusions remain nontoxic until the dimerizer is added, resulting in activation of intein splicing and ligation of toxin fragments to form an active toxin. Considerations for the engineering and implementation of conditional toxin splicing (CTS) systems include: choice of toxin split site, split site (extein) chemistry, and temperature sensitivity. The following method outlines design criteria and implementation notes for CTS using a previously engineered system for splicing a toxin called sarcin, as well as for developing alternative CTS systems.

  7. A Predictive Model of Intein Insertion Site for Use in the Engineering of Molecular Switches

    PubMed Central

    Apgar, James; Ross, Mary; Zuo, Xiao; Dohle, Sarah; Sturtevant, Derek; Shen, Binzhang; de la Vega, Humberto; Lessard, Philip; Lazar, Gabor; Raab, R. Michael

    2012-01-01

    Inteins are intervening protein domains with self-splicing ability that can be used as molecular switches to control activity of their host protein. Successfully engineering an intein into a host protein requires identifying an insertion site that permits intein insertion and splicing while allowing for proper folding of the mature protein post-splicing. By analyzing sequence and structure based properties of native intein insertion sites we have identified four features that showed significant correlation with the location of the intein insertion sites, and therefore may be useful in predicting insertion sites in other proteins that provide native-like intein function. Three of these properties, the distance to the active site and dimer interface site, the SVM score of the splice site cassette, and the sequence conservation of the site showed statistically significant correlation and strong predictive power, with area under the curve (AUC) values of 0.79, 0.76, and 0.73 respectively, while the distance to secondary structure/loop junction showed significance but with less predictive power (AUC of 0.54). In a case study of 20 insertion sites in the XynB xylanase, two features of native insertion sites showed correlation with the splice sites and demonstrated predictive value in selecting non-native splice sites. Structural modeling of intein insertions at two sites highlighted the role that the insertion site location could play on the ability of the intein to modulate activity of the host protein. These findings can be used to enrich the selection of insertion sites capable of supporting intein splicing and hosting an intein switch. PMID:22649521

  8. VDE-initiated intein homing in Saccharomyces cerevisiae proceeds in a meiotic recombination-like manner.

    PubMed

    Fukuda, Tomoyuki; Nogami, Satoru; Ohya, Yoshikazu

    2003-07-01

    Inteins and group I introns found in prokaryotic and eukaryotic organisms occasionally behave as mobile genetic elements. During meiosis of the yeast Saccharomyces cerevisiae, the site-specific endonuclease encoded by VMA1 intein, VDE, triggers a single double-strand break (DSB) at an inteinless allele, leading to VMA1 intein homing. Besides the accumulating information on the in vitro activity of VDE, very little has been known about the molecular mechanism of intein homing in yeast nucleus. We developed an assay to detect the product of VMA1 intein homing in yeast genome. We analysed mutant phenotypes of RecA homologs, Rad51p and Dmc1p, and their interacting proteins, Rad54p and Tid1p, and found that they all play critical roles in intein inheritance. The absence of DSB end processing proteins, Sae2p and those in the Mre11-Rad50-Xrs2 complex, also causes partial reduction in homing efficiency. As with meiotic recombination, crossover events are frequently observed during intein homing. We also observed that the absence of premeiotic DNA replication caused by hydroxyurea (HU) or clb5delta clb6delta mutation reduces VDE-mediated DSBs. The repairing system working in intein homing shares molecular machinery with meiotic recombination induced by Spo11p. Moreover, like Spo11p-induced DNA cleavage, premeiotic DNA replication is a prerequisite for a VDE-induced DSB. VMA1 intein thus utilizes several host factors involved in meiotic and recombinational processes to spread its genetic information and guarantee its progeny through establishment of a parasitic relationship with the organism.

  9. Intein-mediated assembly of a functional β-glucuronidase in transgenic plants

    PubMed Central

    Yang, Jianjun; Fox, George C.; Henry-Smith, Tina V.

    2003-01-01

    The DnaE intein in Synechocystis sp. strain PCC6803 is the first and only naturally split intein that has been identified so far. It is capable of catalyzing a protein trans-splicing mechanism to assemble a mature protein from two separate precursors. Therefore, it is a powerful tool for protein modification and engineering. Inteins have not been identified, nor have intein-mediated protein splicing reactions been demonstrated, in plant cells. In this paper, we describe the use of the Ssp DnaE split intein in transgenic plants for reconstitution of a protein trans-splicing reaction. We have synthesized artificial genes that encode for N-terminal half (Int-n) and C-terminal half (Int-c) fragments of Ssp DnaE split intein and divided β-glucuronidase (GUS) gene to encode GUS-n and GUS-c parts of the enzyme as reporter. The in-frame fusions of GUSn/Intn and Intc/GUSc were constructed and transfected into Arabidopsis. We have observed in vivo reassembly of functional β-glucuronidase when both GUSn/Intn and Intc/GUSc constructs were introduced into the same Arabidopsis genome either by cotransformation or through genetic crossing, hereby signifying an intein-mediated protein trans-splicing mechanism reconstituted in plant cells. PMID:12629210

  10. Purification of Microbially Expressed Recombinant Proteins via a Dual ELP Split Intein System.

    PubMed

    Shi, Changhua; Han, Tzu-Chiang; Wood, David W

    2017-01-01

    Fusions of elastin-like peptide (ELP) purification tags and self-cleaving inteins provide a powerful platform for purifying tagless recombinant proteins without the need for conventional packed-bed columns. A drawback to this method has been premature cleaving of the ELP tag during expression, before the purification procedure can take place. Here we demonstrate a split-intein method, where the self-cleaving intein is divided into two inactive segments during expression and purification. Spontaneous assembly of the purified intein segments then restores self-cleaving activity to deliver the tagless target protein.

  11. Protein trans-splicing on an M13 bacteriophage: towards directed evolution of a semisynthetic split intein by phage display.

    PubMed

    Garbe, Daniel; Thiel, Ilka V; Mootz, Henning D

    2010-10-01

    Split inteins link their fused peptide or protein sequences with a peptide bond in an autocatalytic reaction called protein trans-splicing. This reaction is becoming increasingly important for a variety of applications in protein semisynthesis, polypeptide circularisation, construction of biosensors, or segmental isotopic labelling of proteins. However, split inteins exhibit greatly varying solubility, efficiency and tolerance towards the nature of the fused sequences as well as reaction conditions. We envisioned that phage display as an in vitro selection technique would provide a powerful tool for the directed evolution of split inteins with improved properties. As a first step towards this goal, we show that presentation of active split inteins on an M13 bacteriophage is feasible. Two different C-terminal intein fragments of the Ssp DnaB intein, artificially split at amino acid positions 104 and 11, were encoded in a phagemid vector in fusion to a truncated gpIII protein. For efficient production of hybrid phages, the presence of a soluble domain tag at their N-termini was necessary. Immunoblot analysis revealed that the hybrid phages supported protein trans-splicing with a protein or a synthetic peptide, respectively, containing the complementary intein fragment. Incorporation of biotin or desthiobiotin by this reaction provides a straightforward strategy for future enrichment of desired mutants from randomised libraries of the C-terminal intein fragments on streptavidin beads. Protein semisynthesis on a phage could also be exploited for the selection of chemically modified proteins with unique properties. © 2010 European Peptide Society and John Wiley & Sons, Ltd.

  12. Affinity Purification of Proteins in Tag-Free Form: Split Intein-Mediated Ultrarapid Purification (SIRP).

    PubMed

    Guan, Dongli; Chen, Zhilei

    2017-01-01

    Proteins purified using affinity-based chromatography often exploit a recombinant affinity tag. Existing methods for the removal of the extraneous tag, needed for many applications, suffer from poor efficiency and/or high cost. Here we describe a simple, efficient, and potentially low-cost approach-split intein-mediated ultrarapid purification (SIRP)-for both the purification of the desired tagged protein from Escherichia coli lysate and removal of the tag in less than 1 h. The N- and C-fragment of a self-cleaving variant of a naturally split DnaE intein from Nostoc punctiforme are genetically fused to the N-terminus of an affinity tag and a protein of interest (POI), respectively. The N-intein/affinity tag is used to functionalize an affinity resin. The high affinity between the N- and C-fragment of DnaE intein enables the POI to be purified from the lysate via affinity to the resin, and the intein-mediated C-terminal cleavage reaction causes tagless POI to be released into the flow-through. The intein cleavage reaction is strongly inhibited by divalent ions (e.g., Zn 2+ ) under non-reducing conditions and is significantly enhanced by reducing conditions. The POI is cleaved efficiently regardless of the identity of the N-terminal amino acid except in the cases of threonine and proline, and the N-intein-functionalized affinity resin can be regenerated for multiple cycles of use.

  13. Molecular mechanism of VDE-initiated intein homing in yeast nuclear genome.

    PubMed

    Fukuda, Tomoyuki; Nagai, Yuri; Ohya, Yoshikazu

    2004-01-01

    In Saccharomyces cerevisiae, VMA1 intein encodes a homing endonuclease termed VDE which is produced by an autocatalytic protein splicing reaction. VDE introduces a DSB at its recognition sequence on intein-minus allele, resulting in the lateral transfer of VMA1 intein. In this review, we summarize a decade of in vitro study on VDE and describe our recent study on the in vivo behavior of both VDE and host proteins involved in intein mobility. Meiotic DSBs caused by VDE are repaired in the similar pathway to that working in meiotic recombination induced by Spo11p-mediated DSBs. Meiosis-specific DNA cleavage and homing is shown to be guaranteed by the two distinct mechanisms, the subcellular localization of VDE and a requirement of premeiotic DNA replication. Based on these lines of evidence, we present the whole picture of molecular mechanism of VDE-initiated homing in yeast cells.

  14. Molecular mechanism of vde-initiated intein homing in yeast nuclear genome.

    PubMed

    Fukuda, Tomoyuki; Nagai, Yuri; Ohya, Yoshikazu

    2004-01-01

    In Saccharomyces cerevisiae, VMAI intein encodes a homing endonuclease termed VDE which is produced by an autocatalytic protein splicing reaction. VDE introduces a DSB at its recognition sequence on intein-minus allele, resulting in the lateral transfer of VMAI intein. In this review, we summarize a decade of in vitro study on VDE and describe our recent study on the in vivo behavior of both VDE and host proteins involved in intein mobility. Meiotic DSBs caused by VDE are repaired in the similar pathway to that working in meiotic recombination induced by Spollp-mediated DSBs. Meiosis-specific DNA cleavage and homing is shown to be guaranteed by the two distinct mechanisms, the subcellular localization of VDE and a requirement of premeiotic DNA replication. Based on these lines of evidence, we present the whole picture of molecular mechanism of VDEinitiated homing in yeast cells.

  15. Intein-modified enzymes, their production and industrial applications

    DOEpatents

    Apgar, James; Lessard, Philip; Raab, Michael R.; Shen, Binzhang; Lazar, Gabor; de la Vega, Humberto

    2016-10-11

    A method of predicting an intein insertion site in a protein that will lead to a switching phenotype is provided. The method includes identifying a plurality of C/T/S sites within the protein; selecting from the plurality of C/T/S/ sites those that are ranked 0.75 or higher by a support vector machine, within ten angstroms of the active site of the protein, and at or near a loop-.beta.-sheet junction or a loop-.alpha.-helix junction. A method of controlling protein activity and hosts including proteins with controlled activity are also provided. Also, intein modified proteins and plants containing intein modified proteins are provided.

  16. Evolution and Application of Inteins in Candida species: A Review

    PubMed Central

    Fernandes, José A. L.; Prandini, Tâmara H. R.; Castro, Maria da Conceiçao A.; Arantes, Thales D.; Giacobino, Juliana; Bagagli, Eduardo; Theodoro, Raquel C.

    2016-01-01

    Inteins are invasive intervening sequences that perform an autocatalytic splicing from their host proteins. Among eukaryotes, these elements are present in many fungal species, including those considered opportunistic or primary pathogens, such as Candida spp. Here we reviewed and updated the list of Candida species containing inteins in the genes VMA, THRRS and GLT1 and pointed out the importance of these elements as molecular markers for molecular epidemiological researches and species-specific diagnosis, since the presence, as well as the size of these inteins, is polymorphic among the different species. Although absent in Candida albicans, these elements are present in different sizes, in some environmental Candida spp. and also in most of the non-albicans Candida spp. considered emergent opportunistic pathogens. Besides, the possible role of these inteins in yeast physiology was also discussed in the light of the recent findings on the importance of these elements as post-translational modulators of gene expression, reinforcing their relevance as alternative therapeutic targets for the treatment of non-albicans Candida infections, because, once the splicing of an intein is inhibited, its host protein, which is usually a housekeeping protein, becomes non-functional. PMID:27777569

  17. Efficient system of artificial oil bodies for functional expression and purification of recombinant nattokinase in Escherichia coli.

    PubMed

    Chiang, Chung-Jen; Chen, Hong-Chen; Chao, Yun-Peng; Tzen, Jason T C

    2005-06-15

    Nattokinase, a serine protease, and pronattokinase, when expressed in Escherichia coli, formed insoluble aggregates without enzymatic activity. For functional expression and purification, nattokinase or pronattokinase was first overexpressed in E. coli as an insoluble recombinant protein linked to the C terminus of oleosin, a structural protein of seed oil bodies, by an intein fragment. Artificial oil bodies were reconstituted with triacylglycerol, phospholipid, and the insoluble recombinant protein thus formed. Soluble nattokinase was subsequently released through self-splicing of intein induced by temperature alteration, with the remaining oleosin-intein residing in oil bodies and the leading propeptide of pronattokinase, when present, spontaneously cleaved in the process. Active nattokinase with fibrinolytic activity was harvested by concentrating the supernatant. Nattokinase released from oleosin-intein-pronattokinase exhibited 5 times higher activity than that released from oleosin-intein-nattokinase, although the production yields were similar in both cases. Furthermore, active nattokinase could be harvested in the same system by fusing pronattokinase to the N terminus of oleosin via a different intein linker, with self-splicing induced by 1,4-dithiothreitol. These results have shown a great potential of this system for bacterial expression and purification of functional recombinant proteins.

  18. Oriented covalent immobilization of antibodies for measurement of intermolecular binding forces between zipper-like contact surfaces of split inteins.

    PubMed

    Sorci, Mirco; Dassa, Bareket; Liu, Hongwei; Anand, Gaurav; Dutta, Amit K; Pietrokovski, Shmuel; Belfort, Marlene; Belfort, Georges

    2013-06-18

    In order to measure the intermolecular binding forces between two halves (or partners) of naturally split protein splicing elements called inteins, a novel thiol-hydrazide linker was designed and used to orient immobilized antibodies specific for each partner. Activation of the surfaces was achieved in one step, allowing direct intermolecular force measurement of the binding of the two partners of the split intein (called protein trans-splicing). Through this binding process, a whole functional intein is formed resulting in subsequent splicing. Atomic force microscopy (AFM) was used to directly measure the split intein partner binding at 1 μm/s between native (wild-type) and mixed pairs of C- and N-terminal partners of naturally occurring split inteins from three cyanobacteria. Native and mixed pairs exhibit similar binding forces within the error of the measurement technique (~52 pN). Bioinformatic sequence analysis and computational structural analysis discovered a zipper-like contact between the two partners with electrostatic and nonpolar attraction between multiple aligned ion pairs and hydrophobic residues. Also, we tested the Jarzynski's equality and demonstrated, as expected, that nonequilibrium dissipative measurements obtained here gave larger energies of interaction as compared with those for equilibrium. Hence, AFM coupled with our immobilization strategy and computational studies provides a useful analytical tool for the direct measurement of intermolecular association of split inteins and could be extended to any interacting protein pair.

  19. V67L Mutation Fills an Internal Cavity To Stabilize RecA Mtu Intein

    DOE PAGES

    Zwarycz, Allison S.; Fossat, Martin; Akanyeti, Otar; ...

    2017-05-10

    Inteins mediate protein splicing, which has found extensive applications in protein science and biotechnology. In the Mycobacterium tuberculosis RecA mini–mini intein (ΔΔIhh), a single valine to leucine substitution at position 67 (V67L) dramatically increases intein stability and activity. However, crystal structures show that the V67L mutation causes minimal structural rearrangements, with a root-mean-square deviation of 0.2 Å between ΔΔIhh-V67 and ΔΔIhh-L67. Thus, the structural mechanisms for V67L stabilization and activation remain poorly understood. In this paper, we used intrinsic tryptophan fluorescence, high-pressure nuclear magnetic resonance (NMR), and molecular dynamics (MD) simulations to probe the structural basis of V67L stabilization ofmore » the intein fold. Guanidine hydrochloride denaturation monitored by fluorescence yielded free energy changes (ΔG f°) of -4.4 and -6.9 kcal mol –1 for ΔΔIhh-V67 and ΔΔIhh-L67, respectively. High-pressure NMR showed that ΔΔIhh-L67 is more resistant to pressure-induced unfolding than ΔΔIhh-V67 is. The change in the volume of folding (ΔV f) was significantly larger for V67 (71 ± 2 mL mol –1) than for L67 (58 ± 3 mL mol –1) inteins. The measured difference in ΔV f (13 ± 3 mL mol –1) roughly corresponds to the volume of the additional methylene group for Leu, supporting the notion that the V67L mutation fills a nearby cavity to enhance intein stability. In addition, we performed MD simulations to show that V67L decreases side chain dynamics and conformational entropy at the active site. Finally, it is plausible that changes in cavities in V67L can also mediate allosteric effects to change active site dynamics and enhance intein activity.« less

  20. V67L Mutation Fills an Internal Cavity To Stabilize RecA Mtu Intein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zwarycz, Allison S.; Fossat, Martin; Akanyeti, Otar

    Inteins mediate protein splicing, which has found extensive applications in protein science and biotechnology. In the Mycobacterium tuberculosis RecA mini–mini intein (ΔΔIhh), a single valine to leucine substitution at position 67 (V67L) dramatically increases intein stability and activity. However, crystal structures show that the V67L mutation causes minimal structural rearrangements, with a root-mean-square deviation of 0.2 Å between ΔΔIhh-V67 and ΔΔIhh-L67. Thus, the structural mechanisms for V67L stabilization and activation remain poorly understood. In this paper, we used intrinsic tryptophan fluorescence, high-pressure nuclear magnetic resonance (NMR), and molecular dynamics (MD) simulations to probe the structural basis of V67L stabilization ofmore » the intein fold. Guanidine hydrochloride denaturation monitored by fluorescence yielded free energy changes (ΔG f°) of -4.4 and -6.9 kcal mol –1 for ΔΔIhh-V67 and ΔΔIhh-L67, respectively. High-pressure NMR showed that ΔΔIhh-L67 is more resistant to pressure-induced unfolding than ΔΔIhh-V67 is. The change in the volume of folding (ΔV f) was significantly larger for V67 (71 ± 2 mL mol –1) than for L67 (58 ± 3 mL mol –1) inteins. The measured difference in ΔV f (13 ± 3 mL mol –1) roughly corresponds to the volume of the additional methylene group for Leu, supporting the notion that the V67L mutation fills a nearby cavity to enhance intein stability. In addition, we performed MD simulations to show that V67L decreases side chain dynamics and conformational entropy at the active site. Finally, it is plausible that changes in cavities in V67L can also mediate allosteric effects to change active site dynamics and enhance intein activity.« less

  1. A Recessive Pollination Control System for Wheat Based on Intein-Mediated Protein Splicing.

    PubMed

    Gils, Mario

    2017-01-01

    A transgene-expression system for wheat that relies on the complementation of inactive precursor protein fragments through a split-intein system is described. The N- and C-terminal fragments of a barnase gene from Bacillus amyloliquifaciens were fused to intein sequences from Synechocystis sp. and transformed into wheat plants. Upon translation, both barnase fragments are assembled by an autocatalytic intein-mediated trans-splicing reaction, thus forming a cytotoxic enzyme. This chapter focuses on the use of introns and flexible polypeptide linkers to foster the expression of a split-barnase expression system in plants. The methods and protocols that were employed with the objective to test the effects of such genetic elements on transgene expression and to find the optimal design of expression vectors for use in wheat are provided. Split-inteins can be used to form an agriculturally important trait (male sterility) in wheat plants. The use of this principle for the production of hybrid wheat seed is described. The suggested toolbox will hopefully be a valuable contribution to future optimization strategies in this commercially important crop.

  2. Backbone dynamics and global effects of an activating mutation in minimized Mtu RecA inteins.

    PubMed

    Du, Zhenming; Liu, Yangzhong; Ban, David; Lopez, Maria M; Belfort, Marlene; Wang, Chunyu

    2010-07-23

    Inteins mediate protein splicing, which has found many applications in biotechnology and protein engineering. A single valine-to-leucine mutation (V67L) can globally enhance splicing and related cleavage reactions in minimized Mycobacterium tuberculosis RecA inteins. However, V67L mutation causes little change in crystal structures. To test whether protein dynamics contribute to activity enhancement in the V67L mutation, we have studied the conformations and dynamics of the minimized and engineered intein DeltaDeltaIhh-V67CM and a single V67L mutant, DeltaDeltaIhh-L67CM, by solution NMR. Chemical shift perturbations established that the V67L mutation causes global changes, including changes at the N-terminus and C-terminus of the intein, which are active sites for protein splicing. The single V67L mutation significantly slows hydrogen-exchange rates globally, indicating a shift to more stable conformations and reduction in ensemble distribution. Whereas the V67L mutation causes little change for motions on the picosecond-to-nanosecond timescale, motions on the microsecond-to-millisecond timescale affect a region involving the conserved F-block histidine and C-terminal asparagine, which are residues important for C-terminal cleavage. The V67L mutation is proposed to activate splicing by reducing the ensemble distribution of the intein structure and by modifying the active sites. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  3. pH-Dependent Activation of Streptomyces hygroscopicus Transglutaminase Mediated by Intein

    PubMed Central

    Du, Kun; Liu, Zhongmei; Cui, Wenjing; Zhou, Li; Liu, Yi; Chen, Jian

    2014-01-01

    Microbial transglutaminase (MTG) from Streptomyces is naturally secreted as a zymogen (pro-MTG), which is then activated by the removal of its N-terminal proregion by additional proteases. Inteins are protein-intervening sequences that catalyze protein splicing without cofactors. In this study, a pH-dependent Synechocystis sp. strain PCC6803 DnaB mini-intein (SDB) was introduced into pro-MTG to simplify its activation process by controlling pH. The recombinant protein (pro-SDB-MTG) was obtained, and the activation process was determined to take 24 h at pH 7 in vitro. To investigate the effect of the first residue in MTG on the activity and the cleavage time, two variants, pro-SDB-MTG(D1S) and pro-SDB-MTG(ΔD1), were expressed, and the activation time was found to be 6 h and 30 h, respectively. The enzymatic property and secondary structure of the recombinant MTG and two variants were similar to those of the wild type, indicating that the insertion of mini-intein did not affect the function of MTG. This insignificant effect was further illustrated by molecular dynamics simulations. This study revealed a controllable and effective strategy to regulate the activation process of pro-MTG mediated by a mini-intein, and it may have great potential for industrial MTG production. PMID:24242235

  4. Intein-mediated one-step purification of Escherichia coli secreted human antibody fragments.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, Wan-Yi; Miller, Keith D.; Coolbaugh, Michael

    In this work, we apply self-cleaving affinity tag technology to several target proteins secreted into the Escherichia coli periplasm, including two with disulfide bonds. The target proteins were genetically fused to a self-cleaving chitin-binding domain intein tag for purification via a chitin agarose affinity resin. By attaching the intein-tagged fusion genes to the PelB secretion leader sequence, the tagged target proteins were secreted to the periplasmic space and could be recovered in active form by simple osmotic shock. After chitin-affinity purification, the target proteins were released from the chitin-binding domain tag via intein self-cleaving. This was induced by a smallmore » change in pH from 8.5 to 6.5 at room temperature, allowing direct elution of the cleaved target protein from the chitin affinity resin. The target proteins include the E. coli maltose-binding protein and b-lactamase enzyme, as well as two human antibody fragments that contain disulfide bonds. In all cases, the target proteins were purified with good activity and yield, without the need for refolding. Overall, this work demonstrates the compatibility of the DI-CM intein with the PelB secretion system in E. coli, greatly expanding its potential to more complex proteins.« less

  5. A Dual-Intein Autoprocessing Domain that Directs Synchronized Protein Co-Expression in Both Prokaryotes and Eukaryotes

    PubMed Central

    Zhang, Bei; Rapolu, Madhusudhan; Liang, Zhibin; Han, Zhenlin; Williams, Philip G.; Su, Wei Wen

    2015-01-01

    Being able to coordinate co-expression of multiple proteins is necessary for a variety of important applications such as assembly of protein complexes, trait stacking, and metabolic engineering. Currently only few options are available for multiple recombinant protein co-expression, and most of them are not applicable to both prokaryotic and eukaryotic hosts. Here, we report a new polyprotein vector system that is based on a pair of self-excising mini-inteins fused in tandem, termed the dual-intein (DI) domain, to achieve synchronized co-expression of multiple proteins. The DI domain comprises an Ssp DnaE mini-intein N159A mutant and an Ssp DnaB mini-intein C1A mutant connected in tandem by a peptide linker to mediate efficient release of the flanking proteins via autocatalytic cleavage. Essentially complete release of constituent proteins, GFP and RFP (mCherry), from a polyprotein precursor, in bacterial, mammalian, and plant hosts was demonstrated. In addition, successful co-expression of GFP with chloramphenicol acetyltransferase, and thioredoxin with RFP, respectively, further substantiates the general applicability of the DI polyprotein system. Collectively, our results demonstrate the DI-based polyprotein technology as a highly valuable addition to the molecular toolbox for multi-protein co-expression which finds vast applications in biotechnology, biosciences, and biomedicine. PMID:25712612

  6. Production of Nα-acetylated thymosin α1 in Escherichia coli

    PubMed Central

    2011-01-01

    Background Thymosin α1 (Tα1), a 28-amino acid Nα-acetylated peptide, has a powerful general immunostimulating activity. Although biosynthesis is an attractive means of large-scale manufacture, to date, Tα1 can only be chemosynthesized because of two obstacles to its biosynthesis: the difficulties in expressing small peptides and obtaining Nα-acetylation. In this study, we describe a novel production process for Nα-acetylated Tα1 in Escherichia coli. Results To obtain recombinant Nα-acetylated Tα1 efficiently, a fusion protein, Tα1-Intein, was constructed, in which Tα1 was fused to the N-terminus of the smallest mini-intein, Spl DnaX (136 amino acids long, from Spirulina platensis), and a His tag was added at the C-terminus. Because Tα1 was placed at the N-terminus of the Tα1-Intein fusion protein, Tα1 could be fully acetylated when the Tα1-Intein fusion protein was co-expressed with RimJ (a known prokaryotic Nα-acetyltransferase) in Escherichia coli. After purification by Ni-Sepharose affinity chromatography, the Tα1-Intein fusion protein was induced by the thiols β-mercaptoethanol or d,l-dithiothreitol, or by increasing the temperature, to release Tα1 through intein-mediated N-terminal cleavage. Under the optimal conditions, more than 90% of the Tα1-Intein fusion protein was thiolyzed, and 24.5 mg Tα1 was obtained from 1 L of culture media. The purity was 98% after a series of chromatographic purification steps. The molecular weight of recombinant Tα1 was determined to be 3107.44 Da by mass spectrometry, which was nearly identical to that of the synthetic version (3107.42 Da). The whole sequence of recombinant Tα1 was identified by tandem mass spectrometry and its N-terminal serine residue was shown to be acetylated. Conclusions The present data demonstrate that Nα-acetylated Tα1 can be efficiently produced in recombinant E. coli. This bioprocess could be used as an alternative to chemosynthesis for the production of Tα1. The described methodologies may also be helpful for the biosynthesis of similar peptides. PMID:21513520

  7. The Hedgehog gene family of the cnidarian, Nematostella vectensis, and implications for understanding metazoan Hedgehog pathway evolution.

    PubMed

    Matus, David Q; Magie, Craig R; Pang, Kevin; Martindale, Mark Q; Thomsen, Gerald H

    2008-01-15

    Hedgehog signaling is an important component of cell-cell communication during bilaterian development, and abnormal Hedgehog signaling contributes to disease and birth defects. Hedgehog genes are composed of a ligand ("hedge") domain and an autocatalytic intein ("hog") domain. Hedgehog (hh) ligands bind to a conserved set of receptors and activate downstream signal transduction pathways terminating with Gli/Ci transcription factors. We have identified five intein-containing genes in the anthozoan cnidarian Nematostella vectensis, two of which (NvHh1 and NvHh2) contain definitive hedgehog ligand domains, suggesting that to date, cnidarians are the earliest branching metazoan phylum to possess definitive Hh orthologs. Expression analysis of NvHh1 and NvHh2, the receptor NvPatched, and a downstream transcription factor NvGli (a Gli3/Ci ortholog) indicate that these genes may have conserved roles in planar and trans-epithelial signaling during gut and germline development, while the three remaining intein-containing genes (NvHint1,2,3) are expressed in a cell-type-specific manner in putative neural precursors. Metazoan intein-containing genes that lack a hh ligand domain have previously only been identified within nematodes. However, we have identified intein-containing genes from both Nematostella and in two newly annotated lophotrochozoan genomes. Phylogenetic analyses suggest that while nematode inteins may be derived from an ancestral true hedgehog gene, the newly identified cnidarian and lophotrochozoan inteins may be orthologous, suggesting that both true hedgehog and hint genes may have been present in the cnidarian-bilaterian ancestor. Genomic surveys of N. vectensis suggest that most of the components of both protostome and deuterostome Hh signaling pathways are present in anthozoans and that some appear to have been lost in ecdysozoan lineages. Cnidarians possess many bilaterian cell-cell signaling pathways (Wnt, TGFbeta, FGF, and Hh) that appear to act in concert to pattern tissues along the oral-aboral axis of the polyp. Cnidarians represent a diverse group of animals with a predominantly epithelial body plan, and perhaps selective pressures to pattern epithelia resulted in the ontogeny of the hedgehog pathway in the common ancestor of the Cnidaria and Bilateria.

  8. SPLICEFINDER – A Fast and Easy Screening Method for Active Protein Trans-Splicing Positions

    PubMed Central

    Eppmann, Simone; Busche, Alena; Dikovskaya, Dina; Dötsch, Volker; Mootz, Henning D.

    2013-01-01

    Split intein enabled protein trans-splicing (PTS) is a powerful method for the ligation of two protein fragments, thereby paving the way for various protein modification or protein function control applications. PTS activity is strongly influenced by the amino acids directly flanking the splice junctions. However, to date no reliable prediction can be made whether or not a split intein is active in a particular foreign extein context. Here we describe SPLICEFINDER, a PCR-based method, allowing fast and easy screening for active split intein insertions in any target protein. Furthermore we demonstrate the applicability of SPLICEFINDER for segmental isotopic labeling as well as for the generation of multi-domain and enzymatically active proteins. PMID:24023792

  9. Efficient production of native lunasin with correct N-terminal processing by using the pH-induced self-cleavable Ssp DnaB mini-intein system in Escherichia coli.

    PubMed

    Setrerrahmane, Sarra; Zhang, Yi; Dai, Guangzhi; Lv, Jing; Tan, Shuhua

    2014-09-01

    To develop an efficient and cost-effective approach for the production of small preventive peptide lunasin with correct natural N terminus, a synthetic gene was designed by OPTIMIZER & Gene Designer and cloned into pTWIN1 vector at SapI and PstI sites. Thus, lunasin was N-terminally fused to the pH-induced self-cleavable Ssp DnaB mini-intein linked to a chitin binding domain (CBD) with no extra residues. The resultant fusion protein was highly expressed by lactose induction in Escherichia coli BL21 (DE3) in a 7-l bioreactor and bound to a chitin affinity column. After washing the impurities, the Ssp DnaB intein mediated on-column self-cleavage was easily triggered by shifting pH and temperature to allow the native lunasin released. The final purified lunasin yielded up to 75 mg/l medium. Tricine/SDS-PAGE and matrix-assisted laser desorption time-of-flight (MALDI-TOF)/mass spectrometry (MS) verified the structural authenticity of the product, implying the correct cleavage at the junction between Ssp DnaB intein and lunasin. MTT assay confirmed its potent proliferation inhibitory activity to human cancer cells HCT-116 and MDA-MB-231; however, no cytotoxicity to normal human lens epithelial cell SRA01/04 and hepatoma HepG2. Taken together, we provide a novel strategy to produce recombinant native lunasin with correct N-terminal processing by using the pH-induced self-cleavable Ssp DnaB mini-intein.

  10. Production and purification of recombinant human glucagon overexpressed as intein fusion protein in Escherichia coli.

    PubMed

    Esipov, Roman S; Stepanenko, Vasily N; Gurevich, Alexandr I; Chupova, Larisa A; Miroshnikov, Anatoly I

    2006-01-01

    Chemico-enzymatic synthesis and cloning in Esherichia coli of an artificial gene coding human glucagon was performed. Recombinant plasmid containing hybrid glucagons gene and intein Ssp dnaB from Synechocestis sp. was designed. Expression of the obtained hybrid gene in E. coli, properties of the formed hybrid protein, and conditions of its autocatalytic cleavage leading to glucagon formation were studied.

  11. The Hedgehog gene family of the cnidarian, Nematostella vectensis, and implications for understanding metazoan Hedgehog pathway evolution

    PubMed Central

    Matus, David Q.; Magie, Craig; Pang, Kevin; Martindale, Mark Q; Thomsen, Gerald H.

    2008-01-01

    Hedgehog signaling is an important component of cell-cell communication during bilaterian development, and abnormal Hedgehog signaling contributes to disease and birth defects. Hedgehog genes are composed of a ligand (“hedge”) domain and an autocatalytic intein (“hog”) domain. Hedgehog (hh) ligands bind to a conserved set of receptors and activate downstream signal transduction pathways terminating with Gli/Ci transcription factors. We have identified five intein-containing genes in the anthozoan cnidarian Nematostella vectensis, two of which (NvHh1 and NvHh2) contain definitive hedgehog ligand domains, suggesting that to date, cnidarians are the earliest branching metazoan phylum to possess definitive Hh orthologs. Expression analysis of NvHh1 and NvHh2, the receptor NvPatched and a downstream transcription factor NvGli (a Gli3/Ci ortholog) indicate that these genes may have conserved roles in planar and trans-epithelial signaling during gut and germline development, while the three remaining intein-containing genes (NvHint1,2,3) are expressed in a cell-type specific manner in putative neural precursors. Metazoan intein-containing genes that lack a ligand domain have previously only been identified within nematodes. However, phylogenetic analyses suggest that these nematode inteins may be derived from an ancestral nematode true hedgehog gene, and that the non-bilaterian intein-containing genes identified here may represent an ancestral state prior to the domain swapping events that resulted in the formation of true hedgehog genes in the cnidarian-bilaterian ancestor. Genomic surveys of N. vectensis suggest that most of the components of both protostome and deuterostome Hh signaling pathways are present in anthozoans and that some appear to have been lost in ecdysozoan lineages. Cnidarians possess many bilaterian cell-cell signaling pathways (Wnt, TGFß, FGF and Hh) that appear to act in concert to pattern tissues along the oral-aboral axis of the polyp. Cnidarians represent a diverse group of animals with a predominantly epithelial body plan, and perhaps selective pressures to pattern epithelia resulted in the ontogeny of the hedgehog pathway in the common ancestor of the Cnidaria and Bilateria. PMID:18068698

  12. Hyperactivity and reactivity of peripheral blood neutrophils in chronic periodontitis.

    PubMed

    Matthews, J B; Wright, H J; Roberts, A; Cooper, P R; Chapple, I L C

    2007-02-01

    Some evidence exists that peripheral neutrophils from patients with chronic periodontitis generate higher levels of reactive oxygen species (ROS) after Fcgamma-receptor stimulation than those from healthy controls. We hypothesized that peripheral neutrophils in periodontitis also show both hyper-reactivity to plaque organisms and hyperactivity in terms of baseline, unstimulated generation and release of ROS. Peripheral neutrophils from chronic periodontitis patients and age/sex/smoking-matched healthy controls (18 pairs) were assayed for total ROS generation and extracellular ROS release, with and without stimulation (Fcgamma-receptor and Fusobacterium nucleatum), using luminol and isoluminol chemiluminescence. Assays were performed with and without priming with Escherichia coli lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Phox gene expression (p22, p47, p67, gp91) was investigated using reverse transcription-polymerase chain reaction (RT-PCR). Neutrophils from patients produced higher mean levels of ROS in all assays. Total generation and extracellular release of ROS by patients' cells were significantly greater than those from controls after FcgammaR-stimulation, with (P = 0.023) and without (P < or = 0.023) priming with GM-CSF. Differences in unstimulated total ROS generation were not significant. By contrast, patients' cells demonstrated greater baseline, extracellular ROS release than those from controls (P = 0.004). This difference was maintained after priming with LPS (P = 0.028) but not GM-CSF (P = 0.217). Phox gene expression was similar in patient and control cells at baseline and stimulation with F. nucleatum (3 h) consistently reduced gp91(PHOX) transcripts. Our data demonstrate that peripheral neutrophils from periodontitis patients exhibit hyper-reactivity following stimulation (Fcgamma-receptor and F. nucleatum) and hyperactivity in terms of excess ROS release in the absence of exogenous stimulation. This hyperactive/-reactive neutrophil phenotype is not associated with elevated phox gene expression.

  13. Purification of target proteins from intracellular inclusions mediated by intein cleavable polyhydroxyalkanoate synthase fusions.

    PubMed

    Du, Jinping; Rehm, Bernd H A

    2017-11-02

    Recombinant protein production and purification from Escherichia coli is often accompanied with expensive and complicated procedures, especially for therapeutic proteins. Here it was demonstrated that, by using an intein cleavable polyhydroxyalkanoate synthase fusion, recombinant proteins can be first produced and sequestered on a natural resin, the polyhydroxyalkanoate (PHA) inclusions, then separated from contaminating host proteins via simple PHA bead isolation steps, and finally purified by specific release into the soluble fraction induced by a pH reduction. By translationally fusing a target protein to PHA synthase using a self-cleaving intein as linker, intracellular production of PHA beads was achieved. Upon isolation of respective PHA beads the soluble pure target protein was released by a simple pH shift to 6. The utility of this approach was exemplified by producing six target proteins, including Aequorea victoria green fluorescent protein (GFP), Mycobacterium tuberculosis vaccine candidate Rv1626, the immunoglobulin G (IgG) binding ZZ domain of protein A derived from Staphylococcus aureus, human tumor necrosis factor alpha (TNFα), human granulocyte colony-stimulating factor (G-CSF), and human interferon alpha 2b (IFNα2b). Here a new method for production and purification of a tag-less protein was developed through intein cleavable polyhydroxyalkanoate synthase fusion. Pure target protein could be easily obtained without laborious downstream processing.

  14. Oculomotor Performance Identifies Underlying Cognitive Deficits in Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Loe, Irene M.; Feldman, Heidi M.; Yasui, Enami; Luna, Beatriz

    2009-01-01

    The evaluation of the cognitive control in children with attention-deficit hyperactivity disorder through the use of oculomotor tests reveal that this group showed susceptibility to peripheral distractors and deficits in response inhibition. All subjects were found to have intact sensorimotor function and working memory.

  15. Hyperactivity and reactivity of peripheral blood neutrophils in chronic periodontitis

    PubMed Central

    Matthews, J B; Wright, H J; Roberts, A; Cooper, P R; Chapple, I L C

    2007-01-01

    Some evidence exists that peripheral neutrophils from patients with chronic periodontitis generate higher levels of reactive oxygen species (ROS) after Fcγ-receptor stimulation than those from healthy controls. We hypothesized that peripheral neutrophils in periodontitis also show both hyper-reactivity to plaque organisms and hyperactivity in terms of baseline, unstimulated generation and release of ROS. Peripheral neutrophils from chronic periodontitis patients and age/sex/smoking-matched healthy controls (18 pairs) were assayed for total ROS generation and extracellular ROS release, with and without stimulation (Fcγ-receptor and Fusobacterium nucleatum), using luminol and isoluminol chemiluminescence. Assays were performed with and without priming with Escherichia coli lipopolysaccharide (LPS) and granulocyte–macrophage colony-stimulating factor (GM-CSF). Phox gene expression (p22, p47, p67, gp91) was investigated using reverse transcription–polymerase chain reaction (RT–PCR). Neutrophils from patients produced higher mean levels of ROS in all assays. Total generation and extracellular release of ROS by patients' cells were significantly greater than those from controls after FcγR-stimulation, with (P = 0·023) and without (P ≤ 0·023) priming with GM-CSF. Differences in unstimulated total ROS generation were not significant. By contrast, patients' cells demonstrated greater baseline, extracellular ROS release than those from controls (P = 0·004). This difference was maintained after priming with LPS (P = 0·028) but not GM-CSF (P = 0·217). Phox gene expression was similar in patient and control cells at baseline and stimulation with F. nucleatum (3 h) consistently reduced gp91PHOX transcripts. Our data demonstrate that peripheral neutrophils from periodontitis patients exhibit hyper-reactivity following stimulation (Fcγ-receptor and F. nucleatum) and hyperactivity in terms of excess ROS release in the absence of exogenous stimulation. This hyperactive/-reactive neutrophil phenotype is not associated with elevated phox gene expression. PMID:17223966

  16. Biomarkers and Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analyses

    ERIC Educational Resources Information Center

    Scassellati, Catia; Bonvicini, Cristian; Faraone, Stephen V.; Gennarelli, Massimo

    2012-01-01

    Objective: To determine whether peripheral biochemical markers (biomarkers) might differentiate patients with attention-deficit/hyperactivity disorder (ADHD) from non-ADHD individuals. Method: We conducted a systematic search and a series of meta-analyses of case-control studies comprising studies from 1969 to 2011. Results: We identified 210…

  17. Investigation of the mechanism of meiotic DNA cleavage by VMA1-derived endonuclease uncovers a meiotic alteration in chromatin structure around the target site.

    PubMed

    Fukuda, Tomoyuki; Ohta, Kunihiro; Ohya, Yoshikazu

    2006-06-01

    VMA1-derived endonuclease (VDE), a homing endonuclease in Saccharomyces cerevisiae, is encoded by the mobile intein-coding sequence within the nuclear VMA1 gene. VDE recognizes and cleaves DNA at the 31-bp VDE recognition sequence (VRS) in the VMA1 gene lacking the intein-coding sequence during meiosis to insert a copy of the intein-coding sequence at the cleaved site. The mechanism underlying the meiosis specificity of VMA1 intein-coding sequence homing remains unclear. We studied various factors that might influence the cleavage activity in vivo and found that VDE binding to the VRS can be detected only when DNA cleavage by VDE takes place, implying that meiosis-specific DNA cleavage is regulated by the accessibility of VDE to its target site. As a possible candidate for the determinant of this accessibility, we analyzed chromatin structure around the VRS and revealed that local chromatin structure near the VRS is altered during meiosis. Although the meiotic chromatin alteration exhibits correlations with DNA binding and cleavage by VDE at the VMA1 locus, such a chromatin alteration is not necessarily observed when the VRS is embedded in ectopic gene loci. This suggests that nucleosome positioning or occupancy around the VRS by itself is not the sole mechanism for the regulation of meiosis-specific DNA cleavage by VDE and that other mechanisms are involved in the regulation.

  18. Investigation of the Mechanism of Meiotic DNA Cleavage by VMA1-Derived Endonuclease Uncovers a Meiotic Alteration in Chromatin Structure around the Target Site

    PubMed Central

    Fukuda, Tomoyuki; Ohta, Kunihiro; Ohya, Yoshikazu

    2006-01-01

    VMA1-derived endonuclease (VDE), a homing endonuclease in Saccharomyces cerevisiae, is encoded by the mobile intein-coding sequence within the nuclear VMA1 gene. VDE recognizes and cleaves DNA at the 31-bp VDE recognition sequence (VRS) in the VMA1 gene lacking the intein-coding sequence during meiosis to insert a copy of the intein-coding sequence at the cleaved site. The mechanism underlying the meiosis specificity of VMA1 intein-coding sequence homing remains unclear. We studied various factors that might influence the cleavage activity in vivo and found that VDE binding to the VRS can be detected only when DNA cleavage by VDE takes place, implying that meiosis-specific DNA cleavage is regulated by the accessibility of VDE to its target site. As a possible candidate for the determinant of this accessibility, we analyzed chromatin structure around the VRS and revealed that local chromatin structure near the VRS is altered during meiosis. Although the meiotic chromatin alteration exhibits correlations with DNA binding and cleavage by VDE at the VMA1 locus, such a chromatin alteration is not necessarily observed when the VRS is embedded in ectopic gene loci. This suggests that nucleosome positioning or occupancy around the VRS by itself is not the sole mechanism for the regulation of meiosis-specific DNA cleavage by VDE and that other mechanisms are involved in the regulation. PMID:16757746

  19. Formation of active inclusion bodies induced by hydrophobic self-assembling peptide GFIL8.

    PubMed

    Wang, Xu; Zhou, Bihong; Hu, Weike; Zhao, Qing; Lin, Zhanglin

    2015-06-16

    In the last few decades, several groups have observed that proteins expressed as inclusion bodies (IBs) in bacteria could still be biologically active when terminally fused to an appropriate aggregation-prone partner such as pyruvate oxidase from Paenibacillus polymyxa (PoxB). More recently, we have demonstrated that three amphipathic self-assembling peptides, an alpha helical peptide 18A, a beta-strand peptide ELK16, and a surfactant-like peptide L6KD, have properties that induce target proteins into active IBs. We have developed an efficient protein expression and purification approach for these active IBs by introducing a self-cleavable intein molecule. In this study, the self-assembling peptide GFIL8 (GFILGFIL) with only hydrophobic residues was analyzed, and this peptide effectively induced the formation of cytoplasmic IBs in Escherichia coli when terminally attached to lipase A and amadoriase II. The protein aggregates in cells were confirmed by transmission electron microscopy analysis and retained ~50% of their specific activities relative to the native counterparts. We constructed an expression and separation coupled tag (ESCT) by incorporating an intein molecule, the Mxe GyrA intein. Soluble target proteins were successfully released from active IBs upon cleavage of the intein between the GFIL8 tag and the target protein, which was mediated by dithiothreitol. A variant of GFIL8, GFIL16 (GFILGFILGFILGFIL), improved the ESCT scheme by efficiently eliminating interference from the soluble intein-GFIL8 molecule. The yields of target proteins at the laboratory scale were 3.0-7.5 μg/mg wet cell pellet, which is comparable to the yields from similar ESCT constructs using 18A, ELK16, or the elastin-like peptide tag scheme. The all-hydrophobic self-assembling peptide GFIL8 induced the formation of active IBs in E. coli when terminally attached to target proteins. GFIL8 and its variant GFIL16 can act as a "pull-down" tag to produce purified soluble proteins with reasonable quantity and purity from active aggregates. Owing to the structural simplicity, strong hydrophobicity, and high aggregating efficiency, these peptides can be further explored for enzyme production and immobilization.

  20. Protein C-Terminal Labeling and Biotinylation Using Synthetic Peptide and Split-Intein

    PubMed Central

    Volkmann, Gerrit; Liu, Xiang-Qin

    2009-01-01

    Background Site-specific protein labeling or modification can facilitate the characterization of proteins with respect to their structure, folding, and interaction with other proteins. However, current methods of site-specific protein labeling are few and with limitations, therefore new methods are needed to satisfy the increasing need and sophistications of protein labeling. Methodology A method of protein C-terminal labeling was developed using a non-canonical split-intein, through an intein-catalyzed trans-splicing reaction between a protein and a small synthetic peptide carrying the desired labeling groups. As demonstrations of this method, three different proteins were efficiently labeled at their C-termini with two different labels (fluorescein and biotin) either in solution or on a solid surface, and a transferrin receptor protein was labeled on the membrane surface of live mammalian cells. Protein biotinylation and immobilization on a streptavidin-coated surface were also achieved in a cell lysate without prior purification of the target protein. Conclusions We have produced a method of site-specific labeling or modification at the C-termini of recombinant proteins. This method compares favorably with previous protein labeling methods and has several unique advantages. It is expected to have many potential applications in protein engineering and research, which include fluorescent labeling for monitoring protein folding, location, and trafficking in cells, and biotinylation for protein immobilization on streptavidin-coated surfaces including protein microchips. The types of chemical labeling may be limited only by the ability of chemical synthesis to produce the small C-intein peptide containing the desired chemical groups. PMID:20027230

  1. Intein-mediated site-specific synthesis of tumor-targeting protein delivery system: Turning PEG dilemma into prodrug-like feature

    PubMed Central

    Chen, Yingzhi; Zhang, Meng; Jin, Hongyue; Tang, Yisi; Wang, Huiyuan; Xu, Qin; Li, Yaping; Li, Feng; Huang, Yongzhuo

    2017-01-01

    Poor tumor-targeted and cytoplasmic delivery is a bottleneck for protein toxin-based cancer therapy. Ideally, a protein toxin drug should remain stealthy in circulation for prolonged half-life and reduced side toxicity, but turn activated at tumor. PEGylation is a solution to achieve the first goal, but creates a hurdle for the second because PEG rejects interaction between the drugs and tumor cells therein. Such PEG dilemma is an unsolved problem in protein delivery. Herein proposed is a concept of turning PEG dilemma into prodrug-like feature. A site-selectively PEGylated, gelatinase-triggered cell-penetrating trichosanthin protein delivery system is developed with three specific aims. The first is to develop an intein-based ligation method for achieving site-specific modification of protein toxins. The second is to develop a prodrug feature that renders protein toxins remaining stealthy in blood for reduced side toxicity and improved EPR effect. The third is to develop a gelatinase activatable cell-penetration strategy for enhanced tumor targeting and cytoplasmic delivery. Of note, site-specific modification is a big challenge in protein drug research, especially for such a complicated, multifunctional protein delivery system. We successfully develop a protocol for constructing a macromolecular prodrug system with intein-mediated ligation synthesis. With an on-column process of purification and intein-mediated cleavage, the site-specific PEGylation then can be readily achieved by conjugation with the activated C-terminus, thus constructing a PEG-capped, cell-penetrating trichosanthin system with a gelatinase-cleavable linker that enables tumor-specific activation of cytoplasmic delivery. It provides a promising method to address the PEG dilemma for enhanced protein drug delivery, and importantly, a facile protocol for site-specific modification of such a class of protein drugs for improving their druggability and industrial translation. PMID:27914267

  2. Conditional protein splicing: a new tool to control protein structure and function in vitro and in vivo.

    PubMed

    Mootz, Henning D; Blum, Elyse S; Tyszkiewicz, Amy B; Muir, Tom W

    2003-09-03

    Protein splicing is a naturally occurring process in which an intervening intein domain excises itself out of a precursor polypeptide in an autocatalytic fashion with concomitant linkage of the two flanking extein sequences by a native peptide bond. We have recently reported an engineered split VMA intein whose splicing activity in trans between two polypeptides can be triggered by the small molecule rapamycin. In this report, we show that this conditional protein splicing (CPS) system can be used in mammalian cells. Two model constructs harboring maltose-binding protein (MBP) and a His-tag as exteins were expressed from a constitutive promoter after transient transfection. The splicing product MBP-His was detected by Western blotting and immunoprecipitation in cells treated with rapamycin or a nontoxic analogue thereof. No background splicing in the absence of the small-molecule inducer was observed over a 24-h time course. Product formation could be detected within 10 min of addition of rapamycin, indicating the advantage of the posttranslational nature of CPS for quick responses. The level of protein splicing was dose dependent and could be competitively attenuated with the small molecule ascomycin. In related studies, the geometric flexibility of the CPS components was investigated with a series of purified proteins. The FKBP and FRB domains, which are dimerized by rapamycin and thereby induce the reconstitution of the split intein, were fused to the extein sequences of the split intein halves. CPS was still triggered by rapamycin when FKBP and FRB occupied one or both of the extein positions. This finding suggests yet further applications of CPS in the area of proteomics. In summary, CPS holds great promise to become a powerful new tool to control protein structure and function in vitro and in living cells.

  3. Decreased anxiety- and depression-like behaviors and hyperactivity in a type 3 deiodinase-deficient mouse showing brain thyrotoxicosis and peripheral hypothyroidism.

    PubMed

    Stohn, J Patrizia; Martinez, M Elena; Hernandez, Arturo

    2016-12-01

    Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 -/- mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 -/- mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 -/- mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Decreased Anxiety- and Depression-like Behaviors and Hyperactivity in a Type 3 Deiodinase-Deficient Mouse Showing Brain Thyrotoxicosis and Peripheral Hypothyroidism

    PubMed Central

    Stohn, J. Patrizia; Martinez, M. Elena; Hernandez, Arturo

    2016-01-01

    Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 −/− mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 −/− mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 −/− mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. PMID:27580013

  5. Expression and purification of ELP-intein-tagged target proteins in high cell density E. coli fermentation.

    PubMed

    Fong, Baley A; Wood, David W

    2010-10-19

    Elastin-like polypeptides (ELPs) are useful tools that can be used to non-chromatographically purify proteins. When paired with self-cleaving inteins, they can be used as economical self-cleaving purification tags. However, ELPs and ELP-tagged target proteins have been traditionally expressed using highly enriched media in shake flask cultures, which are generally not amenable to scale-up. In this work, we describe the high cell-density expression of self-cleaving ELP-tagged targets in a supplemented minimal medium at a 2.5 liter fermentation scale, with increased yields and purity compared to traditional shake flask cultures. This demonstration of ELP expression in supplemented minimal media is juxtaposed to previous expression of ELP tags in extract-based rich media. We also describe several sets of fed-batch conditions and their impact on ELP expression and growth medium cost. By using fed batch E. coli fermentation at high cell density, ELP-intein-tagged proteins can be expressed and purified at high yield with low cost. Further, the impact of media components and fermentation design can significantly impact the overall process cost, particularly at large scale. This work thus demonstrates an important advances in the scale up of self-cleaving ELP tag-mediated processes.

  6. Expression and purification of ELP-intein-tagged target proteins in high cell density E. coli fermentation

    PubMed Central

    2010-01-01

    Background Elastin-like polypeptides (ELPs) are useful tools that can be used to non-chromatographically purify proteins. When paired with self-cleaving inteins, they can be used as economical self-cleaving purification tags. However, ELPs and ELP-tagged target proteins have been traditionally expressed using highly enriched media in shake flask cultures, which are generally not amenable to scale-up. Results In this work, we describe the high cell-density expression of self-cleaving ELP-tagged targets in a supplemented minimal medium at a 2.5 liter fermentation scale, with increased yields and purity compared to traditional shake flask cultures. This demonstration of ELP expression in supplemented minimal media is juxtaposed to previous expression of ELP tags in extract-based rich media. We also describe several sets of fed-batch conditions and their impact on ELP expression and growth medium cost. Conclusions By using fed batch E. coli fermentation at high cell density, ELP-intein-tagged proteins can be expressed and purified at high yield with low cost. Further, the impact of media components and fermentation design can significantly impact the overall process cost, particularly at large scale. This work thus demonstrates an important advances in the scale up of self-cleaving ELP tag-mediated processes. PMID:20959011

  7. Impaired reflexive orienting to social cues in attention deficit hyperactivity disorder.

    PubMed

    Marotta, Andrea; Casagrande, Maria; Rosa, Caterina; Maccari, Lisa; Berloco, Bianca; Pasini, Augusto

    2014-08-01

    The present study investigated whether another person's social attention, specifically the direction of their eye gaze, and non-social directional cues triggered reflexive orienting in individuals with Attention Deficit Hyperactivity Disorder (ADHD) and age-matched controls. A choice reaction time and a detection tasks were used in which eye gaze, arrow and peripheral cues correctly (congruent) or incorrectly (incongruent) signalled target location. Independently of the type of the task, differences between groups were specific to the cue condition. Typically developing individuals shifted attention to the location cued by both social and non-social cues, whereas ADHD group showed evidence of reflexive orienting only to locations previously cued by non-social stimuli (arrow and peripheral cues) but failed to show such orienting effect in response to social eye gaze cues. The absence of reflexive orienting effect for eye gaze cues observed in the participants with ADHD may reflect an attentional impairment in responding to socially relevant information.

  8. High-throughput purification of recombinant proteins using self-cleaving intein tags.

    PubMed

    Coolbaugh, M J; Shakalli Tang, M J; Wood, D W

    2017-01-01

    High throughput methods for recombinant protein production using E. coli typically involve the use of affinity tags for simple purification of the protein of interest. One drawback of these techniques is the occasional need for tag removal before study, which can be hard to predict. In this work, we demonstrate two high throughput purification methods for untagged protein targets based on simple and cost-effective self-cleaving intein tags. Two model proteins, E. coli beta-galactosidase (βGal) and superfolder green fluorescent protein (sfGFP), were purified using self-cleaving versions of the conventional chitin-binding domain (CBD) affinity tag and the nonchromatographic elastin-like-polypeptide (ELP) precipitation tag in a 96-well filter plate format. Initial tests with shake flask cultures confirmed that the intein purification scheme could be scaled down, with >90% pure product generated in a single step using both methods. The scheme was then validated in a high throughput expression platform using 24-well plate cultures followed by purification in 96-well plates. For both tags and with both target proteins, the purified product was consistently obtained in a single-step, with low well-to-well and plate-to-plate variability. This simple method thus allows the reproducible production of highly pure untagged recombinant proteins in a convenient microtiter plate format. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Neuropathic Pain Causes Pyramidal Neuronal Hyperactivity in the Anterior Cingulate Cortex.

    PubMed

    Zhao, Ruohe; Zhou, Hang; Huang, Lianyan; Xie, Zhongcong; Wang, Jing; Gan, Wen-Biao; Yang, Guang

    2018-01-01

    The anterior cingulate cortex (ACC) is thought to be important for acute pain perception as well as the development of chronic pain after peripheral nerve injury. Nevertheless, how ACC neurons respond to sensory stimulation under chronic pain states is not well understood. Here, we used an in vivo two-photon imaging technique to monitor the activity of individual neurons in the ACC of awake, head restrained mice. Calcium imaging in the dorsal ACC revealed robust somatic activity in layer 5 (L5) pyramidal neurons in response to peripheral noxious stimuli, and the degree of evoked activity was correlated with the intensity of noxious stimulation. Furthermore, the activation of ACC neurons occurred bilaterally upon noxious stimulation to either contralateral or ipsilateral hind paws. Notably, with nerve injury-induced neuropathic pain in one limb, L5 pyramidal neurons in both sides of the ACC showed enhanced activity in the absence or presence of pain stimuli. These results reveal hyperactivity of L5 pyramidal neurons in the bilateral ACC during the development of neuropathic pain.

  10. Behavioral and monoamine perturbations in adult male mice with chronic inflammation induced by repeated peripheral lipopolysaccharide administration.

    PubMed

    Krishna, Saritha; Dodd, Celia A; Filipov, Nikolay M

    2016-04-01

    Considering the limited information on the ability of chronic peripheral inflammation to induce behavioral alterations, including on their persistence after inflammatory stimuli termination and on associated neurochemical perturbations, this study assessed the effects of chronic (0.25 mg/kg; i.p.; twice weekly) lipopolysaccharide (LPS) treatment on selected behavioral, neurochemical and molecular measures at different time points in adult male C57BL/6 mice. Behaviorally, LPS-treated mice were hypoactive after 6 weeks, whereas significant hyperactivity was observed after 12 weeks of LPS and 11 weeks after 13 week LPS treatment termination. Similar biphasic responses, i.e., early decrease followed by a delayed increase were observed in the open field test center time, suggestive of, respectively, increased and decreased anxiety. In a forced swim test, mice exhibited increased immobility (depressive behavior) at all times they were tested. Chronic LPS also produced persistent increase in splenic serotonin (5-HT) and time-dependent, brain region-specific alterations in striatal and prefrontocortical dopamine and 5-HT homeostasis. Microglia, but not astrocytes, were activated by LPS early and late, but their activation did not persist after LPS treatment termination. Above findings demonstrate that chronic peripheral inflammation initially causes hypoactivity and increased anxiety, followed by persistent hyperactivity and decreased anxiety. Notably, chronic LPS-induced depressive behavior appears early, persists long after LPS termination, and is associated with increased splenic 5-HT. Collectively, our data highlight the need for a greater focus on the peripheral/central monoamine alterations and lasting behavioral deficits induced by chronic peripheral inflammation as there are many pathological conditions where inflammation of a chronic nature is a hallmark feature. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Hyperphagia, Severe Obesity, Impaired Cognitive Function, and Hyperactivity Associated With Functional Loss of One Copy of the Brain-Derived Neurotrophic Factor (BDNF) Gene

    PubMed Central

    Gray, Juliette; Yeo, Giles S.H.; Cox, James J.; Morton, Jenny; Adlam, Anna-Lynne R.; Keogh, Julia M.; Yanovski, Jack A.; El Gharbawy, Areeg; Han, Joan C.; Tung, Y.C. Loraine; Hodges, John R.; Raymond, F. Lucy; O’Rahilly, Stephen; Farooqi, I. Sadaf

    2008-01-01

    The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits food intake, and rodent models of BDNF disruption all exhibit increased food intake and obesity, as well as hyperactivity. We report an 8-year-old girl with hyperphagia and severe obesity, impaired cognitive function, and hyperactivity who harbored a de novo chromosomal inversion, 46,XX,inv(11)(p13p15.3), a region encompassing the BDNF gene. We have identified the proximal inversion breakpoint that lies 850 kb telomeric of the 5′ end of the BDNF gene. The patient’s genomic DNA was heterozygous for a common coding polymorphism in BDNF, but monoallelic expression was seen in peripheral lymphocytes. Serum concentration of BDNF protein was reduced compared with age- and BMI-matched subjects. Haploinsufficiency for BDNF was associated with increased ad libitum food intake, severe early-onset obesity, hyper-activity, and cognitive impairment. These findings provide direct evidence for the role of the neurotrophin BDNF in human energy homeostasis, as well as in cognitive function, memory, and behavior. PMID:17130481

  12. Laquinimod dampens hyperactive cytokine production in Huntington's disease patient myeloid cells.

    PubMed

    Dobson, Lucianne; Träger, Ulrike; Farmer, Ruth; Hayardeny, Liat; Loupe, Pippa; Hayden, Michael R; Tabrizi, Sarah J

    2016-06-01

    Huntington's disease (HD) is a neurodegenerative condition characterized by pathology in the brain and peripheral tissues. Hyperactivity of the innate immune system, due in part to NFκB pathway dysregulation, is an early and active component of HD. Evidence suggests targeting immune disruption may slow disease progression. Laquinimod is an orally active immunomodulator that down-regulates proinflammatory cytokine production in peripheral blood mononuclear cells, and in the brain down-regulates astrocytic and microglial activation by modulating NFκB signalling. Laquinimod had beneficial effects on inflammation, brain atrophy and disease progression in multiple sclerosis (MS) in two phase III clinical trials. This study investigated the effects of laquinimod on hyperactive proinflammatory cytokine release and NFκB signalling in HD patient myeloid cell cultures. Monocytes from manifest (manHD) and pre-manifest (preHD) HD gene carriers and healthy volunteers (HV) were treated with laquinimod and stimulated with lipopolysaccharide. After 24 h pre-treatment with 5 μM laquinimod, manHD monocytes released lower levels of IL-1β, IL-5, IL-8, IL-10, IL-13 and TNFα in response to stimulation. PreHD monocytes released lower levels of IL-8, IL-10 and IL-13, with no reduction observed in HV monocytes. The effects of laquinimod on dysfunctional NFκB signalling in HD was assessed by inhibitor of kappa B (IκB) degradation kinetics, nuclear translocation of NFκB and interactions between IκB kinase (IKK) and HTT, in HD myeloid cells. No differences were observed between laquinimod-treated and untreated conditions. These results provide evidence that laquinimod dampens hyper-reactive cytokine release from manHD and preHD monocytes, with a much reduced effect on HV monocytes. Evidence suggests targeting CNS and peripheral immune disruption may slow Huntington's disease (HD) neurodegenerative processes. The effects of laquinimod, an orally active immunomodulator, on hyperactive cytokine release and dysfunctional NFκB signalling in stimulated myeloid cell cultures from pre-manifest and manifest HD gene carriers and healthy volunteers were investigated. Laquinimod dampened cytokine release but did not impact NFκB signalling. Read the Editorial Highlight for this article on page 670. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

  13. Rapid synthesis of DNA-cysteine conjugates for expressed protein ligation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lovrinovic, Marina; Niemeyer, Christof M.

    2005-09-30

    We report a rapid method for the covalent modification of commercially available amino-modified DNA oligonucleotides with a cysteine moiety. The resulting DNA-cysteine conjugates are versatile reagents for the efficient preparation of covalent DNA-protein conjugates by means of expressed protein ligation (EPL). The EPL method allows for the site-specific coupling of cysteine-modified DNA oligomers with recombinant intein-fusion proteins, the latter of which contain a C-terminal thioester enabling the mild and highly specific reaction with N-terminal cysteine compounds. We prepared a cysteine-modifier reagent in a single-step reaction which allows for the rapid and near quantitative synthesis of cysteine-DNA conjugates. The latter weremore » ligated with the green fluorescent protein mutant EYFP, recombinantly expressed as an intein-fusion protein, allowing for the mild and selective formation of EYFP-DNA conjugates in high yields of about 60%. We anticipate many applications of our approach, ranging from protein microarrays to the arising field of nanobiotechnology.« less

  14. beta-Adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses.

    PubMed Central

    Cowen, P. J.; Grahame-Smith, D. G.; Green, A. R.; Heal, D. J.

    1982-01-01

    The beta-adrenoceptor agonists, salbutamol, terbutaline and clenbuterol, were investigated for their effect on 5-hydroxytryptamine-mediated (5-HT) hyperactivity. 2 The lipophilic beta-adrenoceptor agonist, clenbuterol (5 mg/kg) enhanced the behaviours induced by quipazine (25 mg/kg), including headweaving, forepaw treading and hind-limb abduction and thus increased automated activity recording. Clenbuterol (5 mg/kg) also enhanced the hyperactivity syndrome produced by the 5-HT agonist, 5-methoxy N,N-dimethyltryptamine (2 mg/kg) and the combination of tranylcypromine (10 mg/kg) and L-tryptophan (50 mg/kg). Salbutamol and terbutaline potentiated quipazine-induced hyperactivity only when given at the higher dose of 20 mg/kg. 3 The effect of clenbuterol in enhancing quipazine hyperactivity was blocked by the centrally acting beta 1-adrenoceptor antagonist, metoprolol (5 mg/kg), but not by the beta 2-adrenoceptor antagonist, butoxamine (5 mg/kg) or the peripherally acting beta 1-adrenoceptor antagonist, atenolol (5 mg/kg). 4 Clenbuterol (5 mg/kg) did not enhance the circling responses produced by methamphetamine (0.5 mg/kg) in unilateral nigrostriatal-lesioned rats. 5 The results suggest that beta-adrenoceptor agonists in common with some established antidepressant treatments produce enhancement of 5-HT-mediated behavioural responses. PMID:6124294

  15. [Meta analysis of variables related to attention deficit hyperactivity disorder in school-age children].

    PubMed

    Park, Wan Ju; Seo, Ji Yeong; Kim, Mi Ye

    2011-04-01

    The purpose of this study was to use meta-analysis to examine recent domestic articles related to attention deficit hyperactivity disorder (ADHD) in school-age children. After reviewing 213 articles published between 1990 and 2009 from and cited in RISS, KISS, and DBpia, the researchers identified 24 studies with 440 research variables that had appropriate data for methodological study. SPSS 17.0 program was used. The outcome variables were divided into five types: Inattention, hyperactive impulsive, intrinsic, extrinsic, and academic ability variables. Effects size of overall core symptoms was 0.47 which is moderate level in terms of Cohen criteria and effects size of overall negative variables related ADHD was 0.27 which is small level. The most dominant variable related to ADHD was obtained from hyperactive-impulsive (0.70). Also academic ability (0.45), inattention (0.37), and intrinsic variables (0.29) had a small effect whereas extrinsic variables (0.13) had little effect on descriptive ADHD study. The results reveal that ADHD core symptoms have moderate effect size and peripheral negative variables related ADHD have small effect size. To improve the reliability of the meta-analysis results by minimizing publication bias, more intervention studies using appropriate study designs should be done.

  16. Homing endonucleases from mobile group I introns: discovery to genome engineering

    PubMed Central

    2014-01-01

    Homing endonucleases are highly specific DNA cleaving enzymes that are encoded within genomes of all forms of microbial life including phage and eukaryotic organelles. These proteins drive the mobility and persistence of their own reading frames. The genes that encode homing endonucleases are often embedded within self-splicing elements such as group I introns, group II introns and inteins. This combination of molecular functions is mutually advantageous: the endonuclease activity allows surrounding introns and inteins to act as invasive DNA elements, while the splicing activity allows the endonuclease gene to invade a coding sequence without disrupting its product. Crystallographic analyses of representatives from all known homing endonuclease families have illustrated both their mechanisms of action and their evolutionary relationships to a wide range of host proteins. Several homing endonucleases have been completely redesigned and used for a variety of genome engineering applications. Recent efforts to augment homing endonucleases with auxiliary DNA recognition elements and/or nucleic acid processing factors has further accelerated their use for applications that demand exceptionally high specificity and activity. PMID:24589358

  17. Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

    PubMed

    Bauché, Stéphanie; Boerio, Delphine; Davoine, Claire-Sophie; Bernard, Véronique; Stum, Morgane; Bureau, Cécile; Fardeau, Michel; Romero, Norma Beatriz; Fontaine, Bertrand; Koenig, Jeanine; Hantaï, Daniel; Gueguen, Antoine; Fournier, Emmanuel; Eymard, Bruno; Nicole, Sophie

    2013-12-01

    Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Inteins, introns, and homing endonucleases: recent revelations about the life cycle of parasitic genetic elements

    PubMed Central

    Gogarten, J Peter; Hilario, Elena

    2006-01-01

    Self splicing introns and inteins that rely on a homing endonuclease for propagation are parasitic genetic elements. Their life-cycle and evolutionary fate has been described through the homing cycle. According to this model the homing endonuclease is selected for function only during the spreading phase of the parasite. This phase ends when the parasitic element is fixed in the population. Upon fixation the homing endonuclease is no longer under selection, and its activity is lost through random processes. Recent analyses of these parasitic elements with functional homing endonucleases suggest that this model in its most simple form is not always applicable. Apparently, functioning homing endonuclease can persist over long evolutionary times in populations and species that are thought to be asexual or nearly asexual. Here we review these recent findings and discuss their implications. Reasons for the long-term persistence of a functional homing endonuclease include: More recombination (sexual and as a result of gene transfer) than previously assumed for these organisms; complex population structures that prevent the element from being fixed; a balance between active spreading of the homing endonuclease and a decrease in fitness caused by the parasite in the host organism; or a function of the homing endonuclease that increases the fitness of the host organism and results in purifying selection for the homing endonuclease activity, even after fixation in a local population. In the future, more detailed studies of the population dynamics of the activity and regulation of homing endonucleases are needed to decide between these possibilities, and to determine their relative contributions to the long term survival of parasitic genes within a population. Two outstanding publications on the amoeba Naegleria group I intron (Wikmark et al. BMC Evol Biol 2006, 6:39) and the PRP8 inteins in ascomycetes (Butler et al.BMC Evol Biol 2006, 6:42) provide important stepping stones towards integrated studies on how these parasitic elements evolve through time together with, or despite, their hosts. PMID:17101053

  19. Comparative Genomics of Chrysochromulina Ericina Virus and Other Microalga-Infecting Large DNA Viruses Highlights Their Intricate Evolutionary Relationship with the Established Mimiviridae Family.

    PubMed

    Gallot-Lavallée, Lucie; Blanc, Guillaume; Claverie, Jean-Michel

    2017-07-15

    Chrysochromulina ericina virus CeV-01B (CeV) was isolated from Norwegian coastal waters in 1998. Its icosahedral particle is 160 nm in diameter and encloses a 474-kb double-stranded DNA (dsDNA) genome. This virus, although infecting a microalga (the haptophyceae Haptolina ericina , formerly Chrysochromulina ericina ), is phylogenetically related to members of the Mimiviridae family, initially established with the acanthamoeba-infecting mimivirus and megavirus as prototypes. This family was later split into two genera ( Mimivirus and Cafeteriavirus ) following the characterization of a virus infecting the heterotrophic stramenopile Cafeteria roenbergensis (CroV). CeV, as well as two of its close relatives, which infect the unicellular photosynthetic eukaryotes Phaeocystis globosa (Phaeocystis globosa virus [PgV]) and Aureococcus anophagefferens (Aureococcus anophagefferens virus [AaV]), are currently unclassified by the International Committee on Viral Taxonomy (ICTV). The detailed comparative analysis of the CeV genome presented here confirms the phylogenetic affinity of this emerging group of microalga-infecting viruses with the Mimiviridae but argues in favor of their classification inside a distinct clade within the family. Although CeV, PgV, and AaV share more common features among them than with the larger Mimiviridae , they also exhibit a large complement of unique genes, attesting to their complex evolutionary history. We identified several gene fusion events and cases of convergent evolution involving independent lateral gene acquisitions. Finally, CeV possesses an unusual number of inteins, some of which are closely related despite being inserted in nonhomologous genes. This appears to contradict the paradigm of allele-specific inteins and suggests that the Mimiviridae are especially efficient in spreading inteins while enlarging their repertoire of homing genes. IMPORTANCE Although it infects the microalga Chrysochromulina ericina , CeV is more closely related to acanthamoeba-infecting viruses of the Mimiviridae family than to any member of the Phycodnaviridae , the ICTV-approved family historically including all alga-infecting large dsDNA viruses. CeV, as well as its relatives that infect the microalgae Phaeocystic globosa (PgV) and Aureococcus anophagefferens (AaV), remains officially unclassified and a source of confusion in the literature. Our comparative analysis of the CeV genome in the context of this emerging group of alga-infecting viruses suggests that they belong to a distinct clade within the established Mimiviridae family. The presence of a large number of unique genes as well as specific gene fusion events, evolutionary convergences, and inteins integrated at unusual locations document the complex evolutionary history of the CeV lineage. Copyright © 2017 American Society for Microbiology.

  20. Split2 Protein-Ligation Generates Active IL-6-Type Hyper-Cytokines from Inactive Precursors.

    PubMed

    Moll, Jens M; Wehmöller, Melanie; Frank, Nils C; Homey, Lisa; Baran, Paul; Garbers, Christoph; Lamertz, Larissa; Axelrod, Jonathan H; Galun, Eithan; Mootz, Henning D; Scheller, Jürgen

    2017-12-15

    Trans-signaling of the major pro- and anti-inflammatory cytokines Interleukin (IL)-6 and IL-11 has the unique feature to virtually activate all cells of the body and is critically involved in chronic inflammation and regeneration. Hyper-IL-6 and Hyper-IL-11 are single chain designer trans-signaling cytokines, in which the cytokine and soluble receptor units are trapped in one complex via a flexible peptide linker. Albeit, Hyper-cytokines are essential tools to study trans-signaling in vitro and in vivo, the superior potency of these designer cytokines are accompanied by undesirable stress responses. To enable tailor-made generation of Hyper-cytokines, we developed inactive split-cytokine-precursors adapted for posttranslational reassembly by split-intein mediated protein trans-splicing (PTS). We identified cutting sites within IL-6 (E 134 /S 135 ) and IL-11 (G 116 /S 117 ) and obtained inactive split-Hyper-IL-6 and split-Hyper-IL-11 cytokine precursors. After fusion with split-inteins, PTS resulted in reconstitution of active Hyper-cytokines, which were efficiently secreted from transfected cells. Our strategy comprises the development of a background-free cytokine signaling system from reversibly inactivated precursor cytokines.

  1. A novel expression vector for the improved solubility of recombinant scorpion venom in Escherichia coli

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Han, Tianqing; Ming, Hongyan; Deng, Lili

    Recombinant scorpion anti-excitation peptide (rANEP) has previously been expressed using the pET32a system and purified via affinity chromatography. However, rANEP is expressed in BL21(DE3) cells as an inclusion body, and the affinity tag can not be removed. To overcome this problem, we used a variety of protein, DsbA, MBP, TrxA, intein, and affinity tags in fusion and co-expression to achieve soluble and functional rANEP without any affinity tag. In the pCIT-ANEP expression vector, the highest soluble expression level was approximately 90% of the total cellular proteins in E. coli, and the rANEP was cleaved by the intein protein and subsequently purifiedmore » to obtain rANEP, which had the same activity as the natural ANEP. The purity of rANEP obtained using this method was over 95%, with a quantity of 5.1 mg from of purified rANEP from 1 L of culture. This method could expand the application of the soluble expression of disulfide-rich peptides in E. coli.« less

  2. Two- and three-input TALE-based AND logic computation in embryonic stem cells.

    PubMed

    Lienert, Florian; Torella, Joseph P; Chen, Jan-Hung; Norsworthy, Michael; Richardson, Ryan R; Silver, Pamela A

    2013-11-01

    Biological computing circuits can enhance our ability to control cellular functions and have potential applications in tissue engineering and medical treatments. Transcriptional activator-like effectors (TALEs) represent attractive components of synthetic gene regulatory circuits, as they can be designed de novo to target a given DNA sequence. We here demonstrate that TALEs can perform Boolean logic computation in mammalian cells. Using a split-intein protein-splicing strategy, we show that a functional TALE can be reconstituted from two inactive parts, thus generating two-input AND logic computation. We further demonstrate three-piece intein splicing in mammalian cells and use it to perform three-input AND computation. Using methods for random as well as targeted insertion of these relatively large genetic circuits, we show that TALE-based logic circuits are functional when integrated into the genome of mouse embryonic stem cells. Comparing construct variants in the same genomic context, we modulated the strength of the TALE-responsive promoter to improve the output of these circuits. Our work establishes split TALEs as a tool for building logic computation with the potential of controlling expression of endogenous genes or transgenes in response to a combination of cellular signals.

  3. Review of the relationship of restless legs syndrome and periodic limb movements in sleep to hypertension, heart disease, and stroke.

    PubMed

    Walters, Arthur S; Rye, David B

    2009-05-01

    Evidence is reviewed documenting an intimate relationship among restless legs syndrome (RLS) / periodic limb movements in sleep (PLMS) and hypertension and cardiovascular and cerebrovascular disease. Sympathetic overactivity is associated with RLS/PLMS, as manifested by increased pulse rate and blood pressure coincident with PLMS. Causality is far from definitive. Mechanisms are explored as to how RLS/PLMS may lead to high blood pressure, heart disease, and stroke: (a) the sympathetic hyperactivity associated with RLS/PLMS may lead to daytime hypertension that in turn leads to heart disease and stroke; (b) in the absence of daytime hypertension, this sympathetic hyperactivity may predispose to heart disease and stroke either directly or indirectly via atherosclerotic plaque formation and rupture; and (c) comorbidities associated with RLS/PLMS, such as renal failure, diabetes, iron deficiency, and insomnia, may predispose to heart disease and stroke. One theoretical cause for sympathetic hyperactivity is insufficient All diencephalospinal dopaminergic neuron inhibition of sympathetic preganglionic neurons residing in the intermediolateral cell columns of the spinal cord. We cannot exclude the possibility that peripheral vascular, cardiovascular, and cerebrovascular disease may also contribute to RLS/PLMS, and mechanisms for these possibilities are also discussed.

  4. A new fusion protein platform for quantitatively measuring activity of multiple proteases

    PubMed Central

    2014-01-01

    Background Recombinant proteins fused with specific cleavage sequences are widely used as substrate for quantitatively analyzing the activity of proteases. Here we propose a new fusion platform for multiple proteases, by using diaminopropionate ammonia-lyase (DAL) as the fusion protein. It was based on the finding that a fused His6-tag could significantly decreases the activities of DAL from E. coli (eDAL) and Salmonella typhimurium (sDAL). Previously, we have shown that His6GST-tagged eDAL could be used to determine the activity of tobacco etch virus protease (TEVp) under different temperatures or in the denaturant at different concentrations. In this report, we will assay different tags and cleavage sequences on DAL for expressing yield in E. coli, stability of the fused proteins and performance of substrate of other common proteases. Results We tested seven different protease cleavage sequences (rhinovirus 3C, TEV protease, factor Xa, Ssp DnaB intein, Sce VMA1 intein, thrombin and enterokinase), three different tags (His6, GST, CBD and MBP) and two different DALs (eDAL and sDAL), for their performance as substrate to the seven corresponding proteases. Among them, we found four active DAL-fusion substrates suitable for TEVp, factor Xa, thrombin and DnaB intein. Enterokinase cleaved eDAL at undesired positions and did not process sDAL. Substitution of GST with MBP increase the expression level of the fused eDAL and this fusion protein was suitable as a substrate for analyzing activity of rhinovirus 3C. We demonstrated that SUMO protease Ulp1 with a N-terminal His6-tag or MBP tag displayed different activity using the designed His6SUMO-eDAL as substrate. Finally, owing to the high level of the DAL-fusion protein in E. coli, these protein substrates can also be detected directly from the crude extract. Conclusion The results show that our designed DAL-fusion proteins can be used to quantify the activities of both sequence- and conformational-specific proteases, with sufficient substrate specificity. PMID:24649897

  5. Modifiable Arousal in Attention-Deficit/Hyperactivity Disorder and Its Etiological Association With Fluctuating Reaction Times.

    PubMed

    James, Sarah-Naomi; Cheung, Celeste H M; Rijsdijk, Fruhling; Asherson, Philip; Kuntsi, Jonna

    2016-11-01

    Cognitive theories of attention-deficit/hyperactivity disorder (ADHD) propose that high within-subject fluctuations of cognitive performance in ADHD, particularly reaction time (RT) variability (RTV), may reflect arousal dysregulation. However, direct evidence of arousal dysregulation and how it may account for fluctuating RTs in ADHD is limited. We used skin conductance (SC) as a measure of peripheral arousal and aimed to investigate its phenotypic and familial association with RTV in a large sample of ADHD and control sibling pairs. Adolescents and young adults ( N = 292), consisting of 73 participants with ADHD and their 75 siblings, and 72 controls and their 72 siblings, completed the baseline (slow, unrewarded) and fast-incentive conditions of a RT task, while SC was simultaneously recorded. A significant group-by-condition interaction emerged for SC level (SCL). Participants with ADHD had decreased SCL, compared with controls, in the baseline condition but not the fast-incentive condition. Baseline SCL was negatively associated with RTV, and multivariate model fitting demonstrated that the covariance of SCL with RTV, and of SCL with ADHD, was mostly explained by shared familial effects. ADHD is associated with decreased, but modifiable, tonic peripheral arousal. A shared familial cause underlies the relationship between arousal and RTV and between arousal and ADHD. Given the malleability of SCL, if our findings are replicated, it warrants further exploration as a potential treatment target for ADHD.

  6. Design of Fusion Proteins for Efficient and Soluble Production of Immunogenic Ebola Virus Glycoprotein in Escherichia coli.

    PubMed

    Ji, Yang; Lu, Yuan; Yan, Yishu; Liu, Xinxin; Su, Nan; Zhang, Chong; Bi, Shengli; Xing, Xin-Hui

    2018-03-03

    The Ebola hemorrhagic fever caused by Ebola virus is an extremely dangerous disease, and effective therapeutic agents are still lacking. Platforms for the efficient production of vaccines are crucial to ensure quick response against an Ebola virus outbreak. Ebola virus glycoprotein (EbolaGP) on the virion surface is responsible for membrane binding and virus entry, thus becoming the key target for vaccine development. However, heterologous expression of this protein still faces engineering challenges such as low production levels and insoluble aggregation. Here, the authors design and compare various fusion strategies, attaching great importance to the solubility-enhancing effect, and tag removal process. It is found that a C-terminal intein-based tag greatly enhances the solubility of EbolaGP and allows one-step chromatographic purification of the untagged EbolaGP through thiol-catalyzed self-cleavage. The purified untagged EbolaGP alone or with Freund's adjuvant are highly immunogenic, as confirmed in a mouse model. Consequently, the present study puts forward a new strategy for the efficient and soluble expression of untagged immunogenic EbolaGP. The intein-based protein fusion approach may be of importance for the large-scale production of Ebola virus subunit vaccine. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. [New concepts in hyperactive malarial splenomegaly].

    PubMed

    Moraes, M F; Soares, M; Arroz, M J; Do Rosário, V E; Da Graça, J Pimenta; Abecasis, P

    2003-01-01

    Hyperreactive malarial splenomegaly is thought to represent an immunological dysfunction due to recurrent episodes of malaria. The authors present a case of hyperreactive malarial splenomegaly in a patient from São Tomé e Príncipe and discuss aspects of its differential diagnosis and treatment. A revision is made of recent concepts related to its pathogenesis and relationship with lymphoproliferative disorders. Malarial DNA was found in the absence of parasite forms in the peripheral blood. This may indicate that latent infection plays a role in its pathogenesis.

  8. Myokymia and neuromyotonia in veterinary medicine: a comparison with peripheral nerve hyperexcitability syndrome in humans.

    PubMed

    Vanhaesebrouck, An E; Bhatti, Sofie F M; Franklin, Robin J M; Van Ham, Luc

    2013-08-01

    Involuntary muscle hyperactivity can result from muscle or peripheral nerve hyperexcitability or central nervous system dysfunction. In humans, diseases causing hyperexcitability of peripheral nerves are grouped together under the term 'peripheral nerve hyperexcitability' (PNH). Hyperexcitability of the peripheral motor nerve can result into five different phenotypic main variants, i.e. fasciculations, myokymia, neuromyotonia, cramps and tetany, each with their own clinical and electromyographic characteristics. This review focuses on the most commonly described expressions of PNH in veterinary medicine, i.e. myokymia and neuromyotonia, in particular in young Jack Russell terriers. Data from 58 veterinary cases with generalized myokymia and neuromyotonia were analyzed, including unpublished treatment and follow-up data on eight Jack Russell terriers from a previous study and seven additional Jack Russell terriers. A dysfunction of the potassium channel or its associated proteins has been found in many human syndromes characterized by PNH, in particular in generalized myokymia and neuromyotonia, and is suspected to occur in veterinary medicine. Potential pathomechanisms of potassium channel dysfunction leading to signs of PNH are broad and include genetic mutations, antibody-mediated attack or ion channel maldistribution due to axonal degeneration or demyelination. A more accurate classification of the different PNH syndromes will facilitate a more rapid diagnosis and guide further research into natural occurring PNH in animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Growth hormone response to guanfacine in boys with attention deficit hyperactivity disorder: a preliminary study.

    PubMed

    Halperin, Jeffrey M; Newcorn, Jeffrey H; McKay, Kathleen E; Siever, Larry J; Sharma, Vanshdeep

    2003-01-01

    This preliminary study evaluated a method for assessing central noradrenergic function in children via the growth hormone response to a single dose of the alpha-2 adrenergic receptor agonist guanfacine and examined whether this measure distinguishes between attention deficit hyperactivity disorder (ADHD) boys with and without reading disabilities (RD). Plasma growth hormone was assessed before and after the oral administration of guanfacine and placebo in boys with ADHD who were divided into subgroups based on the presence (n = 3) or absence (n = 5) of RD. Guanfacine and placebo conditions did not differ at baseline, but peak growth hormone was significantly higher following guanfacine. The increase in growth hormone following guanfacine was significantly greater in boys without RD as compared to those with RD, with no overlap between the groups. Consistent with findings using peripheral measures of noradrenergic function, these preliminary data suggest that ADHD boys with and without RD may differ in central noradrenergic function.

  10. Molecular chaperones (TrxA, SUMO, Intein, and GST) mediating expression, purification, and antimicrobial activity assays of plectasin in Escherichia coli.

    PubMed

    Chen, Xin; Shi, Jiawei; Chen, Rui; Wen, Yaoan; Shi, Yu; Zhu, Zhe; Guo, Songwen; Li, Ling

    2015-01-01

    Plectasin (PS) is the first defensin to be isolated from a fungus, the saprophytic ascomycete Pseudoplectania nigrella, and active against Streptococcus pneumoniae and S. aureus, including antibiotic-resistant pathogens. To establish a bacterium-based production system, we compared the efficiency of four molecular chaperones and corresponding cleavage to the expression and purification of plectasin. The results showed that the yield of plectasin combined with thioredoxin A (TrxA) and small ubiquitin-related modifier (SUMO) was at a higher level (0.0356 and 0.0358 g L(-1), respectively) than that with intein (0.0238 g L(-1)) and glutathione-S-transferase (GST) (0.0243 g L(-1)). TrxA-plectasin, SUMO-plectasin, and 2-plectasin were cleaved at the correct site and purified, but their considerable amount was not cleaved and remained as a fusion peptide. The antimicrobial activity of plectasin cleaved from SUMO--plectasin against methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant S. pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE)--was stronger than ampicillin (Amp) for the same amount of substance (P ≤ 0.05). This is the first study to complete and compare the effect of different molecular chaperones and corresponding cleavage with the expression and purification of plectasin in the Escherichia coli expression system, which laid the foundation for future research and may develop the application and production of plectasin. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  11. Bacterial inclusion bodies as potential synthetic devices for pathogen recognition and a therapeutic substance release.

    PubMed

    Talafová, Klaudia; Hrabárová, Eva; Chorvát, Dušan; Nahálka, Jozef

    2013-02-07

    Adhesins of pathogens recognise the glycans on the host cell and mediate adherence. They are also crucial for determining the tissue preferences of pathogens. Currently, glyco-nanomaterials provide potential tool for antimicrobial therapy. We demonstrate that properly glyco-tailored inclusion bodies can specifically bind pathogen adhesins and release therapeutic substances. In this paper, we describe the preparation of tailored inclusion bodies via the conjugation of indicator protein aggregated to form inclusion bodies with soluble proteins. Whereas the indicator protein represents a remedy, the soluble proteins play a role in pathogen recognition. For conjugation, glutaraldehyde was used as linker. The treatment of conjugates with polar lysine, which was used to inactivate the residual glutaraldehyde, inhibited unwanted hydrophobic interactions between inclusion bodies. The tailored inclusion bodies specifically interacted with the SabA adhesin from Helicobacter pylori aggregated to form inclusion bodies that were bound to the sialic acids decorating the surface of human erythrocytes. We also tested the release of indicator proteins from the inclusion bodies using sortase A and Ssp DNAB intein self-cleaving modules, respectively. Sortase A released proteins in a relatively short period of time, whereas the intein cleavage took several weeks. The tailored inclusion bodies are promising "nanopills" for biomedical applications. They are able to specifically target the pathogen, while a self-cleaving module releases a soluble remedy. Various self-cleaving modules can be enabled to achieve the diverse pace of remedy release.

  12. Bacterial inclusion bodies as potential synthetic devices for pathogen recognition and a therapeutic substance release

    PubMed Central

    2013-01-01

    Background Adhesins of pathogens recognise the glycans on the host cell and mediate adherence. They are also crucial for determining the tissue preferences of pathogens. Currently, glyco-nanomaterials provide potential tool for antimicrobial therapy. We demonstrate that properly glyco-tailored inclusion bodies can specifically bind pathogen adhesins and release therapeutic substances. Results In this paper, we describe the preparation of tailored inclusion bodies via the conjugation of indicator protein aggregated to form inclusion bodies with soluble proteins. Whereas the indicator protein represents a remedy, the soluble proteins play a role in pathogen recognition. For conjugation, glutaraldehyde was used as linker. The treatment of conjugates with polar lysine, which was used to inactivate the residual glutaraldehyde, inhibited unwanted hydrophobic interactions between inclusion bodies. The tailored inclusion bodies specifically interacted with the SabA adhesin from Helicobacter pylori aggregated to form inclusion bodies that were bound to the sialic acids decorating the surface of human erythrocytes. We also tested the release of indicator proteins from the inclusion bodies using sortase A and Ssp DNAB intein self-cleaving modules, respectively. Sortase A released proteins in a relatively short period of time, whereas the intein cleavage took several weeks. Conclusions The tailored inclusion bodies are promising “nanopills” for biomedical applications. They are able to specifically target the pathogen, while a self-cleaving module releases a soluble remedy. Various self-cleaving modules can be enabled to achieve the diverse pace of remedy release. PMID:23391325

  13. Visual function and color vision in adults with Attention-Deficit/Hyperactivity Disorder.

    PubMed

    Kim, Soyeon; Chen, Samantha; Tannock, Rosemary

    2014-01-01

    Color vision and self-reported visual function in everyday life in young adults with Attention-Deficit/Hyperactivity Disorder (ADHD) were investigated. Participants were 30 young adults with ADHD and 30 controls matched for age and gender. They were tested individually and completed the Visual Activities Questionnaire (VAQ), Farnsworth-Munsell 100 Hue Test (FMT) and A Quick Test of Cognitive Speed (AQT). The ADHD group reported significantly more problems in 4 of 8 areas on the VAQ: depth perception, peripheral vision, visual search and visual processing speed. Further analyses of VAQ items revealed that the ADHD group endorsed more visual problems associated with driving than controls. Color perception difficulties on the FMT were restricted to the blue spectrum in the ADHD group. FMT and AQT results revealed slower processing of visual stimuli in the ADHD group. A comprehensive investigation of mechanisms underlying visual function and color vision in adults with ADHD is warranted, along with the potential impact of these visual problems on driving performance. Copyright © 2013 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

  14. The Botulinum Toxin as a Therapeutic Agent: Molecular Structure and Mechanism of Action in Motor and Sensory Systems.

    PubMed

    Kumar, Raj; Dhaliwal, Harkiran Preet; Kukreja, Roshan Vijay; Singh, Bal Ram

    2016-02-01

    Botulinum neurotoxin (BoNT) produced by Clostridium botulinum is the most potent molecule known to mankind. Higher potency of BoNT is attributed to several factors, including structural and functional uniqueness, target specificity, and longevity. Although BoNT is an extremely toxic molecule, it is now increasingly used for the treatment of disorders related to muscle hyperactivity and glandular hyperactivity. Weakening of muscles due to peripheral action of BoNT produces a therapeutic effect. Depending on the target tissue, BoNT can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. In recent observations of the analgesic properties of BoNT, the toxin modifies the sensory feedback loop to the central nervous system. Differential effects of BoNT in excitatory and inhibitory neurons provide a unique therapeutic tool. In this review the authors briefly summarize the structure and mechanism of actions of BoNT on motor and sensory neurons to explain its therapeutic effects and future potential. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice.

    PubMed

    Akubuiro, A; Bridget Zimmerman, M; Boles Ponto, L L; Walsh, S A; Sunderland, J; McCormick, L; Singh, M

    2013-04-01

    ADAR2 transgenic mice misexpressing the RNA editing enzyme ADAR2 (Adenosine Deaminase that act on RNA) show characteristics of overeating and experience adult onset obesity. Behavioral patterns and brain changes related to a possible addictive overeating in these transgenic mice were explored as transgenic mice display chronic hyperphagia. ADAR2 transgenic mice were assessed in their food preference and motivation to overeat in a competing reward environment with ad lib access to a running wheel and food. Metabolic activity of brain and peripheral tissue were assessed with [(18) F] fluorodeoxyglucose positron emission tomography (FDG-PET) and RNA expression of feeding related genes, ADAR2, dopamine and opiate receptors from the hypothalamus and striatum were examined. The results indicate that ADAR2 transgenic mice exhibit, (1) a food preference for diets with higher fat content, (2) significantly increased food intake that is non-distractible in a competing reward environment, (3) significantly increased messenger RNA (mRNA) expressions of ADAR2, serotonin 2C receptor (5HT2C R), D1, D2 and mu opioid receptors and no change in corticotropin-releasing hormone mRNAs and significantly reduced ADAR2 protein expression in the hypothalamus, (4) significantly increased D1 receptor and altered bioamines with no change in ADAR2, mu opioid and D2 receptor mRNA expression in the striatum and (5) significantly greater glucose metabolism in the hypothalamus, brain stem, right hippocampus, left and right mid brain regions and suprascapular peripheral tissue than controls. These results suggest that highly motivated and goal-oriented overeating behaviors of ADAR2 transgenic mice are associated with altered feeding, reward-related mRNAs and hyperactive brain mesolimbic region. Genes, Brain and Behavior © 2013 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  16. Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice

    PubMed Central

    Akubuiro, Ashley; Zimmerman, M. Bridget; Boles Ponto, Laura L.; Walsh, Susan A.; Sunderland, John; McCormick, Laurie; Singh, Minati

    2013-01-01

    ADAR2 transgenic mice misexpressing the RNA editing enzyme ADAR2 (Adenosine Deaminase that act on RNA) show characteristics of overeating and experience adult onset obesity. Behavioral patterns and brain changes related to a possible addictive overeating in these transgenic mice were explored as transgenic mice display chronic hyperphagia. ADAR2 transgenic mice were assessed in their food preference and motivation to overeat in a competing reward environment with ad lib access to a running wheel and food. Metabolic activity of brain and peripheral tissue were assessed with [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) and RNA expression of feeding related genes, ADAR2, dopamine and opiate receptors from the hypothalamus and striatum were examined. The results indicate that ADAR2 transgenic mice exhibit, (1) a food preference for diets with higher fat content, (2) significantly increased food intake that is non-distractible in a competing reward environment, (3) significantly increased mRNA expressions of ADAR2, serotonin 2C receptor (5HT2CR), D1, D2, and mu opioid receptors and no change in CRH mRNAs and significantly reduced ADAR2 protein expression in the hypothalamus, (4) significantly increased D1 receptor and altered bioamines with no change in ADAR2, mu opioid and D2 receptor mRNA expression in the striatum, and (5) significantly greater glucose metabolism in the hypothalamus, brain stem, right hippocampus, left and right mid brain regions and suprascapular peripheral tissue than controls. These results suggest that highly motivated and goal-oriented overeating behaviors of ADAR2 transgenic mice are associated with altered feeding, reward-related mRNAs, and hyperactive brain mesolimbic region. PMID:23323881

  17. Detection of membrane protein-protein interaction in planta based on dual-intein-coupled tripartite split-GFP association.

    PubMed

    Liu, Tzu-Yin; Chou, Wen-Chun; Chen, Wei-Yuan; Chu, Ching-Yi; Dai, Chen-Yi; Wu, Pei-Yu

    2018-05-01

    Despite the great interest in identifying protein-protein interactions (PPIs) in biological systems, only a few attempts have been made at large-scale PPI screening in planta. Unlike biochemical assays, bimolecular fluorescence complementation allows visualization of transient and weak PPIs in vivo at subcellular resolution. However, when the non-fluorescent fragments are highly expressed, spontaneous and irreversible self-assembly of the split halves can easily generate false positives. The recently developed tripartite split-GFP system was shown to be a reliable PPI reporter in mammalian and yeast cells. In this study, we adapted this methodology, in combination with the β-estradiol-inducible expression cassette, for the detection of membrane PPIs in planta. Using a transient expression assay by agroinfiltration of Nicotiana benthamiana leaves, we demonstrate the utility of the tripartite split-GFP association in plant cells and affirm that the tripartite split-GFP system yields no spurious background signal even with abundant fusion proteins readily accessible to the compartments of interaction. By validating a few of the Arabidopsis PPIs, including the membrane PPIs implicated in phosphate homeostasis, we proved the fidelity of this assay for detection of PPIs in various cellular compartments in planta. Moreover, the technique combining the tripartite split-GFP association and dual-intein-mediated cleavage of polyprotein precursor is feasible in stably transformed Arabidopsis plants. Our results provide a proof-of-concept implementation of the tripartite split-GFP system as a potential tool for membrane PPI screens in planta. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

  18. Sudden Death in a Patient with Carney's Complex

    PubMed Central

    Rothschild, James Adam; Kreso, Melissa; Slodzinski, Martin

    2013-01-01

    Carney’s complex is a rare autosomal dominantly inherited multiple endocrine neoplasia syndrome that involves spotty skin pigmentations, recurrent cardiac myxomas, endocrine hyperactivity, pituitary adenomas, peripheral nerve tumors, testicular tumors, and ovarian lesions. We present a case of sudden cardiac death in a 40 year old female with a history of Carney’s complex with recurrent cardiac myxomas presenting for exploratory laparotomy and enblock adnexal resection of a slowly enlarging right sided ovarian mass. This case highlights the risk for sudden death in these patients as well as the preoperative assessment that should be undertaken by the anesthesiologist as it relates to Carney’s complex. PMID:24223358

  19. Deletion and duplication within the p11.2 region of chromosome 17

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McCorquodale, D.J.; McCorquodale, M.; Bereziouk, O.

    1994-09-01

    A 7 1/2-year-old male patient presented with mild mental retardation, speech delay, hyperactivity, behavioral problems, mild facial hypoplasia, short broad hands, digital anomalies, and self-injurious behavior. Chromosomes obtained from peripheral blood cells revealed a deletion of 17p11.2 in about 40% of the metaphases examined, suggesting that the patient had Smith-Magenis Syndrome. A similar pattern of mosaicism in peripheral blood cells, but not in fibroblasts in which all cells displayed the deletion, has been previously reported. Since some cases of Smith-Magenis Syndrome have a deletion that extends into the region associated with Charcot-Marie-Tooth (CMT) Syndrome, we examined interphase cells with amore » CMT1A-specific probe by the method of fluorescence in situ hybridization. The CMT1A region was not deleted, but about 40% of the cells gave signals indicating a duplication of the CMT1A region. The patient has not presented neuropathies associated with CMT at this time. Future tracking of the patient should be informative.« less

  20. Mothers' parenting stress is associated with salivary cortisol profiles in children with attention deficit hyperactivity disorder.

    PubMed

    Korpa, Terpsichori; Pervanidou, Panagiota; Angeli, Eleni; Apostolakou, Filia; Papanikolaou, Katerina; Papassotiriou, Ioannis; Chrousos, George P; Kolaitis, Gerasimos

    2017-03-01

    The aim of this study was to explore the relation between mothers' parenting stress and the functioning of the hypothalamic-pituitary-adrenal axis (HPAA), as expressed by daily salivary cortisol concentrations, in their children diagnosed with attention deficit hyperactivity disorder (ADHD). Seventy-five children aged 6-11 years diagnosed with ADHD predominant hyperactive-impulsive/combined (ADHD-HI/C, N = 49) and inattentive symptoms (ADHD-I, N = 26) and 45 healthy peers and their mothers participated in the study. Μothers completed measures assessing their children's ADHD status, perceived parenting stress (Parenting Stress Index - Short Form, PSI-SF), mothers' symptoms of psychopathology, social support and socioeconomic status. Children's salivary cortisol samples were collected at six different time points on a single day. Mothers of children with ADHD-HI/C reported higher levels of parenting stress than mothers of children with ADHD-I and controls. All PSI-SF subscales showed significant associations with children's cortisol awakening response (CAR) in both ADHD groups, with the exception of the parental distress subscale in the ADHD-I group. In both ADHD groups, the parent-child dysfunctional interaction subscale, the difficult child subscale and the PSI total score were significantly associated with children's CAR. An interrelation is revealed between mothers' high levels of parenting stress and HPAA functioning in children with ADHD. In this population, CAR has been identified as a sensitive peripheral measure of HPAA functioning in children. Lay summaryThis study showed that in families of children diagnosed with ADHD, there is a complex relation between the mothers' high levels of parenting stress and children's atypical hypothalamic-pituitary-adrenal axis functioning.

  1. mTORC1 promotes proliferation of immature Schwann cells and myelin growth of differentiated Schwann cells

    PubMed Central

    Milbrandt, Jeffrey

    2017-01-01

    The myelination of axons in peripheral nerves requires precisely coordinated proliferation and differentiation of Schwann cells (SCs). We found that the activity of the mechanistic target of rapamycin complex 1 (mTORC1), a key signaling hub for the regulation of cellular growth and proliferation, is progressively extinguished as SCs differentiate during nerve development. To study the effects of different levels of sustained mTORC1 hyperactivity in the SC lineage, we disrupted negative regulators of mTORC1, including TSC2 or TSC1, in developing SCs of mutant mice. Surprisingly, the phenotypes ranged from arrested myelination in nerve development to focal hypermyelination in adulthood, depending on the level and timing of mTORC1 hyperactivity. For example, mice lacking TSC2 in developing SCs displayed hyperproliferation of undifferentiated SCs incompatible with normal myelination. However, these defects and myelination could be rescued by pharmacological mTORC1 inhibition. The subsequent reconstitution of SC mTORC1 hyperactivity in adult animals resulted in focal hypermyelination. Together our data suggest a model in which high mTORC1 activity promotes proliferation of immature SCs and antagonizes SC differentiation during nerve development. Down-regulation of mTORC1 activity is required for terminal SC differentiation and subsequent initiation of myelination. In distinction to this developmental role, excessive SC mTORC1 activity stimulates myelin growth, even overgrowth, in adulthood. Thus, our work delineates two distinct functions of mTORC1 in the SC lineage essential for proper nerve development and myelination. Moreover, our studies show that SCs retain their plasticity to myelinate and remodel myelin via mTORC1 throughout life. PMID:28484008

  2. SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder.

    PubMed

    Merker, Sören; Reif, Andreas; Ziegler, Georg C; Weber, Heike; Mayer, Ute; Ehlis, Ann-Christine; Conzelmann, Annette; Johansson, Stefan; Müller-Reible, Clemens; Nanda, Indrajit; Haaf, Thomas; Ullmann, Reinhard; Romanos, Marcel; Fallgatter, Andreas J; Pauli, Paul; Strekalova, Tatyana; Jansch, Charline; Vasquez, Alejandro Arias; Haavik, Jan; Ribasés, Marta; Ramos-Quiroga, Josep Antoni; Buitelaar, Jan K; Franke, Barbara; Lesch, Klaus-Peter

    2017-07-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory-inhibitory balance impacting both brain development and activity-dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD. Case-control association analyses of SLC2A3 single-nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by SLC2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Meta-analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population-specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC2A3 mRNA expression in peripheral blood cells and altered event-related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high-caloric food. Taken together, our results indicate that both common and rare SLC2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk. © 2017 Association for Child and Adolescent Mental Health.

  3. Iron and attention deficit/hyperactivity disorder: What is the empirical evidence so far? A systematic review of the literature.

    PubMed

    Cortese, Samuele; Angriman, Marco; Lecendreux, Michel; Konofal, Eric

    2012-10-01

    The authors systematically reviewed evidence on iron status, as well as studies of iron supplementation, in individuals with attention deficit/hyperactivity disorder (ADHD). PubMed, Ovid, EMBASE and Web of Knowledge were searched on 4 July 2012. Quantitative appraisal of trials was performed using Jadad's score. Most (n = 20) of the retrieved studies assessed an index of peripheral iron status (i.e., serum ferritin), with overall mixed results - that is, both significant and nonsignificant association between ADHD symptoms and serum ferritin levels. One MRI study reported significantly lower indices of thalamic iron in ADHD versus comparison subjects. Two trials, an open-label and a pilot randomized placebo-controlled study with high Jaded score (4), showed improvement in some but not all measures of ADHD symptoms. Three studies showed that children with ADHD plus sleep disorders, in particular restless legs syndrome, are at risk of iron deficiency. Finally, two studies suggested that iron deficiency might decrease the effectiveness of psychostimulant treatment. The authors discussed how the field could move from initial research mainly focused on serum ferritin towards a more comprehensive and translational investigation of iron in ADHD, with the potential to inform clinical practice in terms of screening and treating iron deficiency in individuals with ADHD.

  4. [Some neurologic and psychiatric complications in endocrine disorders: the thyroid gland].

    PubMed

    Aszalós, Zsuzsa

    2007-02-18

    Thyroid hormones are of primary importance for the perinatal development of the central nervous system, and for normal function of the adult brain. These hormones primarily regulate the transcription of specific target genes. They increase the cortical serotonergic neurotransmission, and play an important role in regulating central noradrenergic and GABA function. Thyroid deficiency during the perinatal period results in mental retardation. Hypothyroidism of the adults causes most frequently dementia and depression. Other less common clinical pictures include myxoedema coma, dysfunction of cerebellum and cranial nerves. Hypothyroidism also increases predisposition of stroke. Peripheral diseases frequently include polyneuropathy, carpal tunnel syndrome, myalgic state, and rarely myokymia. Nearly all the hyperthyroid patients show minor psychiatric signs, and infrequently psychosis, dementia, confusion state, depression, apathetic thyrotoxicosis, thyrotoxic crisis, seizures, pyramidal signs, or chorea occur. The peripheral complications may be indicated by chronic thyrotoxic myopathy, infiltrative ophthalmopathy, myasthenia gravis, periodic hypokalemic paralysis and polyneuropathy. Generalized resistance to thyroid hormone was confirmed in a number of patients with attention deficit-hyperactivity disorder. Significantly elevated antithyroid antibody titers characterize Hashimoto's encephalopathy. This condition is a rare, acute - subacute, serious, life threatening, but steroid-responsive, relapsing-remitting, autoimmune disease.

  5. Immune and Neuroendocrine Mechanisms of Stress Vulnerability and Resilience

    PubMed Central

    Ménard, Caroline; Pfau, Madeline L; Hodes, Georgia E; Russo, Scott J

    2017-01-01

    Diagnostic criteria for mood disorders including major depressive disorder (MDD) largely ignore biological factors in favor of behavioral symptoms. Compounding this paucity of psychiatric biomarkers is a need for therapeutics to adequately treat the 30–50% of MDD patients who are unresponsive to traditional antidepressant medications. Interestingly, MDD is highly prevalent in patients suffering from chronic inflammatory conditions, and MDD patients exhibit higher levels of circulating pro-inflammatory cytokines. Together, these clinical findings suggest a role for the immune system in vulnerability to stress-related psychiatric illness. A growing body of literature also implicates the immune system in stress resilience and coping. In this review, we discuss the mechanisms by which peripheral and central immune cells act on the brain to affect stress-related neurobiological and neuroendocrine responses. We specifically focus on the roles of pro-inflammatory cytokine signaling, peripheral monocyte infiltration, microglial activation, and hypothalamic-pituitary-adrenal axis hyperactivity in stress vulnerability. We also highlight recent evidence suggesting that adaptive immune responses and treatment with immune modulators (exogenous glucocorticoids, humanized antibodies against cytokines) may decrease depressive symptoms and thus represent an attractive alternative to the current antidepressant treatments. PMID:27291462

  6. Cardiovascular considerations of attention deficit hyperactivity disorder medications: a report of the European Network on Hyperactivity Disorders work group, European Attention Deficit Hyperactivity Disorder Guidelines Group on attention deficit hyperactivity disorder drug safety meeting.

    PubMed

    Hamilton, Robert M; Rosenthal, Eric; Hulpke-Wette, Martin; Graham, John G I; Sergeant, Joseph

    2012-02-01

    Regulatory decisions regarding attention deficit hyperactivity disorder drug licensing and labelling, along with recent statements from professional associations, raise questions of practice regarding the evaluation and treatment of patients with attention deficit hyperactivity disorder. To address these issues for the European community, the European Network for Hyperkinetic Disorders, through its European Attention Deficit Hyperactivity Disorder Guidelines Group, organised a meeting between attention deficit hyperactivity disorder specialists, paediatric cardiovascular specialists, and representatives of the major market authorisation holders for attention deficit hyperactivity disorder medications. This manuscript represents their consensus on cardiovascular aspects of attention deficit hyperactivity disorder medications. Although sudden death has been identified in multiple young individuals on attention deficit hyperactivity disorder medication causing regulatory concern, when analysed for exposure using currently available data, sudden death does not appear to exceed that of the general population. There is no current evidence to suggest an incremental benefit to electrocardiography assessment of the general attention deficit hyperactivity disorder patient. Congenital heart disease patients have an increased prevalence of attention deficit hyperactivity disorder, and can benefit from attention deficit hyperactivity disorder therapies, including medication. The attention deficit hyperactivity disorder specialist is the appropriate individual to evaluate benefit and risk and recommend therapy in all patients, although discussion with a heart specialist is reasonable for congenital heart disease patients. For attention deficit hyperactivity disorder patients with suspected heart disease or risk factor/s for sudden death, assessment by a heart specialist is recommended, as would also be the case for a non-attention deficit hyperactivity disorder patient. The identification of risk factors for sudden death should not automatically exclude the use of attention deficit hyperactivity disorder medication.

  7. Engineering protein scaffolds for protein separation, biocatalysis and nanotechnology applications

    NASA Astrophysics Data System (ADS)

    Liu, Fang

    Globally, there is growing appreciation for developing a sustainable economy that uses eco-efficient bio-processes. Biotechnology provides an increasing range of tools for industry to help reduce cost and improve environmental performance. Inspired by the naturally evolved machineries of protein scaffolds and their binding ligands, synthetic protein scaffolds were engineered based on cohesin-dockerin interactions and metal chelating peptides to tackle the challenges and make improvements in three specific areas: (1) protein purification, (2) biofuel cells, and (3) nanomaterial synthesis. The first objective was to develop efficient and cost-effective non-chromatographic purification processes to purify recombinant proteins in an effort to meet the dramatically growing market of protein drugs. In our design, the target protein was genetically fused with a dockerin domain from Clostridium thermocellum and direct purification and recovery was achieved using thermo-responsive elastin-like polypeptide (ELP) scaffold containing the cohesin domain from the same species. By exploiting the highly specific interaction between the dockerin and cohesin domain and the reversible aggregation property of ELP, highly purified and active dockerin-tagged proteins, such as endoglucanase CelA, chloramphenicol acetyl transferase (CAT) and enhanced green fluorescence protein (EGFP), were recovered directly from crude cell extracts in a single purification step with yields achieving over 90%. Incorporation of a self-cleaving intein domain enabled rapid removal of the affinity tag from the target proteins by another cycle of thermal precipitation. The purification cost can be further reduced by regenerating and recycling the ELP-cohesin capturing scaffolds. However, due to the high binding affinity between cohesin and dockerin domains, the bound dockerin-intein tag cannot be completely disassociated from ELP-cohesin scaffold after binding. Therefore, a truncated dockerin with the calcium-coordinating function impaired was used in replace of the original full length dockerin domain. The truncated dockerin domain maintained its functionality as an effective affinity tag, and efficient EDTA mediated dissociation of the bound dockerin-intein tag was also realized. The regenerated ELP capturing scaffold was reused for additional purification cycles without any decrease in efficiency. The second objective was to assemble biocatalysts for biofuel cells. Three beta-NAD dependent dehydrogenases, alcohol dehydrogenase (ADH), formaldehyde dehydrogenase (FALDH) and formate dehydrogenase (FDH), were site-specifically co-localized onto the scaffolds displayed on the yeast surface based on the high-affinity interactions between three orthogonal cohesin/dockerin pairs. The assembled multi-enzyme cascades, which can completely convert methanol to CO2, showed improved production yield compared with that of the non-complexed enzyme mixture, indicating efficient substrate channeling among the three enzymes. This strategy can be easily extended to other complex cascade reactions for enzymatic fuel cell applications. To further explore the role of biotechnology toward environmental sustainability, Escherichia coli was engineered to express phytochelatin synthase, which converted glutathione into the metal-binding peptide phytochelatin (PC). PCs served as peptide scaffolds and mediated synthesis of CdS nanocrystals. This approach may be generalized to guide the in vitro self-assembly of a wide range of nanocrystals with different compositions and sizes.

  8. Psychiatric comorbidities of adults with early- and late-onset attention-deficit/hyperactivity disorder.

    PubMed

    Lin, Yu-Ju; Yang, Li-Kuang; Gau, Susan Shur-Fen

    2016-06-01

    We evaluated the psychiatric comorbidities in adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder as a function of recalled symptom onset before and after the age of 7 years and whether the childhood attention-deficit/hyperactivity disorder symptoms were associated with psychiatric comorbidities. In all, 214 adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder and 174 non-attention-deficit/hyperactivity disorder controls (aged 17-40 years) received psychiatric interviews to confirm their previous and current attention-deficit/hyperactivity disorder status and other psychiatric diagnoses. Demographics and risks of lifetime psychiatric disorders were compared among three groups: (1) attention-deficit/hyperactivity disorder, onset <7 years (early-onset); (2) attention-deficit/hyperactivity disorder, onset between 7 and 12 years (late-onset) and (3) non-attention-deficit/hyperactivity disorder controls. We also tested the effects of attention-deficit/hyperactivity disorder symptoms on the risk of later psychiatric comorbidities by Cox regression analyses. Regardless of the age of onset, attention-deficit/hyperactivity disorder was significantly associated with a wide range of psychiatric comorbidities. There were similar comorbid patterns between early- and late-onset attention-deficit/hyperactivity disorder. Regardless of attention-deficit/hyperactivity disorder diagnosis, increased severity of attention-deficit/hyperactivity disorder symptoms was associated with higher risks of oppositional defiant disorder, conduct disorder, dysthymia and sleep disorder but not major depression, which was associated with the attention-deficit/hyperactivity disorder diagnosis. Our findings suggest that elevating the threshold of age of onset to 12 years in Diagnostic and Statistical Manual of Mental disorders, 5th edition would not over-diagnose attention-deficit/hyperactivity disorder in the adult population. Recalled childhood attention-deficit/hyperactivity disorder symptom severity was correlated with conduct disorder, oppositional defiant disorder, dysthymia and sleep disorders. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  9. Physical Development of Hyperactive Boys.

    ERIC Educational Resources Information Center

    McGee, Rob; And Others

    1985-01-01

    Anthropometric data collected on groups of 7-year-old New Zealand boys, identified as hyperactive-only, aggressive-hyperactive, aggressive-only and nonaggressive/nonhyperactive did not confirm the hypothesis that hyperactive-only Ss would show delayed maturation. However, hyperactive-only Ss were significantly more lean than Ss in other groups.…

  10. The two main theories on dental bruxism.

    PubMed

    Behr, Michael; Hahnel, Sebastian; Faltermeier, Andreas; Bürgers, Ralf; Kolbeck, Carola; Handel, Gerhard; Proff, Peter

    2012-03-20

    Bruxism is characterized by non-functional contact of mandibular and maxillary teeth resulting in clenching or grating of teeth. Theories on factors causing bruxism are a matter of controversy in current literature. The dental profession has predominantly viewed peripheral local morphological disorders, such as malocclusion, as the cause of clenching and gnashing. This etiological model is based on the theory that occlusal maladjustment results in reduced masticatory muscle tone. In the absence of occlusal equilibration, motor neuron activity of masticatory muscles is triggered by periodontal receptors. The second theory assumes that central disturbances in the area of the basal ganglia are the main cause of bruxism. An imbalance in the circuit processing of the basal ganglia is supposed to be responsible for muscle hyperactivity during nocturnal dyskinesia such as bruxism. Some authors assume that bruxism constitutes sleep-related parafunctional activity (parasomnia). A recent model, which may explain the potential imbalance of the basal ganglia, is neuroplasticity. Neural plasticity is based on the ability of synapses to change the way they work. Activation of neural plasticity can change the relationship between inhibitory and excitatory neurons. It seems obvious that bruxism is not a symptom specific to just one disease. Many forms (and causes) of bruxism may exist simultaneously, as, for example, peripheral or central forms. Copyright © 2011 Elsevier GmbH. All rights reserved.

  11. Neuropathic Pain-like Alterations in Muscle Nociceptor Function Associated with Vibration-induced Muscle Pain

    PubMed Central

    Chen, Xiaojie; Green, Paul G.; Levine, Jon D.

    2010-01-01

    We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ~15% of nociceptors demonstrated an intense and long-lasting barrage of action potentials in response to sustained suprathreshold mechanical stimulation (average of 2635 action potentials with frequency of ~44 Hz during a 1 minute suprathreshold stimulus) much greater than has been reported to be produced even by potent inflammatory mediators. While these high-firing nociceptors had lower mechanical thresholds than the remaining nociceptors, exposure to vibration had no effect on conduction velocity and did not induce spontaneous activity. Hyperactivity was not observed in any of 19 neurons from vibration exposed rats pretreated with intrathecal antisense for the IL-6 receptor subunit gp130. Since vibration can injure peripheral nerves, and IL-6 has been implicated in painful peripheral neuropathies, we suggest that the dramatic change in sensory neuron function and development of muscles pain, induced by exposure to vibration, reflects a neuropathic muscle pain syndrome. PMID:20800357

  12. Does collateral retrospective information about childhood attention-deficit/hyperactivity disorder symptoms assist in the diagnosis of attention-deficit/hyperactivity disorder in adults? Findings from a large clinical sample.

    PubMed

    Breda, Vitor; Rovaris, Diego Luiz; Vitola, Eduardo Schneider; Mota, Nina Roth; Blaya-Rocha, Paula; Salgado, Carlos Alberto Iglesias; Victor, Marcelo Moraes; Picon, Felipe Almeida; Karam, Rafael Gomes; Silva, Katiane Lilian; Rohde, Luis Augusto; Bau, Claiton Henrique Dotto; Grevet, Eugenio Horacio

    2016-06-01

    In accordance with consolidated clinical practice, Diagnostic and Statistical Manual of Mental Disorders, 5th edition suggests a key role of collateral information in the evaluation of retrospective childhood attention-deficit/hyperactivity disorder symptoms in adults despite poor evidence supporting its use. This study aims to assess the incremental value of collateral information on the presence of childhood attention-deficit/hyperactivity disorder symptoms when evaluating adults with attention-deficit/hyperactivity disorder. Adult patients with attention-deficit/hyperactivity disorder (n = 449) and non-attention-deficit/hyperactivity disorder subjects (n = 143) underwent an extensive clinical assessment based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. For patients, retrospective collateral information regarding childhood attention-deficit/hyperactivity disorder was obtained and used to sort them into two groups: agreement (n = 277) and disagreement (n = 172) between self- and collateral reports. We compared demographic, clinical and response to treatment profiles among groups to test the relevance of collateral information on the specific issue of childhood attention-deficit/hyperactivity disorder symptoms. Both attention-deficit/hyperactivity disorder groups had higher rates of several comorbidities (oppositional defiant, conduct, substance use and bipolar disorders; all p < 0.001) and impairments than controls. Disagreement between self- and collateral reports on childhood attention-deficit/hyperactivity disorder symptoms occurred in 38% of patients. Overall, attention-deficit/hyperactivity disorder disagreement and agreement groups had similar profiles in response to treatment and comorbidity, and the few differences detected in impairment measures were of small magnitude (Eta(2) < 0.05). Although collateral report has an important role for diagnosing attention-deficit/hyperactivity disorder in children, it has no incremental value in the evaluation of childhood attention-deficit/hyperactivity disorder symptoms in adults with a self-reported history of attention-deficit/hyperactivity disorder assessed in clinical settings. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  13. Hyperactivity

    MedlinePlus

    ... Causes Conditions that may lead to hyperactivity include: Attention deficit hyperactivity disorder (ADHD) Brain or central nervous system ... and the A.D.A.M. Editorial team. Attention Deficit Hyperactivity Disorder Read more NIH MedlinePlus Magazine Read ...

  14. Serotonin syndrome: a complex but easily avoidable condition.

    PubMed

    Dvir, Yael; Smallwood, Patrick

    2008-01-01

    Serotonin syndrome is a potentially life-threatening adverse drug reaction caused by excessive serotonergic agonism in central and peripheral nervous system serotonergic receptors (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120). Symptoms are characterized by a triad of neuron-excitatory features, which include (a) neuromuscular hyperactivity -- tremor, clonus, myoclonus, hyperreflexia and, in advanced stages, pyramidal rigidity; (b) autonomic hyperactivity -- diaphoresis, fever, tachycardia and tachypnea; (c) altered mental status -- agitation, excitement and, in advanced stages, confusion (Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005;95:434-441). It arises when pharmacological agents increase serotonin neurotransmission at postsynaptic 5-hydroxytryptamine 1A and 5-hydroxytryptamine 2A receptors through increased serotonin synthesis, decreased serotonin metabolism, increased serotonin release, inhibition of serotonin reuptake or direct agonism of the serotonin receptors (Houlihan D. Serotonin syndrome resulting from coadministration of tramodol, venlafaxine, and mirtazapine. Ann Pharmacother 2004;38:411-413). The etiology is often the result of therapeutic drug use, intentional overdosing of serotonergic agents or complex interactions between drugs that directly or indirectly modulate the serotonin system (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120). Due to the increasing availability of agents with serotonergic activity, physicians need to more aware of serotonin syndrome. The following case highlights the complex nature in which serotonin syndrome can arise, as well as the proper recognition and treatment of a potentially life-threatening yet easily avoidable condition.

  15. [Decreased beta-phenylethylamine in urine of children with attention deficit hyperactivity disorder and autistic disorder].

    PubMed

    Kusaga, Akira

    2002-05-01

    beta-phenylethylamine (PEA), a biogenic trace amine, acts as a neuromodulator in the nigrostriatal dopaminergic pathway and stimulates the release of dopamine. To clarify the mechanism of neurochemical metabolism in attention deficit hyperactivity disorder (ADHD), we measured the urine levels of PEA using gas chromatography-chemical ionization-mass spectrometry. The urinary levels of 3-methoxy-4-hydroxyphenyl glycol (MHPG), homovanillic acid (HVA), and 5-hydroxy-indoleacetic acid (5-HIAA) were determined by high performance liquid chromatography. Urine samples were collected in a 24 hour period. Findings were compared with those obtained from controls (N = 15), children with ADHD (N = 15), and children with autistic disorder (AD) (N = 5). The mean urinary levels of MHPG, HVA, and 5-HIAA in the children with ADHD were not significantly different from those of the controls or those with AD, whereas PEA levels were significantly lower in children with ADHD (11.23 +/- 13.40 micrograms/g creatinine) compared with controls (56.01 +/- 52.18 micrograms/g creatinine). PEA and MHPG levels in children with AD (14.75 +/- 14.37 micrograms/g creatine, 1.10 +/- 0.61 micrograms/mg creatine, respectively) were significantly decreased compared to controls (MHPG, 2.2 +/- 0.9 micrograms/mg creatine). The decreased urine PEA in children with ADHD and AD may suggest a common underlying pathophysiology. The decreased urine MHPG in children with AD might indicate the existence of an alteration in central and peripheral noradrenergic function.

  16. No objectively measured sleep disturbances in children with attention-deficit/hyperactivity disorder.

    PubMed

    Bergwerff, Catharina E; Luman, Marjolein; Oosterlaan, Jaap

    2016-10-01

    The main goal of this study was to gain more insight into sleep disturbances in children with attention-deficit/hyperactivity disorder, using objective measures of sleep quality and quantity. The evidence for sleep problems in children with attention-deficit/hyperactivity disorder thus far is inconsistent, which might be explained by confounding influences of comorbid internalizing and externalizing problems and low socio-economic status. We therefore investigated the mediating and moderating role of these factors in the association between attention-deficit/hyperactivity disorder and sleep problems. To control for the effects of stimulant medication use, all participants were tested free of medication. Sixty-three children with attention-deficit/hyperactivity disorder and 61 typically developing children, aged 6-13 years, participated. Sleep was monitored for one to three school nights using actigraphy. Parent and teacher questionnaires assessed symptoms of attention-deficit/hyperactivity disorder, internalizing behaviour, oppositional defiant disorder and conduct disorder. Results showed no differences between the attention-deficit/hyperactivity disorder and typically developing group in any sleep parameter. Within the attention-deficit/hyperactivity disorder group, severity of attention-deficit/hyperactivity disorder symptoms was not related to sleep quality or quantity. Moderation analyses in the attention-deficit/hyperactivity disorder group showed an interaction effect between attention-deficit/hyperactivity disorder symptoms and internalizing and externalizing behaviour on total sleep time, time in bed and average sleep bout duration. The results of our study suggest that having attention-deficit/hyperactivity disorder is not a risk factor for sleep problems. Internalizing and externalizing behaviour moderate the association between attention-deficit/hyperactivity disorder and sleep, indicating a complex interplay between psychiatric symptoms and sleep. © 2016 European Sleep Research Society.

  17. Adult Attention-Deficit / Hyperactivity Disorder (ADHD)

    MedlinePlus

    Adult attention-deficit/hyperactivity disorder (ADHD) Overview Adult attention-deficit/hyperactivity disorder (ADHD) is a mental health disorder that ... combination of persistent problems, such as difficulty paying attention, hyperactivity and impulsive behavior. Adult ADHD can lead ...

  18. [Hyperactivity and anorexia nervosa: behavioural and biological perspective].

    PubMed

    Kohl, M; Foulon, C; Guelfi, J-D

    2004-01-01

    Anorexia nervosa is an eating disorder defined by a symptomatic triad, anorexia, emaciation and amenorrhoea. This disease mainly affects young women. Besides these three symptoms, hyperactivity is often associated with anorexia nervosa. Hyperactivity can be considered as a strategy to lose weight, but studies on animal models have shown that it could be explained by more complicated mechanisms. Hyperactivity is defined by an excess of physical activity, which can induce social, professional and family consequences. Hyperactivity can take different forms, most striking is the restless one. Patients with anorexia nervosa are not all hyperactive. Brewerton et al. have compared patients with anorexia nervosa and hyperactivity to patients without hyperactivity. Hyperactive patients are more dissatisfied by their body image, they use less means of purging (laxatives, vomiting), and they start starving earlier than patients without hyperactivity. Many factors can promote the emergence and maintenance of hyperactivity, especially social and cultural requirements, sports environment, family influences. Various models can explain the links between excessive exercise and anorexia nervosa. Epling and Pierce have exposed a behavioural model which shows how hyperactivity can lead to starvation, creating a self-maintained cycle. Eisler and Le Grande have described four models to explain the links between hyperactivity and anorexia nervosa. First, excessive exercise can be considered as a symptom of anorexia nervosa. It can also promote the development of eating disorders. Anorexia nervosa and hyperactivity can be a manifestation of an other psychiatric disorder. At least, hyperactivity can be a variant of anorexia nervosa, which has the same effects, as weight loss. Hyperactivity can also be considered as a kind of obsessive compulsive disorder. Hyperactivity and obsessive compulsive disorders actually share some clinical and neurochemical characteristics. An other model consists in comparing excessive exercise in anorexia nervosa to an addictive behaviour. Self-starvation exacerbated by hyperactivity can be considered as an addiction to endogenous opioid. Few studies are carried out in order to estimate the prevalence of high level exercise in the eating disorders. Davis et al. have achieved a prevalence study. The results indicate that a large majority of patients with anorexia nervosa (80,8%) were exercising excessively during an acute phase of the disorder. Research on animals, specially on rats, brings us an interesting model explaining interactions between anorexia nervosa and hyperactivity. With animal models, we have noticed that, when rats with access to a running wheel, are restricted in their food intake, they become excessively active, and paradoxically reduce food consumption. Many searchers have tried to explain this phenomenon. Morse et al. have pointed from animal models that the level of hyperactivity was linked to the severity of food restriction. This result can be explained by a failure of a part of the brain involved in rest and activity regulation. Animal research brings us explanations about the effects of starvation on the endocrine system and the neurotransmitters. Broocks et al. have shown that corticosterone concentration in plasma was synergistically increased by semi starvation and exercise, and the reduction of triiodothyronine by semi starvation was significantly greater in the running wheel group. An other study of Broocks et al. has revealed an increased hypothalamic serotonin metabolism with the combined effect of hyperactivity and food restriction. Tryptophan, an amid acid involved in serotonin synthesis, can also play a role in the maintenance of anorexia nervosa. In starvation conditions, opioid releasing caused by physical exercise would decrease food intake. Exner's study and Adan's one have shown that leptin would be involved in semi starvation induced hyperactivity mechanisms. In spite of animal models can not be entirely generalized to human, they are useful to try to explain biological supports of hyperactivity. Hyperactivity is not only a strategy to lose weight, but also a specific symptom which completes the clinical triad. Animal studies have led to promising results; we might use medicine, such as serotonin reuptake inhibitors or opioid antagonists in the treatment of hyperactivity in anorexia nervosa.

  19. Bacterial Expression and Purification of the Amyloidogenic Peptide PAPf39 for Multidimensional NMR Spectroscopy

    PubMed Central

    Shanmuganathan, Aranganathan; Bishop, Anthony C.; French, Kinsley C.; McCallum, Scott A.; Makhatadze, George I.

    2013-01-01

    PAPf39 is a 39 residue peptide fragment from human prostatic acidic phosphatase that forms amyloid fibrils in semen. These fibrils have been implicated in facilitating HIV transmission. To enable structural studies of PAPf39 by NMR spectroscopy, efficient methods allowing the production of milligram quantities of isotopically labeled peptide are essential. Here, we report the high-yield expression, as a fusion to ubiquitin at the N-terminus and an intein at the C-terminus, and purification of uniformly labeled 13C- and 15N-labeled PAPf39 peptide. This allows the study of the PAPf39 monomer conformational ensemble by NMR spectroscopy. To this end, we performed the NMR chemical shift assignment of the PAPf39 peptide in the monomeric state at low pH. PMID:23314347

  20. Ghrelin: Central and Peripheral Implications in Anorexia Nervosa

    PubMed Central

    Méquinion, Mathieu; Langlet, Fanny; Zgheib, Sara; Dickson, Suzanne; Dehouck, Bénédicte; Chauveau, Christophe; Viltart, Odile

    2012-01-01

    Increasing clinical and therapeutic interest in the neurobiology of eating disorders reflects their dramatic impact on health. Chronic food restriction resulting in severe weight loss is a major symptom described in restrictive anorexia nervosa (AN) patients, and they also suffer from metabolic disturbances, infertility, osteopenia, and osteoporosis. Restrictive AN, mostly observed in young women, is the third largest cause of chronic illness in teenagers of industrialized countries. From a neurobiological perspective, AN-linked behaviors can be considered an adaptation that permits the endurance of reduced energy supply, involving central and/or peripheral reprograming. The severe weight loss observed in AN patients is accompanied by significant changes in hormones involved in energy balance, feeding behavior, and bone formation, all of which can be replicated in animals models. Increasing evidence suggests that AN could be an addictive behavior disorder, potentially linking defects in the reward mechanism with suppressed food intake, heightened physical activity, and mood disorder. Surprisingly, the plasma levels of ghrelin, an orexigenic hormone that drives food-motivated behavior, are increased. This increase in plasma ghrelin levels seems paradoxical in light of the restrained eating adopted by AN patients, and may rather result from an adaptation to the disease. The aim of this review is to describe the role played by ghrelin in AN focusing on its central vs. peripheral actions. In AN patients and in rodent AN models, chronic food restriction induces profound alterations in the « ghrelin » signaling that leads to the development of inappropriate behaviors like hyperactivity or addiction to food starvation and therefore a greater depletion in energy reserves. The question of a transient insensitivity to ghrelin and/or a potential metabolic reprograming is discussed in regard of new clinical treatments currently investigated. PMID:23549309

  1. The Hyperactive Child.

    ERIC Educational Resources Information Center

    Murphy, Linda; Della Corte, Suzanne

    1987-01-01

    The newsletter's main article focuses on hyperactivity and attention deficit disorder. The causes of hyperactivity, which affects 3-5 percent of all children, are elusive but may include neurological immaturity, inherent genetic problems, or fetal exposure to harmful substances. Patterns of behavior that typify a hyperactive child include a short…

  2. [Relationship among inattentive and hyperactive-impulsive behavior, aggression, and depression in Japanese elementary and junior high school students].

    PubMed

    Noda, Wataru; Okada, Ryo; Tani, Iori; Ohnishi, Masafumi; Naoto, Mochizuki; Nakajima, Syunji; Tsujii, Masatsugu

    2013-06-01

    The present study examines the relationship among inattentive, and hyperactive-impulsive behavior, aggression, and depression in elementary school and junior high school students. The participants were 3,885 children and their teachers and caregivers. Children's inattentive and hyperactive-impulsive behavior was rated by their teachers and caregivers (ADHD-RS). Children rated aggression (HAQ-C) and depression (DSRS-C) themselves. Inattentive and hyperactive-impulsive behavior rated by teachers and caregivers were positively related to aggression and depression. Inattention predicted higher levels of aggression and depression. Inattentive and hyperactive-impulsive behavior as rated by teachers was more highly related to depression than those behaviors as rated by caregivers. The relationships among inattentive, and hyperactive-impulsive behavior, aggression, and depression were almost the same for both elementary school and junior high school students. This study suggests the importance of assessing inattentive and hyperactive-impulsive behavior from multiple views to examine the relationship between inattentive and hyperactive-impulsive behavior and mental health problems.

  3. Afferent control mechanisms involved in the development of soleus fiber alterations in simulated hypogravity

    NASA Astrophysics Data System (ADS)

    Shenkman, B. S.; Nemirovskaya, T. L.; Shapovalova, K. B.; Podlubnaya, Z. A.; Vikhliantsev, I. M.; Moukhina, A. M.; Kozlovskaya, I. B.

    2007-02-01

    It was recently established that support withdrawal (withdrawal of support reaction force) in microgravity provokes a sequence of functional shifts in the activity of motor units (inactivation of slow ones) and peripheral muscle apparatus which lead to the decline of postural muscle contractility and alterations in fiber characteristics. However, mechanisms involved in inactivation of the slow motor units and appropriate slow-twitch muscle fiber disuse under the supportless conditions remained unknown. We show here that artificial inactivation of muscles-antagonists (which are known to be hyperactive during unloading) counteracts some of the unloading-induced events in the rat soleus (fiber size reduction, slow-to-fast fiber-type transition and decline of titin and nebulin content). It was also demonstrated that direct activation of the muscarinic receptors of the neostriatum neurons prevented slow-to-fast fiber-type transformation in soleus of hindlimb suspended rats.

  4. A Longitudinal Twin Study on the Association between Inattentive and Hyperactive-Impulsive ADHD Symptoms

    ERIC Educational Resources Information Center

    Greven, Corina U.; Asherson, Philip; Rijsdijk, Fruhling V.; Plomin, Robert

    2011-01-01

    DSM-IV distinguishes two symptom domains of attention deficit hyperactivity disorder (ADHD): inattentiveness and hyperactivity-impulsivity. The present study examines the aetiologies and developmental relations underlying the associations between inattentiveness and hyperactivity-impulsivity over time, based on a representative population sample…

  5. Chemical biology-based approaches on fluorescent labeling of proteins in live cells.

    PubMed

    Jung, Deokho; Min, Kyoungmi; Jung, Juyeon; Jang, Wonhee; Kwon, Youngeun

    2013-05-01

    Recently, significant advances have been made in live cell imaging owing to the rapid development of selective labeling of proteins in vivo. Green fluorescent protein (GFP) was the first example of fluorescent reporters genetically introduced to protein of interest (POI). While GFP and various types of engineered fluorescent proteins (FPs) have been actively used for live cell imaging for many years, the size and the limited windows of fluorescent spectra of GFP and its variants set limits on possible applications. In order to complement FP-based labeling methods, alternative approaches that allow incorporation of synthetic fluorescent probes to target POIs were developed. Synthetic fluorescent probes are smaller than fluorescent proteins, often have improved photochemical properties, and offer a larger variety of colors. These synthetic probes can be introduced to POIs selectively by numerous approaches that can be largely categorized into chemical recognition-based labeling, which utilizes metal-chelating peptide tags and fluorophore-carrying metal complexes, and biological recognition-based labeling, such as (1) specific non-covalent binding between an enzyme tag and its fluorophore-carrying substrate, (2) self-modification of protein tags using substrate variants conjugated to fluorophores, (3) enzymatic reaction to generate a covalent binding between a small molecule substrate and a peptide tag, and (4) split-intein-based C-terminal labeling of target proteins. The chemical recognition-based labeling reaction often suffers from compromised selectivity of metal-ligand interaction in the cytosolic environment, consequently producing high background signals. Use of protein-substrate interactions or enzyme-mediated reactions generally shows improved specificity but each method has its limitations. Some examples are the presence of large linker protein, restriction on the choice of introducible probes due to the substrate specificity of enzymes, and competitive reaction mediated by an endogenous analogue of the introduced protein tag. These limitations have been addressed, in part, by the split-intein-based labeling approach, which introduces fluorescent probes with a minimal size (~4 amino acids) peptide tag. In this review, the advantages and the limitations of each labeling method are discussed.

  6. Glioma Dual-Targeting Nanohybrid Protein Toxin Constructed by Intein-Mediated Site-Specific Ligation for Multistage Booster Delivery

    PubMed Central

    Chen, Yingzhi; Zhang, Meng; Jin, Hongyue; Li, Dongdong; Xu, Fan; Wu, Aihua; Wang, Jinyu; Huang, Yongzhuo

    2017-01-01

    Malignant glioma is one of the most untreatable cancers because of the formidable blood-brain barrier (BBB), through which few therapeutics can penetrate and reach the tumors. Biologics have been booming in cancer therapy in the past two decades, but their application in brain tumor has long been ignored due to the impermeable nature of BBB against effective delivery of biologics. Indeed, it is a long unsolved problem for brain delivery of macromolecular drugs, which becomes the Holy Grail in medical and pharmaceutical sciences. Even assisting by targeting ligands, protein brain delivery still remains challenging because of the synthesis difficulties of ligand-modified proteins. Herein, we propose a rocket-like, multistage booster delivery system of a protein toxin, trichosanthin (TCS), for antiglioma treatment. TCS is a ribosome-inactivating protein with the potent activity against various solid tumors but lack of specific action and cell penetration ability. To overcome the challenge of its poor druggability and site-specific modification, intein-mediated ligation was applied, by which a gelatinase-cleavable peptide and cell-penetrating peptide (CPP)-fused recombinant TCS toxin can be site-specifically conjugated to lactoferrin (LF), thus constructing a BBB-penetrating, gelatinase-activatable cell-penetrating nanohybrid TCS toxin. This nanohybrid TCS system is featured by the multistage booster strategy for glioma dual-targeting delivery. First, LF can target to the BBB-overexpressing low-density lipoprotein receptor-related protein-1 (LRP-1), and assist with BBB penetration. Second, once reaching the tumor site, the gelatinase-cleavable peptide acts as a separator responsive to the glioma-associated matrix metalloproteinases (MMPs), thus releasing to the CPP-fused toxin. Third, CPP mediates intratumoral and intracellular penetration of TCS toxin, thereby enhancing its antitumor activity. The BBB penetration and MMP-2-activability of this delivery system were demonstrated. The antiglioma activity was evaluated in the subcutaneous and orthotopic animal models. Our work provides a useful protocol for improving the druggability of such class of protein toxins and promoting their in-vivo application for targeted cancer therapy. PMID:28912890

  7. A Divided Attention Experiment with Pervasively Hyperactive Children.

    ERIC Educational Resources Information Center

    van der Meere, Jaap; Sergeant, Joseph

    1987-01-01

    Task performance of 12 pervasive hyperactives and controls (ages 8-13) was studied in a divided attention reaction time experiment. Hyperactives were slower than controls, had more variable reaction times, and made more frequent errors. Task inefficiency in hyperactives could not be explained by a divided attention deficiency or impulsive…

  8. Assessment of Preschool Hyperactivity: Combining Rating Scale and Objective Observation Measures.

    ERIC Educational Resources Information Center

    Mayes, Susan Dickerson

    1987-01-01

    Advantages and disadvantages of behavior rating scales and observation systems are presented, followed by preliminary validity data for the Mayes Hyperactivity Observation System, a clinically feasible system to identify preschool children with both Attention Deficit Disorder and Hyperactivity. Hyperactive and normal children were identified with…

  9. Attention-Deficit Hyperactivity Disorder (ADHD)

    MedlinePlus

    ... Tube DysfunctionStrep ThroatAnemiaHyperthyroidismOpioid AddictionDiabetesCroup Home Diseases and Conditions Attention-Deficit Hyperactivity Disorder (ADHD) Condition Attention-Deficit Hyperactivity ...

  10. Attention deficit hyperactivity symptoms in children with autistic disorder: a cross-sectional descriptive study.

    PubMed

    Charnsil, Chawanun; Sriapai, Payupol

    2011-02-01

    (1) to examine the co-occurrence of attention deficit and hyperactivity symptoms in children with autistic disorder, and (2) to study the correlation between attention deficit hyperactivity symptoms and the severity of autistic disorder. This was a clinical based study. The authors used Childhood Autistic Rating scale (CARs) to evaluate the severity of autistic disorder Swanson, Nolan, and Pelham Teacher and Parent Rating Scale, Version IV (SNAP-IV) was used to measure attention deficit and hyperactive symptoms in children with autism. Thirty (n=30) children enrolled in this study. All participants displayed attention deficit symptoms and 18 participants demonstrated hyperactivity as well. Nonparametric correlation showed a high positive correlation (Spa = 0.90, p = 0.00) between the severity of autistic disorder and hyperactivity and not the attention deficit symptoms (Spa = 0.29, p = 0.16). The authors finding shows a high comorbid rate of attention deficit and hyperactive symptoms among the participants.

  11. Attention-deficit hyperactivity disorder (ADHD) and tuberous sclerosis complex.

    PubMed

    D'Agati, Elisa; Moavero, Romina; Cerminara, Caterina; Curatolo, Paolo

    2009-10-01

    The neurobiological basis of attention-deficit hyperactivity disorder (ADHD) in tuberous sclerosis complex is still largely unknown. Cortical tubers may disrupt several brain networks that control different types of attention. Frontal lobe dysfunction due to seizures or epileptiform electroencephalographic discharges may perturb the development of brain systems that underpin attentional and hyperactive functions during a critical early stage of brain maturation. Comorbidity of attention-deficit hyperactivity disorder (ADHD) with mental retardation and autism spectrum disorders is frequent in children with tuberous sclerosis. Attention-deficit hyperactivity disorder (ADHD) may also reflect a direct effect of the abnormal genetic program. Treatment of children with tuberous sclerosis complex with combined symptoms of attention-deficit hyperactivity disorder (ADHD) and epilepsy may represent a challenge for clinicians, because antiepileptic therapy and drugs used to treat attention-deficit hyperactivity disorder (ADHD) may aggravate the clinical picture of each other.

  12. Teacher Response to the Methylphenidate (Ritalin) versus Placebo Status of Hyperactive Boys in the Classroom.

    ERIC Educational Resources Information Center

    Whalen, Carol K.; And Others

    1981-01-01

    Teacher behaviors toward hyperactive boys on methylphenidate (ritalin), toward hyperactive boys on placebo, and toward normal comparison peers were compared. Teachers were more intense and controlling toward hyperactive boys on placebo, but no differences emerged between comparison and medicated groups. Need for broader monitoring of treatment…

  13. Hyperactivity in Boys with Attention-Deficit/Hyperactivity Disorder (ADHD): A Ubiquitous Core Symptom or Manifestation of Working Memory Deficits?

    ERIC Educational Resources Information Center

    Rapport, Mark D.; Bolden, Jennifer; Kofler, Michael J.; Sarver, Dustin E.; Raiker, Joseph S.; Alderson, R. Matt

    2009-01-01

    Hyperactivity is currently considered a core and ubiquitous feature of attention-deficit/hyperactivity disorder (ADHD); however, an alternative model challenges this premise and hypothesizes a functional relationship between working memory (WM) and activity level. The current study investigated whether children's activity level is functionally…

  14. Development and Persistence of Methamphetamine Conditioned Hyperactivity in Swiss-Webster Mice

    PubMed Central

    Rauhut, Anthony S.; Bialecki, Victoria

    2011-01-01

    The present experiments examined the development and persistence of methamphetamine conditioned hyperactivity in Swiss-Webster mice. Experiments 1 and 2 examined the development of conditioned hyperactivity, varying the methamphetamine dose (0.25 – 2.0 mg/kg), the temporal injection parameters (continuous; Experiment 1 or intermittent; Experiment 2), and the comparison control group (saline; Experiment 1 or unpaired; Experiment 2). Experiment 3 examined the persistence of methamphetamine conditioned hyperactivity by comparing mice 1 (Immediate) or 28 (Delay) days after drug withdrawal. In each experiment, several behavioral measures (vertical counts, distance travelled and velocity) were recorded and temporal analyses conducted to assess methamphetamine conditioned hyperactivity. In Experiments 1 and 2, it was found that methamphetamine conditioned hyperactivity was 1) dose-dependent, 2) detected early in the session, 3) detected by a behavioral measure indicative of general activity (i.e., distance travelled), and 4) varied as a function of the number of conditioning sessions. In Experiment 3, it was found that conditioned hyperactivity persisted for 28 days, though was weakened by non-associative factors, following methamphetamine withdrawal. Collectively, these results suggest that conditioned hyperactivity to methamphetamine is robust and persists following prolonged periods of drug withdrawal in mice. Furthermore, these results are consistent with an excitatory classical conditioning interpretation of conditioned hyperactivity. PMID:21448061

  15. Reading and listening comprehension and their relation to inattention and hyperactivity.

    PubMed

    Cain, Kate; Bignell, Simon

    2014-03-01

    Children with diagnoses of attention-deficit/hyperactivity disorder (ADHD) frequently have reading problems. To date, it is not clear whether poor reading is associated with both inattention and hyperactivity and also whether poor reading comprehension is the result of poor word reading skills or more general language comprehension weaknesses. We report two studies to examine how reading and listening comprehension skills are related to inattention and hyperactivity/impulsivity. Separate groups of 7- to 11-year-olds participated in each study. In both studies, we used teacher ratings of inattention and hyperactivity/impulsivity to identify three groups at risk of ADHD: poor attention, high hyperactivity, poor attention and high hyperactivity, and also same-age controls. In Study 1, we explored how inattention and hyperactivity predicted reading after controlling for non-verbal IQ and vocabulary. In Study 2, we compared listening and reading comprehension in these groups. Poor attention was related to poor reading comprehension, although the relation was partially mediated by word reading skill (Study 1). Groups with high hyperactivity had weak listening comprehension relative to reading comprehension (Study 2). These results indicate that the reading comprehension problems of children with attention difficulties are related to poor word reading and that listening comprehension is particularly vulnerable in children at risk of ADHD. © 2013 The British Psychological Society.

  16. Preschool hyperactivity specifically elevates long-term mental health risks more strongly in males than females: a prospective longitudinal study through to young adulthood.

    PubMed

    Smith, Elizabeth; Meyer, Brenda J; Koerting, Johanna; Laver-Bradbury, Cathy; Lee, Louise; Jefferson, Harriet; Sayal, Kapil; Treglown, Luke; Thompson, Margaret; Sonuga-Barke, Edmund J S

    2017-01-01

    Evidence of continuities between preschool hyperactivity and adult mental health problems highlights the potential value of targeting early identification and intervention strategies. However, specific risk factors are currently unclear. This large-scale prospective longitudinal study aimed to identify which hyperactive preschoolers are at the greatest long-term risk of poor mental health. One hundred and seventy children (89 females) rated as hyperactive by their parents, and 88 non-hyperactive controls (48 females) were identified from a community sample of 4215 3-year-olds. Baseline data relating to behavioral/emotional problems and background characteristics were collected. Follow-up mental health and functional impairment outcomes were collected between 14 and 25 years of age. At age 3 years, males and females in the hyperactive group had similarly raised levels of hyperactivity and other behavior problems. In adolescence/young adulthood, these individuals showed elevated symptoms of ADHD, conduct disorder, mood disorder, anxiety and autism, as well as functional impairment. Preschool hyperactivity was strongly predictive of poor adolescent/adult outcomes for males across domains with effects being specifically driven by hyperactivity. For females, the effects of preschool hyperactivity were smaller and dropped to non-significant levels when other preschool problems were taken into account. Environmental risk factors also differed between the sexes, although these may also have been mediated by genetic risk. In conclusion, these results demonstrate marked sex differences in preschool predictors of later adolescent/adult mental health problems. Future research should include a measure of preschool inattention as well as hyperactivity. The findings highlight the potential value of tailored approaches to early identification strategies.

  17. The Quality of Life of Adults with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Goldenberg, Matthew; Perry, Robert; Ishak, Waguih William

    2012-01-01

    Objective: Across all medical specialties, quality of life has become an important measure of outcomes in both research and clinical settings. However, to date, there has not been a systematic review of the research relevant to quality of life in populations with adult attention deficit hyperactivity disorder. We approach quality of life in adult attention deficit hyperactivity disorder by answering the following questions: 1) What specific metrics are used to assess quality of life in adult attention deficit hyperactivity disorder? 2) What is the impact of adult attention deficit hyperactivity disorder on quality of life? 3) What effects do attention deficit hyperactivity disorder treatments have on quality of life? Searches of major electronic databases were conducted, and reference lists from the identified articles were searched for additional studies, with a focus on studies that utilized quality of life measures. Design: Thirty-six relevant studies are included in our review. Results: There are multiple unique measures currently used to measure quality of life in adult attention deficit hyperactivity disorder, ranging from general quality of life scales to those specifically designed for use in attention deficit hyperactivity disorder. Attention deficit hyperactivity disorder was found to significantly worsen the quality of life in adults. Treatment with atomoxetine and mixed amphetamine salts has shown beneficial effects on quality of life even in cases without symptomatology improvement. Conclusion: Pharmacological treatment and early diagnosis have a positive impact on outcomes, longterm prognosis, and quality of life in adults with attention deficit hyperactivity disorder. Having multiple unique measures of quality of life have limited the direct comparison of different classes of attention deficit hyperactivity disorder medication treatments and future research should be aimed to address this. PMID:22808445

  18. Inattention and hyperactivity/impulsivity among children with attention-deficit/hyperactivity-disorder, autism spectrum disorder, and intellectual disability.

    PubMed

    McClain, Maryellen Brunson; Hasty Mills, Amber M; Murphy, Laura E

    2017-11-01

    Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Intellectual Disability (ID) are common co-occurring neurodevelopmental disorders; however, limited research exists regarding the presentation and severity of overlapping symptomology, particularly inattention and hyperactivity/impulsivity, when a child is diagnosed with one of more of these neurodevelopmental disorders. As difficulties with inattention and hyperactivity/impulsivity are symptoms frequently associated with these disorders, the current study aims to determine the differences in the severity of inattention and hyperactivity/impulsivity in children diagnosed with ADHD, ASD, ID, and co-occurring diagnosis of ADHD/ID, ASD/ADHD, and ASD/ID. Participants in the current study included 113 children between the ages of 6 and 11 who were diagnosed with ADHD, ASD, ID, ADHD/ID, ASD/ADHD, or ASD/ID. Two MANOVA analyses were used to compare these groups witih respsect to symptom (i.e., inattention, hyperactivity/impulsivity) severity. Results indicated that the majority of diagnostic groups experienced elevated levels of both inattention and hyperactivity/impulsivity. However, results yielded differences in inattention and hyperactivity/impulsivity severity. In addition, differences in measure sensitivity across behavioral instruments was found. Children with neurodevelopmental disorders often exhibit inattention and hyperactivity/impulsivity, particularly those with ADHD, ASD, ASD/ADHD, and ADHD/ID; therefore, differential diagnosis may be complicated due to similarities in ADHD symptom severity. However, intellectual abilities may be an important consideration for practitioners in the differential diagnosis process as children with ID and ASD/ID exhibited significantly less inattention and hyperactive/impulsive behaviors. Additionally, the use of multiple behavior rating measures in conjunction with other assessment procedures may help practitioners determine the most appropriate diagnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Cortical morphology as a shared neurobiological substrate of attention-deficit/hyperactivity symptoms and executive functioning: a population-based pediatric neuroimaging study

    PubMed Central

    Mous, Sabine E.; White, Tonya; Muetzel, Ryan L.; El Marroun, Hanan; Rijlaarsdam, Jolien; Polderman, Tinca J.C.; Jaddoe, Vincent W.; Verhulst, Frank C.; Posthuma, Danielle; Tiemeier, Henning

    2017-01-01

    Background Attention-deficit/hyperactivity symptoms have repeatedly been associated with poor cognitive functioning. Genetic studies have demonstrated a shared etiology of attention-deficit/hyperactivity disorder (ADHD) and cognitive ability, suggesting a common underlying neurobiology of ADHD and cognition. Further, neuroimaging studies suggest that altered cortical development is related to ADHD. In a large population-based sample we investigated whether cortical morphology, as a potential neurobiological substrate, underlies the association between attention-deficit/hyperactivity symptoms and cognitive problems. Methods The sample consisted of school-aged children with data on attention-deficit/hyperactivity symptoms, cognitive functioning and structural imaging. First, we investigated the association between attention-deficit/hyperactivity symptoms and different domains of cognition. Next, we identified cortical correlates of attention-deficit/hyperactivity symptoms and related cognitive domains. Finally, we studied the role of cortical thickness and gyrification in the behaviour–cognition associations. Results We included 776 children in our analyses. We found that attention-deficit/hyperactivity symptoms were associated specifically with problems in attention and executive functioning (EF; b = −0.041, 95% confidence interval [CI] −0.07 to −0.01, p = 0.004). Cortical thickness and gyrification were associated with both attention-deficit/hyperactivity symptoms and EF in brain regions that have been previously implicated in ADHD. This partly explained the association between attention-deficit/hyperactivity symptoms and EF (bindirect = −0.008, bias-corrected 95% CI −0.018 to −0.001). Limitations The nature of our study did not allow us to draw inferences regarding temporal associations; longitudinal studies are needed for clarification. Conclusion In a large, population-based sample of children, we identified a shared cortical morphology underlying attention-deficit/hyperactivity symptoms and EF. PMID:27673503

  20. Association Between Childhood to Adolescent Attention Deficit/Hyperactivity Disorder Symptom Trajectories and Late Adolescent Disordered Eating.

    PubMed

    Yilmaz, Zeynep; Javaras, Kristin N; Baker, Jessica H; Thornton, Laura M; Lichtenstein, Paul; Bulik, Cynthia M; Larsson, Henrik

    2017-08-01

    Disordered eating is more prevalent among adolescents with attention deficit/hyperactivity disorder. Both inattention and hyperactivity/impulsivity symptoms show strong associations with disordered eating, but few investigations of these associations have been longitudinal. Thus, we examined the effect of childhood to adolescent inattention and hyperactivity/impulsivity symptom trajectories on late adolescent disordered eating. We used growth mixture modeling to identify distinct inattention and hyperactivity/impulsivity symptom trajectories (called "classes") across three time points (ages 8-9, 13-14, and 16-17 years) in the Swedish Twin study of CHild and Adolescent Development. The resulting classes were used to predict Eating Disorder Inventory-2 Bulimia, Drive for Thinness, and Body Dissatisfaction subscales at age 16-17 years, with adjustment for sex and body mass index at age 16-17 years. The combined inattention and hyperactivity/impulsivity symptom trajectory classes included: a "low symptom" class characterized by low inattention and hyperactivity/impulsivity throughout childhood/adolescence; a "predominantly inattention" class characterized by elevated inattention, but not hyperactivity/impulsivity, throughout childhood/adolescence; a "predominantly hyp/imp" class characterized by elevated hyperactivity/impulsivity, but not inattention, throughout childhood/adolescence; and a "both inattention and hyp/imp" class characterized by elevated inattention and hyperactivity/impulsivity throughout childhood/adolescence. After adjusting for sex and body mass index or sex and anxiety/depression symptoms, the "both inattention and hyp/imp" (vs. "low symptom") class predicted significantly higher Eating Disorder Inventory-2 subscale scores during late adolescence. Increased vigilance for disordered eating among children who have both inattention and hyperactivity/impulsivity symptoms throughout childhood and adolescence could aid in early identification of eating disorders. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  1. Cortical morphology as a shared neurobiological substrate of attention-deficit/hyperactivity symptoms and executive functioning: a population-based pediatric neuroimaging study.

    PubMed

    Mous, Sabine E; White, Tonya; Muetzel, Ryan L; El Marroun, Hanan; Rijlaarsdam, Jolien; Polderman, Tinca J C; Jaddoe, Vincent W; Verhulst, Frank C; Posthuma, Danielle; Tiemeier, Henning

    2017-03-01

    Attention-deficit/hyperactivity symptoms have repeatedly been associated with poor cognitive functioning. Genetic studies have demonstrated a shared etiology of attention-deficit/hyperactivity disorder (ADHD) and cognitive ability, suggesting a common underlying neurobiology of ADHD and cognition. Further, neuroimaging studies suggest that altered cortical development is related to ADHD. In a large population-based sample we investigated whether cortical morphology, as a potential neurobiological substrate, underlies the association between attention-deficit/hyperactivity symptoms and cognitive problems. The sample consisted of school-aged children with data on attention-deficit/hyperactivity symptoms, cognitive functioning and structural imaging. First, we investigated the association between attention-deficit/ hyperactivity symptoms and different domains of cognition. Next, we identified cortical correlates of attention-deficit/hyperactivity symptoms and related cognitive domains. Finally, we studied the role of cortical thickness and gyrification in the behaviour-cognition associations. We included 776 children in our analyses. We found that attention-deficit/hyperactivity symptoms were associated specifically with problems in attention and executive functioning (EF; b = -0.041, 95% confidence interval [CI] -0.07 to -0.01, p = 0.004). Cortical thickness and gyrification were associated with both attention-deficit/hyperactivity symptoms and EF in brain regions that have been previously implicated in ADHD. This partly explained the association between attention-deficit/hyperactivity symptoms and EF (b indirect = -0.008, bias-corrected 95% CI -0.018 to -0.001). The nature of our study did not allow us to draw inferences regarding temporal associations; longitudinal studies are needed for clarification. In a large, population-based sample of children, we identified a shared cortical morphology underlying attention-deficit/hyperactivity symptoms and EF.

  2. Three-year latent class trajectories of attention-deficit/hyperactivity disorder (ADHD) symptoms in a clinical sample not selected for ADHD.

    PubMed

    Arnold, L Eugene; Ganocy, Stephen J; Mount, Katherine; Youngstrom, Eric A; Frazier, Thomas; Fristad, Mary; Horwitz, Sarah M; Birmaher, Boris; Findling, Robert; Kowatch, Robert A; Demeter, Christine; Axelson, David; Gill, Mary Kay; Marsh, Linda

    2014-07-01

    This study aims to examine trajectories of attention-deficit/hyperactivity disorder (ADHD) symptoms in the Longitudinal Assessment of Manic Symptoms (LAMS) sample. The LAMS study assessed 684 children aged 6 to 12 years with the Kiddie-Schedule for Affective Disorders and Schizophrenia (K-SADS) and rating scales semi-annually for 3 years. Although they were selected for elevated manic symptoms, 526 children had baseline ADHD diagnoses. With growth mixture modeling (GMM), we separately analyzed inattentive and hyperactive/impulsive symptoms, covarying baseline age. Multiple standard methods determined optimal fit. The χ(2) and Kruskal-Wallis analysis of variance compared resulting latent classes/trajectories on clinical characteristics and medication. Three latent class trajectories best described inattentive symptoms, and 4 classes best described hyperactive/impulsive symptoms. Inattentive trajectories maintained their relative position over time. Hyperactive/impulsive symptoms had 2 consistent trajectories (least and most severe). A third trajectory (4.5%) started mild, then escalated; and a fourth (14%) started severe but improved dramatically. The improving trajectory was associated with the highest rate of ADHD and lowest rate of bipolar diagnoses. Three-fourths of the mildest inattention class were also in the mildest hyperactive/impulsive class; 72% of the severest inattentive class were in the severest hyperactive/impulsive class, but the severest inattention class also included 62% of the improving hyperactive-impulsive class. An ADHD rather than bipolar diagnosis prognosticates a better course of hyperactive/impulsive, but not inattentive, symptoms. High overlap of relative severity between inattention and hyperactivity/impulsivity confirms the link between these symptom clusters. Hyperactive/impulsive symptoms wane more over time. Group means are insufficient to understand individual ADHD prognosis. A small subgroup deteriorates over time in hyperactivity/impulsivity and needs better treatments than currently provided. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. The Unique Contribution of Emotional Impulsiveness to Impairment in Major Life Activities in Hyperactive Children as Adults

    ERIC Educational Resources Information Center

    Barkley, Russell A.; Fischer, Mariellen

    2010-01-01

    Objective: Emotional impulsiveness (EI) may be a central feature of attention-deficit/hyperactivity disorder (ADHD) contributing impairment beyond the two ADHD dimensions of inattention and hyperactivity-impulsivity. Method: We evaluated EI in hyperactive (N = 135) and control (N = 75) children followed to adulthood (mean age 27 years). The…

  4. Designing Light-Activated Charge-Separating Proteins with a Naphthoquinone Amino Acid

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lichtenstein, Bruce R.; Bialas, Chris; Cerda, José F.

    2015-09-14

    The first principles design of manmade redox-protein maquettes is used to clarify the physical/chemical engineering supporting the mechanisms of natural enzymes with a view to recapitulate and surpass natural performance. Herein, we use intein-based protein semisynthesis to pair a synthetic naphthoquinone amino acid (Naq) with histidine-ligated photoactive metal–tetrapyrrole cofactors, creating a 100 μs photochemical charge separation unit akin to photosynthetic reaction centers. By using propargyl groups to protect the redox-active para-quinone during synthesis and assembly while permitting selective activation, we gain the ability to employ the quinone amino acid redox cofactor with the full set of natural amino acids inmore » protein design. Direct anchoring of quinone to the protein backbone permits secure and adaptable control of intraprotein electron-tunneling distances and rates.« less

  5. Mechanisms of B cell activation in patients with acquired immunodeficiency syndrome and related disorders. Contribution of antibody-producing B cells, of Epstein-Barr virus-infected B cells, and of immunoglobulin production induced by human T cell lymphotropic virus, type III/lymphadenopathy-associated virus.

    PubMed Central

    Yarchoan, R; Redfield, R R; Broder, S

    1986-01-01

    Patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) have hyperimmunoglobulinemia and increased numbers of circulating immunoglobulin-secreting cells. In this paper, we studied the basis for this B cell hyperactivity. Limiting dilution studies of B cells from seven patients with ARC and four with AIDS revealed that some B cells spontaneously produced antibodies to human T cell lymphotropic virus, type III/lymphadenopathy-associated virus (HTLV-III/LAV) (39:10(6) and 7:10(6) B cells, respectively), suggesting that chronic antigenic stimulation by HTLV-III/LAV was one contributing factor. The patients also had an increased number of spontaneously outgrowing B cells than did normals (6:10(6) vs. less than 2:10(6) B cells), suggesting that they had an increased number of Epstein-Barr virus (EBV)-infected B cells. However, fewer B cells from patients were immortalized by exogenously added EBV than were B cells from normals. In additional studies, HTLV-III/LAV induced immunoglobulin secretion (mean 2,860 ng/ml) by peripheral blood mononuclear cells from normals; this HTLV-III/LAV-induced immunoglobulin secretion required the presence of both B and T cells. Thus, antigenic stimulation by HTLV-III/LAV, increased numbers of EBV-infected B cells, and HTLV-III/LAV-induced T cell-dependent B cell activation all contribute to the B cell hyperactivity in patients with HTLV-III/LAV disease. PMID:3016028

  6. Testosterone and Androgen Receptor Sensitivity in Relation to Hyperactivity Symptoms in Boys with Autism Spectrum Disorders

    PubMed Central

    2016-01-01

    Introduction Autism spectrum disorders (ASD) and hyperactivity symptoms exhibit an incidence that is male-biased. Thus androgen activity can be considered a plausible biological risk factor for these disorders. However, there is insufficient information about the association between increased androgen activity and hyperactivity symptoms in children with ASD. Methods In the present study, the relationship between parameters of androgenicity (plasmatic testosterone levels and androgen receptor sensitivity) and hyperactivity in 60 boys (age 3–15) with ASD is investigated. Given well documented differences in parent and trained examiners ratings of symptom severity, we employed a standardized parent`s questionnaire (Nisonger Child Behavior Rating Form) as well as a direct examiner`s rating (Autism diagnostic observation schedule) for assessment of hyperactivity symptoms. Results Although it was found there was no significant association between actual plasmatic testosterone levels and hyperactivity symptoms, the number of CAG triplets was significantly negatively correlated with hyperactivity symptoms (R2 = 0.118, p = 0.007) in the sample, indicating increased androgen receptor sensitivity in association with hyperactivity symptoms. Direct trained examiner´s assessment appeared to be a relevant method for evaluating of behavioral problems in the investigation of biological underpinnings of these problems in our study. Conclusions A potential ASD subtype characterized by increased rates of hyperactivity symptoms might have distinct etiopathogenesis and require a specific behavioral and pharmacological approach. We propose an increase of androgen receptor sensitivity as a biomarker for a specific ASD subtype accompanied with hyperactivity symptoms. Findings are discussed in terms of their implications for practice and future research. PMID:26910733

  7. Relationship between attention deficit hyperactive disorder symptoms and perceived parenting practices of school-age children.

    PubMed

    Kim, Dong Hee; Yoo, Il Young

    2013-04-01

    To examine the relationship between the perception on parenting practices and attention deficit hyperactivity disorder (ADHD) symptoms in school-age children. Psychosocial attention deficit hyperactivity disorder intervention approaches emphasise environmental risk factors at the individual, family and community level. Parenting variables are strongly related to attention deficit hyperactivity disorder symptom severity. A cross-sectional questionnaire survey. The participants were 747 children and their parents in two elementary schools. The instruments used were Korean Conners Abbreviated Parent Questionnaire and Korean version Maternal Behavior Research Instrument (measuring four dimensions of parenting practices: affection, autonomy, rejection, control). Descriptive and logistic regression analyses were performed. The rejective parenting practice was statistically significant in logistic regression controlling gender and age of children, family structure, maternal education level and socio-economic status. The rejection parenting is associated with attention deficit hyperactivity disorder symptoms in children (OR=1.356). These results suggest the importance of specific parenting educational programmes for parents to prevent and decrease attention deficit hyperactivity disorder symptoms. It would be more effective rather than focusing only on the child's attention deficit hyperactivity disorder symptoms, developing educational programmes for parents to prevent rejection parenting practice and improve parenting skills in the family system. When developing a treatment programme for children with attention deficit hyperactivity disorder, healthcare providers should consider not only the child's attention deficit hyperactivity disorder symptoms, but also the parenting practices. Comprehensive interventions designed to prevent rejection and improve parenting skills may be helpful in mitigating attention deficit hyperactivity disorder symptoms. © 2012 Blackwell Publishing Ltd.

  8. Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

    PubMed

    Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

    2017-07-04

    This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

  9. Duration-dependence of the effect of treadmill exercise on hyperactivity in attention deficit hyperactivity disorder rats.

    PubMed

    Ji, Eun-Sang; Kim, Chang-Ju; Park, Jun Heon; Bahn, Geon Ho

    2014-04-01

    Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder, and its symptoms are hyperactivity and deficits in learning and memory. Physical exercise increases dopamine synthesis and neuronal activity in various brain regions. In the present study, we investigate the duration-dependence of the treadmill exercise on hyperactivity in relation with dopamine expression in ADHD. Spontaneously hypertensive rats were used for the ADHD rats and Wistar-Kyoto rats were used for the control rats. The rats in the exercise groups were forced to run on a treadmill for 10 min, 30 min, and 60 min once daily for 28 consecutive days. For this experiment, open field test and immunohistochemistry for tyrosine hydroxylase were conducted. The present results revealed that ADHD rats showed hyperactivity, and tyrosine hydroxylase expression in the striatum and substantia nigra were decreased in ADHD rats. Treadmill exercise alleviated hyperactivity and also increased TH expression in ADHD rats. Treadmill exercise for 30 min per day showed most potent suppressing effect on hyperactivity, and this dose of treadmill exercise also most potently inhibited tyrosine hydroxylase expression. The present study suggests that treadmill exercise for 30 min once a day is the most effective therapeutic intervention for ADHD patients.

  10. Reaction time, impulsivity, and attention in hyperactive children and controls: a video game technique.

    PubMed

    Mitchell, W G; Chavez, J M; Baker, S A; Guzman, B L; Azen, S P

    1990-07-01

    Maturation of sustained attention was studied in a group of 52 hyperactive elementary school children and 152 controls using a microcomputer-based test formatted to resemble a video game. In nonhyperactive children, both simple and complex reaction time decreased with age, as did variability of response time. Omission errors were extremely infrequent on simple reaction time and decreased with age on the more complex tasks. Commission errors had an inconsistent relationship with age. Hyperactive children were slower, more variable, and made more errors on all segments of the game than did controls. Both motor speed and calculated mental speed were slower in hyperactive children, with greater discrepancy for responses directed to the nondominant hand, suggesting that a selective right hemisphere deficit may be present in hyperactives. A summary score (number of individual game scores above the 95th percentile) of 4 or more detected 60% of hyperactive subjects with a false positive rate of 5%. Agreement with the Matching Familiar Figures Test was 75% in the hyperactive group.

  11. Attention-deficit hyperactivity disorder in ancient Greece: The Obtuse Man of Theophrastus.

    PubMed

    Victor, Marcelo M; S da Silva, Bruna; Kappel, Djenifer B; Bau, Claiton Hd; Grevet, Eugenio H

    2018-06-01

    We present an ancient Greek description written by the philosopher Theophrastus in his classic book ' Characters' comparable with modern attention-deficit hyperactivity disorder. The arguments are based in one chapter of this book-The Obtuse Man-presenting features of a character closely resembling the modern description of attention-deficit hyperactivity disorder. In a free comparative exercise, we compared Theophrastus descriptions with modern Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) attention-deficit hyperactivity disorder symptoms. The sentences describing The Obtuse Man written by Theophrastus are similar to several symptoms of attention-deficit hyperactivity disorder and he would probably be currently diagnosed with this disorder as an adult. To our knowledge, this is the oldest description compatible with the current conception of attention-deficit hyperactivity disorder in adults in the Western literature. Differently than the moralistic view of ancient Greece regarding those symptoms, the medical attention-deficit hyperactivity disorder conception may be advantageous to patients since it might reduce prejudice and allow individuals to seek treatment.

  12. Hyperactives as young adults: preliminary report.

    PubMed Central

    Hechtman, L.; Weiss, G.; Finklestein, J.; Werner, A.; Benn, R.

    1976-01-01

    Thirty-five individuals aged 17 to 24 in whom severe chronic hyperactivity had been diagnosed 10 years before were studied together with 25 matched controls. There were no significant differences in mean height or weight or in electroencephalographic findings, but the mean pulse rate was significantly higher in the hyperactive group. Cognitive style tests indicated continued difficulty in reflection (resulting in more errors) but less impulsivity (longer reaction time) in the hyperactive individuals. Compared with controls, hyperactive subjects were continuing to have more scholastic difficulty, although this difference seemed to be less pronounced than 5 years before. Their adjustment in work situations and living arrangements did not differ significantly from that of the controls. Restlessness, both reported and observed, continued to be a problem for the hyperactive individuals, and socialization skills and sense of well-being continued to be poorer than in the controls. The hyperactive individuals did not show significantly more antisocial behaviour, nonmedical use of drugs or serious psychiatric disturbances. PMID:974949

  13. Hyperactives as young adults: preliminary report.

    PubMed

    Hechtman, L; Weiss, G; Finklestein, J; Werner, A; Benn, R

    1976-10-09

    Thirty-five individuals aged 17 to 24 in whom severe chronic hyperactivity had been diagnosed 10 years before were studied together with 25 matched controls. There were no significant differences in mean height or weight or in electroencephalographic findings, but the mean pulse rate was significantly higher in the hyperactive group. Cognitive style tests indicated continued difficulty in reflection (resulting in more errors) but less impulsivity (longer reaction time) in the hyperactive individuals. Compared with controls, hyperactive subjects were continuing to have more scholastic difficulty, although this difference seemed to be less pronounced than 5 years before. Their adjustment in work situations and living arrangements did not differ significantly from that of the controls. Restlessness, both reported and observed, continued to be a problem for the hyperactive individuals, and socialization skills and sense of well-being continued to be poorer than in the controls. The hyperactive individuals did not show significantly more antisocial behaviour, nonmedical use of drugs or serious psychiatric disturbances.

  14. Stimulation seeking and hyperactivity in children with ADHD. Attention Deficit Hyperactivity Disorder.

    PubMed

    Antrop, I; Roeyers, H; Van Oost, P; Buysse, A

    2000-02-01

    Thirty hyperactive and 30 non-hyperactive children were confronted with a delay, consisting of a waiting situation of 15 minutes, either with or without extra stimulation provided by the presentation of a videotape. The behaviour of the child during the waiting period was videotaped and later coded by two naive observers. In line with theories that emphasise the stimulation-seeking function of hyperactive behaviours, such as the optimal stimulation account and the delay aversion theory, a group by stimulation effect was hypothesised. For two categories of activity this was found, with ADHD children displaying more activity than non-ADHD children in the no-stimulation but not in the stimulation condition. These data provide support for the stimulation-seeking function of certain features of ADHD hyperactivity.

  15. Parental happiness and strain among young adult parents diagnosed with Attention Deficit Hyperactivity Disorder.

    PubMed

    Kroeger, Rhiannon A

    2018-03-01

    This study used data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to examine whether young adult parents diagnosed with Attention Deficit Hyperactivity Disorder experience less parental happiness and/or more parental strain than their counterparts not diagnosed with Attention Deficit Hyperactivity Disorder. Results from logistic regression models indicated that young adult parents ever diagnosed with Attention Deficit Hyperactivity Disorder have significantly greater odds of feeling overwhelmed as parents and significantly lower odds of feeling close to their children or happy in their role as parents compared to those never diagnosed with Attention Deficit Hyperactivity Disorder. Potential implications of these results for scholars as well as health professionals treating adult Attention Deficit Hyperactivity Disorder patients with children are discussed.

  16. The history of attention deficit hyperactivity disorder

    PubMed Central

    Reichl, Susanne; Lange, Katharina M.; Tucha, Lara; Tucha, Oliver

    2010-01-01

    The contemporary concept of attention deficit hyperactivity disorder (ADHD) as defined in the DSM-IV-TR (American Psychiatric Association 2000) is relatively new. Excessive hyperactive, inattentive, and impulsive children have been described in the literature since the nineteenth century. Some of the early depictions and etiological theories of hyperactivity were similar to current descriptions of ADHD. Detailed studies of the behavior of hyperactive children and increasing knowledge of brain function have changed the concepts of the fundamental behavioral and neuropathological deficits underlying the disorder. This article presents an overview of the conceptual history of modern-day ADHD. PMID:21258430

  17. Attention deficit hyperactivity disorder (ADHD)

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001551.htm Attention deficit hyperactivity disorder To use the sharing features on this page, please enable JavaScript. Attention deficit hyperactivity disorder (ADHD) is a problem caused ...

  18. The Etiology of Hyperactivity.

    ERIC Educational Resources Information Center

    Johnson, Jean Ann

    1981-01-01

    There is little evidence implicating genetics, social learning, and organic factors as causes of hyperactivity. Environmental factors such as lead poisoning and, in particular, food additives show a somewhat stronger association with hyperactivity. (Author)

  19. Prevalence of Attention Deficit Hyperactivity Disorder among School Children and Associated Co-morbidities - A Hospital Based Descriptive Study.

    PubMed

    Rimal, H; Pokharel, A

    Attention Deficit Hyperactivity Disorder is the most common neuro- developmental disorders of childhood characterized by the core symptoms including inattentiveness and distractibility and frequently involve impairments in executive functioning, increased impulsivity, and restlessness. Objective To find out the prevalence of Attention Deficit Hyperactivity Disorder among school aged children Presented to Pediatric clinic and also to investigate associated comorbidities. Method This study was conducted at Nobel Medical College Teaching Hospital, Biratnagar during April 2014 - March 2015. Attention Deficit Hyperactivity Disorder was diagnosed by the developmental Pediatrician after taking relevant history and the clinical assessment using Attention Deficit Hyperactivity Disorder rating scale with diagnostic criteria consistent with Diagnostic Statistical Manual - IV classification. Spence anxiety scale child and parent rated version and Strength and Difficulty Questionnaire were also used. Result Result showed the yearly prevalence of Attention Deficit Hyperactivity Disorder being 41(11.7%) with male: female ratio of 4:1. The study reported that Attention Deficit Hyperactivity Disorder combined type was the commonest type that was 26(63%) cases followed by Inattentive type 9(22%) cases and 6(15%) were hyperactive type. The mean age for Attention Deficit Hyperactivity Disorder was 7 years and 5 months. The most common co-morbidities were sleep problem 12(29.3%), Learning difficulty 10(24.4%), Anxiety disorder 10(24.4), Oppositional Defiant Disorder 9(22%), Autism Spectrum Disorder 5(12%), speech delay 6(14.6%), and 4(10%) had associated tics. There was abnormal SDQ prevalence of 29.3% across the area of emotional distress. The mean abnormal SDQ score in total difficulty area 8 (20.7%), socializing with peer 9(22%), behavioral difficulty 11(26.8%), hyperactivity/inattention 23(56.1%) and impact of difficulties in young person's life being 5(12.2%). Conclusion There is high prevalence of Attention Deficit Hyperactivity Disorder in children and adolescents in Nepal. This study has also looked at co-morbidities associated with Attention Deficit Hyperactivity Disorder and the findings of the study have thrown lights on the mental health and other developmental issues associated with it.

  20. Developmental trajectories of DSM-IV symptoms of attention-deficit/hyperactivity disorder: genetic effects, family risk and associated psychopathology.

    PubMed

    Larsson, Henrik; Dilshad, Rezin; Lichtenstein, Paul; Barker, Edward D

    2011-09-01

    DSM-IV specifies three ADHD subtypes; the combined, the hyperactive-impulsive and the inattentive. Little is known about the developmental relationships underlying these subtypes. The objective of this study was to describe the development of parent-reported hyperactivity-impulsivity and inattention symptoms from childhood to adolescence and to study their associations with genetic factors, family risk, and later adjustment problems in early adulthood. Data in this study comes from 1,450 twin pairs participating in a population-based, longitudinal twin study. Developmental trajectories were defined using parent-ratings of hyperactivity-impulsivity and inattention symptoms at age 8-9, 13-14, and 16-17. Twin methods were used to explore genetic influences on trajectories. Family risk measures included low socioeconomic status, large family size and divorce. Self-ratings of externalizing and internalizing problems in early adulthood were used to examine adjustment problems related to the different trajectory combinations. We found two hyperactivity-impulsivity trajectories (low, high/decreasing) and two inattention trajectories (low, high/increasing). Twin modeling revealed a substantial genetic component underlying both the hyperactivity-impulsivity and the inattention trajectory. Joint trajectory analyses identified four groups of adolescents with distinct developmental patterns of hyperactivity-impulsivity and inattention: a low/low group, a primarily hyperactive, a primarily inattentive and a combined (high/high) trajectory type. These trajectory combinations showed discriminant relations to adjustment problems in early adulthood. The hyperactive, inattentive and combined trajectory subtypes were associated with higher rates of family risk environments compared to the low/low group. Study results showed that for those on a high trajectory, hyperactivity decreased whereas inattention increased. The combinations of these trajectories lend developmental insight into how children shift from (i) a combined to inattentive subtype, and (ii) a hyperactive-impulsive to a combined subtype. This study suggests that ADHD subtypes cannot be viewed as discrete and stable categories. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

  1. The nucleus accumbens 5-HTR₄-CART pathway ties anorexia to hyperactivity.

    PubMed

    Jean, A; Laurent, L; Bockaert, J; Charnay, Y; Dusticier, N; Nieoullon, A; Barrot, M; Neve, R; Compan, V

    2012-12-11

    In mental diseases, the brain does not systematically adjust motor activity to feeding. Probably, the most outlined example is the association between hyperactivity and anorexia in Anorexia nervosa. The neural underpinnings of this 'paradox', however, are poorly elucidated. Although anorexia and hyperactivity prevail over self-preservation, both symptoms rarely exist independently, suggesting commonalities in neural pathways, most likely in the reward system. We previously discovered an addictive molecular facet of anorexia, involving production, in the nucleus accumbens (NAc), of the same transcripts stimulated in response to cocaine and amphetamine (CART) upon stimulation of the 5-HT(4) receptors (5-HTR(4)) or MDMA (ecstasy). Here, we tested whether this pathway predisposes not only to anorexia but also to hyperactivity. Following food restriction, mice are expected to overeat. However, selecting hyperactive and addiction-related animal models, we observed that mice lacking 5-HTR(1B) self-imposed food restriction after deprivation and still displayed anorexia and hyperactivity after ecstasy. Decryption of the mechanisms showed a gain-of-function of 5-HTR(4) in the absence of 5-HTR(1B), associated with CART surplus in the NAc and not in other brain areas. NAc-5-HTR(4) overexpression upregulated NAc-CART, provoked anorexia and hyperactivity. NAc-5-HTR(4) knockdown or blockade reduced ecstasy-induced hyperactivity. Finally, NAc-CART knockdown suppressed hyperactivity upon stimulation of the NAc-5-HTR(4). Additionally, inactivating NAc-5-HTR(4) suppressed ecstasy's preference, strengthening the rewarding facet of anorexia. In conclusion, the NAc-5-HTR(4)/CART pathway establishes a 'tight-junction' between anorexia and hyperactivity, suggesting the existence of a primary functional unit susceptible to limit overeating associated with resting following homeostasis rules.

  2. The nucleus accumbens 5-HTR4-CART pathway ties anorexia to hyperactivity

    PubMed Central

    Jean, A; Laurent, L; Bockaert, J; Charnay, Y; Dusticier, N; Nieoullon, A; Barrot, M; Neve, R; Compan, V

    2012-01-01

    In mental diseases, the brain does not systematically adjust motor activity to feeding. Probably, the most outlined example is the association between hyperactivity and anorexia in Anorexia nervosa. The neural underpinnings of this ‘paradox', however, are poorly elucidated. Although anorexia and hyperactivity prevail over self-preservation, both symptoms rarely exist independently, suggesting commonalities in neural pathways, most likely in the reward system. We previously discovered an addictive molecular facet of anorexia, involving production, in the nucleus accumbens (NAc), of the same transcripts stimulated in response to cocaine and amphetamine (CART) upon stimulation of the 5-HT4 receptors (5-HTR4) or MDMA (ecstasy). Here, we tested whether this pathway predisposes not only to anorexia but also to hyperactivity. Following food restriction, mice are expected to overeat. However, selecting hyperactive and addiction-related animal models, we observed that mice lacking 5-HTR1B self-imposed food restriction after deprivation and still displayed anorexia and hyperactivity after ecstasy. Decryption of the mechanisms showed a gain-of-function of 5-HTR4 in the absence of 5-HTR1B, associated with CART surplus in the NAc and not in other brain areas. NAc-5-HTR4 overexpression upregulated NAc-CART, provoked anorexia and hyperactivity. NAc-5-HTR4 knockdown or blockade reduced ecstasy-induced hyperactivity. Finally, NAc-CART knockdown suppressed hyperactivity upon stimulation of the NAc-5-HTR4. Additionally, inactivating NAc-5-HTR4 suppressed ecstasy's preference, strengthening the rewarding facet of anorexia. In conclusion, the NAc-5-HTR4/CART pathway establishes a ‘tight-junction' between anorexia and hyperactivity, suggesting the existence of a primary functional unit susceptible to limit overeating associated with resting following homeostasis rules. PMID:23233022

  3. Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies

    PubMed Central

    Bonvicini, C; Faraone, S V; Scassellati, C

    2016-01-01

    The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug. Finally some peripheral biomarkers were identified in ADHD adult patients. We believe this work is the first systematic review and meta-analysis of candidate gene association studies, pharmacogenetic and biochemical (metabolomics) studies performed in adults with ADHD to identify potential genetic, predictive and peripheral markers linked specifically to ADHD in adults. After screening 5129 records, we selected 87 studies of which 61 were available for candidate gene association studies, 5 for pharmacogenetics and 21 for biochemical studies. Of these, 15 genetic, 2 pharmacogenetic and 6 biochemical studies were included in the meta-analyses. We obtained an association between adult ADHD and the gene BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), even after Bonferroni correction, with any heterogeneity in effect size and no publication bias. If we did not apply the Bonferroni correction, a trend was found for the carriers allele 9R of dopamine transporter SLC6A3 40 bp variable tandem repeat polymorphism (VNTR) and for 6/6 homozygotes of SLC6A3 30 bp VNTR. Negative results were obtained for the 9-6 haplotype, the dopamine receptor DRD4 48 bp VNTR, and the enzyme COMT SNP rs4680. Concerning pharmacogenetic studies, no association was found for the SLC6A3 40 bp and response to MPH with only two studies selected. For the metabolomics studies, no differences between ADHD adults and controls were found for salivary cortisol, whereas lower serum docosahexaenoic acid (DHA) levels were found in ADHD adults. This last association was significant even after Bonferroni correction and in absence of heterogeneity. Other polyunsaturated fatty acids (PUFAs) such as AA (arachidonic acid), EPA (eicosapentaenoic acid) and DyLA (dihomogammalinolenic acid) levels were not different between patients and controls. No publication biases were observed for these markers. Genes linked to dopaminergic, serotoninergic and noradrenergic signaling, metabolism (DBH, TPH1, TPH2, DDC, MAOA, MAOB, BCHE and TH), neurodevelopment (BDNF and others), the SNARE system and other forty genes/proteins related to different pathways were not meta-analyzed due to insufficient data. In conclusion, we found that there were not enough genetic, pharmacogenetic and biochemical studies of ADHD in adults and that more investigations are needed. Moreover we confirmed a significant role of BAIAP2 and DHA in the etiology of ADHD exclusively in adults. Future research should be focused on the replication of these findings and to assess their specificity for ADHD. PMID:27217152

  4. Attention-Deficit / Hyperactivity Disorder (ADHD): Data and Statistics

    MedlinePlus

    ... Search Form Controls Cancel Submit Search the CDC Attention-Deficit / Hyperactivity Disorder (ADHD) Note: Javascript is disabled ... claims to understand diagnosis and treatment patterns for Attention-Deficit/Hyperactivity Disorder (ADHD). On this page you ...

  5. Children and Adults with Attention-Deficit/Hyperactivity Disorder

    MedlinePlus

    ... Renew CHADD Annual Conference Children and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD), is a national nonprofit ... ADHD community. © 2017 by Children and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD). All Rights Reserved. Press ...

  6. Environmental Stimulation Model

    ERIC Educational Resources Information Center

    Zentall, Sydney S.

    1977-01-01

    An approach to treatment of hyperactive children is suggested which is based on the assumption that the hyperactive child is actually understimulated and hyperactive behaviors function to increase the external stimulation to approach a more optimal level. (Author/GW)

  7. Sustained impact of inattention and hyperactivity-impulsivity on peer problems: mediating roles of prosocial skills and conduct problems in a community sample of children.

    PubMed

    Andrade, Brendan F; Tannock, Rosemary

    2014-06-01

    This prospective 2-year longitudinal study tested whether inattentive and hyperactive/impulsive symptom dimensions predicted future peer problems, when accounting for concurrent conduct problems and prosocial skills. A community sample of 492 children (49 % female) who ranged in age from 6 to 10 years (M = 8.6, SD = .93) was recruited. Teacher reports of children's inattention, and hyperactivity/impulsivity symptoms, conduct problems, prosocial skills and peer problems were collected in two consecutive school years. Elevated inattention and hyperactivity/impulsivity in Year-1 predicted greater peer problems in Year-2. Conduct problems in the first and second years of the study were associated with more peer problems, and explained a portion of the relationship between inattention and hyperactivity/impulsivity with peer problems. However, prosocial skills were associated with fewer peer problems in children with elevated inattention and hyperactivity/impulsivity. Inattention and hyperactivity/impulsivity have negative effects on children's peer functioning after 1-year, but concurrent conduct problems and prosocial skills have important and opposing impacts on these associations.

  8. Association between severity of behavioral phenotype and comorbid attention deficit hyperactivity disorder symptoms in children with autism spectrum disorders.

    PubMed

    Rao, Patricia A; Landa, Rebecca J

    2014-04-01

    Autism spectrum disorder and attention deficit hyperactivity disorder are neurodevelopmental disorders that cannot be codiagnosed under existing diagnostic guidelines (Diagnostic and Statistical Manual of the American Psychiatric Association, 4th ed., text rev.). However, reports are emerging that attention deficit hyperactivity disorder is sometimes comorbid with autism spectrum disorder. In the current study, we examined rates of parent-reported clinically significant symptoms of attention deficit hyperactivity disorder in school-aged children (4-8 years) with autism spectrum disorder, most of whom were first enrolled in our research protocols as toddlers. Results revealed that children with autism spectrum disorder and attention deficit hyperactivity disorder had lower cognitive functioning, more severe social impairment, and greater delays in adaptive functioning than children with autism spectrum disorder only. Implications for clinical practice include the need to assess for attention deficit hyperactivity disorder symptoms at an early age in children diagnosed with autism spectrum disorder. Research is needed to determine efficacious interventions for young children with autism spectrum disorder with comorbid attention deficit hyperactivity disorder to optimize outcomes.

  9. [Associations between concurrent use of tobacco and alcohol and symptoms of attention-deficit hyperactivity disorder among ninth grader students].

    PubMed

    Matuszka, Balázs; Bácskai, Erika; Czobor, Pál; Egri, Tímea; Gerevich, József

    2015-10-25

    Attention-deficit hyperactivity disorder is a risk factor of smoking and alcohol drinking in adolescence. Since attention-deficit hyperactivity disorder and smoking and alcohol drinking in adolescence are predictors for the development of substance use disorders in adulthood, it is important to understand the nature of these associations. The aim of the authors was to investigate associations between attention-deficit hyperactivity disorder symptoms and the joint use of alcohol and nicotine among 9th graders. A representative sample of 944 pupils attending state-run secondary schools in Budapest were recruited. Generalized Linear Mixed Model and logistic regression analyses have been conducted. The prevalence was 29.6% and 41.4% for current smoking and current alcohol drinking, respectively. The prevalence of their concurrent-use was 21.7%. Alcohol drinking and smoking showed a significant positive association with the total scores of Attention-Deficit Hyperactivity Disorder Scale and with the Attention Deficit and Hyperactivity/Impulsivity subscales. The findings highlight the potential importance of attention-deficit hyperactivity disorder in the development of the joint use of these substances.

  10. Roy Porter Student Essay Prize WinnerPsychiatry Limited: Hyperactivity and the Evolution of American Psychiatry, 1957–1980

    PubMed Central

    Smith, Matthew

    2008-01-01

    Summary Hyperactivity is the most commonly diagnosed childhood psychiatric disorder in north America. Most physicians believe that the disorder is a neurological dysfunction which is best treated with stimulants, such as ritalin. Accounts of the history of hyperactivity written by physicians, psychologists and even historians suggest that the disorder was always conceived as such. This paper argues that, on the contrary, the notion that hyperactivity was a neurological condition only emerged after vigorous debate during the 1960s between three competing fields within American psychiatry: specifically psychoanalysis, social psychiatry and biological psychiatry. Biological psychiatry won the debate, not because its approach to hyperactivity was more scientifically valid, but rather because its explanations and methods fit the prevailing social context more readily than that of its rivals. American psychiatry's refusal to draw pluralistic conclusions about hyperactivity undermined the development of a deeper understanding of the disorder. The history of hyperactivity provides an ideal lens through which to view the evolution of psychiatry from a field dominated by Freudian psychoanalysis to one rooted in the neurosciences.

  11. Attention in Hyperactive Children and the Effect of Methylphenidate (Ritalin)

    ERIC Educational Resources Information Center

    Sykes, Donald H.; And Others

    1971-01-01

    Hyperactive children treated with methylphenidate (ritalin) showed a significant improvement in all aspects of performance in an experimenter-paced task when compared to a control group of hyperactive children given a placebo. (Author/WY)

  12. Hyperactivity and sugar

    MedlinePlus

    ... Elsevier; 2016:chap 2. Lyon M, Murray MT. Attention deficit hyperactivity disorder. In: Pizzorno JE, Murray MT, eds. Textbook of ... Livingstone; 2013:chap 150. Sawni A, Kemper KJ. Attention deficit hyperactivity disorder. In: Rakel D, ed. Integrative Medicine . 4th ed. ...

  13. Attention-deficit hyperactivity disorder in children with benign epilepsy and their siblings.

    PubMed

    Bennett-Back, Odeya; Keren, Amit; Zelnik, Nathanel

    2011-03-01

    This prospective study explores the prevalence and characteristics of attention-deficit hyperactivity disorder in children with benign epilepsy, compared with its prevalence in their siblings. Among 40 patients with benign epilepsy, 28 (70%) were diagnosed with attention-deficit hyperactivity disorder: 19 with the inattentive type, one with the hyperactive type, and eight with the combined type. In the control group of 12 siblings, only two (16.7%) were diagnosed with attention-deficit hyperactivity disorder (P<0.03). A trend toward an increased risk for attentional difficulties was evident in children whose seizures were more resistant and required more than one antiepileptic drug for seizure control. Children with more epileptiform features in their electroencephalograms were also more subject to signs of attention deficit hyperactivity disorder. Larger scale studies are required to validate our findings. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. GAD1 gene polymorphisms are associated with hyperactivity in Attention-Deficit/Hyperactivity Disorder.

    PubMed

    Bruxel, Estela M; Akutagava-Martins, Glaucia C; Salatino-Oliveira, Angélica; Genro, Julia P; Zeni, Cristian P; Polanczyk, Guilherme V; Chazan, Rodrigo; Schmitz, Marcelo; Rohde, Luis A; Hutz, Mara H

    2016-12-01

    Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood. Recent studies suggest a role for γ-aminobutyric acid (GABA) on ADHD hyperactive/impulsive symptoms due to behavioral disinhibition resulting from inappropriate modulation of both glutamatergic and GABAergic signaling. The glutamic acid decarboxylase (GAD1) gene encodes a key enzyme of GABA biosynthesis. The aim of the present study was to investigate the possible influence of GAD1 SNPs rs3749034 and rs11542313 on ADHD susceptibility. The clinical sample consisted of 547 families with ADHD probands recruited at the ADHD Outpatient Clinics from Hospital de Clínicas de Porto Alegre. Hyperactive/impulsive symptoms were evaluated based on parent reports from the Swanson, Nolan, and Pelham Scale-version IV (SNAP-IV). The C allele of rs11542313 was significantly overtransmitted from parents to ADHD probands (P = 0.02). Hyperactive/impulsive score was higher in rs3749034G allele (P = 0.005, Cohen's D = 0.19) and rs11542313C allele (P = 0.03; Cohen's D = 0.16) carriers. GAD1 haplotypes were also associated with higher hyperactive/impulsive scores in ADHD youths (global P-value = 0.01). In the specific haplotype test, the GC haplotype was the one with the highest hyperactive/impulsive scores (P = 0.03). Our results suggest that the GAD1 gene is associated with ADHD susceptibility, contributing particularly to the hyperactive/impulsive symptom domain. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Temperament and character as endophenotype in adults with autism spectrum disorders or attention deficit/hyperactivity disorder.

    PubMed

    Sizoo, Bram B; van der Gaag, Rutger Jan; van den Brink, Wim

    2015-05-01

    Autism spectrum disorder and attention deficit/hyperactivity disorder overlap in several ways, raising questions about the nature of this comorbidity. Rommelse et al. published an innovative review of candidate endophenotypes for autism spectrum disorder and attention deficit/hyperactivity disorder in cognitive and brain domains. They found that all the endophenotypic impairments that were reviewed in attention deficit/hyperactivity disorder were also present in autism spectrum disorder, suggesting a continuity model with attention deficit/hyperactivity disorder as "a light form of autism spectrum disorder." Using existing data, 75 adults with autism spectrum disorder and 53 with attention deficit/hyperactivity disorder were directly compared on autistic symptoms with the autism spectrum quotient, and on the endophenotypic measure of temperament and character, using the Abbreviated (Dutch: Verkorte) Temperament and Character Inventory. Based on the hypothesis that attention deficit/hyperactivity disorder and autism spectrum disorder are disorders on a continuous spectrum, autism spectrum quotient scores and abbreviated Temperament and Character Inventory scores were expected to be different from normal controls in both disorders in a similar direction. In addition, the autism spectrum quotient and abbreviated Temperament and Character Inventory scores were expected to be closely correlated. These conditions applied to only two of the seven Abbreviated Temperament and Character Inventory scales (harm avoidance and self-directedness), suggesting that temperament and character as an endophenotype of autism spectrum disorder and attention deficit/hyperactivity disorder provides only partial support for the continuity hypothesis of autism spectrum disorder and attention deficit/hyperactivity disorder. © The Author(s) 2014.

  16. Hyperactivity.

    ERIC Educational Resources Information Center

    Kinsbourne, Marcel

    Hyperactivity in children is explained in relation to behavioral characteristics, precipitating factors, and stimulant medication therapy. The basic mechanism of hyperactivity is seen to be impulsive style in motility, attention, and socialization. Problems caused by impulsivity are noted to include feeding problems, school difficulties, and peer…

  17. The effects of reward and punishment on reaction times and autonomic activity in hyperactive and normal children.

    PubMed

    Firestone, P; Douglas, V

    1975-01-01

    The performance of hyperactive and control children was compared on a delayed reaction time task under three reinforcement conditions: reward, punishment, and reward plus punishment. Hyperactives had slower and more variable reaction times, suggesting an attentional deficit. Although each of the three reinforcement conditons was successful in improving reaction times for both subject groups, reward led to a significant increase in impulsive responses in the hyperactive children. Autonomic data revealed that reward also increased arousal to a greater extent than punishment or reward plus punishment. Although resting skin conductance was not different in the two groups of subjects, hyperactives produced fewer specific autonomic responses to signal stimuli.

  18. Access to site-specific Fc-cRGD peptide conjugates through streamlined expressed protein ligation.

    PubMed

    Frutos, S; Jordan, J B; Bio, M M; Muir, T W; Thiel, O R; Vila-Perelló, M

    2016-10-12

    An ideal drug should be highly effective, non-toxic and be delivered by a convenient and painless single dose. We are still far from such optimal treatment but peptides, with their high target selectivity and low toxicity profiles, provide a very attractive platform from which to strive towards it. One of the major limitations of peptide drugs is their high clearance rates, which limit dosage regimen options. Conjugation to antibody Fc domains is a viable strategy to improve peptide stability by increasing their hydrodynamic radius and hijacking the Fc recycling pathway. We report the use of a split-intein based semi-synthetic approach to site-specifically conjugate a synthetic integrin binding peptide to an Fc domain. The strategy described here allows conjugating synthetic peptides to Fc domains, which is not possible via genetic methods, fully maintaining the ability of both the Fc domain and the bioactive peptide to interact with their binding partners.

  19. Split-gene system for hybrid wheat seed production.

    PubMed

    Kempe, Katja; Rubtsova, Myroslava; Gils, Mario

    2014-06-24

    Hybrid wheat plants are superior in yield and growth characteristics compared with their homozygous parents. The commercial production of wheat hybrids is difficult because of the inbreeding nature of wheat and the lack of a practical fertility control that enforces outcrossing. We describe a hybrid wheat system that relies on the expression of a phytotoxic barnase and provides for male sterility. The barnase coding information is divided and distributed at two loci that are located on allelic positions of the host chromosome and are therefore "linked in repulsion." Functional complementation of the loci is achieved through coexpression of the barnase fragments and intein-mediated ligation of the barnase protein fragments. This system allows for growth and maintenance of male-sterile female crossing partners, whereas the hybrids are fertile. The technology does not require fertility restorers and is based solely on the genetic modification of the female crossing partner.

  20. Homing endonucleases: from basics to therapeutic applications.

    PubMed

    Marcaida, Maria J; Muñoz, Inés G; Blanco, Francisco J; Prieto, Jesús; Montoya, Guillermo

    2010-03-01

    Homing endonucleases (HE) are double-stranded DNAses that target large recognition sites (12-40 bp). HE-encoding sequences are usually embedded in either introns or inteins. Their recognition sites are extremely rare, with none or only a few of these sites present in a mammalian-sized genome. However, these enzymes, unlike standard restriction endonucleases, tolerate some sequence degeneracy within their recognition sequence. Several members of this enzyme family have been used as templates to engineer tools to cleave DNA sequences that differ from their original wild-type targets. These custom HEs can be used to stimulate double-strand break homologous recombination in cells, to induce the repair of defective genes with very low toxicity levels. The use of tailored HEs opens up new possibilities for gene therapy in patients with monogenic diseases that can be treated ex vivo. This review provides an overview of recent advances in this field.

  1. Split-gene system for hybrid wheat seed production

    PubMed Central

    Kempe, Katja; Rubtsova, Myroslava; Gils, Mario

    2014-01-01

    Hybrid wheat plants are superior in yield and growth characteristics compared with their homozygous parents. The commercial production of wheat hybrids is difficult because of the inbreeding nature of wheat and the lack of a practical fertility control that enforces outcrossing. We describe a hybrid wheat system that relies on the expression of a phytotoxic barnase and provides for male sterility. The barnase coding information is divided and distributed at two loci that are located on allelic positions of the host chromosome and are therefore “linked in repulsion.” Functional complementation of the loci is achieved through coexpression of the barnase fragments and intein-mediated ligation of the barnase protein fragments. This system allows for growth and maintenance of male-sterile female crossing partners, whereas the hybrids are fertile. The technology does not require fertility restorers and is based solely on the genetic modification of the female crossing partner. PMID:24821800

  2. Water-Soluble Phosphinothiols for Traceless Staudinger Ligation and Integration with Expressed Protein Ligation

    PubMed Central

    Tam, Annie; Soellner, Matthew B.; Raines, Ronald T.

    2010-01-01

    The traceless Staudinger ligation is an effective means to synthesize an amide bond between two groups of otherwise orthogonal reactivity: a phosphinothioester and an azide. An important application of the Staudinger ligation is in the ligation of peptides at a variety of residues. Here, we demonstrate that the traceless Staudinger ligation can be achieved in water with a water-soluble reagent. Those reagents that provide a high yield of amide product discourage protonation of the nitrogen in the key iminophosphorane intermediate. The most efficacious reagent, bis(p-dimethylaminoethylphenyl)phosphinomethanethiol, mediates the rapid ligation of equimolar substrates in water. This reagent is also able to perform a transthioesterification reaction with the thioester intermediate formed during intein-mediated protein splicing. Hence, the traceless Staudinger ligation can be integrated with expressed protein ligation, extending the reach of modern protein chemistry. PMID:17713909

  3. Chemical and Biophysical Modulation of Cas9 for Tunable Genome Engineering.

    PubMed

    Nuñez, James K; Harrington, Lucas B; Doudna, Jennifer A

    2016-03-18

    The application of the CRISPR-Cas9 system for genome engineering has revolutionized the ability to interrogate genomes of mammalian cells. Programming the Cas9 endonuclease to induce DNA breaks at specified sites is achieved by simply modifying the sequence of its cognate guide RNA. Although Cas9-mediated genome editing has been shown to be highly specific, cleavage events at off-target sites have also been reported. Minimizing, and eventually abolishing, unwanted off-target cleavage remains a major goal of the CRISPR-Cas9 technology before its implementation for therapeutic use. Recent efforts have turned to chemical biology and biophysical approaches to engineer inducible genome editing systems for controlling Cas9 activity at the transcriptional and protein levels. Here, we review recent advancements to modulate Cas9-mediated genome editing by engineering split-Cas9 constructs, inteins, small molecules, protein-based dimerizing domains, and light-inducible systems.

  4. Structural, functional and evolutionary relationships between homing endonucleases and proteins from their host organisms

    PubMed Central

    Taylor, Gregory K.; Stoddard, Barry L.

    2012-01-01

    Homing endonucleases (HEs) are highly specific DNA-cleaving enzymes that are encoded by invasive DNA elements (usually mobile introns or inteins) within the genomes of phage, bacteria, archea, protista and eukaryotic organelles. Six unique structural HE families, that collectively span four distinct nuclease catalytic motifs, have been characterized to date. Members of each family display structural homology and functional relationships to a wide variety of proteins from various organisms. The biological functions of those proteins are highly disparate and include non-specific DNA-degradation enzymes, restriction endonucleases, DNA-repair enzymes, resolvases, intron splicing factors and transcription factors. These relationships suggest that modern day HEs share common ancestors with proteins involved in genome fidelity, maintenance and gene expression. This review summarizes the results of structural studies of HEs and corresponding proteins from host organisms that have illustrated the manner in which these factors are related. PMID:22406833

  5. Hyperactivity: nature of the syndrome and its natural history.

    PubMed

    Aman, M G

    1984-03-01

    The composition of hyperactivity as a syndrome is discussed from a historical perspective, and the principal events leading to the recent emphasis on attentional characteristics of hyperactive children are summarized. Some of the major challenges to the legitimacy of hyperactivity as a valid syndrome are set forth, and after critical examination of the most influential work, it is concluded that hyperactivity has not been disproved. This is followed by a survey of the large follow-up literature dealing with the natural history of children diagnosed as hyperactive. It is noted that the manifestations of the syndrome appear to change with age but there is little indication that problems simply remit with maturity. The evidence indicates that hyperactivity, as diagnosed in the past, is often a serious disorder with long-term and far-reaching consequences for the children and their families. Multivariate studies are also discussed, as they have important implications for differential outcome. Different symptoms such as aggression, overactivity, and learning disability appear to contain unique information about current and future status, and therefore it appears useful to retain these distinctions rather than view such children as part of an undifferentiated group. It is unknown whether the recent guidelines for diagnosing Attention Deficit Disorder with Hyperactivity will alter or refine the outlook for children so identified, but this is an active area of research at present.

  6. A Comparative Study on the Visual Perceptions of Children with Attention Deficit Hyperactivity Disorder

    NASA Astrophysics Data System (ADS)

    Ahmetoglu, Emine; Aral, Neriman; Butun Ayhan, Aynur

    This study was conducted in order to (a) compare the visual perceptions of seven-year-old children diagnosed with attention deficit hyperactivity disorder with those of normally developing children of the same age and development level and (b) determine whether the visual perceptions of children with attention deficit hyperactivity disorder vary with respect to gender, having received preschool education and parents` educational level. A total of 60 children, 30 with attention deficit hyperactivity disorder and 30 with normal development, were assigned to the study. Data about children with attention deficit hyperactivity disorder and their families was collected by using a General Information Form and the visual perception of children was examined through the Frostig Developmental Test of Visual Perception. The Mann-Whitney U-test and Kruskal-Wallis variance analysis was used to determine whether there was a difference of between the visual perceptions of children with normal development and those diagnosed with attention deficit hyperactivity disorder and to discover whether the variables of gender, preschool education and parents` educational status affected the visual perceptions of children with attention deficit hyperactivity disorder. The results showed that there was a statistically meaningful difference between the visual perceptions of the two groups and that the visual perceptions of children with attention deficit hyperactivity disorder were affected meaningfully by gender, preschool education and parents` educational status.

  7. Attention Deficit Hyperactivity Disorder Subtypes and Symptom Response in Adults Treated with Lisdexamfetamine Dimesylate

    PubMed Central

    Mattingly, Greg; Weisler, Richard; Dirks, Bryan; Babcock, Thomas; Adeyi, Ben; Scheckner, Brian; Lasser, Robert

    2012-01-01

    Objective: To evaluate the efficacy of lisdexamfetamine dimesylate in adults with attention deficit hyperactivity disorder symptom subtypes who exhibit predominantly inattention, hyperactivity/ impulsivity, or combined symptom clusters. Design/Setting/Participants: This is a post-hoc analysis from a multicenter, one-year, open-label lisdexamfetamine dimesylate study in adults with attention deficit hyperactivity disorder previously completing two weeks or more in a four-week, randomized, placebo-controlled lisdexamfetamine dimesylate study, using Attention Deficit Hyperactivity Disorder Rating Scale IV symptom ratings as an attention deficit hyperactivity disorder subtype proxy (N=349). Measurements: Attention Deficit Hyperactivity Disorder Rating Scale IV was measured at baseline of prior study and throughout the open-label study. Proxy subtypes were based on item scores of 2 (moderate) or 3 (severe), representing endorsement of at least six of nine symptoms on respective subscales; predominantly combined type endorsed at least six of nine symptoms on each subscale. Overall safety evaluations included treatment-emergent adverse events. Results: At baseline, 93 of 345 participants exhibited predominantly inattention, 13 predominantly hyperactivity/ impulsivity, 236 combined symptom clusters, and three were unassigned. For the three subgroups, respectively, mean (standard deviation) Attention Deficit Hyperactivity Disorder Rating Scale IV total scores at baseline were 34.5 (4.02), 33.8 (3.27), and 43.6 (5.24); change from baseline to endpoint scores were -19.3 (9.48), -24.0 (7.22), and -27.3 (11.78). Mean (standard deviation) end-of-study lisdexamfetamine dimesylate dose was 57.7 (14.75), 53.1 (16.01), and 56.9 (14.94)mg/day, respectively. Treatment-emergent adverse events (>5%) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), irritability (11.2%), anxiety (8.3%), nasopharyngitis (7.4%), sinusitis (6.6%), decreased weight (6.0%), back pain (5.4%), and muscle spasms (5.2%). Conclusions: Lisdexamfetamine dimesylate was effective in participants with predominantly inattention, hyperactivity/ impulsivity, and combined attention deficit hyperactivity disorder symptom clusters. Groups exhibiting specific predominant subtype symptoms did not differ in clinical response to lisdexamfetamine dimesylate. PMID:22808446

  8. The Severity of Vestibular Dysfunction in Deafness as a Determinant of Comorbid Hyperactivity or Anxiety

    PubMed Central

    McKeehan, Nicholas

    2017-01-01

    Attention-deficit/hyperactivity disorder (ADHD) and anxiety-related disorders occur at rates 2–3 times higher in deaf compared with hearing children. Potential explanations for these elevated rates and the heterogeneity of behavioral disorders associated with deafness have usually focused on socio-environmental rather than biological effects. Children with the 22q11.2 deletion or duplication syndromes often display hearing loss and behavioral disorders, including ADHD and anxiety-related disorders. Here, we show that mouse mutants with either a gain or loss of function of the T-Box transcription factor gene, Tbx1, which lies within the 22q11.2 region and is responsible for most of the syndromic defects, exhibit inner ear defects and hyperactivity. Furthermore, we show that (1) inner ear dysfunction due to the tissue-specific loss of Tbx1 or Slc12a2, which encodes a sodium-potassium-chloride cotransporter and is also necessary for inner ear function, causes hyperactivity; (2) vestibular rather than auditory failure causes hyperactivity; and (3) the severity rather than the age of onset of vestibular dysfunction differentiates whether hyperactivity or anxiety co-occurs with inner ear dysfunction. Together, these findings highlight a biological link between inner ear dysfunction and behavioral disorders and how sensory abnormalities can contribute to the etiology of disorders traditionally considered of cerebral origin. SIGNIFICANCE STATEMENT This study examines the biological rather than socio-environmental reasons why hyperactivity and anxiety disorders occur at higher rates in deaf individuals. Using conditional genetic approaches in mice, the authors show that (1) inner ear dysfunction due to either Tbx1 or Slc12a2 mutations cause hyperactivity; (2) it is vestibular dysfunction, which frequently co-occurs with deafness but often remains undiagnosed, rather than auditory dysfunction that causes hyperactivity and anxiety-related symptoms; and (3) the severity of vestibular dysfunction can predict whether hyperactivity or anxiety coexist with inner ear dysfunction. These findings suggest a need to evaluate vestibular function in hearing impaired individuals, especially those who exhibit hyperactive and anxiety-related symptoms. PMID:28438970

  9. The Severity of Vestibular Dysfunction in Deafness as a Determinant of Comorbid Hyperactivity or Anxiety.

    PubMed

    Antoine, Michelle W; Vijayakumar, Sarath; McKeehan, Nicholas; Jones, Sherri M; Hébert, Jean M

    2017-05-17

    Attention-deficit/hyperactivity disorder (ADHD) and anxiety-related disorders occur at rates 2-3 times higher in deaf compared with hearing children. Potential explanations for these elevated rates and the heterogeneity of behavioral disorders associated with deafness have usually focused on socio-environmental rather than biological effects. Children with the 22q11.2 deletion or duplication syndromes often display hearing loss and behavioral disorders, including ADHD and anxiety-related disorders. Here, we show that mouse mutants with either a gain or loss of function of the T-Box transcription factor gene, Tbx1 , which lies within the 22q11.2 region and is responsible for most of the syndromic defects, exhibit inner ear defects and hyperactivity. Furthermore, we show that (1) inner ear dysfunction due to the tissue-specific loss of Tbx1 or Slc12a2 , which encodes a sodium-potassium-chloride cotransporter and is also necessary for inner ear function, causes hyperactivity; (2) vestibular rather than auditory failure causes hyperactivity; and (3) the severity rather than the age of onset of vestibular dysfunction differentiates whether hyperactivity or anxiety co-occurs with inner ear dysfunction. Together, these findings highlight a biological link between inner ear dysfunction and behavioral disorders and how sensory abnormalities can contribute to the etiology of disorders traditionally considered of cerebral origin. SIGNIFICANCE STATEMENT This study examines the biological rather than socio-environmental reasons why hyperactivity and anxiety disorders occur at higher rates in deaf individuals. Using conditional genetic approaches in mice, the authors show that (1) inner ear dysfunction due to either Tbx1 or Slc12a2 mutations cause hyperactivity; (2) it is vestibular dysfunction, which frequently co-occurs with deafness but often remains undiagnosed, rather than auditory dysfunction that causes hyperactivity and anxiety-related symptoms; and (3) the severity of vestibular dysfunction can predict whether hyperactivity or anxiety coexist with inner ear dysfunction. These findings suggest a need to evaluate vestibular function in hearing impaired individuals, especially those who exhibit hyperactive and anxiety-related symptoms. Copyright © 2017 the authors 0270-6474/17/375144-11$15.00/0.

  10. Tryptophan circuit in fatigue: From blood to brain and cognition.

    PubMed

    Yamashita, Masatoshi; Yamamoto, Takanobu

    2017-11-15

    Brain tryptophan and its neuroactive metabolites play key roles in central fatigue. However, previous brain function analysis targets may have included both glia and neurons together. Here, we clarified the fatigue-cognitive circuit of the central-peripheral linkage, including the role of glial-neuronal interaction in cognition. Using a rat model of central fatigue induced by chronic sleep disorder (CFSD), we isolated presynaptic terminals and oligodendrocytes. Results showed that compared to control group, presynaptic levels of tryptophan, kynurenine, and kynurenic acid, but not serotonin, in the CFSD group were higher in the hypothalamus and hippocampus. Moreover, CFSD group had higher oligodendrocytic levels of tryptophan, and impaired spatial cognitive memory accuracy and increased hyperactivity and impulsivity. These findings suggest that dynamic change in glial-neuronal interactions within the hypothalamus-hippocampal circuit causes central fatigue, and increased tryptophan-kynurenic acid pathway activity in this circuit causes reduced cognitive function. Additionally, CFSD group had 1.5 times higher plasma levels of tryptophan and kynurenine. Furthermore, in rats undergoing intraperitoneal administration of kynurenine (100mg/kg) versus vehicle, kynurenine-treated rats showed enhanced production of kynurenic acid in the hippocampus, with suppressed recall of retained spatial cognitive memory. The study revealed that uptake of periphery-derived kynurenine and tryptophan into the brain enhances kynurenic acid production in the brain, and the three factors produce amplification effect involved in the role of central-peripheral linkage in central fatigue, triggering cognitive dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation

    PubMed Central

    Ashton, Jesse L.; Burton, Rebecca A. B.; Bub, Gil; Smaill, Bruce H.; Montgomery, Johanna M.

    2018-01-01

    Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the neurons innervating the heart. The atria receive rich innervation from the autonomic branch of the peripheral nervous system. Sympathetic neurons are clustered in stellate and cervical ganglia alongside the spinal cord and extend fibers to the heart directly innervating the myocardium. These neurons are major drivers of hyperactive sympathetic activity observed in heart disease, ventricular arrhythmias, and sudden cardiac death. Both pre- and postsynaptic changes have been observed to occur at synapses formed by sympathetic ganglion neurons, suggesting that plasticity at sympathetic neuro-cardiac synapses is a major contributor to arrhythmias. Less is known about the plasticity in parasympathetic neurons located in clusters on the heart surface. These neuronal clusters, termed ganglionated plexi, or “little brains,” can independently modulate neural control of the heart and stimulation that enhances their excitability can induce arrhythmia such as atrial fibrillation. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by ganglionated plexi neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation. PMID:29615932

  12. Color and luminance increment thresholds in poor readers.

    PubMed

    Dain, Stephen J; Floyd, Richard A; Elliot, Robert T

    2008-01-01

    The hypotheses of a visual basis to reading disabilities in some children have centered around deficits in the visual processes displaying more transient responses to stimuli although hyperactivity in the visual processes displaying sustained responses to stimuli has also been proposed as a mechanism. In addition, there is clear evidence that colored lenses and/or colored overlays and/or colored backgrounds can influence performance in reading and/or may assist in providing comfortable vision for reading and, as a consequence, the ability to maintain reading for longer. As a consequence, it is surprising that the color vision of poor readers is relatively little studied. We assessed luminance increment thresholds and equi-luminous red-green and blue-yellow increment thresholds using a computer based test in central vision and at 10 degrees nasally employing the paradigm pioneered by King-Smith. We examined 35 poor readers (based on the Neale Analysis of Reading) and compared their performance with 35 normal readers matched for age and IQ. Poor readers produced similar luminance contrast thresholds for both foveal and peripheral presentation compared with normals. Similarly, chromatic contrast discrimination for the red/green stimuli was the same in normal and poor readers. However, poor readers had significantly lower thresholds/higher sensitivity for the blue/yellow stimuli, for both foveal and peripheral presentation, compared with normal readers. This hypersensitivity in blue-yellow discrimination may point to why colored lenses and overlays are often found to be effective in assisting many poor readers.

  13. Preschool hyperactivity is associated with long-term economic burden: evidence from a longitudinal health economic analysis of costs incurred across childhood, adolescence and young adulthood.

    PubMed

    Chorozoglou, Maria; Smith, Elizabeth; Koerting, Johanna; Thompson, Margaret J; Sayal, Kapil; Sonuga-Barke, Edmund J S

    2015-09-01

    Preschool hyperactivity is an early risk factor for adult mental health problems and criminality. Little is known about; (a) the patterns of long-term service costs associated with this behavioural marker in the general population and (b) the specific factors predicting hyperactivity-related costs. We undertook a prospective study investigating associations between preschool hyperactivity and average individual annual service costs up to late adolescent and young adulthood. One-hundred and seventy individuals rated as hyperactive by their parents and 88 nonhyperactive controls were identified from a community sample of 4,215 three years olds. Baseline information about behaviour/emotional problems and background characteristics were collected. At follow-up (when individuals were aged between 14 and 25 years) information was obtained on service use, and associated costs since the age of three. Based on this information we calculated the average cost per annum incurred by each individual. Compared to controls, preschoolers with hyperactivity had 17.6 times higher average costs per annum across domains (apart from nonmental health costs). These were £562 for each hyperactive individual compared with £30 for controls. Average annual costs decreased as a function of age, with higher costs incurred at younger ages. The effects of hyperactivity remained significant when other baseline factors were added to the model. Effects were fully mediated by later psychiatric morbidity. When the hyperactive group were examined separately, costs were consistently predicted by male gender and, for some cost codes, by conduct problems. Preventative approaches targeting early hyperactivity may be of value. Services should be targeted towards high-risk individuals with careful consideration given to the cost-to-benefit trade-off of early intervention strategies. © 2015 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

  14. Childhood Hyperactivity, Physical Aggression and Criminality: A 19-Year Prospective Population-Based Study

    PubMed Central

    Pingault, Jean-Baptiste; Côté, Sylvana M.; Lacourse, Eric; Galéra, Cédric; Vitaro, Frank; Tremblay, Richard E.

    2013-01-01

    Background Research shows that children with Attention Deficit/Hyperactivity Disorder are at elevated risk of criminality. However, several issues still need to be addressed in order to verify whether hyperactivity in itself plays a role in the prediction of criminality. In particular, co-occurrence with other behaviors as well as the internal heterogeneity in ADHD symptoms (hyperactivity and inattention) should be taken into account. The aim of this study was to assess the unique and interactive contributions of hyperactivity to the development of criminality, whilst considering inattention, physical aggression and family adversity. Methodology/Principal Findings We monitored the development of a population-based sample of kindergarten children (N = 2,741). Hyperactivity, inattention, and physical aggression were assessed annually between the ages of 6 and 12 years by mothers and teachers. Information on the presence, the age at first charge and the type of criminal charge was obtained from official records when the participants were aged 25 years. We used survival analysis models to predict the development of criminality in adolescence and adulthood: high childhood hyperactivity was highly predictive when bivariate analyses were used; however, with multivariate analyses, high hyperactivity was only marginally significant (Hazard Ratio: 1.38; 95% CI: 0.94–2.02). Sensitivity analyses revealed that hyperactivity was not a consistent predictor. High physical aggression was strongly predictive (Hazard Ratio: 3.44; 95% CI: 2.43–4.87) and its role was consistent in sensitivity analyses and for different types of crime. Inattention was not predictive of later criminality. Conclusions/Significance Although the contribution of childhood hyperactivity to criminality may be detected in large samples using multi-informant longitudinal designs, our results show that it is not a strong predictor of later criminality. Crime prevention should instead target children with the highest levels of childhood physical aggression and family adversity. PMID:23658752

  15. Concordance of actigraphy with polysomnography in children with and without attention-deficit/hyperactivity disorder.

    PubMed

    Waldon, Jessica; Begum, Esmot; Gendron, Melissa; Rusak, Benjamin; Andreou, Pantelis; Rajda, Malgorzata; Corkum, Penny

    2016-10-01

    This study sought to: (1) compare actigraphy-derived estimated sleep variables to the same variables based on the gold-standard of sleep assessment, polysomnography; (2) examine whether the correlations between the measures differ between children with attention-deficit/hyperactivity disorder and typically developing children; and (3) determine whether these correlations are altered when children with attention-deficit/hyperactivity disorder are treated with medication. Participants (24 attention-deficit/hyperactivity disorder; 24 typically developing), aged 6-12 years, completed a 1-week baseline assessment of typical sleep and daytime functioning. Following the baseline week, participants in the attention-deficit/hyperactivity disorder group completed a 4-week blinded randomized control trial of methylphenidate hydrochloride, including a 2-week placebo and 2-week methylphenidate hydrochloride treatment period. At the end of each observation (typically developing: baseline; attention-deficit/hyperactivity disorder: baseline, placebo and methylphenidate hydrochloride treatment), all participants were invited to a sleep research laboratory, where overnight polysomnography and actigraphy were recorded concurrently. Findings from intra-class correlations and Bland-Altman plots were consistent. Actigraphy was found to provide good estimates (e.g. intra-class correlations >0.61) of polysomnography results for sleep duration for all groups and conditions, as well as for sleep-onset latency and sleep efficiency for the typically developing group and attention-deficit/hyperactivity disorder group while on medication, but not for the attention-deficit/hyperactivity disorder group during baseline or placebo. Based on the Bland-Altman plots, actigraphy tended to underestimate for sleep duration (8.6-18.5 min), sleep efficiency (5.6-9.3%) and sleep-onset latency, except for attention-deficit/hyperactivity disorder during placebo in which actigraphy overestimated (-2.1 to 6.3 min). The results of the current study highlight the importance of utilizing a multimodal approach to sleep assessment in children with attention-deficit/hyperactivity disorder. © 2016 European Sleep Research Society.

  16. The long-term significance of teacher-rated hyperactivity and reading ability in childhood: findings from two longitudinal studies.

    PubMed

    McGee, Rob; Prior, Margot; Willams, Sheila; Smart, Diana; Sanson, Anne

    2002-11-01

    The aims of this study were twofold: first, to examine behavioural and academic outcomes of children with hyperactivity, using data from two longitudinal studies; and second, to examine comparable psychosocial outcomes for children with early reading difficulties. Measures of teacher-rated persistent hyperactivity, and reading ability obtained during early primary school were available for children from the Australian Temperament Project and the Dunedin Multidisciplinary Health and Development Study. Both samples were followed up to assess behavioural and academic outcomes during the adolescent and early adult years. Family background, antisocial behaviour and literacy were controlled in the first set of analyses to examine the influence of early hyperactivity. There were strong linear relationships between early hyperactivity and later adverse outcomes. Adjustment for other childhood variables suggested that early hyperactivity was associated with continuing school difficulties, problems with attention and poor reading in adolescence. Early reading difficulties, after controlling for early hyperactivity, predicted continuing reading problems in high school and leaving school with no qualifications. The findings suggest that there are dual pathways from early inattentive behaviours to later inattention and reading problems, and from early reading difficulties to substantial impairments in later academic outcomes.

  17. Inattention/hyperactivity and aggression from early childhood to adolescence: heterogeneity of trajectories and differential influence of family environment characteristics.

    PubMed

    Jester, Jennifer M; Nigg, Joel T; Adams, Kenneth; Fitzgerald, Hiram E; Puttler, Leon I; Wong, Maria M; Zucker, Robert A

    2005-01-01

    Inattention/hyperactivity and aggressive behavior problems were measured in 335 children from school entry throughout adolescence, at 3-year intervals. Children were participants in a high-risk prospective study of substance use disorders and comorbid problems. A parallel process latent growth model found aggressive behavior decreasing throughout childhood and adolescence, whereas inattentive/hyperactive behavior levels were constant. Growth mixture modeling, in which developmental trajectories are statistically classified, found two classes for inattention/hyperactivity and two for aggressive behavior, resulting in a total of four trajectory classes. Different influences of the family environment predicted development of the two types of behavior problems when the other behavior problem was held constant. Lower emotional support and lower intellectual stimulation by the parents in early childhood predicted membership in the high problem class of inattention/hyperactivity when the trajectory of aggression was held constant. Conversely, conflict and lack of cohesiveness in the family environment predicted membership in a worse developmental trajectory of aggressive behavior when the inattention/hyperactivity trajectories were held constant. The implications of these findings for the development of inattention/hyperactivity and for the development of risk for the emergence of substance use disorders are discussed.

  18. Vitamin D Status at Birth and Future Risk of Attention Deficit/Hyperactivity Disorder (ADHD).

    PubMed

    Gustafsson, Peik; Rylander, Lars; Lindh, Christian H; Jönsson, Bo A G; Ode, Amanda; Olofsson, Per; Ivarsson, Sten A; Rignell-Hydbom, Anna; Haglund, Nils; Källén, Karin

    2015-01-01

    To investigate whether children with Attention Deficit/Hyperactivity Disorder have lower levels of Vitamin D3 at birth than matched controls. Umbilical cord blood samples collected at birth from 202 children later diagnosed with Attention Deficit/Hyperactivity Disorder were analysed for vitamin D content and compared with 202 matched controls. 25-OH vitamin D3 was analysed by liquid chromatography tandem mass spectrometry. No differences in cord blood vitamin D concentration were found between children with Attention Deficit/Hyperactivity Disorder (median 13.0 ng/ml) and controls (median 13.5 ng/ml) (p = 0.43). In a logistic regression analysis, Attention Deficit/Hyperactivity Disorder showed a significant association with maternal age (odds ratio: 0.96, 95% confidence interval: 0.92-0.99) but not with vitamin D levels (odds ratio: 0.99, 95% confidence interval: 0.97-1.02). We found no difference in intrauterine vitamin D levels between children later developing Attention Deficit/Hyperactivity Disorder and matched control children. However, the statistical power of the study was too weak to detect an eventual small to medium size association between vitamin D levels and Attention Deficit/Hyperactivity Disorder.

  19. Outpatient screening of Japanese children with epilepsy for attention-deficit/hyperactivity disorder (AD/HD).

    PubMed

    Tanabe, Takuya; Kashiwagi, Mitsuru; Shimakawa, Shuichi; Tamai, Hiroshi; Wakamiya, Eiji

    2014-04-01

    The significance of the Strengths and Difficulties Questionnaire (SDQ) score for AD/HD (attention-deficit/hyperactivity disorder) screening was assessed in Japanese epileptic children. Sixty-eight epileptic children were enrolled in this study. Parents were asked to fill out both the SDQ and AD/HD-rating scale (AD/HD-RS) simultaneously. The SDQ subscale of hyperactivity showed the highest score. The AD/HD-RS showed higher scores for both inattention and hyperactivity-impulsivity. Twenty-two (32.4%) of these subjects were diagnosed as having AD/HD. The SDQ subscale for hyperactivity showed 86.4% sensitivity and 95% specificity, respectively, for detection of AD/HD. All SDQ subscales correlated significantly with inattention and hyperactivity-impulsivity scores of the AD/HD-RS. The SDQ is a good screening tool which can contribute to the detection of AD/HD, not only of the hyperactive/impulsive but also the inattentive subtype. Furthermore, the SDQ can elucidate more complicated behavioral problems than the core symptoms of AD/HD that are not noticed in the epilepsy clinic. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  20. Alternatives to Drug Treatment for Hyperactivity.

    ERIC Educational Resources Information Center

    Den Houtter, Kathryn

    1980-01-01

    Results from recent studies on the effectiveness of Ritalin for "hyperactivity" show that this treatment is dubious at best. This article presents an alternative treatment approach, placing emphasis on devising an appropriate learning situation that meets the needs of the so-called hyperactive child. (Author)

  1. Effects of a Stimulant Drug on Extraversion Level in Hyperactive Children.

    ERIC Educational Resources Information Center

    Mc Manis, Donald L.; And Others

    1978-01-01

    Seven hyperactive children in a pilot study, and 15 hyperactive and 15 nonhyperactive control children in a later study, were assessed for salivation to lemon juice stimulation, reactive inhibition on an audio-vigilance task, and visual-motor maze errors. (Author)

  2. Psychopharmacotherapy of Attention Deficit-Hyperactivity Disorder in Children with Comorbid Conditions.

    PubMed

    Naguy, Ahmed

    2018-05-01

    One or more comorbidities occur in up to 80% of children with attention deficit-hyperactivity disorder. Attention deficit-hyperactivity disorder is also over-represented in several special populations. Pharmacotherapy can be challenging in these individuals with other conditions due to a suboptimal therapeutic response and an increased likelihood of adverse reactions. This article reviews the evidence supporting the psychopharmacologic management attention deficit-hyperactivity disorder when it occurs in individuals with common comorbidities. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. [Epidemiological characteristics and relevant factors on the comorbidity of hyperactivity behavior and allergic diseases in preschool children].

    PubMed

    Weng, T T; Yan, S Q; Cao, H; Gu, C L; Xu, Y Q; Ni, L L; Tao, H H; Shao, T; Tao, F B

    2017-12-06

    Objective: To understand the epidemiological characteristics and relevant factors on the comorbidity of hyperactivity behavior and allergic disease among preschool children in urban areas of Ma'anshan city. Methods: During April 2014 to April 2015, 91 kindergartens over 3 years old were investigated. In the investigation, 16 439 questionnaires were distributed to parents, and 15 291 valid questionnaires were collected. Conners abbreviated symptom questionnaire ( brief symptom questionnaire ) was filled out by parents to assess the children's hyperactive behaviors. Information of allergic disease history was reported by parents, including allergic dermatitis/eczema, food/drug allergy, allergic rhinitis and asthma. Multivariate unconditional logistic regression was used to analyze the relevant factors of comorbidity of hyperactivity behavior and allergy diseases. Results: The average age of the 15 291 children were (4.5±1.0) years old, among which 53.7% (8 218/15 291) were boys. The prevalence of hyperactive behaviors was 8.6%(1 317/15 291), and the comorbidity rate of hyperactivity and allergic deseases was 1.7% (258/15 291). After confounding factors including gender, age, delivery mode, father's age and pregnancy complications adjusted, poor sleep quality ( OR= 4.45, 95 %CI: 2.85-6.94), long duration of watching TV at weekend ( OR= 1.39, 95 %CI : 1.00-1.94) and poor eating behavior ( OR= 1.78, 95 %CI : 1.07-2.98) were relevant factors of the comorbidity of hyperactivity and allergic diseases. Conclusion: The prevalence of comorbidity of hyperactivity behavior and allergic disease among preschool children in urban areas of Ma'anshan city was not high. Poor night sleep quality, long duration of watching TV and frequently picky eating were relevant factors of the comorbidity of hyperactive behaviors and allergic diseases.

  4. Attention Deficit Hyperactivity Disorder in Adolescents With Epilepsy.

    PubMed

    Kwong, Karen L; Lam, David; Tsui, Sarah; Ngan, Mary; Tsang, Brian; Lam, Siu M

    2016-04-01

    We examined attention-deficit hyperactivity disorder in adolescents with epilepsy and the association with seizure-related and sociodemographic variables. Strengths and Weakness of Attention-Deficit Hyperactivity Disorder Symptoms and Normal Behaviors rating scale was administered to 122 children with epilepsy and 50 children with asthma, aged 10 to 18 years attending mainstream schools. Twenty-nine (23.7%) adolescents with epilepsy compared with five (10%) with asthma had attention deficit hyperactivity disorder (P = 0.037). Adolescents with epilepsy had a significantly higher score in the inattention subscale when compared with those with asthma (-0.25 ± 1.2 vs -0.64 ± 1.07, P = 0.049). Combined subtype was most frequent in the epilepsy group. Oppositional defiant disorders were more prevalent in those having attention deficit hyperactivity disorder. Psychiatric assistance had only been provided to one third of our patients with epilepsy and attention deficit hyperactivity disorder at the time of study. There was a negative correlation between attention deficit hyperactivity disorder scores and age of seizure onset. A positive correlation was observed between the number of antiepileptic drugs and the inattentive subscale score. The impact of various correlates on individual subtypes was not identical. Independent risk factors associated with attention deficit hyperactivity disorder were medical comorbidities (odds ratio = 12.82, 95% confidence interval 4.44, 37.03, P < 0.0001) and age at seizure onset (odds ratio = 0.73, 95% confidence interval 0.56, 0.94, P = 0.016). Attention deficit hyperactivity disorder is overrepresented in adolescents with epilepsy; screening for its symptoms should be an integral part of management in adolescents with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Statistical Evidence Suggests that Inattention Drives Hyperactivity/Impulsivity in Attention Deficit-Hyperactivity Disorder

    PubMed Central

    Sokolova, Elena; Groot, Perry; Claassen, Tom; van Hulzen, Kimm J.; Glennon, Jeffrey C.; Franke, Barbara

    2016-01-01

    Background Numerous factor analytic studies consistently support a distinction between two symptom domains of attention-deficit/hyperactivity disorder (ADHD), inattention and hyperactivity/impulsivity. Both dimensions show high internal consistency and moderate to strong correlations with each other. However, it is not clear what drives this strong correlation. The aim of this paper is to address this issue. Method We applied a sophisticated approach for causal discovery on three independent data sets of scores of the two ADHD dimensions in NeuroIMAGE (total N = 675), ADHD-200 (N = 245), and IMpACT (N = 164), assessed by different raters and instruments, and further used information on gender or a genetic risk haplotype. Results In all data sets we found strong statistical evidence for the same pattern: the clear dependence between hyperactivity/impulsivity symptom level and an established genetic factor (either gender or risk haplotype) vanishes when one conditions upon inattention symptom level. Under reasonable assumptions, e.g., that phenotypes do not cause genotypes, a causal model that is consistent with this pattern contains a causal path from inattention to hyperactivity/impulsivity. Conclusions The robust dependency cancellation observed in three different data sets suggests that inattention is a driving factor for hyperactivity/impulsivity. This causal hypothesis can be further validated in intervention studies. Our model suggests that interventions that affect inattention will also have an effect on the level of hyperactivity/impulsivity. On the other hand, interventions that affect hyperactivity/impulsivity would not change the level of inattention. This causal model may explain earlier findings on heritable factors causing ADHD reported in the study of twins with learning difficulties. PMID:27768717

  6. Auditory and Visual Working Memory Functioning in College Students with Attention-Deficit/Hyperactivity Disorder and/or Learning Disabilities.

    PubMed

    Liebel, Spencer W; Nelson, Jason M

    2017-12-01

    We investigated the auditory and visual working memory functioning in college students with attention-deficit/hyperactivity disorder, learning disabilities, and clinical controls. We examined the role attention-deficit/hyperactivity disorder subtype status played in working memory functioning. The unique influence that both domains of working memory have on reading and math abilities was investigated. A sample of 268 individuals seeking postsecondary education comprise four groups of the present study: 110 had an attention-deficit/hyperactivity disorder diagnosis only, 72 had a learning disability diagnosis only, 35 had comorbid attention-deficit/hyperactivity disorder and learning disability diagnoses, and 60 individuals without either of these disorders comprise a clinical control group. Participants underwent a comprehensive neuropsychological evaluation, and licensed psychologists employed a multi-informant, multi-method approach in obtaining diagnoses. In the attention-deficit/hyperactivity disorder only group, there was no difference between auditory and visual working memory functioning, t(100) = -1.57, p = .12. In the learning disability group, however, auditory working memory functioning was significantly weaker compared with visual working memory, t(71) = -6.19, p < .001, d = -0.85. Within the attention-deficit/hyperactivity disorder only group, there were no auditory or visual working memory functioning differences between participants with either a predominantly inattentive type or a combined type diagnosis. Visual working memory did not incrementally contribute to the prediction of academic achievement skills. Individuals with attention-deficit/hyperactivity disorder did not demonstrate significant working memory differences compared with clinical controls. Individuals with a learning disability demonstrated weaker auditory working memory than individuals in either the attention-deficit/hyperactivity or clinical control groups. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters: associations with HPA-axis hyperactivity

    PubMed Central

    Lindqvist, D; Fernström, J; Grudet, C; Ljunggren, L; Träskman-Bendz, L; Ohlsson, L; Westrin, Å

    2016-01-01

    Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and would be associated with hypothalamic–pituitary–adrenal (HPA)-axis hyperactivity. Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared with healthy controls at different time points (pre- and post-DST; all P-values<2.98E−12, Cohen's d ranging from 2.55 to 4.01). Pre-DST plasma levels of mtDNA were positively correlated with post-DST cortisol levels (rho=0.49, P<0.003). Suicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with an increased cellular or mitochondrial damage. The specific cells and tissues contributing to plasma levels of free-circulating mtDNA are not known, as is the specificity of this finding for suicide attempters. Future studies are needed in order to better understand the relevance of increased free-circulating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression. PMID:27922635

  8. Chemohypersensitivity and autonomic modulation of venous capacitance in the pathophysiology of acute decompensated heart failure.

    PubMed

    Burchell, Amy E; Sobotka, Paul A; Hart, Emma C; Nightingale, Angus K; Dunlap, Mark E

    2013-06-01

    Heart failure is increasing in prevalence around the world, with hospitalization and re-hospitalization as a result of acute decompensated heart failure (ADHF) presenting a huge social and economic burden. The mechanism for this decompensation is not clear. Whilst in some cases it is due to volume expansion, over half of patients with an acute admission for ADHF did not experience an increase in total body weight. This calls into question the current treatment strategy of targeting salt and water retention in ADHF. An alternative hypothesis proposed by Fallick et al. is that an endogenous fluid shift from the splanchnic bed is implicated in ADHF, rather than an exogenous fluid gain. The hypothesis states further that this shift is triggered by an increase in sympathetic tone causing vasoconstriction in the splanchnic bed, a mechanism that can translocate blood rapidly into the effective circulating volume, generating the raised venous pressure and congestion seen in ADHF. This hypothesis encourages a new clinical paradigm which focuses on the underlying mechanisms of congestion, and highlights the importance of fluid redistribution and neurohormonal activation in its pathophysiology. In this article, we consider the concept that ADHF is attributable to episodic sympathetic hyperactivity, resulting in fluid shifts from the splanchnic bed. Chemosensitivity is a pathologic autonomic mechanism associated with mortality in patients with systolic heart failure. Tonic and episodic activity of the peripheral chemoreceptors may underlie the syndrome of acute decompensation without total body salt and water expansion. We suggest in this manuscript that chemosensitivity in response to intermittent hypoxia, such as experienced in sleep disordered breathing, may explain the intermittent sympathetic hyperactivity underlying renal sodium retention and acute volume redistribution from venous storage sites. This hypothesis provides an alternative structure to guide novel diagnostic and treatment strategies for ADHF.

  9. Why are hyperactivity and academic achievement related?

    PubMed

    Saudino, Kimberly J; Plomin, Robert

    2007-01-01

    Although a negative association between hyperactivity and academic achievement is well documented, little is known about the genetic and/or environmental mechanisms responsible for the association. The present study explored links between parent and teacher ratings of hyperactive behavior problems and teacher-assessed achievement in a sample of 1,876 twin pairs (mean age 7.04 years). The results did not differ across rater, nor were there significant differences between males or females or for twins in the same or different classrooms. Hyperactivity was significantly correlated with achievement. Multivariate model-fitting analyses revealed significant genetic and nonshared environmental covariance between the two phenotypes. In addition, bivariate heritabilities were substantial, indicating that the phenotypic correlations between hyperactivity and achievement were largely mediated by genetic influences.

  10. Hyperactivity and Motoric Activity in ADHD: Characterization, Assessment, and Intervention

    PubMed Central

    Gawrilow, Caterina; Kühnhausen, Jan; Schmid, Johanna; Stadler, Gertraud

    2014-01-01

    The aim of the present literature review is threefold. (1) We will review theories, models, and studies on symptomatic hyperactivity and motoric activity in attention-deficit/hyperactivity disorder (ADHD). (2) Another focus will be on assessment methods that have been proven to be effective in the detection of hyperactivity and motoric activity in children, adolescents, and adults with and without ADHD and emerging areas of research in the field of ADHD. We will compare subjective methods (i.e., rating scales) and objective methods (i.e., accelerometers). (3) Finally, physical activity intervention studies aiming at a modification of activity and overactive behavior will be summarized that seem to be promising candidates for alleviating hyperactivity symptoms in children, adolescents, and adults with ADHD. PMID:25506329

  11. Acute and chronic suppression of the central ghrelin signaling system reveals a role in food anticipatory activity.

    PubMed

    Verhagen, Linda A W; Egecioglu, Emil; Luijendijk, Mieneke C M; Hillebrand, Jacquelien J G; Adan, Roger A H; Dickson, Suzanne L

    2011-05-01

    Using the rodent activity-based anorexia (ABA) model that mimics clinical features of anorexia nervosa that include food restriction-induced hyperlocomotion, we found that plasma ghrelin levels are highly associated with food anticipatory behaviour, measured by running wheel activity in rats. Furthermore, we showed that ghrelin receptor (GHS-R1A) knockout mice do not anticipate food when exposed to the ABA model, unlike their wild type littermate controls. Likewise, food anticipatory activity in the ABA model was suppressed by a GHS-R1A antagonist administered either by acute central (ICV) injection to rats or by chronic peripheral treatment to mice. Interestingly, the GHS-R1A antagonist did not alter food intake in any of these models. Therefore, we hypothesize that suppression of the central ghrelin signaling system via GHS-R1A provides an interesting therapeutic target to treat hyperactivity in patients suffering from anorexia nervosa. Copyright © 2010. Published by Elsevier B.V.

  12. Diabetes mellitus in a girl with thyroid hormone resistance syndrome: a little recognized interaction between the two diseases.

    PubMed

    Stagi, Stefano; Manoni, Cristina; Cirello, Valentina; Covelli, Danila; Giglio, Sabrina; Chiarelli, Francesco; Seminara, Salvatore; de Martino, Maurizio

    2014-01-01

    The syndrome of resistance to thyroid hormone (RTH) is characterized by elevated serum free thyroid hormones (FT4 and FT3) in the presence of unsuppressed TSH levels, reflecting resistance to the normal negative feedback mechanisms in the hypothalamus and pituitary. The degree of resistance within peripheral tissues determines whether thyrotoxic clinical features are associated with this condition. Classic features include attention deficit hyperactivity disorder, growth delay, tachycardia, and goiter. However, other features, such as frequent ear, nose and throat infections, hearing deficit, and decreased bone mass have recently been recognized. The phenotype of RTH is variable, with most patients presenting with mild to moderate symptoms. In this report we describe a girl with familiar RTH and diabetes mellitus. This is, to our knowledge, the first report regarding this association. Nearly one year after long-term triiodothyroacetic acid (Triac) therapy, we observed a reduction of thyroid hormone levels with an amelioration of insulin resistance. The possible interactions between these disorders are discussed.

  13. Prevalence of myofascial trigger points in fibromyalgia: the overlap of two common problems.

    PubMed

    Ge, Hong-You

    2010-10-01

    With the objective evidence of their existence, myofascial trigger points (MTrPs) contribute to an increasing number of chronic regional and widespread pain conditions. The widespread spontaneous pain pattern in fibromyalgia (FM) is a summation of multiple regional pains due to active MTrPs. A regional pain in FM is from local active MTrPs and/or referred from remote active MTrPs. Positive tender points specified in FM are MTrPs, either active or latent. Manual stimulation of active MTrPs located in the muscles in different body regions completely reproduced overall spontaneous FM pain pattern. Active MTrPs as tonic peripheral nociceptive input contribute tremendously to the initiation and maintenance of central sensitization, to the impairment of descending inhibition, to the increased excitability of motor units, and to the induction of sympathetic hyperactivity observed in FM. The considerable overlap of MTrPs and FM in pain characteristics and pathophysiology suggests that FM pain is largely due to MTrPs.

  14. Design, Synthesis and Inhibitory Activity of Photoswitchable RET Kinase Inhibitors

    NASA Astrophysics Data System (ADS)

    Ferreira, Rubén; Nilsson, Jesper R.; Solano, Carlos; Andréasson, Joakim; Grøtli, Morten

    2015-05-01

    REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase required for normal development and maintenance of neurons of the central and peripheral nervous systems. Deregulation of RET and hyperactivity of the RET kinase is intimately connected to several types of human cancers, most notably thyroid cancers, making it an attractive therapeutic target for small-molecule kinase inhibitors. Novel approaches, allowing external control of the activity of RET, would be key additions to the signal transduction toolbox. In this work, photoswitchable RET kinase inhibitors based on azo-functionalized pyrazolopyrimidines were developed, enabling photonic control of RET activity. The most promising compound displays excellent switching properties and stability with good inhibitory effect towards RET in cell-free as well as live-cell assays and a significant difference in inhibitory activity between its two photoisomeric forms. As the first reported photoswitchable small-molecule kinase inhibitor, we consider the herein presented effector to be a significant step forward in the development of tools for kinase signal transduction studies with spatiotemporal control over inhibitor concentration in situ.

  15. Capturing side-effect of medication to identify persons at risk of delirium.

    PubMed

    Lauretani, Fulvio; Ceda, Gian Paolo; Maggio, Marcello; Nardelli, Anna; Saccavini, Marsilio; Ferrucci, Luigi

    2010-01-01

    Delirium, an acute confusional state characterized by decline in attention and cognition, is a common, life-threatening, but potentially preventable clinical syndrome among older persons. Deficits in cholinergic function have been postulated to cause delirium and cognitive decline. In particular, an imbalance between levels of acetylcholine and monoamine (such as dopamine) may cause delirium. We describe two cases of delirium in hospitalized older patients, supporting the "cholinergic deficiency hypothesis". In the first patient, hypo-reactive delirium developed a few hours after a dose of the long-acting opiate tramadol (a drug with anticholinergic effect) as analgesic for pain related to advanced peripheral artery disease. In the second patient, with vascular parkinsonism plus pre-frontal cortex vascular lesions, hyper-reactive delirium developed a few hours after a prescribed administration of L-dopa. These symptoms disappeared completely on the following day. These two "natural" experiments support the hypothesis that both hypo-reactive and hyper-active delirium may be caused by a reduction in cholinergic signaling.

  16. Helping the Hyperactive Child: Caring about Kids.

    ERIC Educational Resources Information Center

    National Inst. of Mental Health (DHHS), Rockville, MD.

    This booklet describes characteristics of hyperactive children and discusses identification procedures, causes, treatment, and future developments in this area. Actual diagnosis of hyperkinetic behavior syndrome, commonly referred to as hyperactivity, is complex and should include a thorough examination by a pediatrician, and sometimes a child…

  17. Neuropsychological Disorders in Children: Effects of Medication on Learning and Behavior in Hyperactivity.

    ERIC Educational Resources Information Center

    Hartlage, Lawrence C.; Telzrow, Cathy Fultz

    1982-01-01

    Hyperactivity is defined, and the relationships among minimal brain dysfunction, cerebral stimulants, and student characteristics such as activity level, attention and learning, and behavior are discussed. Hyperactive children's responses to the use of Ritalin and methylphenidate are reported. (CJ)

  18. Lead and Hyperactivity: Lead Levels Among Hyperactive Children

    ERIC Educational Resources Information Center

    David, Oliver J.; And Others

    1977-01-01

    In the study it is shown that within a group of 84 hyperactive children (4 to 11 years old) those for whom an organic etiology is present have lead burdens lower than in those for whom no apparent cause could be found. (Author/SBH)

  19. Early determinants of attention and hyperactivity problems in adolescents: the 11-year follow-up of the 1993 Pelotas (Brazil) birth cohort study.

    PubMed

    Anselmi, Luciana; Menezes, Ana M B; Barros, Fernando C; Hallal, Pedro C; Araújo, Cora Luiza; Domingues, Marlos R; Rohde, Luis A

    2010-10-01

    The aim of this study was to assess early determinants of attention and hyperactivity problems in adolescents. In 1993, all hospital births in the city of Pelotas, Rio Grande do Sul State, Brazil, were monitored and mothers were interviewed (N = 5,249). At 11 years of age, 4,423 mothers answered the Strengths and Difficulties Questionnaire (SDQ) in order to evaluate attention and hyperactivity problems in the adolescents. Crude and adjusted prevalence ratios were calculated using Poisson regression. Prevalence of attention and hyperactivity problems was 19.9%. Factors associated with the outcome in the adjusted analysis were: male gender, low family income, smoking during pregnancy, minor psychiatric disorders in the mother, and history of child's behavioral/emotional problems at four years of age. Early life events impacted attention and hyperactivity problems in adolescence. Risk factors for attention and hyperactivity problems found in this study were similar to those reported in other cultures.

  20. The direct effects of inattention and hyperactivity/impulsivity on peer problems and mediating roles of prosocial and conduct problem behaviors in a community sample of children.

    PubMed

    Andrade, Brendan F; Tannock, Rosemary

    2013-11-01

    This study tested whether children's symptoms of inattention and hyperactivity/impulsivity were associated with peer problems and whether these associations were mediated by conduct problems and prosocial behaviors. A community sample of 500 children, including 245 boys and 255 girls, who ranged in age from 6 to 9 years (M = 7.6, SD = 0.91) were recruited. Teachers' report of children's inattention, hyperactivity/impulsivity, conduct problems, prosocial behaviors, and peer problems was collected. Symptoms of inattention and hyperactivity/impulsivity were significantly positively associated with peer problems. Conduct problems were associated with more peer problems and prosocial behaviors with less peer problems. Conduct problems and prosocial behaviors partially mediated the association between hyperactivity/impulsivity and peer problems and fully mediated the inattention-peer problems association. Findings show that prosocial behaviors and conduct problems are important variables that account for some of the negative impact of symptoms of inattention and hyperactivity/impulsivity on peer functioning.

  1. Why are hyperactive ice-binding-proteins so active?

    NASA Astrophysics Data System (ADS)

    Braslavsky, Ido; Celik, Yeliz; Pertaya, Natalya; Eun Choi, Young; Bar, Maya; Davies, Peter L.

    2008-03-01

    Ice binding proteins (IBPs), also called `antifreeze proteins' or `ice structuring proteins', are a class of proteins that protect organisms from freezing injury. These proteins have many applications in medicine and agriculture, and as a platform for future biotechnology applications. One of the interesting questions in this field focuses on the hyperactivity of some IBPs. Ice binding proteins can be classified in two groups: moderate ones that can depress the freezing point up to ˜1.0 ^oC and hyperactive ones that can depress the freezing point several-fold further even at lower concentrations. It has been suggested that the hyperactivity of IBPs stem from the fact that they block growth out of specific ice surfaces, more specifically the basal planes of ice. Here we show experimental results based on fluorescence microscopy, highlighting the differences between moderate IBPs and hyperactive IBPs. These include direct evidence for basal plane affinity of hyperactive IBPs, the effects of IBPs on growth-melt behavior of ice and the dynamics of their interaction with ice.

  2. The interactions of normal and hyperactive children with their mothers in free play and structured tasks.

    PubMed

    Cunningham, C E; Barkley, R A

    1979-03-01

    Groups of 20 normal and 20 hyperactive boys ranging in age from 6 to 12 years were observed interacting with their mothers in 15-min free-play and 15-min structured-task situations. Using a 15-sec interval coding procedure, 1 observer recorded the mother's response to specific antecedent behaviors of the child while a second observer recorded the child's response to specific behaviors of the mother. Hyperactive boys proved more active, less compliant, and less likely to remain on task than nonhyperactive peers. Mothers of hyperactive boys were less likely to respond positively to the child's social interactions, solitary play activities, or compliant on-task behavior. In addition, mothers of hyperactive boys imposed more structure and control on the child's play, social interactions, and task-oriented activities. It is suggested that the controlling intrusive style observed among the mothers of hyperactive boys, while initially a response to the child's overactive, impulsive, inattentive style, may further contribute to the child's behavioral difficulties.

  3. Medication Treatment for Attention Deficit Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Ryan, Joseph B.; Katsiyannis, Antonis; Hughes, Elizabeth M.

    2011-01-01

    Attention deficit hyperactivity disorder (ADHD) has become the most commonly diagnosed psychiatric disorder among school-age children. For more than half a century, physicians have prescribed medications to help manage behaviors such as hyperactivity, impulsivity, and inattention. Today, there is a growing consensus that ADHD is a biologically…

  4. Inattention and Hyperactivity and the Achievement Gap among Urban Minority Youth

    ERIC Educational Resources Information Center

    Basch, Charles E.

    2011-01-01

    Objectives: To outline the prevalence and disparities of inattention and hyperactivity among school-aged urban minority youth, causal pathways through which inattention and hyperactivity adversely affects academic achievement, and proven or promising approaches for schools to address these problems. Methods: Literature review. Results:…

  5. Peer Popularity and Peer Communication Patterns: Hyperactive versus Active but Normal Boys.

    ERIC Educational Resources Information Center

    King, Cheryl A.; Young, Richard David

    1981-01-01

    Classroom peer perceptions of 18 teacher-nominated hyperactive and 18 teacher-nominated active but normal elementary school-age boys were compared. Results indicated that hyperactives were significantly different from actives on all sociometric measures in that they were perceived more negatively. (Author/SB)

  6. A Social Ecology of Hyperactive Boys: Medication Effects in Structured Classroom Environments.

    ERIC Educational Resources Information Center

    Whalen, Carol K.; And Others

    1979-01-01

    Among the findings were that hyperactive Ss on placebo showed lower rates of task attention and higher rates of gross motor movement, regular and negative verbalization, noise making, physical contact, social initiation, and other responses than did normal Ss and hyperactive Ss on Ritalin. (Author/DLS)

  7. Gender Differences in University EFL Students' Language Proficiency Corresponding to Self-Rated Attention, Hyperactivity and Impulsivity

    ERIC Educational Resources Information Center

    Liang, Hsin-Yi; Kelsen, Brent A.

    2017-01-01

    Introduction: This study examines university students' self-reported inattention, hyperactivity and impulsivity, and their relation to performance on a high-stakes English proficiency test while taking gender into consideration. Method: Inattention, hyperactivity and impulsivity attributes were assessed using the Adult Attention…

  8. Structured Tasks: Effects on Activity and Performance of Hyperactive and Comparison Children.

    ERIC Educational Resources Information Center

    Zentall, Sydney S.; Leib, Susan L.

    1985-01-01

    In this study, visual motor performance was assessed for 15 hyperactive and 16 nonhyperactive children under structured and nonstructured conditions. Decreased activity was observed for both hyperactive and control children in the structured condition, suggesting that structure is useful in decreasing activity level. (Author/MT)

  9. Fathering and Mothering of Preschool Boys with Hyperactivity

    ERIC Educational Resources Information Center

    Keown, Louise

    2011-01-01

    This study examined links between paternal and maternal parenting factors and preschool hyperactivity in a community sample. Forty-one hyperactive and 38 comparison boys (aged 47-62 months) and their fathers and mothers were assessed on a range of interview, parent questionnaire, and observational measures of parenting and child behavior. Results…

  10. Self-Control under Self-Focus Conditions for Students with AD/HD.

    ERIC Educational Resources Information Center

    Zentall, S. S.; And Others

    This study examined the hypothesis that focusing attention away from external stimulation and on the self might improve the task performance of students with attention deficit/hyperactivity disorder. Forty-three middle school students, (12 with hyperactivity, 4 without hyperactivity but inattention, and 27 without either attention deficit disorder…

  11. The Relationship between Attention Deficit Hyperactivity Disorder and Child Temperament

    ERIC Educational Resources Information Center

    Foley, Marie; McClowry, Sandra Graham; Castellanos, Francisco X.

    2008-01-01

    This study examined empirical and theoretical differences and similarities between attention deficit hyperactivity disorder (ADHD) and child temperament in 32 ADHD children aged 6-11 years, and a comparison group of 23 children with similar sociodemographic characteristics. Children were assessed for ADHD symptoms (hyperactivity, impulsivity, and…

  12. Attention Deficit Hyperactivity Disorder and Sensory Modulation Disorder: A Comparison of Behavior and Physiology

    ERIC Educational Resources Information Center

    Miller, Lucy Jane; Nielsen, Darci M.; Schoen, Sarah A.

    2012-01-01

    Children with attention deficit hyperactivity disorder (ADHD) are impulsive, inattentive and hyperactive, while children with sensory modulation disorder (SMD), one subtype of Sensory Processing Disorder, have difficulty responding adaptively to daily sensory experiences. ADHD and SMD are often difficult to distinguish. To differentiate these…

  13. The Cumulative Effect of Hyperactivity and Peer Relationships on Reading Comprehension

    ERIC Educational Resources Information Center

    Johnson, Kaprea F.

    2014-01-01

    The impact of hyperactivity and peer relationships on academic achievement has long been highlighted in the professional literature. This study highlights how much variation in reading comprehension scores, an indicator of academic achievement, are accounted for by hyperactivity, conduct problems, and peer problems. The participants included 129…

  14. Attention-Deficit/Hyperactivity Disorder (ADHD). NetNews. Volume 7, Number 2

    ERIC Educational Resources Information Center

    LDA of Minnesota, 2007

    2007-01-01

    Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurobiological disorder that is characterized by developmentally inappropriate levels of inattention, impulsivity, and hyperactivity. Between 3% and 7% of school-aged children are affected by ADHD. ADHD is a lifespan condition that affects children, adolescents and adults of all ages. It…

  15. An Experimental Evaluation of Hyperactivity and Food Additives. 1977-Phase I.

    ERIC Educational Resources Information Center

    Harley, J. Preston

    Reported are findings of a study involving 46 families in which the effect of the Feingold (additive free) diet on hyperactivity in preschool and elementary age children was investigated. Eleven sections cover the following project components: introduction (definition of hyperactivity and the B. Feingold hypothesis), methodology, demographic…

  16. Classroom Behavior and Family Climate in Students with Learning Disabilities and Hyperactive Behavior.

    ERIC Educational Resources Information Center

    Margalit, Malka; Almougy, Katrina

    1991-01-01

    Questioning of teachers and mothers of 84 Israeli students (ages 7-10) classified as either hyperactive, learning disabled, both, or neither, found higher distractibility and hostility among hyperactive children whose families were also reported as less supportive. Learning-disabled students were characterized by dependent interpersonal relations…

  17. Links between Co-Occurring Social-Communication and Hyperactive-Inattentive Trait Trajectories

    ERIC Educational Resources Information Center

    St. Pourcain, Beate; Mandy, William P.; Heron, Jon; Golding, Jean; Smith, George Davey; Skuse, David H.

    2011-01-01

    Objective: There is overlap between an autistic and hyperactive-inattentive symptomatology when studied cross-sectionally. This study is the first to examine the longitudinal pattern of association between social-communication deficits and hyperactive-inattentive symptoms in the general population, from childhood through adolescence. We explored…

  18. Optimal stimulation as theoretical basis of hyperactivity.

    PubMed

    Zentall, Sydney

    1975-07-01

    Current theory and practice in the clinical and educational management of hyperactive children recommend reduction of environmental stimulation, assuming hyperactive and distractable behaviors to be due to overstimulation. This paper reviews research suggesting that hyperactive behavior may result from a homeostatic mechanism that functions to increase stimulation for a child experienceing insufficient sensory stimulation. It is suggested that the effectiveness of drug and behavior therapies, as well as evidence from the field of sensory deprivation, further support the theory of a homeostatic mechanism that attempts to optimize sensory input.

  19. Hyperactive Children: Examination Into the Causes of Hyperactive Children and the Methods Used for Treating These Young Children: Joint Hearing Before the Subcommittee on Health of the Committee on Labor and Public Welfare and the Subcommittee on Administrative Practice and Procedure of the Committee on the Judiciary. United States Senate, 94th, First Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Committee on Labor and Public Welfare.

    Presented is the text of the Congressional hearings examining the etiology of hyperactivity and methods of treatment for hyperactive children. Sections cover witness testimony; statements; and additional information consisting of 15 reports, articles, and publications on the topic of food additives and drug therapy. Included are communications to…

  20. Gendering attention deficit hyperactivity disorder: a discursive analysis of UK newspaper stories.

    PubMed

    Horton-Salway, Mary

    2013-08-01

    Discursive psychology is used to study the gendering of attention deficit hyperactivity disorder in UK national newspapers in the period of 2009-2011. The analysis examines how gendering is embedded in causal attributions and identity constructions. Attention deficit hyperactivity disorder is portrayed as a predominantly male phenomenon with representations of attention deficit hyperactivity disorder being gendered through extreme stories about victims, villains or heroes that depict boys and men as marginalised, exceptional or dangerous. There is also a focus on mothers as the spokespersons and caretakers for parenting and family health while fathers are rendered more invisible. This contributes to our understanding of how attention deficit hyperactivity disorder is constructed in the media using a range of gendered representations that draw on cultural stereotypes familiar in Western societies.

  1. Mathematical performance and behavior of children with hyperactivity with and without coexisting aggression.

    PubMed

    Zentall, S S; Smith, Y N

    1993-09-01

    An analysis was made of a basic skill deficit and collateral behavior that could differentiate youth with hyperactivity from children with both hyperactivity and aggression. A total of 92 boys (with hyperactivity, with hyperactivity and aggression, and without disorders) were assessed for their timed performance and accuracy of computer-generated math operations. Response time differences documented between disordered and nondisordered groups, and between the diagnostic groups, were not explained by the group differences that were also observed in behavior or motor response speed (typing). Conclusions derived from these findings, and from prior work, indicated that speed of addition may be a marker of academic and social dysfunction. The overall importance of this assessment is related to the potential sensitivity of math fluency data for assessment and treatment monitoring.

  2. Unilateral hemimandibular hyperactivity: Clinical features of a population of 128 patients.

    PubMed

    Vernucci, Roberto Antonio; Mazzoli, Valentina; Galluccio, Gabriella; Silvestri, Alessandro; Barbato, Ersilia

    2018-07-01

    Facial asymmetries due to unilateral condylar hyperactivity are often a challenge both for maxillo-facial surgeons and for orthodontists; the current literature shows different opinions about aetiology, classification, treatment approach and timing. We made a retrospective study on patients suffering from unilateral condylar hyperactivity between 1997 and 2015 in our Department; clinical features and treatment options were grouped and compared with literature. The descriptive analysis investigated variables like sex, age, side and direction of the asymmetry, condylar activity and type of intervention. The population was composed of 128 patients. The hemimandibular hyperactivity occurs equally in both sexes around the second decade, although the range of the first consultation goes from 7 to 49 y.o. The vertical hyperdevelopment group is almost equal to the horizontal. All the patients with horizontal hyperactivity showed negative scintigraphy and were treated with pre-surgical orthodontics and orthognathic surgery; patients with vertical hyperactivity and positive scintigraphy were treated with condylectomy and post-surgical orthodontics. In our group of patients, direction of the hyperactivity and results of the scintigraphy lead to treatment choice and timing. Further studies are necessary to explain why, in our group, all the patients with horizontal involvement are negative to scintigraphy. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  3. Inattention/hyperactivity and aggression from early childhood to adolescence: Heterogeneity of trajectories and differential influence of family environment characteristics

    PubMed Central

    JESTER, JENNIFER M.; NIGG, JOEL T.; ADAMS, KENNETH; FITZGERALD, HIRAM E.; PUTTLER, LEON I.; WONG, MARIA M.; ZUCKER, ROBERT A.

    2008-01-01

    In attention/hyperactivity and aggressive behavior problems were measured in 335 children from school entry throughout adolescence, at 3-year intervals. Children were participants in a high-risk prospective study of substance use disorders and comorbid problems. A parallel process latent growth model found aggressive behavior decreasing throughout childhood and adolescence, whereas inattentive/hyperactive behavior levels were constant. Growth mixture modeling, in which developmental trajectories are statistically classified, found two classes for inattention/hyperactivity and two for aggressive behavior, resulting in a total of four trajectory classes. Different influences of the family environment predicted development of the two types of behavior problems when the other behavior problem was held constant. Lower emotional support and lower intellectual stimulation by the parents in early childhood predicted membership in the high problem class of inattention/hyperactivity when the trajectory of aggression was held constant. Conversely, conflict and lack of cohesiveness in the family environment predicted membership in a worse developmental trajectory of aggressive behavior when the inattention/hyperactivity trajectories were held constant. The implications of these findings for the development of inattention/hyperactivity and for the development of risk for the emergence of substance use disorders are discussed. PMID:15971762

  4. Co-morbidity in Attention-Deficit Hyperactivity Disorder: A Clinical Study from India.

    PubMed

    Jacob, P; Srinath, S; Girimaji, S; Seshadri, S; Sagar, J V

    2016-12-01

    To assess the prevalence of neurodevelopmental and psychiatric co-morbidities in children and adolescents diagnosed with attention-deficit hyperactivity disorder at a tertiary care child and adolescent psychiatry centre. A total of 63 children and adolescents who were diagnosed with attention-deficit hyperactivity disorder and fulfilled the inclusion criteria were comprehensively assessed for neurodevelopmental and psychiatric co-morbidities. The tools used included the Mini-International Neuropsychiatric Interview for Children and Adolescents, Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHD-RS), Children's Global Assessment Scale, Clinical Global Impression Scale, Vineland Social Maturity Scale, and Childhood Autism Rating Scale. All except 1 subject had neurodevelopmental and / or psychiatric disorder co-morbid with attention-deficit hyperactivity disorder; 66.7% had both neurodevelopmental and psychiatric disorders. Specific learning disability was the most common co-existing neurodevelopmental disorder and oppositional defiant disorder was the most common psychiatric co-morbidity. The mean baseline ADHD-RS scores were significantly higher in the group with psychiatric co-morbidities, especially in the group with oppositional defiant disorder. Co-morbidity is present at a very high frequency in clinic-referred children diagnosed with attention-deficit hyperactivity disorder. Psychiatric co-morbidity, specifically oppositional defiant disorder, has an impact on the severity of attention-deficit hyperactivity disorder. Co-morbidity needs to be explicitly looked for during evaluation and managed appropriately.

  5. Students Diagnosed with Attention Deficit Hyperactivity Disorder: Collaborative Strategies for School Counselors

    ERIC Educational Resources Information Center

    Shillingford-Butler, M. Ann; Theodore, Lea

    2013-01-01

    The school setting can be a difficult place for children with attention deficit hyperactivity disorder (ADHD). The core symptoms of ADHD, which include inattention, hyperactivity, and impulsivity, make meeting the curriculum demands of the classroom challenging. That ADHD negatively impacts not only academic performance but also social and…

  6. The Relation between 3-Year-Old Children's Skills and Their Hyperactivity, Inattention, and Aggression

    ERIC Educational Resources Information Center

    Friedman-Weieneth, Julie L.; Harvey, Elizabeth A.; Youngwirth, Sara D.; Goldstein, Lauren H.

    2007-01-01

    This study examines the relation between 3-year-old children's (N = 280) symptoms of inattention, hyperactivity, and aggression and their cognitive, motor, and preacademic skills. When the authors controlled for other types of attention and behavior problems, maternal ratings of hyperactivity and teacher ratings of inattention were uniquely and…

  7. Case Studies of Effects of Artificial Food Colors on Hyperactivity.

    ERIC Educational Resources Information Center

    Spring, Carl; And Others

    1981-01-01

    A double blind, double crossover study with six hyperactive boys (8 to 13 years old) tested B. Feingold's hypothesis that synthetic food colors cause hyperactivity in some children. All Ss were on the Feingold diet, eliminating artificial colors and flavors. The authors conclude that evidence for Feingold's hypothesis is weak. (Author)

  8. Attention-deficit/hyperactive disorder: making a case for multidisciplinary management.

    PubMed

    Ramanathan, G; White, G E

    2001-01-01

    Attention Deficit/Hyperactivity Disorder (AD/HD) is characterized by a cluster of age-inappropriate behavioral abnormalities comprising inattentivity, hyperactivity and impulsivity. The definition is controversial and without an accurate diagnosis. Therefore, it seems prudent that a multidisciplinary treatment protocol should begin with non-drug psychological and behavioral strategies plus nutritional intervention.

  9. Sex Differences in the Pathway from Low Birth Weight to Inattention/Hyperactivity

    ERIC Educational Resources Information Center

    Martel, Michelle M.; Lucia, Victoria C.; Nigg, Joel T.; Breslau, Naomi

    2007-01-01

    Inattention/hyperactivity is a childhood outcome of low birth weight. However, the mechanisms by which low birth weight leads to inattention/hyperactivity are unclear. This study examined arousal, activation, motor speed, and motor coordination as possible mechanisms, attending to sex differences. 823 children (400 males) from Detroit and…

  10. Neurofeedback as an Intervention to Improve Reading Achievement in Students with Attention- Deficit/Hyperactivity Disorder, Inattentive Subtype

    ERIC Educational Resources Information Center

    La Marca, Jeffry P.; O'Connor, Rollanda E.

    2016-01-01

    Research consistently demonstrates that attention deficits have a deleterious effect on academic achievement. Impairments in attention, and not hyperactivity/impulsivity, are associated with learning difficulties and academic problems in students with attention-deficit/hyperactivity disorder (ADHD). To date, most studies have focused on symptoms…

  11. Color Effects on the Impulsivity and Activity of Hyperactive Children.

    ERIC Educational Resources Information Center

    Zentall, Sydney S.; Dwyer, Anne M.

    1989-01-01

    Administered to hyperactive second and third graders either black/white form of Matching Familiar Figures Test and one month later a colored version, or the reverse color order in a repeated crossover design. Found addition of nonrelevant color to this task normalized activity of hyperactive children such that group differences were observed only…

  12. Temperament and Character as Endophenotype in Adults with Autism Spectrum Disorders or Attention Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Sizoo, Bram B.; van der Gaag, Rutger Jan; van den Brink, Wim

    2015-01-01

    Autism spectrum disorder and attention deficit/hyperactivity disorder overlap in several ways, raising questions about the nature of this comorbidity. Rommelse et al. published an innovative review of candidate endophenotypes for autism spectrum disorder and attention deficit/hyperactivity disorder in cognitive and brain domains. They found that…

  13. Attention-Deficit/Hyperactivity Disorder. NICHCY Briefing Paper. Revised Edition.

    ERIC Educational Resources Information Center

    Fowler, Mary

    This briefing paper is intended to improve understanding of attention/deficit hyperactivity disorder (Ad/HD)--what it is, what to look for, and what to do. Three subtypes are identified: (1) the predominantly combined type; (2) the predominantly inattentive type; and (3) the predominantly hyperactive/impulsive type. Causes and incidence of ADHD…

  14. Pre- and Peri-Natal Environmental Risks for Attention-Deficit Hyperactivity Disorder (ADHD): The Potential Role of Epigenetic Processes in Mediating Susceptibility

    ERIC Educational Resources Information Center

    Mill, Jonathan; Petronis, Arturas

    2008-01-01

    Attention-deficit hyperactivity disorder (ADHD) is a common childhood neurobehavioural disorder defined by symptoms of developmentally inappropriate inattention, impulsivity and hyperactivity. As is the norm for most psychiatric phenotypes, traditional aetiological studies have focused primarily on the interplay between genetic and environmental…

  15. Hyperactive and Normal Girls and Boys: Mother-Child Interaction, Parent Psychiatric Status and Child Psychopathology.

    ERIC Educational Resources Information Center

    Befera, Marilyn Schulte; Barkley, Russell A.

    1985-01-01

    Hyperactive children were less compliant and more negative than were nonhyperactive controls, and their mothers responded more negatively to their compliance than mothers of nonhyperactive children. Mothers of hyperactive children reported more psychological difficulties in relatives and rated their children as more deviant than nonhyperactive…

  16. Motivational Incentives and Methylphenidate Enhance Electrophysiological Correlates of Error Monitoring in Children with Attention Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Groom, Madeleine J.; Liddle, Elizabeth B.; Scerif, Gaia; Liddle, Peter F.; Batty, Martin J.; Liotti, Mario; Hollis, Chris P.

    2013-01-01

    Background: Children with attention deficit hyperactivity disorder (ADHD) are characterised by developmentally inappropriate levels of hyperactivity, impulsivity and/or inattention and are particularly impaired when performing tasks that require a high level of cognitive control. Methylphenidate (MPH) and motivational incentives may help improve…

  17. A Meta-Analysis of Behavioral Parent Training for Children with Attention Deficit Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Lee, Pei-chin; Niew, Wern-ing; Yang, Hao-jan; Chen, Vincent Chin-hung; Lin, Keh-chung

    2012-01-01

    This meta-analysis examined the effect of behavioral parent training on child and parental outcomes for children with attention deficit hyperactivity disorder. Meta-analytic procedures were used to estimate the effect of behavioral parent training on children with attention deficit hyperactivity disorder. Variables moderating the intervention…

  18. Factor Structure of Attention Deficit Hyperactivity Disorder Symptoms for Children Age 3 to 5 Years

    ERIC Educational Resources Information Center

    McGoey, Kara E.; Schreiber, James; Venesky, Lindsey; Westwood, Wendy; McGuirk, Lindsay; Schaffner, Kristen

    2015-01-01

    The diagnosis of attention deficit hyperactivity disorder (ADHD) distinguishes two dimensions of symptoms, inattention and hyperactivity-impulsivity for ages 3 to adulthood. Currently, no separate classification for preschool-age children exists, whereas preliminary research suggests that the two-factor structure of ADHD may not match the…

  19. Mother-Child Dyadic Synchrony Is Associated with Better Functioning in Hyperactive/Inattentive Preschool Children

    ERIC Educational Resources Information Center

    Healey, Dione M.; Gopin, Chaya B.; Grossman, Bella R.; Campbell, Susan B.; Halperin, Jeffrey M.

    2010-01-01

    Background: Hyperactive/inattentive (HI) behaviors are common in preschoolers, but they result in functional impairment and attention deficit/hyperactivity disorder (ADHD) diagnoses in only some children. We examined whether the quality of mother-child interaction accounts for variance in level of functioning among preschool children with elevated…

  20. Risperidone Augmentation for Treatment-Resistant Aggression in Attention-Deficit/Hyperactivity Disorder: A Placebo-Controlled Pilot Study

    ERIC Educational Resources Information Center

    Armenteros, Jorge L.; Lewis, John E.; Davalos, Marisabel

    2007-01-01

    Objective: To evaluate the effects of risperidone augmentation for treatment-resistant aggression in children with attention-deficit/hyperactivity disorder (ADHD). Method: Twenty-five children (ages 7-12 years) with attention-deficit/hyperactivity disorder(ADHD) and significant aggressive behaviors were randomized to risperidone or placebo for 4…

  1. Inattention and Hyperactivity Predict Alterations in Specific Neural Circuits among 6-Year-Old Boys

    ERIC Educational Resources Information Center

    Qiu, Anqi; Rifkin-Graboi, Anne; Tuan, Ta Anh; Zhong, Jidan; Meaney, Michael J.

    2012-01-01

    Objective: Assessment of inattention and hyperactivity in preschoolers is highly dependent upon parental reports. Such reports are compromised by parental attitudes and mental health. Our study aimed to examine associations of inattention and hyperactivity/impulsivity from maternal reports on the Conners' Parent Rating Scale (CPRS) with brain…

  2. Identification of Autism Spectrum Disorders Using the Child Behavior Checklist in Singapore

    ERIC Educational Resources Information Center

    Ooi, Yoon Phaik; Rescorla, Leslie; Ang, Rebecca P.; Woo, Bernardine; Fung, Daniel S. S.

    2011-01-01

    We tested the ability of the 2001 CBCL syndromes to discriminate among 86 children with Autism Spectrum Disorder (ASD), 117 children with Attention Deficit Hyperactivity Disorder-Inattentive type, 426 children with Attention Deficit Hyperactivity Disorder-Hyperactive-Impulsive or Combined type, 200 clinically referred children who did not receive…

  3. Maternal Positive Parenting Style Is Associated with Better Functioning in Hyperactive/Inattentive Preschool Children

    ERIC Educational Resources Information Center

    Healey, Dione M.; Flory, Janine D.; Miller, Carlin J.; Halperin, Jeffrey M.

    2011-01-01

    Many preschoolers are highly inattentive, impulsive, and hyperactive; but only some are impaired in their functioning. Yet factors leading to functional impairment, above and beyond the severity of inattentive and hyperactive symptoms, have not been systematically examined. This study examined a model suggesting that after controlling for…

  4. Attention Deficit Hyperactivity Disorder: A Rasch Analysis of the SWAN Rating Scale

    ERIC Educational Resources Information Center

    Young, Deidra J.; Levy, Florence; Martin, Neilson C.; Hay, David A.

    2009-01-01

    The prevalence of attention-deficit/hyperactivity disorder (ADHD) has been estimated at 3-7% in the population. Children with this disorder are often characterized by symptoms of inattention and/or impulsivity and hyperactivity, which can significantly impact on many aspects of their behaviour and performance. This study investigated the…

  5. The Cheshire Cat Enigma: Emotion Recognition Abilities of Preschool Boys with and without Hyperactivity and Aggression

    ERIC Educational Resources Information Center

    Arnold, Megan

    2010-01-01

    This research examined the emotion recognition abilities of preschoolers with and without hyperactivity and aggression. Previous research identified that school age children with Attention Deficit Hyperactivity Disorder (ADHD) have more difficulty understanding facial expressions associated with emotions, take longer than their age-matched peers…

  6. Hyper-Activity in Children Having Behavior Disorders

    ERIC Educational Resources Information Center

    Childers, A. T.

    2009-01-01

    Frequently, child guidance clinics, pediatricians, teachers, and others have brought to their attention children who manifest hyper-activity as an outstanding feature and of such a degree as to be regarded outside the bounds of normal conduct. The literature on this subject, except for hyper-activity in infancy, has mostly to do with the…

  7. Use of Digital Console Game for Children with Attention Deficit Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Chuang, Tsung-Yen; Lee, I-Ching; Chen, Wen-Chih

    2010-01-01

    ADHD or ADD (Attention Deficit/Hyperactivity Disorder) is one of the most frequently diagnosed mental and behavioral disorders of children. Children with ADHD are characterized by poor attention and distractibility and/or hyperactive and impulsive behaviors. Although there is no "cure" for ADHD, there are accepted treatments that…

  8. Inattention, Hyperactivity, and Emergent Literacy: Different Facets of Inattention Relate Uniquely to Preschoolers' Reading-Related Skills

    ERIC Educational Resources Information Center

    Sims, Darcey M.; Lonigan, Christopher J.

    2013-01-01

    Although extant studies indicate that there is a strong association between attention deficit/hyperactivity disorder and reading ability in elementary school children, knowledge regarding the relation between inattentive and hyperactive/impulsive behaviors and emergent literacy in preschool children is less established. This study examined the…

  9. A Meta-Analysis of Previous Research on the Treatment of Hyperactivity. Final Report.

    ERIC Educational Resources Information Center

    White, Karl R.; And Others

    Using meta-analysis techniques, the study sought to identify, integrate, and synthesize the literature from 61 articles which review the efficacy of various treatments for hyperactive children. The major objectives were to determine if drugs can be used effectively with hyperactive children, what child and intervention characteristics covary with…

  10. Reading and Listening Comprehension and Their Relation to Inattention and Hyperactivity

    ERIC Educational Resources Information Center

    Cain, Kate; Bignell, Simon

    2014-01-01

    Background: Children with diagnoses of attention-deficit/hyperactivity disorder (ADHD) frequently have reading problems. To date, it is not clear whether poor reading is associated with both inattention and hyperactivity and also whether poor reading comprehension is the result of poor word reading skills or more general language comprehension…

  11. Hyperactivity-inattention symptoms in childhood and substance use in adolescence: the youth gazel cohort.

    PubMed

    Galéra, Cédric; Bouvard, Manuel Pierre; Messiah, Antoine; Fombonne, Eric

    2008-04-01

    This study addresses in both genders the relationship between childhood Hyperactivity-inattention symptoms and subsequent adolescent substance use, while controlling for psychiatric comorbidity, temperament and environmental risk factors. 916 subjects (421 males, 495 females) aged 7-18 were recruited from the general population and surveyed in 1991 and 1999. Child psychopathology and substance use patterns were evaluated through parent and adolescent self-reports. Multivariate modeling was performed to assess the effects of childhood Hyperactivity-inattention symptoms and other risk factors on adolescent substance use. In males, Hyperactivity-inattention symptoms alone accounted for the risk of subsequent regular cannabis smoking (OR=3.14, p=0.03) and subsequent lifetime use of other drugs including stimulants, opiates, inhalants and sedatives (OR=2.72, p=0.02). In females, Hyperactivity-inattention symptoms did not independently increase the liability to later substance use. In males, the temperament trait activity was a significant predictor of subsequent regular cannabis smoking (OR=2.32, p=0.04). This survey points to a possible specific link between Hyperactivity-inattention symptoms and subsequent cannabis use and experimentation of harder drugs in males.

  12. New insights into ice growth and melting modifications by antifreeze proteins

    PubMed Central

    Bar-Dolev, Maya; Celik, Yeliz; Wettlaufer, J. S.; Davies, Peter L.; Braslavsky, Ido

    2012-01-01

    Antifreeze proteins (AFPs) evolved in many organisms, allowing them to survive in cold climates by controlling ice crystal growth. The specific interactions of AFPs with ice determine their potential applications in agriculture, food preservation and medicine. AFPs control the shapes of ice crystals in a manner characteristic of the particular AFP type. Moderately active AFPs cause the formation of elongated bipyramidal crystals, often with seemingly defined facets, while hyperactive AFPs produce more varied crystal shapes. These different morphologies are generally considered to be growth shapes. In a series of bright light and fluorescent microscopy observations of ice crystals in solutions containing different AFPs, we show that crystal shaping also occurs during melting. In particular, the characteristic ice shapes observed in solutions of most hyperactive AFPs are formed during melting. We relate these findings to the affinities of the hyperactive AFPs for the basal plane of ice. Our results demonstrate the relation between basal plane affinity and hyperactivity and show a clear difference in the ice-shaping mechanisms of most moderate and hyperactive AFPs. This study provides key aspects associated with the identification of hyperactive AFPs. PMID:22787007

  13. Managing attention deficit hyperactivity disorder in adults using illicit psychostimulants: A systematic review.

    PubMed

    Cook, Jon; Lloyd-Jones, Martyn; Arunogiri, Shalini; Ogden, Edward; Bonomo, Yvonne

    2017-09-01

    Attention deficit hyperactivity disorder and stimulant use disorder commonly co-exist, and appropriate treatments have not been well established. To provide guidance for treatment of co-existing attention deficit hyperactivity disorder and stimulant use disorder. A systematic review of published English articles using MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane, utilising consistent search terms. Randomised controlled trials, comparing any treatment arm with a control group, for participants meeting Diagnostic and Statistical Manual of Mental Disorders or equivalent criteria for both attention deficit hyperactivity disorder and stimulant use disorder. Eight trials were identified for inclusion in this review. Four of eight studies showed improvement in attention deficit hyperactivity disorder outcome measures compared with placebo. Two of six studies that reported substance use outcomes showed improvement in treatment arms compared with placebo. Studies to show effect tended to be those with the highest treatment dosage. Evidence for the efficacy of treatment of patients with comorbid stimulant use disorder and attention deficit hyperactivity disorder is limited. Promising outcomes need replication in further studies utilising higher treatment dosage.

  14. Assisting people with attention deficit hyperactivity disorder by actively reducing limb hyperactive behavior with a gyration air mouse through a controlled environmental stimulation.

    PubMed

    Shih, Ching-Hsiang

    2011-01-01

    The latest researches have adopted software technology turning the gyration air mouse into a high performance limb movement detector, and have assessed whether two persons with multiple disabilities would be able to control an environmental stimulation using limb movement. This study extends gyration air mouse functionality by actively reducing limb hyperactive behavior to assess whether two persons with attention deficit hyperactivity disorder (ADHD) would be able to actively reduce their limb hyperactive behavior by controlling their favorite stimulation on/off using a gyration air mouse with a newly developed actively limb hyperactive behavior reducing program (ALHBRP). The study was performed according to an ABAB design, in which A represented the baseline and B represented intervention phases. Data showed that both participants significantly increased their time duration of maintaining a static limb posture (TDMSLP) to activate the control system in order to produce environmental stimulation during the intervention phases. Practical and developmental implications of the findings are discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Behavioral management of the hyperactive child.

    PubMed

    Murray, M E

    1980-09-01

    This paper provides a general outline of the principles of behavioral management of the hyperactive child. The use of stimulant medications and special considerations in school are briefly discussed and then suggestions for initial parent counseling, family assessment, and the analysis of specific behavior problems are reviewed. Techniques of behavioral management are presented for the younger hyperactive child (3 to 7 years) and for the older hyperactive child (8 to 13 years). Among management techniques discussed are positive reinforcement, extinction procedures, and punishment through isolation. The problems involved in the use of corporal punishment are outlined as well as specific guidelines for parents as to when and how corporal punishment can be used effectively. A step-by-step summary of how to employ a token economy to manage both home and school behavior problems in older hyperactive children is presented.

  16. Impulsivity-hyperactivity and subtypes of aggression in early childhood: an observational and short-term longitudinal study.

    PubMed

    Ostrov, Jamie M; Godleski, Stephanie A

    2009-08-01

    This short-term longitudinal study (N = 112) was conducted to explore the concurrent and prospective associations between teacher-reported impulsive-hyperactive behavior and observed relational and physical aggression during early childhood (M = 45.54 months old, SD = 9.07). Multiple informants and methods including observational methods (i.e., 160 min per child) were used to assess aggression and impulsivity-hyperactivity. All measures were found to be valid and reliable. Prospective hierarchical regression analyses revealed that impulsivity-hyperactivity was associated with increases in observed physical aggression across time, controlling for initial relational aggression and gender. These findings add to the growing developmental psychopathology literature that suggests that distinguishing between subtypes of aggression during early childhood may be important for understanding the course of impulsivity-hyperactivity in young children. Implications for practice are discussed.

  17. Effects of distractors on upright balance performance in school-aged children with attention deficit hyperactivity disorder, preliminary study.

    PubMed

    Aydinli, Fatma Esen; Çak, Tuna; Kirazli, Meltem Çiğdem; Çinar, Betül Çiçek; Pektaş, Alev; Çengel, Ebru Kültür; Aksoy, Songül

    Attention deficit hyperactivity disorder is a common impairing neuropsychiatric disorder with onset in early childhood. Almost half of the children with attention deficit hyperactivity disorder also experience a variety of motor-related dysfunctions ranging from fine/gross motor control problems to difficulties in maintaining balance. The main purpose of this study was to investigate the effects of distractors two different auditory distractors namely, relaxing music and white noise on upright balance performance in children with attention deficit hyperactivity disorder. We compared upright balance performance and the involvement of different sensory systems in the presence of auditory distractors between school-aged children with attention deficit hyperactivity disorder (n=26) and typically developing controls (n=20). Neurocom SMART Balance Master Dynamic Posturography device was used for the sensory organization test. Sensory organization test was repeated three times for each participant in three different test environments. The balance scores in the silence environment were lower in the attention deficit hyperactivity disorder group but the differences were not statistically significant. In addition to lower balance scores the visual and vestibular ratios were also lower. Auditory distractors affected the general balance performance positively for both groups. More challenging conditions, using an unstable platform with distorted somatosensory signals were more affected. Relaxing music was more effective in the control group, and white noise was more effective in the attention deficit hyperactivity disorder group and the positive effects of white noise became more apparent in challenging conditions. To the best of our knowledge, this is the first study evaluating balance performance in children with attention deficit hyperactivity disorder under the effects of auditory distractors. Although more studies are needed, our results indicate that auditory distractors may have enhancing effects on upright balance performance in children with attention deficit hyperactivity disorder. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  18. Positive association between attention-deficit/ hyperactivity disorder medication use and academic achievement during elementary school.

    PubMed

    Scheffler, Richard M; Brown, Timothy T; Fulton, Brent D; Hinshaw, Stephen P; Levine, Peter; Stone, Susan

    2009-05-01

    Approximately 4.4 million (7.8%) children in the United States have been diagnosed with attention-deficit/hyperactivity disorder, and 56% of affected children take prescription medications to treat the disorder. Attention-deficit/hyperactivity disorder is strongly linked with low academic achievement, but the association between medication use and academic achievement in school settings is largely unknown. Our objective was to determine if reported medication use for attention-deficit/hyperactivity disorder is positively associated with academic achievement during elementary school. To estimate the association between reported medication use and standardized mathematics and reading achievement scores for a US sample of 594 children with attention-deficit/hyperactivity disorder, we used 5 survey waves between kindergarten and fifth grade from the nationally representative Early Childhood Longitudinal Study--Kindergarten Class of 1998-1999 to estimate a first-differenced regression model, which controlled for time-invariant confounding variables. Medicated children had a mean mathematics score that was 2.9 points higher than the mean score of unmedicated peers with attention-deficit/hyperactivity disorder. Children who were medicated for a longer duration (at >2 waves) had a mean reading score that was 5.4 points higher than the mean score of unmedicated peers with attention-deficit/hyperactivity disorder. The medication-reading association was lower for children who had an individualized education program than for those without such educational accommodation. The finding of a positive association between medication use and standardized mathematics and reading test scores is important, given the high prevalence of attention-deficit/hyperactivity disorder and its association with low academic achievement. The 2.9-point mathematics and 5.4-point reading score differences are comparable with score gains of 0.19 and 0.29 school years, respectively, but these gains are insufficient to eliminate the test-score gap between children with attention-deficit/hyperactivity disorder and those without the disorder. Long-term trials are needed to better understand the relationship between medication use and academic achievement.

  19. Manual morphometry of hippocampus and amygdala in adults with attention-deficit hyperactivity disorder.

    PubMed

    Nickel, Kathrin; Tebartz van Elst, Ludger; Perlov, Evgeniy; Jitten-Schachenmeier, Renate; Beier, Daniel; Endres, Dominique; Goll, Peter; Philipsen, Alexandra; Maier, Simon

    2017-09-30

    Previous studies have pointed to the involvement of limbic structures in the genesis of attention deficit hyperactivity disorder (ADHD). The present researchers manually segmented magnetic resonance images of 30 individuals with ADHD and 30 individually matched controls, focusing on amygdala and hippocampus volumes. Neither hippocampus nor amygdala volume differed significantly between individuals with and without ADHD. However, ADHD patients with higher hyperactivity scores had significantly smaller left amygdala volumes. This finding suggests that limbic alterations are significant in hyperactive symptoms in the pathophysiology of ADHD. Copyright © 2017. Published by Elsevier B.V.

  20. Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management.

    PubMed

    Spiller, Henry A; Hays, Hannah L; Aleguas, Alfred

    2013-07-01

    The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4-9% in children and 4% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80% occurring in children <19 years old and 20% in adults. The drugs used for the treatment of ADHD are diverse but can be roughly separated into two groups: the stimulants such as amphetamine, methylphenidate, and modafinil; and the non-stimulants such as atomoxetine, guanfacine, and clonidine. This review focuses on mechanisms of toxicity after overdose with ADHD medications, clinical effects from overdose, and management. Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical syndrome involves prominent neurological and cardiovascular effects, but secondary complications can involve renal, muscle, pulmonary, and gastrointestinal (GI) effects. In overdose, the patient may present with mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures. The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Modafinil is not US FDA approved for treatment of ADHD; however, it has been shown to improve ADHD signs and symptoms and has been used as an off-label pharmaceutical for this diagnosis in both adults and children. The mechanism of action of modafinil is complex and not fully understood. It is known to cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8 g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The management of guanfacine overdose is largely supportive, with a focus on support of blood pressure. Overdose with ADHD medications can produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare with appropriate care.

  1. Psychosocial Stress and Brain Function in Adolescent Psychopathology.

    PubMed

    Quinlan, Erin Burke; Cattrell, Anna; Jia, Tianye; Artiges, Eric; Banaschewski, Tobias; Barker, Gareth; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Brühl, Rüdiger; Conrod, Patricia J; Desrivieres, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Martinot, Jean-Luc; Paillère Martinot, Marie-Laure; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Paus, Tomáš; Poustka, Luise; Smolka, Michael N; Vetter, Nora C; Walter, Henrik; Whelan, Robert; Glennon, Jeffrey C; Buitelaar, Jan K; Happé, Francesca; Loth, Eva; Barker, Edward D; Schumann, Gunter

    2017-08-01

    The authors sought to explore how conduct, hyperactivity/inattention, and emotional symptoms are associated with neural reactivity to social-emotional stimuli, and the extent to which psychosocial stress modulates these relationships. Participants were community adolescents recruited as part of the European IMAGEN study. Bilateral amygdala regions of interest were used to assess the relationship between the three symptom domains and functional MRI neural reactivity during passive viewing of dynamic angry and neutral facial expressions. Exploratory functional connectivity and whole brain multiple regression approaches were used to analyze how the symptoms and psychosocial stress relate to other brain regions. In response to the social-emotional stimuli, adolescents with high levels of conduct or hyperactivity/inattention symptoms who had also experienced a greater number of stressful life events showed hyperactivity of the amygdala and several regions across the brain. This effect was not observed with emotional symptoms. A cluster in the midcingulate was found to be common to both conduct problems and hyperactivity symptoms. Exploratory functional connectivity analyses suggested that amygdala-precuneus connectivity is associated with hyperactivity/inattention symptoms. The results link hyperactive amygdala responses and regions critical for top-down emotional processing with high levels of psychosocial stress in individuals with greater conduct and hyperactivity/inattention symptoms. This work highlights the importance of studying how psychosocial stress affects functional brain responses to social-emotional stimuli, particularly in adolescents with externalizing symptoms.

  2. Childhood symptoms of inattention-hyperactivity predict cannabis use in first episode psychosis.

    PubMed

    Cassidy, Clifford M; Joober, Ridha; King, Suzanne; Malla, Ashok K

    2011-11-01

    A history of childhood symptoms of inattention-hyperactivity is often reported in first episode psychosis (FEP) as is cannabis use. In the general population childhood ADHD predicts future cannabis use but the relationship has not been tested in FEP. Parents of patients with a first episode of psychosis (n=75) retrospectively assessed their affected child for symptoms of early-life disorders, namely, attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD) using the Child Behaviour Checklist (CBCL). Assessments were made prospectively of cannabis use over two years following a FEP and of SCID diagnosis of cannabis-use disorder. Childhood hyperactivity-inattention symptoms predicted inability to maintain abstinence from cannabis following treatment (Wald=8.4, p=.004) and lifetime cannabis-use diagnosis (Wald=5.3, p=.022) in a logistic regression controlling for relevant covariates including symptoms of CD and ODD from ages 12 to 18. When the symptom of inattention was considered in place of the hyperactivity-inattention syndrome it predicted cannabis-use diagnosis (Wald=6.4, p=.011) and persistent abstinence from cannabis (Wald=5.3, p=.021). Symptoms of CD and ODD did not predict cannabis use when hyperactivity-inattention symptoms were controlled for. Symptoms of childhood inattention-hyperactivity predict subsequent cannabis use in FEP. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Time-Dependent Effects of Prazosin on the Development of Methamphetamine Conditioned Hyperactivity and Context-Specific Sensitization in Mice

    PubMed Central

    White, André O.; Rauhut, Anthony S.

    2014-01-01

    The present experiments examined the effects of prazosin, a selective α1-adrenergic receptor antagonist, on the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Mice received an injection of vehicle (distilled water) or prazosin (0.5, 1.0 or 2.0 mg/kg) 30 minutes prior to a second injection of vehicle (saline) or methamphetamine (1.0 mg/kg) during the conditioning sessions (Experiment 1). Following the conditioning sessions, mice were tested for conditioned hyperactivity and then tested for context-specific sensitization. In subsequent experiments, mice received an injection of vehicle (distilled water) or prazosin (2.0 mg/kg) immediately (Experiment 2) or 24 hours (Experiment 3) after the conditioning sessions and then tested for conditioned hyperactivity and context-specific sensitization. Prazosin dose-dependently blocked the development of methamphetamine conditioned hyperactivity and context-specific sensitization when administered prior to the methamphetamine during the conditioning phase; however nonspecific motor impairments also were observed (Experiment 1). Immediate (Experiment 2), but not the 24-hour delay (Experiment 3), post-session administration of prazosin attenuated the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Nonspecific motor impairments were not observed in these latter experiments. Collectively, these results suggest that the α1-adrenergic receptor mediates the development of methamphetamine-conditioned hyperactivity and context-specific sensitization, perhaps by altering memory consolidation and/or reconsolidation processes. PMID:24487011

  4. Prevalence and factors of addictive Internet use among adolescents in Wuhan, China: interactions of parental relationship with age and hyperactivity-impulsivity.

    PubMed

    Wu, Xianhua; Chen, Xinguang; Han, Juan; Meng, Heng; Luo, Jianghong; Nydegger, Liesl; Wu, Hanrong

    2013-01-01

    This study examined the prevalence of addictive Internet use and analyzed the role of parental relationship in affecting this behavior among a random sample of adolescents in Wuhan, China. Students (n = 1,101) were randomly selected from four schools, including 638 boys and 463 girls with a mean age of 13.8 (standard deviation = 1.2) years. Addictive Internet use, parental relationship, hyperactivity-impulsivity were measured by validated instruments. Prevalence rate, ANOVA and multiple linear regression method were used to analyze the level of Internet addiction and its association with parental relationship, hyperactivity-impulsivity, as well as the interaction of parental relationship with chronological age and hyperactivity-impulsivity. The prevalence rate of Internet addiction was 13.5% (16.5% for boys and 9.5% for girls, p<0.01). Compared to non-addictive users, addictive Internet users were scored significantly lower on parental relationships and significantly higher on hyperactivity-impulsivity. Interaction analysis indicated that better parental relationship was associated with more reductions in risk of addictive Internet use for younger students than for older students, and with more risk of Internet addiction among higher than among lower hyperactivity-impulsivity students. Findings of this study indicate that adolescent addictive Internet use is a significant public health threat in China. Prevention interventions targeting parental relationship must consider adolescent's age and hyperactivity-impulsivity tendency.

  5. Inverse associations between cord vitamin D and attention deficit hyperactivity disorder symptoms: A child cohort study.

    PubMed

    Mossin, Mats H; Aaby, Jens B; Dalgård, Christine; Lykkedegn, Sine; Christesen, Henrik T; Bilenberg, Niels

    2017-07-01

    To examine the association between cord 25-hydroxyvitamin D 2+3 (25(OH)D) and attention deficit hyperactivity disorder symptoms in toddlers, using Child Behaviour Checklist for ages 1.5-5. In a population-based birth cohort, a Child Behaviour Checklist for ages 1.5-5 questionnaire was returned from parents of 1233 infants with mean age 2.7 (standard deviation 0.6) years. Adjusted associations between cord 25(OH)D and Child Behaviour Checklist-based attention deficit hyperactivity disorder problems were analysed by multiple regression. Results The median cord 25(OH)D was 44.1 (range: 1.5-127.1) nmol/L. Mean attention deficit hyperactivity disorder problem score was 2.7 (standard deviation 2.1). In adjusted analyses, cord 25(OH)D levels >25 nmol/L and >30 nmol/L were associated with lower attention deficit hyperactivity disorder scores compared to levels ⩽25 nmol/L ( p = 0.035) and ⩽30 nmol/L ( p = 0.043), respectively. The adjusted odds of scoring above the 90th percentile on the Child Behaviour Checklist-based attention deficit hyperactivity disorder problem scale decreased by 11% per 10 nmol/L increase in cord 25(OH)D. An inverse association between cord 25(OH)D and attention deficit hyperactivity disorder symptoms in toddlers was found, suggesting a protective effect of prenatal vitamin D.

  6. Relations of Inattention and Hyperactivity/Impulsivity to Preadolescent Peer Functioning: The Mediating Roles of Aggressive and Prosocial Behaviors

    ERIC Educational Resources Information Center

    Tseng, Wan-Ling; Kawabata, Yoshito; Gau, Susan Shur-Fen; Banny, Adrienne M.; Lingras, Katherine A.; Crick, Nicki R.

    2012-01-01

    This study examined the structural relations of preadolescents' inattention and hyperactivity/impulsivity, aggressive and prosocial behaviors, and peer functioning. There were 739 fourth (n = 239) and fifth (n = 500) graders (52.23% boys) in Taiwan who participated in this study. Preadolescents' inattention and hyperactivity/impulsivity were…

  7. Cross-National Invariance of Attention-Deficit/Hyperactivity Disorder Factors in Japanese and U.S. University Students

    ERIC Educational Resources Information Center

    Davis, J. Mark; Cheung, Shu Fai; Takahashi, Tomone; Shinoda, Haruo; Lindstrom, William A.

    2011-01-01

    Prior research with children generally supports the two-dimensional structure of Attention-Deficit/Hyperactivity Disorder (ADHD; inattentive and hyperactive/impulsive factors) of the DSM-IV-TR as well as invariance of the two-factor structure across nations and cultures. Research with adults supports either a two-factor or three-factor structure…

  8. Hypothalamic-Pituitary-Adrenal Axis Function in Children with Attention-Deficit Hyperactivity Disorder.

    ERIC Educational Resources Information Center

    Kaneko, Motohisa; And Others

    1993-01-01

    This study with 30 children showing attention deficit hyperactivity disorder (ADHD) found a normal diurnal saliva cortisol rhythm in only 43.3 percent of the subjects and a dexamethasone suppression in 46.7 percent, with both these abnormalities more frequent in the severely than the mildly hyperactive group. Results suggest abnormalities in…

  9. A Weak Association between Traits of Attention-Deficit/Hyperactivity Disorder and Gambling in College Students

    ERIC Educational Resources Information Center

    Canu, Will H.; Schatz, Nicole K.

    2011-01-01

    Attention-Deficit/Hyperactivity Disorder (ADHD) has been characterized as a comorbidity to pathological gambling (PG). However, contradictory evidence has emerged, and it has not been established whether nonimpulsive features of ADHD (e.g., inattention, hyperactivity) contribute to PG risk, or how robust this relationship is in college samples.…

  10. Prevalence of Attention Deficit Hyperactivity among Children Attending Outpatient Clinic in Psychiatric Teaching Hospital in Erbil City

    ERIC Educational Resources Information Center

    Shakir, Lana Nabeel; Sulaiman, Karwan Hawez

    2016-01-01

    Background and objectives: Attention deficit hyperactivity disorder is one of the common psychiatric disorder in childhood and it affects on children socially and academically. The aim of this study is to find out the prevalence of Attention deficit hyperactivity disorder among the studied population, describe its association with certain…

  11. Cortical Inhibition in Attention Deficit Hyperactivity Disorder: New Insights from the Electroencephalographic Response to Transcranial Magnetic Stimulation

    ERIC Educational Resources Information Center

    Bruckmann, Sarah; Hauk, Daniela; Roessner, Veit; Resch, Franz; Freitag, Christine M.; Kammer, Thomas; Ziemann, Ulf; Rothenberger, Aribert; Weisbrod, Matthias; Bender, Stephan

    2012-01-01

    Attention deficit hyperactivity disorder is one of the most frequent neuropsychiatric disorders in childhood. Transcranial magnetic stimulation studies based on muscle responses (motor-evoked potentials) suggested that reduced motor inhibition contributes to hyperactivity, a core symptom of the disease. Here we employed the N100 component of the…

  12. Different Neural Patterns Are Associated with Trials Preceding Inhibitory Errors in Children with and without Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Spinelli, Simona; Joel, Suresh; Nelson, Tess E.; Vasa, Roma A.; Pekar, James J.; Mostofsky, Stewart H.

    2011-01-01

    Objective: Attention-deficit/hyperactivity disorder (ADHD) is associated with difficulty inhibiting impulsive, hyperactive, and off-task behavior. However, no studies have examined whether a distinct pattern of brain activity precedes inhibitory errors in typically developing (TD) children and children with ADHD. In healthy adults, increased…

  13. Association between Parent Reports of Attention Deficit Hyperactivity Disorder Behaviours and Child Impulsivity in Children with Severe Intellectual Disability

    ERIC Educational Resources Information Center

    Bigham, K.; Daley, D. M.; Hastings, R. P.; Jones, R. S. P.

    2013-01-01

    Background: Although children with intellectual disability (ID) seemed to be at increased risk for Attention deficit hyperactivity disorder (ADHD)/hyperactivity problems when assessed with parent report questionnaires and clinical interviews, there has been little attention to the associations between parent reports and observed child behaviours.…

  14. Metabolomic Analysis of the Secretome of Human Embryonic Stem Cells Following Methyl Parathion and Methyl Paraoxon Exposure. Phase 3. LC-MS-MS Structural Confirmation

    DTIC Science & Technology

    2014-01-01

    attention deficit - hyperactivity disorder ( ADHD ) in their offspring. The...17 ACRONYMS AND ABBREVIATIONS ADHD attention deficit - hyperactivity disorder ADMA asymmetric dimethylarginine APG Aberdeen Proving...Wright, R.O.; Weisskopf, M.G. Attention - Deficit / Hyperactivity Disorder and Urinary Metabololites or Organophosphate Pesticides. Pediatrics

  15. The Effect of Combat Traumatic Brain Injury on Executive Function

    DTIC Science & Technology

    2011-03-01

    attention deficit / hyperactivity disorder ( ADHD ) as these are similar to problems of executive functioning...affect working memory. Also the neurotransmitters active in attention deficit / hyperactivity disorder ( ADHD ), which displays symptoms similar to those of... disorders such as autism and attention - deficit / hyperactivity disorder (Zelazo, P.D., 2005). As children grow they learn to chose and select,

  16. Les troubles de l'attention avec hyperactivite: une Synthese des connaissances a l'intention des enseignants (Attention Deficit Difficulties with Hyperactivity: A Synthesis of Knowledge for Teachers).

    ERIC Educational Resources Information Center

    Desrosiers, Karen; Royer, Egide

    1995-01-01

    This document presents a brief synthesis of recent literature on attention deficit difficulties with hyperactivity, particularly literature concerning classroom interventions. It describes diagnostic criteria for attention deficit hyperactivity disorder, its incidence, behavioral characteristics of students who exhibit attention difficulties and…

  17. Comprehensive Evaluation of Attention Deficit Disorder with and without Hyperactivity as Defined by Research Criteria.

    ERIC Educational Resources Information Center

    Barkley, Russell A.; And Others

    1990-01-01

    Compared 48 children with attention deficit disorder with hyperactivity (ADD+H), with 42 without hyperactivity, and with learning-disabled and control children. ADD+H children had more externalizing and internalizing symptoms, were more off task during testing, and had more family substance abuse, ADD+H, and aggression. Results suggest two types…

  18. Effects of Age and Ritalin Dosage on the Mother-Child Interactions of Hyperactive Children.

    ERIC Educational Resources Information Center

    Barkley, Russell A.; And Others

    1984-01-01

    Observed the mother-child interactions of three age groups of hyperactive children (N=54) during free play and task settings using two dose levels of Ritalin. Results indicated that the interactions of hyperactive boys with their mothers improve with age, and that Ritalin produces further improvements regardless of age examined. (LLL)

  19. Effects of Feedback on the Vigilance Task Performance of Hyperactive and Hypoactive Children.

    ERIC Educational Resources Information Center

    Ozolins, Delmar A.; Anderson, Robert P.

    1980-01-01

    The effects of feedback on the approaches of 20 hyperactive and 20 hypoactive children (ages 6 to 10) to a vigilance task were studied. Results showed that hyperactive Ss had more errors than hypoactive Ss under the feedback for correct responses condition and fewer errors under the feedback for false alarms condition. (PHR)

  20. An Exploratory Investigation of the Effect on a Biofeedback Technique with Hyperactive, Learning Disabled Children.

    ERIC Educational Resources Information Center

    Martin, Larry L.; Hershey, Myrliss

    Studied was the effectiveness of biofeedback techniques in reducing the hyperactive behavior of five hyperactive and four nonhyperactive children (all in elementary level learning disability classes). After 10 15-minute biofeedback training sessions over an 8-week period, Ss learned to raise their finger temperatures an average of 12.92 degrees…

  1. An Exploratory Study of the Relationship between Attention-Deficit Hyperactivity Disorder and Youth Homelessness

    ERIC Educational Resources Information Center

    Harding, Blake

    2014-01-01

    A 1997 study by Lomas and Garside suggests a 62% prevalence rate of ADHD [Attention-Deficit Hyperactivity Disorder] amongst homeless, which prompts a need for further elucidation of this relationship. This study sought to examine the relationship between Attention-Deficit Hyperactivity Disorder and the homeless youth population aged 18-24. The…

  2. Developmental Trajectories of DSM-IV Symptoms of Attention-Deficit/Hyperactivity Disorder: Genetic Effects, Family Risk and Associated Psychopathology

    ERIC Educational Resources Information Center

    Larsson, Henrik; Dilshad, Rezin; Lichtenstein, Paul; Barker, Edward D.

    2011-01-01

    Background: DSM-IV specifies three ADHD subtypes; the combined, the hyperactive-impulsive and the inattentive. Little is known about the developmental relationships underlying these subtypes. The objective of this study was to describe the development of parent-reported hyperactivity-impulsivity and inattention symptoms from childhood to…

  3. Failure of an Additive-Free Diet to Control Hyperactivity: A Case Study. Technical Report 77-02.

    ERIC Educational Resources Information Center

    Grosek, Robert J.

    Measured were the effects of a diet climinating natural salicylates, preservatives, artificial coloring and artificial flavoring on the hyperactive behavior of a 4-year-old boy. Two of four behavioral measures showed a statistically significant reduction in hyperactivity when the diet was introduced. However, when the diet was terminated, the S…

  4. The Unity and Diversity of Inattention and Hyperactivity/Impulsivity in ADHD: Evidence for a General Factor with Separable Dimensions

    ERIC Educational Resources Information Center

    Toplak, Maggie E.; Pitch, Ashley; Flora, David B.; Iwenofu, Linda; Ghelani, Karen; Jain, Umesh; Tannock, Rosemary

    2009-01-01

    To examine the unity and diversity of inattention and hyperactivity/impulsivity symptom domains of Attention-Deficit/Hyperactivity Disorder (ADHD) in a clinical sample of adolescents with ADHD. Parents and adolescents were administered a semi-structured diagnostic interview, the Schedule for Affective Disorders and Schizophrenia for School-Age…

  5. WWC Review of the Report "Enhancing the Effectiveness of Special Education Programming for Children with Attention Deficit Hyperactivity Disorder Using a Daily Report Card"

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2012

    2012-01-01

    The study described in this report examined whether the use of "daily report cards" ("DRCs") in elementary school classrooms improved behavior and academic achievement among students diagnosed with combined inattentive and hyperactive/impulsive attention deficit hyperactivity disorder (ADHD) and comorbid oppositional defiant…

  6. A 30-Year Prospective Follow-Up Study of Hyperactive Boys with Conduct Problems: Adult Criminality

    ERIC Educational Resources Information Center

    Satterfield, James H.; Faller, Katherine J.; Crinella, Francis M.; Schell, Anne M.; Swanson, James M.; Homer, Louis D.

    2007-01-01

    Objective: To compare the official arrest records for a large number of hyperactive boys (N = 179), most with conduct problems, and 75 control boys; to examine childhood IQ, socioeconomic status, and parent reports of childhood hyperactivity and conduct problems for their contribution to criminal behavior in adulthood; and to compare adult outcome…

  7. Association of screen time with self-perceived attention problems and hyperactivity levels in French students: a cross-sectional study

    PubMed Central

    Guichard, Elie; Kurth, Tobias

    2016-01-01

    Objective To investigate whether high levels of screen time exposure are associated with self-perceived levels of attention problems and hyperactivity in higher education students. Design Cross-sectional study among participants of the i-Share cohort. Setting French-speaking students of universities and higher education institutions. Participants 4816 graduate students who were at least 18 years old. Exposure Screen time was assessed by self-report of the average time spent on five different screen activities on smartphone, television, computer and tablet and categorised into quartiles. Main outcome measure We used the Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS-v1.1) concerning students’ behaviour over the past 6 months to measure self-perceived levels of attention problems and hyperactivity. Responses were summarised into a global score as well as scores for attention problems and hyperactivity. Results The 4816 participants of this study had a mean age of 20.8 years and 75.5% were female. Multivariable ordinary regression models showed significant associations of screen time exposure with quintiles of the total score of self-perceived attention problems and hyperactivity levels as well as the individual domains. Compared to the lowest screen time exposure category, the ORs (95% CI) were 1.58 (1.37 to 1.82) for each increasing level of quintiles of the global score, 1.57 (1.36 to 1.81) for increasing quintiles of attention levels and 1.25 (1.09 to 1.44) for increasing quartiles of hyperactivity. Conclusions Results of this large cross-sectional study among French university and higher education students show dose-dependent associations between screen time and self-perceived levels of attention problems and hyperactivity. Further studies are warranted to evaluate whether interventions could positively influence these associations. PMID:26920440

  8. Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naïve Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial

    PubMed Central

    Lin, Hsiang-Yuan

    2016-01-01

    Background: Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. Methods: After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18–52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. Results: At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. Conclusions: Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder. PMID:26377368

  9. The Contribution of Maternal ADHD Symptomatology, Maternal DAT1, and Home Atmosphere to Child ADHD Symptomatology at 7 Years of Age.

    PubMed

    Auerbach, Judith G; Zilberman-Hayun, Yael; Atzaba-Poria, Naama; Berger, Andrea

    2017-04-01

    Children of mothers with attention-deficit/hyperactivity disorder (ADHD) have an increased genetic and environmental risk for ADHD. The unique and interactive contributions of a maternal dopamine receptor gene (DAT1), maternal ADHD symptoms (hyperactive- impulsive, inattentive), and home atmosphere to the prediction of ADHD symptoms (hyperactive- impulsive, inattentive) in 7- year-old boys (N = 96) were examined using data from a longitudinal study of familial risk for ADHD. During the first 6 months of the study, mothers and their spouses completed a questionnaire about the mother's ADHD symptoms. Home atmosphere questionnaire data were collected 4 years later. At the 7-year assessment, mothers reported on their child's ADHD symptoms. Negative home atmosphere was significantly associated with child hyperactive-impulsive and inattentive symptoms. Maternal inattentive symptoms were significantly correlated with both child symptom dimensions. Regression models, with child genotype and maternal education controlled, showed main effects for maternal inattentive symptoms, maternal DAT1 10/10 genotype, and home atmosphere in the prediction of child inattentive symptoms. Only home atmosphere predicted child hyperactive-impulsive symptoms. There was a significant home atmosphere x maternal hyperactive-impulsive symptoms interaction in the prediction of child hyperactive-impulsive symptoms. Boys with higher levels of symptoms came from homes characterized by higher levels of negative atmosphere and had mothers with higher levels of hyperactive-impulsive symptoms. There was also a trend (p = 0.075) for a maternal DAT1 x home atmosphere interaction. Boys with higher levels of inattentive symptoms came from homes with higher levels of negative atmosphere and had mothers with the homozygous 10/10 genotype. The maternal heterozygous 9/10 genotype did not predict child symptoms.

  10. Is hyperactivity ubiquitous in ADHD or dependent on environmental demands? Evidence from meta-analysis

    PubMed Central

    Kofler, Michael J.; Raiker, Joseph S.; Sarver, Dustin E.; Wells, Erica L.; Soto, Elia F.

    2016-01-01

    Hyperactivity, or excess gross motor activity, is considered a core and ubiquitous characteristic of ADHD. Alternate models question this premise, and propose that hyperactive behavior reflects, to a large extent, purposeful behavior to cope with environmental demands that interact with underlying neurobiological vulnerabilities. The present review critically evaluates the ubiquity and environmental modifiability of hyperactivity in ADHD through meta-analysis of 63 studies of mechanically measured activity level in children, adolescents, and adults with ADHD relative to typically developing (TD) groups. Random effects models corrected for publication bias confirmed elevated gross motor activity in ADHD (d = 0.86); surprisingly, neither participant age (child vs. adult) nor the proportion of each ADHD sample diagnosed with the Inattentive subtype/presentation moderated this effect. In contrast, activity level assessed during high cognitive load conditions in general (d = 1.14) and high executive functioning demands in particular (d = 1.39) revealed significantly higher effect sizes than activity level during low cognitive load (d = 0.36) and in-class schoolwork (d = 0.50) settings. Low stimulation environments, more rigorous diagnostic practices, actigraph measurement of movement frequency and intensity, and ADHD samples that included fewer females were also associated with larger effects. Overall, the results are inconsistent with DSM-5 and ADHD models that a) describe hyperactivity as ubiquitous behavior, b) predict a developmental decline in hyperactivity, or c) differentiate subtypes/presentations according to perceived differences in hyperactive behavior. Instead, results suggest that the presence and magnitude of hyperactive behavior in ADHD may be influenced to a considerable extent by environmental factors in general, and cognitive/executive functioning demands in particular. PMID:27131918

  11. Cortisol Response to Stress in Adults with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Palomar, Gloria; Ferrer, Roser; Real, Alberto; Nogueira, Mariana; Corrales, Montserrat; Casas, Miguel; Ramos-Quiroga, Josep Antoni

    2015-01-01

    Background: Differences in the cortisol response have been reported between children exhibiting the inattentive and hyperactive/impulsive subtypes of attention deficit hyperactivity disorder. However, there is no such information about adults. The aim of the present study was to determine the possible differences between the combined and inattentive subtypes in the cortisol response to stress. Methods: Ninety-six adults with attention deficit hyperactivity disorder, 38 inattentive and 58 combined, without any medical or psychiatric comorbidities and 25 healthy controls were included. The Trier Social Stress Test was used to assess physiological stress responses. Clinical data and subjective stress levels, including the Perceived Stress Scale, were also recorded. Results: No significant differences in the cortisol response to the Trier Social Stress Test were found between patients and controls. However, albeit there were no basal differences, lower cortisol levels at 15 (P=.015), 30 (P=.015), and 45 minutes (P=.045) were observed in the combined compared with the inattentive subtype after the stress induction; these differences disappeared 60 minutes after the stress. In contrast, the subjective stress responses showed significant differences between attention deficit hyperactivity disorder patients and controls (P<.001), but no differences were seen between attention deficit hyperactivity disorder subtypes. In turn, subjective stress measures, such as the Perceived Stress Scale, positively correlated with the whole cortisol stress response (P<.027). Conclusions: Both the combined and inattentive attention deficit hyperactivity disorder adults exhibited a normal cortisol response to stress when challenged. Nevertheless, the inattentive patients displayed a higher level of cortisol after stress compared with the combined patients. Despite the differences in the cortisol response, adults with attention deficit hyperactivity disorder reported high levels of subjective stress in their every-day life. PMID:25782526

  12. Cortisol Response to Stress in Adults with Attention Deficit Hyperactivity Disorder.

    PubMed

    Corominas-Roso, Margarida; Palomar, Gloria; Ferrer, Roser; Real, Alberto; Nogueira, Mariana; Corrales, Montserrat; Casas, Miguel; Ramos-Quiroga, Josep Antoni

    2015-03-17

    Differences in the cortisol response have been reported between children exhibiting the inattentive and hyperactive/impulsive subtypes of attention deficit hyperactivity disorder. However, there is no such information about adults. The aim of the present study was to determine the possible differences between the combined and inattentive subtypes in the cortisol response to stress. Ninety-six adults with attention deficit hyperactivity disorder, 38 inattentive and 58 combined, without any medical or psychiatric comorbidities and 25 healthy controls were included. The Trier Social Stress Test was used to assess physiological stress responses. Clinical data and subjective stress levels, including the Perceived Stress Scale, were also recorded. No significant differences in the cortisol response to the Trier Social Stress Test were found between patients and controls. However, albeit there were no basal differences, lower cortisol levels at 15 (P=.015), 30 (P=.015), and 45 minutes (P=.045) were observed in the combined compared with the inattentive subtype after the stress induction; these differences disappeared 60 minutes after the stress. In contrast, the subjective stress responses showed significant differences between attention deficit hyperactivity disorder patients and controls (P<.001), but no differences were seen between attention deficit hyperactivity disorder subtypes. In turn, subjective stress measures, such as the Perceived Stress Scale, positively correlated with the whole cortisol stress response (P<.027). Both the combined and inattentive attention deficit hyperactivity disorder adults exhibited a normal cortisol response to stress when challenged. Nevertheless, the inattentive patients displayed a higher level of cortisol after stress compared with the combined patients. Despite the differences in the cortisol response, adults with attention deficit hyperactivity disorder reported high levels of subjective stress in their every-day life. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  13. Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naïve Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

    PubMed

    Lin, Hsiang-Yuan; Gau, Susan Shur-Fen

    2015-09-16

    Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18-52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  14. Evidence for shared genetic risk between ADHD symptoms and reduced mathematics ability: a twin study

    PubMed Central

    Greven, Corina U.; Kovas, Yulia; Willcutt, Erik G.; Petrill, Stephen A.; Plomin, Robert

    2013-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) symptoms and mathematics ability are associated, but little is known about the genetic and environmental influences underlying this association. Methods Data came from more than 6,000 12-year-old twin pairs from the U.K. population-representative Twins Early Development Study. Parents rated each twin’s behaviour using a DSM-IV-based 18-item questionnaire of inattentive and hyperactive-impulsive ADHD symptoms. Mathematics tests based on the U.K. National Curriculum were completed by each twin. The twins also completed standardised tests of reading and general cognitive ability. Multivariate twin model fitting was applied. Results Inattentive and hyperactive-impulsive ADHD symptoms were highly heritable (67% and 73%, respectively). Mathematics ability was moderately heritable (46%). Mathematics ability and inattentiveness showed a significantly greater phenotypic correlation (rp=−0.26) and genetic correlation (rA=−0.41) than mathematics ability and hyperactivity-impulsivity (rp=−0.18; rA=−0.22). The genetic correlation between inattentiveness and mathematics ability was largely independent from hyperactivity-impulsivity, and was only partially accounted for by genetic influences related to reading and general cognitive ability. Conclusions Results revealed the novel finding that mathematics ability shows significantly stronger phenotypic and genetic associations with inattentiveness than with hyperactivity-impulsivity. Genetic associations between inattentiveness and mathematics ability could only partially be accounted for by hyperactivity-impulsivity, reading and general cognitive ability. Results suggest that mathematics ability is associated with ADHD symptoms largely because it shares genetic risk factors with inattentiveness, and provide further evidence for considering inattentiveness and hyperactivity-impulsivity separately. DNA markers for ADHD symptoms (especially inattentiveness) may also be candidate risk factors for mathematics ability and vice versa. PMID:23731013

  15. Evidence for shared genetic risk between ADHD symptoms and reduced mathematics ability: a twin study.

    PubMed

    Greven, Corina U; Kovas, Yulia; Willcutt, Erik G; Petrill, Stephen A; Plomin, Robert

    2014-01-01

    Attention-deficit/hyperactivity disorder (ADHD) symptoms and mathematics ability are associated, but little is known about the genetic and environmental influences underlying this association. Data came from more than 6,000 twelve-year-old twin pairs from the UK population-representative Twins Early Development Study. Parents rated each twin's behaviour using a DSM-IV-based 18-item questionnaire of inattentive and hyperactive-impulsive ADHD symptoms. Mathematics tests based on the UK National Curriculum were completed by each twin. The twins also completed standardised tests of reading and general cognitive ability. Multivariate twin model fitting was applied. Inattentive and hyperactive-impulsive ADHD symptoms were highly heritable (67% and 73% respectively). Mathematics ability was moderately heritable (46%). Mathematics ability and inattentiveness showed a significantly greater phenotypic correlation (r(p) = -.26) and genetic correlation (r(A) = -.41) than mathematics ability and hyperactivity-impulsivity (r(p) = -.18; r(A) = -.22). The genetic correlation between inattentiveness and mathematics ability was largely independent from hyperactivity-impulsivity, and was only partially accounted for by genetic influences related to reading and general cognitive ability. Results revealed the novel finding that mathematics ability shows significantly stronger phenotypic and genetic associations with inattentiveness than with hyperactivity-impulsivity. Genetic associations between inattentiveness and mathematics ability could only partially be accounted for by hyperactivity-impulsivity, reading and general cognitive ability. Results suggest that mathematics ability is associated with ADHD symptoms largely because it shares genetic risk factors with inattentiveness, and provide further evidence for considering inattentiveness and hyperactivity-impulsivity separately. DNA markers for ADHD symptoms (especially inattentiveness) may also be candidate risk factors for mathematics ability and vice versa. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

  16. [Teachers' knowledge, misconceptions, and lacks concerning Attention Deficit Hyperactivity Disorder].

    PubMed

    Jarque Fernández, Sonia; Tárraga Mínguez, Raúl; Miranda Casas, Ana

    2007-11-01

    This study was designed to analyze the knowledge, misconceptions, and lacks about Attention Deficit Hyperactivity Disorder (ADHD) in a sample of 193 teachers, as a replication of the study carried by Sciutto, Terjesen and Bender in 2000. Teachers completed the Knowledge of Attention Deficit Hyperactivity Disorder (KADDS) (Spanish version), adapted by the authors of this research, to measure knowledge of ADHD in three content areas: general knowledge, symptoms/diagnosis, and treatment. Results indicated an average of correct responses of 31.67, 63.88 and 40.46% in general knowledge, symptoms/diagnosis and treatment, respectively. Teachers displayed significantly more knowledge in the Symptoms/Diagnosis scale than in the other scales. Their knowledge correlated positively with: years of experience with hyperactive children, number of hyperactive pupils in their classrooms, and level of perceived self-efficacy. These findings are consistent with those obtained by Sciutto and colleagues.

  17. Attentional deficits with and without hyperactivity: teacher and peer perceptions.

    PubMed

    King, C; Young, R D

    1982-12-01

    The present study assessed teacher and peer perceptions of boys classified according to DSM-III criteria for Attention Deficit with Hyperactivity (ADH) and Attention Deficit without Hyperactivity (AD). Teachers completed SNAP checklists (Pelham, Note 1) on all boys in their classrooms (219 boys). Twelve percent fit ADH criteria; less than 5% fit AD criteria. Teacher perceptions were assessed with the Conners Teacher Rating Scale. ADH and AD groups did not differ on the Inattention factor, although the AD group was rated significantly lower than the ADH group on Conduct Problems and Hyperactivity. These profiles were expected on the basis of DSM-III descriptions of ADH and AD; the ADH group seemed to resemble previous research samples of hyperactive children. Classroom peer perceptions, assessed with like-dislike nominations, did not discriminate between diagnostic groups. Both groups were perceived more negatively than the Comparison group, suggesting that both groups are "at risk."

  18. [Study on the association between diet, nutrient and attention deficit hyperactivity disorder among children in Shanghai, Kunshan, Wuxi three kindergarten].

    PubMed

    Liu, Jiayun; He, Ping; Li, Liangli; Shen, Tingting; Wu, Min; Hu, Juxiu; Zhuang, Ye; Yin, Jun; He, Gengsheng

    2014-03-01

    To explore the correlation between nutrition and children with attention deficit hyperactivity disorder (ADHD). For 417 students from Shanghai and Jiangsu Province, Conners Parent Symptom Questionnaire was used to investigate learning disorders and Food Frequency Questionnaire was used to evaluate the dietary and nutrient intake. Correlation between ADHD and Diet was analyzed. The rate of the ADHD abnormalities was 3.2%, there was no statistical difference between both the various regions and the genders. Partial correlation analysis showed that there was a positive correlation between diet intake (processed meat, salty snacks) and hyperactivity index (P < 0.05); A negative correlation was found between vegetables, coarse cereals, aquatic products, beef, mutton, milk and hyperactivity index (P < 0.05). The regression showed that there was a negative correlation between calcium and hyperactivity index (P < 0.05). Children's diet pattern is an important environmental impact foctor for ADHD.

  19. Parental Perceptions of Child Behavior Problems, Parenting Self-Esteem, and Mothers' Reported Stress in Younger and Older Hyperactive and Normal Children.

    ERIC Educational Resources Information Center

    Mash, Eric J.; Johnston, Charlotte

    1983-01-01

    Examined parental perceptions of child behavior, parenting self-esteem, and mothers' reported stress for younger and older hyperactive and normal children. Parenting self-esteem was lower in parents of hyperactives than in parents of normal children. Self-esteem related to skill/knowledge as a parent was age related. (Author/RC)

  20. Prescription Stimulants and the Development of Post-Traumatic Stress Disorder among U.S. Service Members

    DTIC Science & Technology

    2013-08-13

    attention deficit disorder (ADD)/ attention deficit hyperactivity disorder ( ADHD ) or to enhance performance, and such use has...individuals with and without attention deficit hyperactivity disorder : misuse, cognitive impact, and adverse effects. Brain Behav 2012, 2(5), 661-77. 11...36. Antshel KM, Kaul P, Biederman J, et al., Posttraumatic stress disorder in adult attention - deficit / hyperactivity

  1. 1.3 Mb de novo Deletion in Chromosome Band 3q29 Associated with Normal Intelligence in a Child

    DTIC Science & Technology

    2010-09-01

    attention deficit hyperactivity disorder ( ADHD ) of the inattentive type. He also displays some other...learning disabilities and behavioral features consistent with diagnoses of autism and attention deficit hyperactivity disorder ( ADHD ) of the inattentive...esophageal reflux with eosinophilic esophagitis. He was diagnosed with autism at age 3.5 years, attention deficit hyperactivity disorder

  2. Do Hyperactive Children Have Manifestations of Hyperactivity in Their Eye Movements?

    ERIC Educational Resources Information Center

    Cohen, Bernard; And Others

    A study involving 18 hyperkinetic children (from 3- to 12-years old) was conducted to test the hypothesis that hyperactive children manifest the same type of hypermotility in their eyes as in the rest of their body. Ss were observed under a series of test conditions (including manual problem solving) which elicit short and long periods of…

  3. Parent Training Interventions for Attention Deficity Hyperactivity Disorder (ADHD) in Children Aged 5 to 18 Years. Campbell Systematic Reviews. 2012:2

    ERIC Educational Resources Information Center

    Zwi, Morris; Jones, Hannah; Thorgaard, Camilla; York, Ann; Dennis, Jane A.

    2011-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterised by high levels of inattention, hyperactivity and impulsivity that are present before the age of seven years, seen in a range of situations, inconsistent with the child's developmental level and causing social or academic impairment. Parent training…

  4. The Impact of Mindfulness Training on Hyperactive Behaviors Demonstrated by Elementary Age Children with a Diagnosis of Attention Deficit Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Carboni, Jessica A.

    2012-01-01

    Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent childhood disorders in the United States. Although many children with an ADHD diagnosis are prescribed medication to control symptoms, behavioral concerns are still regularly noted in the classroom, home, and other settings. Therefore, school psychologists are often…

  5. Predictive Validity of a Continuous Alternative to Nominal Subtypes of Attention-Deficit/Hyperactivity Disorder for "DSM-V"

    ERIC Educational Resources Information Center

    Lahey, Benjamin B.; Willcutt, Erik G.

    2010-01-01

    Three subtypes of attention-deficit/hyperactivity disorder (ADHD) based on numbers of symptoms of inattention (I) and hyperactivity-impulsivity (HI) were defined in the "Diagnostic and Statistical Manual of Mental Disorders" (4th ed.) to reduce heterogeneity of the disorder, but the subtypes proved to be highly unstable over time. A continuous…

  6. Behavioral response of fifth instar nymphs of Triatoma infestans (Hemiptera: Reduviidae) to pyrethroids.

    PubMed

    Alzogaray, R A; Zerba, E N

    2001-01-15

    The hyperactivity (an increase in locomotor activity) and repellency produced by eight pyrethroids, applied as films on filter paper, were evaluated on fifth instar nymphs of Triatoma infestans (Hemiptera: Reduviidae) using a video tracking technique. All the pyrethroids studied produced hyperactivity. As a trend, hyperactivity produced by cyanopyrethroids was higher than that produced by non-cyanopyrethroids. Hyperactivity was not observed when nymphs were pretreated with the sulphydryl reagent N-ethylmaleimide before exposure to the pyrethroids. The eight pyrethroids failed to produce repellency. No repellency was also observed for the flowable formulation of deltamethrin at the concentration recommended for T. infestans control.

  7. Attention Deficit Hyperactivity Disorder in Preschool-Age Children.

    PubMed

    Tandon, Mini; Pergjika, Alba

    2017-07-01

    Attention deficit hyperactivity disorder is a neurodevelopmental disorder marked by age-inappropriate deficits in attention or hyperactivity/impulsivity that interfere with functioning or development. It is highly correlated with other disorders, such as oppositional defiant disorder, conduct disorder, and mood symptoms. The etiology is multifactorial, and neuroimaging findings are nonspecific. Although assessment tools exist, there is variability among them, and historically, parent-teacher agreement has not been consistent. Treatment algorithm for attention deficit hyperactivity disorder in preschoolers includes behavioral interventions first followed by psychopharmacologic treatment when behavioral therapies fail. Other nonpharmacologic and nonbehavioral interventions are discussed including the role of exercise and nutrition. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. [Blood and urine lead levels in children with attention deficit hyperactivity disorder].

    PubMed

    Sánchez-Villegas, M del Carmen S; Cortés-Vargas, Astrid; Hidalgo-Luna, Ricardo Gerardo; Alam-Escamilla, David Abraham; Vargas-García, Víctor Manuel; Loría-Castellanos, Jorge

    2014-01-01

    Attention deficit hyperactivity disorder is the most common neuropsychiatric disorder in children; symptoms can persist into adult life by 60 %. Our objective was to quantify the levels of lead in blood and urine in pediatric patients with attention deficit hyperactivity disorder. We did an observational study which included a captive population of children diagnosed with attention deficit hyperactivity disorder in the mental health service of Hospital General, from Centro Médico Nacional La Raza. Lead levels were determined in blood and urine by atomic absorption technique. We included 39 patients, 932 % male, with a mean age of 9.2 ± 2.16 years. The deficit and hyperactivity disorder combined type was the most frequent (69.2 %); 49 % of patients were found with toxic lead levels in blood (above 10 mg/dL); 17.9 % with stage III and 5.12 % with stage IV, according to the Mexican Official Standard (NOM-199-SSA-2000). Significant association was found between blood lead levels and the clinical expression of attention deficit hyperactivity disorder. Levels of lead exposure during early childhood have been shown to be inversely proportional to neurological development in the first seven years of life. Data results are insufficient to relate them with causality.

  9. Childhood trajectories of inattention-hyperactivity and academic achievement at 12 years.

    PubMed

    Salla, Julie; Michel, Grégory; Pingault, Jean Baptiste; Lacourse, Eric; Paquin, Stéphane; Galéra, Cédric; Falissard, Bruno; Boivin, Michel; Tremblay, Richard E; Côté, Sylvana M

    2016-11-01

    Few prospective studies spanning early childhood to early adolescence have examined separately the contribution of inattention and hyperactivity to academic achievement. The aim of the present study was to investigate whether the developmental trajectories of inattention and hyperactivity symptoms during early and middle childhood are independently associated with academic achievement at age 12 years. The independent associations between inattention and hyperactivity trajectories during early and middle childhood and academic performance at age 12 years were examined in a population-based longitudinal birth cohort (n = 2120). In adjusted analyses, high early childhood inattention trajectories were associated with teacher-rated academic performance in reading, writing and mathematics and with government exam score in writing. High and moderate inattention trajectories during middle childhood predicted lower performance on both teacher-rated academic performance and government exam scores in reading, writing, and mathematics. Hyperactivity was not a consistent predictor of educational outcomes. Childhood inattention symptoms rather than hyperactivity carry risk of poor educational outcomes at age 12 years. Children with high levels of inattention can be identified during the preschool years. Prevention programs supporting the development of attentional capacities and executive functions could help reduce the negative consequences of inattention.

  10. Hyperactivity and lack of social discrimination in the adolescent Fmr1 knockout mouse.

    PubMed

    Sørensen, Emilie M; Bertelsen, Freja; Weikop, Pia; Skovborg, Maria M; Banke, Tue; Drasbek, Kim R; Scheel-Krüger, Jørgen

    2015-12-01

    The aims of this study were to investigate behaviour relevant to human autism spectrum disorder (ASD) and the fragile X syndrome in adolescent Fmr1 knockout (KO) mice and to evaluate the tissue levels of striatal monoamines. Fmr1 KO mice were evaluated in the open field, marble burying and three-chamber test for the presence of hyperactivity, anxiety, repetitive behaviour, sociability and observation of social novelty compared with wild-type (WT) mice. The Fmr1 KO mice expressed anxiety and hyperactivity in the open field compared with WT mice. This increased level of hyperactivity was confirmed in the three-chamber test. Fmr1 KO mice spent more time with stranger mice compared with the WT. However, after a correction for hyperactivity, their apparent increase in sociability became identical to that of the WT. Furthermore, the Fmr1 KO mice could not differentiate between a familiar or a novel mouse. Monoamines were measured by HPLC: Fmr1 KO mice showed an increase in the striatal dopamine level. We conclude that the fragile X syndrome model seems to be useful for understanding certain aspects of ASD and may have translational interest for studies of social behaviour when hyperactivity coexists in ASD patients.

  11. Basal ganglia structure in Tourette's disorder and/or attention-deficit/hyperactivity disorder.

    PubMed

    Forde, Natalie J; Zwiers, Marcel P; Naaijen, Jilly; Akkermans, Sophie E A; Openneer, Thaira J C; Visscher, Frank; Dietrich, Andrea; Buitelaar, Jan K; Hoekstra, Pieter J

    2017-04-01

    Tourette's disorder and attention-deficit/hyperactivity disorder often co-occur and have both been associated with structural variation of the basal ganglia. However, findings are inconsistent and comorbidity is often neglected. T1-weighted magnetic resonance images from children (n = 141, 8 to 12 years) with Tourette's disorder and/or attention-deficit/hyperactivity disorder and controls were processed with the Oxford Centre for Functional MRI [Magnetic resonance imaging] of the Brain (FMRIB) integrated registration and segmentation tool to determine basal ganglia nuclei volume and shape. Across all participants, basal ganglia nuclei volume and shape were estimated in relation to Tourette's disorder (categorical), attention-deficit/hyperactivity disorder severity (continuous across all participants), and their interaction. The analysis revealed no differences in basal ganglia nuclei volumes or shape between children with and without Tourette's disorder, no association with attention-deficit/hyperactivity disorder severity, and no interaction between the two. We found no evidence that Tourette's disorder, attention-deficit/hyperactivity disorder severity, or a combination thereof are associated with structural variation of the basal ganglia in 8- to 12-year-old patients. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  12. Genetic support for the dual nature of attention deficit hyperactivity disorder: substantial genetic overlap between the inattentive and hyperactive-impulsive components.

    PubMed

    McLoughlin, Gráinne; Ronald, Angelica; Kuntsi, Jonna; Asherson, Philip; Plomin, Robert

    2007-12-01

    Attention deficit hyperactivity disorder (ADHD) is a common, complex and highly heritable disorder, characterised by inattentive, impulsive and overactive behaviour. Evidence for the heritability of ADHD measures in twin population samples has come from the analysis of total scores that combine inattentive and hyperactive-impulsive symptoms subscales. This study investigated, in a community sample, the aetiology of ADHD-like traits and the aetiological overlap between the two dimensions that define the ADHD disorder. Parents of 6,222 approximately 8-year-old twin pairs from the Twins Early Development Study (TEDS) population sample completed the two subscales of the Conners' 18-item DSMIV checklist, a screening instrument for ADHD symptoms. Both subscales were highly heritable (hyperactive-impulsive: 88%; inattentive: 79%). Bivariate genetic modelling indicated substantial genetic overlap between the two components; however, there were significant independent genetic effects. These findings suggest that many genes associated with the hyperactivity-impulsivity dimension will also be associated with the inattentive dimension but that there is significant genetic heterogeneity as well. These results provide genetic support for combining the two behavioural dimensions that define ADHD, but also suggest that some symptom-specific genes will also be identified.

  13. Associations of sleep disturbance with ADHD: implications for treatment.

    PubMed

    Hvolby, Allan

    2015-03-01

    Attention-deficit/hyperactivity disorder (ADHD) is commonly associated with disordered or disturbed sleep. The relationships of ADHD with sleep problems, psychiatric comorbidities and medications are complex and multidirectional. Evidence from published studies comparing sleep in individuals with ADHD with typically developing controls is most concordant for associations of ADHD with: hypopnea/apnea and peripheral limb movements in sleep or nocturnal motricity in polysomnographic studies; increased sleep onset latency and shorter sleep time in actigraphic studies; and bedtime resistance, difficulty with morning awakenings, sleep onset difficulties, sleep-disordered breathing, night awakenings and daytime sleepiness in subjective studies. ADHD is also frequently coincident with sleep disorders (obstructive sleep apnea, peripheral limb movement disorder, restless legs syndrome and circadian-rhythm sleep disorders). Psychostimulant medications are associated with disrupted or disturbed sleep, but also 'paradoxically' calm some patients with ADHD for sleep by alleviating their symptoms. Long-acting formulations may have insufficient duration of action, leading to symptom rebound at bedtime. Current guidelines recommend assessment of sleep disturbance during evaluation of ADHD, and before initiation of pharmacotherapy, with healthy sleep practices the first-line option for addressing sleep problems. This review aims to provide a comprehensive overview of the relationships between ADHD and sleep, and presents a conceptual model of the modes of interaction: ADHD may cause sleep problems as an intrinsic feature of the disorder; sleep problems may cause or mimic ADHD; ADHD and sleep problems may interact, with reciprocal causation and possible involvement of comorbidity; and ADHD and sleep problems may share a common underlying neurological etiology.

  14. Oxidative Stress and Erythrocyte Membrane Alterations in Children with Autism: Correlation with Clinical Features.

    PubMed

    Ghezzo, Alessandro; Visconti, Paola; Abruzzo, Provvidenza M; Bolotta, Alessandra; Ferreri, Carla; Gobbi, Giuseppe; Malisardi, Gemma; Manfredini, Stefano; Marini, Marina; Nanetti, Laura; Pipitone, Emanuela; Raffaelli, Francesca; Resca, Federica; Vignini, Arianna; Mazzanti, Laura

    2013-01-01

    It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na(+)/K(+)-ATPase activity (-66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-ω3 with a consequent increase in ω6/ω3 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD.

  15. An objective measure of hyperactivity aspects with compressed webcam video.

    PubMed

    Wehrmann, Thomas; Müller, Jörg Michael

    2015-01-01

    Objective measures of physical activity are currently not considered in clinical guidelines for the assessment of hyperactivity in the context of Attention-Deficit/Hyperactivity Disorder (ADHD) due to low and inconsistent associations between clinical ratings, missing age-related norm data and high technical requirements. This pilot study introduces a new objective measure for physical activity using compressed webcam video footage, which should be less affected by age-related variables. A pre-test established a preliminary standard procedure for testing a clinical sample of 39 children aged 6-16 years (21 with a clinical ADHD diagnosis, 18 without). Subjects were filmed for 6 min while solving a standardized cognitive performance task. Our webcam video-based video-activity score was compared with respect to two independent video-based movement ratings by students, ratings of Inattentiveness, Hyperactivity and Impulsivity by clinicians (DCL-ADHS) giving a clinical diagnosis of ADHD and parents (FBB-ADHD) and physical features (age, weight, height, BMI) using mean scores, correlations and multiple regression. Our video-activity score showed a high agreement (r = 0.81) with video-based movement ratings, but also considerable associations with age-related physical attributes. After controlling for age-related confounders, the video-activity score showed not the expected association with clinicians' or parents' hyperactivity ratings. Our preliminary conclusion is that our video-activity score assesses physical activity but not specific information related to hyperactivity. The general problem of defining and assessing hyperactivity with objective criteria remains.

  16. Developmental predictors of inattention-hyperactivity from pregnancy to early childhood.

    PubMed

    Foulon, Stéphanie; Pingault, Jean-Baptiste; Larroque, Béatrice; Melchior, Maria; Falissard, Bruno; Côté, Sylvana M

    2015-01-01

    The objective of the study was to characterize the developmental sequence of pre- and postnatal risk factors for inattention-hyperactivity symptoms in preschoolers. Longitudinal data came from a French population based birth cohort study (EDEN; N = 1311 mother-child pairs followed from the pregnancy onwards). Inattention-hyperactivity symptoms were assessed with the Strengths and Difficulties Questionnaire when participating children were 3 years of age. Potential risk factors were classified in four domains (fetal exposures and child somatic characteristics, child temperament, child neurodevelopmental status, psychosocial environment) and four periods (before pregnancy, prenatal/birth, infancy, toddlerhood). Their role as potential moderator or mediator was tested with path analysis to determine the developmental sequence. A low family socioeconomic status before pregnancy was the main environmental risk factor for inattention-hyperactivity symptoms at 3 years, and its effect occurred via two pathways. The first was a risk pathway, where lower SES was associated with higher maternal depression and anxiety during pregnancy; then to higher maternal and child distress and dysregulation in infancy; and in turn to higher levels of inattention-hyperactivity at 3 years. The second was a protective pathway, where higher SES was associated with longer duration of breastfeeding during infancy; then to better child neurodevelopmental status in toddlerhood; and in turn to lower levels of inattention-hyperactivity at 3 years. This study identified psychosocial factors at several developmental periods that represent potential targets for preventing the emergence of inattention-hyperactivity symptoms in early childhood.

  17. Time-dependent effects of prazosin on the development of methamphetamine conditioned hyperactivity and context-specific sensitization in mice.

    PubMed

    White, André O; Rauhut, Anthony S

    2014-04-15

    The present experiments examined the effects of prazosin, a selective α₁-adrenergic receptor antagonist, on the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Mice received an injection of vehicle (distilled water) or prazosin (0.5, 1.0 or 2.0 mg/kg) 30 min prior to a second injection of vehicle (saline) or methamphetamine (1.0 mg/kg) during the conditioning sessions (Experiment 1). Following the conditioning sessions, mice were tested for conditioned hyperactivity and then tested for context-specific sensitization. In subsequent experiments, mice received an injection of vehicle (distilled water) or prazosin (2.0 mg/kg) immediately (Experiment 2) or 24 h (Experiment 3) after the conditioning sessions and then tested for conditioned hyperactivity and context-specific sensitization. Prazosin dose-dependently blocked the development of methamphetamine conditioned hyperactivity and context-specific sensitization when administered prior to the methamphetamine during the conditioning phase; however nonspecific motor impairments also were observed (Experiment 1). Immediate (Experiment 2), but not the 24-h delay (Experiment 3), post-session administration of prazosin attenuated the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Nonspecific motor impairments were not observed in these latter experiments. Collectively, these results suggest that the α₁-adrenergic receptor mediates the development of methamphetamine-conditioned hyperactivity and context-specific sensitization, perhaps by altering memory consolidation and/or reconsolidation processes. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Developmental Predictors of Inattention-Hyperactivity from Pregnancy to Early Childhood

    PubMed Central

    Foulon, Stéphanie; Pingault, Jean-Baptiste; Melchior, Maria; Falissard, Bruno; Côté, Sylvana M.

    2015-01-01

    Objective The objective of the study was to characterize the developmental sequence of pre- and postnatal risk factors for inattention-hyperactivity symptoms in preschoolers. Materials and Methods Longitudinal data came from a French population based birth cohort study (EDEN; N = 1311 mother-child pairs followed from the pregnancy onwards). Inattention-hyperactivity symptoms were assessed with the Strengths and Difficulties Questionnaire when participating children were 3 years of age. Potential risk factors were classified in four domains (fetal exposures and child somatic characteristics, child temperament, child neurodevelopmental status, psychosocial environment) and four periods (before pregnancy, prenatal/birth, infancy, toddlerhood). Their role as potential moderator or mediator was tested with path analysis to determine the developmental sequence. Results A low family socioeconomic status before pregnancy was the main environmental risk factor for inattention-hyperactivity symptoms at 3 years, and its effect occurred via two pathways. The first was a risk pathway, where lower SES was associated with higher maternal depression and anxiety during pregnancy; then to higher maternal and child distress and dysregulation in infancy; and in turn to higher levels of inattention-hyperactivity at 3 years. The second was a protective pathway, where higher SES was associated with longer duration of breastfeeding during infancy; then to better child neurodevelopmental status in toddlerhood; and in turn to lower levels of inattention-hyperactivity at 3 years. Discussion This study identified psychosocial factors at several developmental periods that represent potential targets for preventing the emergence of inattention-hyperactivity symptoms in early childhood. PMID:25938453

  19. Prevalence and Factors of Addictive Internet Use among Adolescents in Wuhan, China: Interactions of Parental Relationship with Age and Hyperactivity-Impulsivity

    PubMed Central

    Wu, Xianhua; Chen, Xinguang; Han, Juan; Meng, Heng; Luo, Jianghong; Nydegger, Liesl; Wu, Hanrong

    2013-01-01

    Purposes This study examined the prevalence of addictive Internet use and analyzed the role of parental relationship in affecting this behavior among a random sample of adolescents in Wuhan, China. Methods Students (n = 1,101) were randomly selected from four schools, including 638 boys and 463 girls with a mean age of 13.8 (standard deviation = 1.2) years. Addictive Internet use, parental relationship, hyperactivity-impulsivity were measured by validated instruments. Prevalence rate, ANOVA and multiple linear regression method were used to analyze the level of Internet addiction and its association with parental relationship, hyperactivity-impulsivity, as well as the interaction of parental relationship with chronological age and hyperactivity-impulsivity. Results The prevalence rate of Internet addiction was 13.5% (16.5% for boys and 9.5% for girls, p<0.01). Compared to non-addictive users, addictive Internet users were scored significantly lower on parental relationships and significantly higher on hyperactivity-impulsivity. Interaction analysis indicated that better parental relationship was associated with more reductions in risk of addictive Internet use for younger students than for older students, and with more risk of Internet addiction among higher than among lower hyperactivity-impulsivity students. Conclusions Findings of this study indicate that adolescent addictive Internet use is a significant public health threat in China. Prevention interventions targeting parental relationship must consider adolescent’s age and hyperactivity-impulsivity tendency. PMID:23596525

  20. Working Memory Arrest in Children with High-Functioning Autism Compared to Children with Attention-Deficit/Hyperactivity Disorder: Results from a 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Andersen, Per N.; Skogli, Erik W.; Hovik, Kjell T.; Geurts, Hilde; Egeland, Jens; Øie, Merete

    2015-01-01

    The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically…

  1. Meta-Analysis of Attention-Deficit/Hyperactivity Disorder or Attention-Deficit/Hyperactivity Disorder Symptoms, Restriction Diet, and Synthetic Food Color Additives

    ERIC Educational Resources Information Center

    Nigg, Joel T.; Lewis, Kara; Edinger, Tracy; Falk, Michael

    2012-01-01

    Objective: The role of diet and of food colors in attention-deficit/hyperactivity disorder (ADHD) or its symptoms warrants updated quantitative meta-analysis, in light of recent divergent policy in Europe and the United States. Method: Studies were identified through a literature search using the PubMed, Cochrane Library, and PsycNET databases…

  2. Confirmation and Extension of Association of Blood Lead with Attention-Deficit/Hyperactivity Disorder (ADHD) and ADHD Symptom Domains at Population-Typical Exposure Levels

    ERIC Educational Resources Information Center

    Nigg, Joel T.; Nikolas, Molly; Mark Knottnerus, G.; Cavanagh, Kevin; Friderici, Karen

    2010-01-01

    Background: Recent studies have suggested that child attention-deficit/hyperactivity disorder (ADHD) and its symptom domains are related to blood lead level, even at background exposure levels typical in western countries. However, recent studies disagreed as to whether lead was related to inattention or hyperactivity-impulsivity within the ADHD…

  3. The Speech of Hyperactive Children and Their Mothers: Comparison with Normal Children and Stimulant Drug Effects.

    ERIC Educational Resources Information Center

    Barkley, Russell A.; And Others

    1983-01-01

    Verbal interactions of 18 hyperactive boys (8 to 11 years old) with their mothers during 15-minute free play and task periods were studied and compared to interactions of 18 normal boys with their mothers. Both hyperactive boys and their mothers were found to use significantly more utterances in free play than normal mother-child dyads.…

  4. Access to site-specific Fc–cRGD peptide conjugates through streamlined expressed protein ligation†

    PubMed Central

    Frutos, S.; Jordan, J. B.; Bio, M. M.; Muir, T. W.; Thiel, O. R.; Vila-Perelló, M.

    2018-01-01

    An ideal drug should be highly effective, non-toxic and be delivered by a convenient and painless single dose. We are still far from such optimal treatment but peptides, with their high target selectivity and low toxicity profiles, provide a very attractive platform from which to strive towards it. One of the major limitations of peptide drugs is their high clearance rates, which limit dosage regimen options. Conjugation to antibody Fc domains is a viable strategy to improve peptide stability by increasing their hydrodynamic radius and hijacking the Fc recycling pathway. We report the use of a split-intein based semi-synthetic approach to site-specifically conjugate a synthetic integrin binding peptide to an Fc domain. The strategy described here allows conjugating synthetic peptides to Fc domains, which is not possible via genetic methods, fully maintaining the ability of both the Fc domain and the bioactive peptide to interact with their binding partners. PMID:27722696

  5. Bioengineering strategies to generate artificial protein complexes.

    PubMed

    Kim, Heejae; Siu, Ka-Hei; Raeeszadeh-Sarmazdeh, Maryam; Sun, Qing; Chen, Qi; Chen, Wilfred

    2015-08-01

    For many applications, increasing synergy between distinct proteins through organization is important for the specificity, regulation, and overall reaction efficiency. Although there are many examples of protein complexes in nature, a generalized method to create these complexes remains elusive. Many conventional techniques such as random chemical conjugation, physical adsorption onto surfaces, and encapsulation within matrices are imprecise approaches and can lead to deactivation of protein native functionalities. More "bio-friendly" approaches such as genetically fused proteins and biological scaffolds often can result in low yields and low complex stability. Alternatively, site-specific protein conjugation or ligation can generate artificial protein complexes that preserve the native functionalities of protein domains and maintain stability through covalent bonds. In this review, we describe three distinct methods to synthesize artificial protein complexes (genetic incorPoration of unnatural amino acids to introduce bio-orthogonal azide and alkyne groups to proteins, split-intein based expressed protein ligation, and sortase mediated ligation) and highlight interesting applications for each technique. © 2015 Wiley Periodicals, Inc.

  6. Correlation of chemical shifts predicted by molecular dynamics simulations for partially disordered proteins.

    PubMed

    Karp, Jerome M; Eryilmaz, Ertan; Erylimaz, Ertan; Cowburn, David

    2015-01-01

    There has been a longstanding interest in being able to accurately predict NMR chemical shifts from structural data. Recent studies have focused on using molecular dynamics (MD) simulation data as input for improved prediction. Here we examine the accuracy of chemical shift prediction for intein systems, which have regions of intrinsic disorder. We find that using MD simulation data as input for chemical shift prediction does not consistently improve prediction accuracy over use of a static X-ray crystal structure. This appears to result from the complex conformational ensemble of the disordered protein segments. We show that using accelerated molecular dynamics (aMD) simulations improves chemical shift prediction, suggesting that methods which better sample the conformational ensemble like aMD are more appropriate tools for use in chemical shift prediction for proteins with disordered regions. Moreover, our study suggests that data accurately reflecting protein dynamics must be used as input for chemical shift prediction in order to correctly predict chemical shifts in systems with disorder.

  7. New Type of Antimicrobial Protein Produced by the Plant Pathogen Clavibacter michiganensis subsp. michiganensis

    PubMed Central

    Liu, Zhanliang; Ma, Ping; Holtsmark, Ingrid; Skaugen, Morten; Eijsink, Vincent G. H.

    2013-01-01

    It has previously been shown that the tomato pathogen Clavibacter michiganensis subsp. michiganensis secretes a 14-kDa protein, C. michiganensis subsp. michiganensis AMP-I (CmmAMP-I), that inhibits growth of Clavibacter michiganensis subsp. sepedonicus, the causal agent of bacterial ring rot of potato. Using sequences obtained from tryptic fragments, we have identified the gene encoding CmmAMP-I and we have recombinantly produced the protein with an N-terminal intein tag. The gene sequence showed that CmmAMP-I contains a typical N-terminal signal peptide for Sec-dependent secretion. The recombinant protein was highly active, with 50% growth inhibition (IC50) of approximately 10 pmol, but was not toxic to potato leaves or tubers. CmmAMP-I does not resemble any known protein and thus represents a completely new type of bacteriocin. Due to its high antimicrobial activity and its very narrow inhibitory spectrum, CmmAMP-1 may be of interest in combating potato ring rot disease. PMID:23851100

  8. Authentic interdomain communication in an RNA helicase reconstituted by expressed protein ligation of two helicase domains.

    PubMed

    Karow, Anne R; Theissen, Bettina; Klostermeier, Dagmar

    2007-01-01

    RNA helicases mediate structural rearrangements of RNA or RNA-protein complexes at the expense of ATP hydrolysis. Members of the DEAD box helicase family consist of two flexibly connected helicase domains. They share nine conserved sequence motifs that are involved in nucleotide binding and hydrolysis, RNA binding, and helicase activity. Most of these motifs line the cleft between the two helicase domains, and extensive communication between them is required for RNA unwinding. The two helicase domains of the Bacillus subtilis RNA helicase YxiN were produced separately as intein fusions, and a functional RNA helicase was generated by expressed protein ligation. The ligated helicase binds adenine nucleotides with very similar affinities to the wild-type protein. Importantly, its intrinsically low ATPase activity is stimulated by RNA, and the Michaelis-Menten parameters are similar to those of the wild-type. Finally, ligated YxiN unwinds a minimal RNA substrate to an extent comparable to that of the wild-type helicase, confirming authentic interdomain communication.

  9. Expression and purification of moricin CM4 and human β-defensins 4 in Escherichia coli using a new technology.

    PubMed

    Shen, Yang; Ai, Hong-Xin; Song, Ren; Liang, Zhen-Ning; Li, Jian-Feng; Zhang, Shuang-Quan

    2010-10-20

    Different strategies have been developed to produce small antimicrobial peptides using recombinant techniques. Here we report a new technology of biosynthesis of moricin CM4 and human β-defensins 4 (HβD4) in the Escherichia coli. The CM4 and HβD4 gene were cloned into a vector containing the tags elastin-like peptide (ELP) and intein to construct the expression vector pET-EI-CM4 and pET-EI-HβD4. All the peptides, expressed as soluble fusions, were isolated from the protein debris by the method called inverse transition cycling (ITC) rather than traditional immobilized metal affinity chromatography (IMAC) and separated from the fusion leader by self-cleavage. Fully reduced peptides that were purified exhibited expected antimicrobial activity. The approach described here is a low-cost, convenient and potential way for generating small antimicrobial peptide. Copyright © 2010 Elsevier GmbH. All rights reserved.

  10. Structural basis for glucose-6-phosphate activation of glycogen synthase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Baskaran, Sulochanadevi; Roach, Peter J.; DePaoli-Roach, Anna A.

    2010-11-22

    Regulation of the storage of glycogen, one of the major energy reserves, is of utmost metabolic importance. In eukaryotes, this regulation is accomplished through glucose-6-phosphate levels and protein phosphorylation. Glycogen synthase homologs in bacteria and archaea lack regulation, while the eukaryotic enzymes are inhibited by protein kinase mediated phosphorylation and activated by protein phosphatases and glucose-6-phosphate binding. We determined the crystal structures corresponding to the basal activity state and glucose-6-phosphate activated state of yeast glycogen synthase-2. The enzyme is assembled into an unusual tetramer by an insertion unique to the eukaryotic enzymes, and this subunit interface is rearranged by themore » binding of glucose-6-phosphate, which frees the active site cleft and facilitates catalysis. Using both mutagenesis and intein-mediated phospho-peptide ligation experiments, we demonstrate that the enzyme's response to glucose-6-phosphate is controlled by Arg583 and Arg587, while four additional arginine residues present within the same regulatory helix regulate the response to phosphorylation.« less

  11. Attention checklist: a rating scale for mildly mentally handicapped adolescents.

    PubMed

    Das, J P; Melnyk, L

    1989-06-01

    A check list for attentional deficits without reference to hyperactive behavior observed in the classroom was constructed, and teachers' ratings were factor analyzed. The check-list rating was compared to a widely used rating scale for attention deficit-hyperactive disorder (AD-HD), the Abbreviated Conners Rating Scale. Both scales were given to 15 teachers to rate 100 mildly mentally handicapped adolescent students. Analysis showed that 33% of the mentally handicapped students were rated above 1.5 on the Conners Scale, which is the cut-off for hyperactivity. This is much higher than the prevalence of hyperactivity in regular classrooms. The two sets of ratings correlated strongly (.84). Check-list items were grouped under one factor explaining 70.7% of variance and so are recommended for use in discriminating attentional deficit in mentally handicapped as well as in regular class students. The high correlation with ratings on the Conners Scale suggests that AD-HD is a unitary syndrome with attention being most problematic for children labeled hyperactive.

  12. Inattention, Hyperactivity, and Emergent Literacy: Different Facets of Inattention Relate Uniquely to Preschoolers’ Reading-Related Skills

    PubMed Central

    Sims, Darcey M.; Lonigan, Christopher J.

    2012-01-01

    Objective Although extant studies indicate that there is a strong association between Attention Deficit/Hyperactivity Disorder (ADHD) and reading ability in elementary school children, knowledge regarding the relation between inattentive and hyperactive/impulsive behaviors and emergent literacy in preschool children is less established. This study examined the unique and overlapping relations between measures that assess inattention and hyperactivity/impulsivity and emergent literacy skills in preschool children. Method Participants included 204 preschool children (Mean age = 56 months; 50.9% female; 79.8% European American). Behavioral rating scales were completed by teachers and the Continuous Performance Test (CPT) and the Test of Preschool Early Literacy were completed by the preschoolers. Results Across measures, inattention was a unique correlate of emergent literacy skills whereas hyperactivity/impulsivity was not. Both rating scales and the CPT indices of inattention were uniquely associated with emergent literacy skills. Conclusions These results suggest that these measures are assessing different manifestations of inattention that are both unique correlates of early reading skills. PMID:23186142

  13. Assisting children with Attention Deficit Hyperactivity Disorder actively reduces limb hyperactive behavior with a Nintendo Wii Remote Controller through controlling environmental stimulation.

    PubMed

    Shih, Ching-Hsiang; Yeh, Jui-Chi; Shih, Ching-Tien; Chang, Man-Ling

    2011-01-01

    The latest studies have adopted software technology which turns the Wii Remote Controller into a high-performance limb action detector, we assessed whether two persons with multiple disabilities would be able to control an environmental stimulus through limb action. This study extends the functionality of the Wii Remote Controller to the correction of limb hyperactive behavior to assess whether two children with Attention Deficit Hyperactivity Disorder (ADHD) would be able to actively reduce their limb hyperactive behavior through controlling their favorite stimuli by turning them on/off using a Wii Remote Controller. An ABAB design, in which A represented the baseline and B represented intervention phases, was adopted in this study. Result showed that both participants significantly increased their time duration of maintaining a static limb posture (TDMSLP) to activate the control system in order to produce environmental stimulation in the intervention phases. Practical and developmental implications of the findings are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. The Role of Reactive Aggression in the Link Between Hyperactive-Impulsive Behaviors and Peer Rejection in Adolescents.

    PubMed

    Evans, Spencer C; Fite, Paula J; Hendrickson, Michelle L; Rubens, Sonia L; Mages, Anna K

    2015-12-01

    Attention-deficit/hyperactivity disorder (ADHD) symptoms and aggressive behaviors are both associated with peer rejection, but little is known the nature of this association with respect to the two symptom dimensions of hyperactivity-impulsivity and inattention and different types of aggression. The present study examines the relations between dimensions of ADHD symptomatology, proactive and reactive aggression, and peer rejection in adolescence. Teacher-reported data were obtained for 200 high school students (grades 9-12; 48% female; predominately Latino). In structural equation modeling path analyses, the indirect effects of reactive aggression accounted for the link between hyperactivity-impulsivity and peer rejection. Within the same model, neither inattention nor proactive aggression were associated with peer rejection. These findings suggest that reactive aggression may be a key mechanism through which hyperactive-impulsive behavior is associated with peer rejection. Future research and intervention efforts should address the role of reactive aggression among youth with ADHD symptomatology.

  15. Understanding the Etiology of Tuberous Sclerosis Complex

    DTIC Science & Technology

    2011-07-01

    heterotopic nodules. Indeed, the cortex of TSC individuals contains pockets of abnormal cells with hyperactive mTOR in an otherwise structurally normal...phosphorylated S6 (phospho-S6). mTOR hyperactivity leads to enhanced S6 phosphorylation. Immunostaining in postnatal day (P) 28 sections from...respectively. In addiiton, hamartin is lost and mTOR hyperactive. Figure 2: In utero single-cell knockout of Tsc1 in cortical cells. (A) Diagram

  16. Invariance and Convergent and Discriminant Validity between Mothers' and Fathers' Ratings of Oppositional Defiant Disorder toward Adults, ADHD-HI, ADHD-IN, and Academic Competence Factors within Brazilian, Thai, and American Children

    ERIC Educational Resources Information Center

    Burns, G. Leonard; de Moura, Marcela Alves; Walsh, James A.; Desmul, Chris; Silpakit, Chatchawan; Sommers-Flanagan, John

    2008-01-01

    Confirmatory factor analysis was used to test the invariance of an oppositional defiant disorder toward adults, attention-deficit/hyperactivity disorder-hyperactivity/impulsivity, attention-deficit/hyperactivity disorder-inattention, and an Academic Competence factor model between mothers' and fathers' ratings within Brazilian (n = 894), Thai (n =…

  17. Mothers' Attributions for Behavior in Nonproblem Boys, Boys with Attention Deficit Hyperactivity Disorder, and Boys with Attention Deficit Hyperactivity Disorder and Oppositional Defiant Behavior

    ERIC Educational Resources Information Center

    Johnston, Charlotte; Chen, Mandy; Ohan, Jeneva

    2006-01-01

    This study compared attributions for child behavior among mothers of 38 nonproblem boys, 26 boys with attention deficit hyperactivity disorder (ADHD), and 25 boys with ADHD and oppositional defiant (OD) behavior. Boys ranged from 7 to 10 years of age. To capture different aspects of mothers' attributions, 2 assessment methods were employed: (a)…

  18. A Multitrait (ADHD-IN, ADHD-HI, ODD toward Adults, Academic and Social Competence) by Multisource (Mothers and Fathers) Evaluation of the Invariance and Convergent/Discriminant Validity of the Child and Adolescent Disruptive Behavior Inventory with Thai Adolescents

    ERIC Educational Resources Information Center

    Burns, G. Leonard; Desmul, Chris; Walsh, James A.; Silpakit, Chatchawan; Ussahawanitchakit, Phapruke

    2009-01-01

    Confirmatory factor analysis was used with a multitrait (attention-deficit/hyperactivity disorder-inattention, attention-deficit/hyperactivity disorder-hyperactivity/impulsivity, oppositional defiant disorder toward adults, academic competence, and social competence) by multisource (mothers and fathers) matrix to test the invariance and…

  19. Relationship between auditory thresholds, central spontaneous activity and hair cell loss after acoustic trauma

    PubMed Central

    Mulders, W.H.A.M.; Ding, D.; Salvi, R.; Robertson, D.

    2011-01-01

    Acoustic trauma caused by exposure to a very loud sound increases spontaneous activity in central auditory structures such as the inferior colliculus. This hyperactivity has been suggested as a neural substrate for tinnitus, a phantom hearing sensation. In previous studies we have described a tentative link between the frequency region of hearing impairment and the corresponding tonotopic regions in the inferior colliculus showing hyperactivity. In this study we further investigated the relationship between cochlear compound action potential threshold loss, cochlear outer and inner hair cell loss and central hyperactivity in inferior colliculus of guinea pigs. Two weeks after a 10 kHz pure tone acoustic trauma, a tight relationship was demonstrated between the frequency region of compound action potential threshold loss and frequency regions in the inferior colliculus showing hyperactivity. Extending the duration of the acoustic trauma from 1 to 2 h did not result in significant increases in final cochlear threshold loss, but did result in a further increase of spontaneous firing rates in the inferior colliculus. Interestingly, hair cell loss was not present in the frequency regions where elevated cochlear thresholds and central hyperactivity were measured, suggesting that subtle changes in hair cell or primary afferent neural function are sufficient for central hyperactivity to be triggered and maintained. PMID:21491427

  20. Distinguishing among disruptive behaviors to help predict high school graduation: does gender matter?

    PubMed

    Lynch, Rebecca J; Kistner, Janet A; Allan, Nicholas P

    2014-08-01

    This study examined unique predictive associations of aggressive and hyperactive-inattentive behaviors in elementary school with high school graduation. The current study also investigated whether these associations were moderated by gender. At Time 1, 745 children in the 3rd through 5th grades completed peer ratings on their classmates' disruptive behaviors. At Time 2, school records were reviewed to determine whether students graduated within four years of entering high school. Results showed that gender and hyperactivity-inattention are uniquely associated with high school graduation, but childhood aggression is not. Results also indicated that gender moderated associations between hyperactivity-inattention and graduation. Among boys, hyperactive-inattentive behaviors were not significantly associated with graduation, above and beyond aggression. In contrast, among girls, hyperactive-inattentive behaviors in childhood were significantly associated with graduation even after controlling for aggression. These findings suggest that in middle childhood, hyperactive-inattentive behaviors may be a more meaningful predictor of high school graduation than other forms of early disruptive behavior (e.g., aggression), especially for girls. Such findings could have significant implications for prevention and intervention programs designed to target children at risk for dropping out of school. Copyright © 2014 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  1. Temperament Pathways to Childhood Disruptive Behavior and Adolescent Substance Abuse: Testing a Cascade Model

    PubMed Central

    Martel, Michelle M.; Pierce, Laura; Nigg, Joel T.; Jester, Jennifer M.; Adams, Kenneth; Puttler, Leon I.; Buu, Anne; Fitzgerald, Hiram; Zucker, Robert A.

    2008-01-01

    Temperament traits may increase risk for developmental psychopathology like Attention-Deficit/Hyperactivity Disorder (ADHD) and disruptive behaviors during childhood, as well as predisposing to substance abuse during adolescence. In the current study, a cascade model of trait pathways to adolescent substance abuse was examined. Component hypotheses were that (a) maladaptive traits would increase risk for inattention/hyperactivity, (b) inattention/hyperactivity would increase risk for disruptive behaviors, and (c) disruptive behaviors would lead to adolescent substance abuse. Participants were 674 children (486 boys) from 321 families in an ongoing, longitudinal high risk study that began when children were three years old. Temperament traits assessed were reactive control, resiliency, and negative emotionality, using examiner ratings on the California Q-Sort. Parent, teacher, and self ratings of inattention/hyperactivity, disruptive behaviors, and substance abuse were also obtained. Low levels of childhood reactive control, but not resiliency or negative emotionality, were associated with adolescent substance abuse, mediated by disruptive behaviors. Using a cascade model, family risk for substance abuse was partially mediated by reactive control, inattention/hyperactivity, and disruptive behavior. Some, but not all, temperament traits in childhood were related to adolescent substance abuse; these effects were mediated via inattentive/hyperactive and disruptive behaviors. PMID:18787942

  2. Prevalence of motor problems in children with attention deficit hyperactivity disorder in Hong Kong.

    PubMed

    Tsui, K W; Lai, Kelly Y C; Lee, Marshall M C; Shea, Caroline K S; Tong, Luke C T

    2016-04-01

    Local data on the occurrence of motor problems in children with attention deficit hyperactivity disorder are not available but an understanding of this important issue may enable better planning of medical services. We aimed to determine the prevalence of motor problems in children with attention deficit hyperactivity disorder in a local population. In this descriptive cross-sectional study, children aged 6 to 9 years diagnosed with attention deficit hyperactivity disorder over a period of 6 months from 1 July to 31 December 2011 were recruited from the Joint Paediatric and Child Psychiatric ADHD Program in New Territories East Cluster in Hong Kong. Movement Assessment Battery for Children and Developmental Coordination Disorder Questionnaire-Chinese version were used to determine the presence of motor problems. Data from 95 participants were included in the final analysis. The number of children who had no, borderline, or definite motor problems was 63, 15, and 17, respectively. It is estimated that up to one third of local children with attention deficit hyperactivity disorder might have developmental coordination disorder. Motor problems are common in local children with attention deficit hyperactivity disorder and figures are comparable with those from other parts of the world. Despite the various limitations of this study, the magnitude of the problem should not be overlooked.

  3. [Teachers and attention deficit and/or hyperactivity disorder: a pilot study on the situation of teachers in Tyrol].

    PubMed

    Plattner, Barbara; Aglan, Anna Zeinab; Juen, Barbara; Conca, Andreas

    2013-01-01

    Given the high prevalence of approximately 5% of Attention Deficit and/or Hyperactivity Disorder in children the level of knowledge of Tyrolean educators at selected educational institutions was examined. As part of the thesis of A. Aglan 170 questionnaires were distributed at selected Tyrolean schools from May to October 2010. The questionnaires were completed voluntarily and anonymously by educators working there and then turned in. The questionnaire consisted of 43 items and was evaluated by means of conventional statistical methods. 98 (58%) of the questionnaires sent out were returned. 93 questionnaires (55%) were evaluated using standard statistical methods. Teachers were well informed about generic aspects of Attention Deficit and/or Hyperactivity Disorder. Knowledge gaps could be identified regarding the underlying causes of the disorder and available treatment options. Teachers demonstrated great willingness to actively cooperate and to learn more about Attention Deficit and/or Hyperactivity Disorder through further education in order to improve the situation of all parties involved. Lack of knowledge was found regarding the subtopics "causes of Attention Deficit and/or Hyperactivity Disorder" and "Treatment Options". The majority of the teachers would appreciate specialized training and is willing to adapt their lessons to the requirements of children, pupils and students affected by Attention Deficit and/or Hyperactivity Disorder.

  4. Speech-language pathology findings in Attention Deficit Hyperactivity Disorder: a systematic literature review.

    PubMed

    Machado-Nascimento, Nárli; Melo E Kümmer, Arthur; Lemos, Stela Maris Aguiar

    2016-01-01

    To systematically review the scientific production on the relationship between Attention Deficit Hyperactivity Disorder (ADHD) and Speech-language Pathology and to methodologically analyze the observational studies on the theme. Systematic review of the literature conducted at the databases Medical Literature Analysis and Retrieval System online (MEDLINE, USA), Literature of Latin America and the Caribbean Health Sciences (LILACS, Brazil) and Spanish Bibliographic Index of Health Sciences (IBECS, Spain) using the descriptors: "Language", "Language Development", "Attention Deficit Hyperactivity Disorder", "ADHD" and "Auditory Perception". Articles published between 2008 and 2013. Inclusion criteria: full articles published in national and international journals from 2008 to 2013. Exclusion criteria: articles not focused on the speech-language pathology alterations present in the attention deficit hyperactivity disorder. The articles were read in full and the data were extracted for characterization of methodology and content. The 23 articles found were separated according to two themes: Speech-language Pathology and Attention Deficit Hyperactivity Disorder. The study of the scientific production revealed that the alterations most commonly discussed were reading disorders and that there are few reports on the relationship between auditory processing and these disorders, as well as on the role of the speech-language pathologist in the evaluation and treatment of children with Attention Deficit Hyperactivity Disorder.

  5. Assisting children with attention deficit hyperactivity disorder to reduce the hyperactive behavior of arbitrary standing in class with a Nintendo Wii remote controller through an active reminder and preferred reward stimulation.

    PubMed

    Shih, Ching-Hsiang; Wang, Shu-Hui; Wang, Yun-Ting

    2014-09-01

    Recent studies in the field of special education have shown that in combination with software technology, high-tech commercial products can be applied as useful assistive technology devices to help people with disabilities. This study extended this concept to turn a Nintendo Wii Remote Controller into a high-performance limb action detector, in order to evaluate whether two students with Attention Deficit Hyperactivity Disorder (ADHD) could reduce their hyperactive behavior through an active reminder and stimulation in the form of the participants' preferred rewards. This study focused on one particular hyperactive behavior common to both students: standing up arbitrarily during class. The active reminder was in the form of vibration feedback provided via the built-in function of the Wii Remote Controller, which was controlled and triggered by a control system to remind participants when they were engaging in standing behavior. This study was performed according to a multiple baseline design across participants. The results showed that both participants significantly improved their control over their hyperactive behavior during the intervention phase, and retained this effective performance in the maintenance phase. The practical and developmental implications of the findings are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Understanding the covariation of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms: A population-based adult twin study.

    PubMed

    Pinto, Rebecca; Monzani, Benedetta; Leckman, James F; Rück, Christian; Serlachius, Eva; Lichtenstein, Paul; Mataix-Cols, David

    2016-10-01

    Chronic tic disorders (TD), attention-deficit/hyperactivity-disorder (ADHD), and obsessive-compulsive disorder (OCD) frequently co-occur in clinical and epidemiological samples. Family studies have found evidence of shared familial transmission between TD and OCD, whereas the familial association between these disorders and ADHD is less clear. This study aimed to investigate to what extent liability of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms is caused by shared or distinct genetic or environmental influences, in a large population-representative sample of Swedish adult twins (n = 21,911). Tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms showed modest, but significant covariation. Model fitting suggested a latent liability factor underlying the three phenotypes. This common factor was relatively heritable, and explained significantly less of the variance of attention-deficit/hyperactivity symptom liability. The majority of genetic variance was specific rather than shared. The greatest proportion of total variance in liability of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms was attributed to specific non-shared environmental influences. Our findings suggest that the co-occurrence of tics and obsessive-compulsive symptoms, and to a lesser extent attention-deficit/hyperactivity symptoms, can be partly explained by shared etiological influences. However, these phenotypes do not appear to be alternative expressions of the same underlying genetic liability. Further research examining sub-dimensions of these phenotypes may serve to further clarify the association between these disorders and identify more genetically homogenous symptom subtypes. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Validity of DSM-IV attention deficit/hyperactivity disorder symptom dimensions and subtypes.

    PubMed

    Willcutt, Erik G; Nigg, Joel T; Pennington, Bruce F; Solanto, Mary V; Rohde, Luis A; Tannock, Rosemary; Loo, Sandra K; Carlson, Caryn L; McBurnett, Keith; Lahey, Benjamin B

    2012-11-01

    Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for attention deficit/hyperactivity disorder (ADHD) specify two dimensions of inattention and hyperactivity-impulsivity symptoms that are used to define three nominal subtypes: predominantly hyperactive-impulsive type (ADHD-H), predominantly inattentive type (ADHD-I), and combined type (ADHD-C). To aid decision making for DSM-5 and other future diagnostic systems, a comprehensive literature review and meta-analysis of 546 studies was completed to evaluate the validity of the DSM-IV model of ADHD. Results indicated that DSM-IV criteria identify individuals with significant and persistent impairment in social, academic, occupational, and adaptive functioning when intelligence, demographic factors, and concurrent psychopathology are controlled. Available data overwhelmingly support the concurrent, predictive, and discriminant validity of the distinction between inattention and hyperactivity-impulsivity symptoms, and indicate that nearly all differences among the nominal subtypes are consistent with the relative levels of inattention and hyperactivity-impulsivity symptoms that define the subtypes. In contrast, the DSM-IV subtype model is compromised by weak evidence for the validity of ADHD-H after first grade, minimal support for the distinction between ADHD-I and ADHD-C in studies of etiological influences, academic and cognitive functioning, and treatment response, and the marked longitudinal instability of all three subtypes. Overall, we conclude that the DSM-IV ADHD subtypes provide a convenient clinical shorthand to describe the functional and behavioral correlates of current levels of inattention and hyperactivity-impulsivity symptoms, but do not identify discrete subgroups with sufficient long-term stability to justify the classification of distinct forms of the disorder. Empirical support is stronger for an alternative model that would replace the subtypes with dimensional modifiers that reflect the number of inattention and hyperactivity-impulsivity symptoms at the time of assessment. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  8. Candidate genetic pathways for attention-deficit/hyperactivity disorder (ADHD) show association to hyperactive/impulsive symptoms in children with ADHD.

    PubMed

    Bralten, Janita; Franke, Barbara; Waldman, Irwin; Rommelse, Nanda; Hartman, Catharina; Asherson, Philip; Banaschewski, Tobias; Ebstein, Richard P; Gill, Michael; Miranda, Ana; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph A; Oosterlaan, Jaap; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; Faraone, Stephen V; Buitelaar, Jan K; Arias-Vásquez, Alejandro

    2013-11-01

    Because multiple genes with small effect sizes are assumed to play a role in attention-deficit/hyperactivity disorder (ADHD) etiology, considering multiple variants within the same analysis likely increases the total explained phenotypic variance, thereby boosting the power of genetic studies. This study investigated whether pathway-based analysis could bring scientists closer to unraveling the biology of ADHD. The pathway was described as a predefined gene selection based on a well-established database or literature data. Common genetic variants in pathways involved in dopamine/norepinephrine and serotonin neurotransmission and genes involved in neuritic outgrowth were investigated in cases from the International Multicentre ADHD Genetics (IMAGE) study. Multivariable analysis was performed to combine the effects of single genetic variants within the pathway genes. Phenotypes were DSM-IV symptom counts for inattention and hyperactivity/impulsivity (n = 871) and symptom severity measured with the Conners Parent (n = 930) and Teacher (n = 916) Rating Scales. Summing genetic effects of common genetic variants within the pathways showed a significant association with hyperactive/impulsive symptoms ((p)empirical = .007) but not with inattentive symptoms ((p)empirical = .73). Analysis of parent-rated Conners hyperactive/impulsive symptom scores validated this result ((p)empirical = .0018). Teacher-rated Conners scores were not associated. Post hoc analyses showed a significant contribution of all pathways to the hyperactive/impulsive symptom domain (dopamine/norepinephrine, (p)empirical = .0004; serotonin, (p)empirical = .0149; neuritic outgrowth, (p)empirical = .0452). The present analysis shows an association between common variants in 3 genetic pathways and the hyperactive/impulsive component of ADHD. This study demonstrates that pathway-based association analyses, using quantitative measurements of ADHD symptom domains, can increase the power of genetic analyses to identify biological risk factors involved in this disorder. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Reduced inattention and hyperactivity and improved cognition after marine oil extract (PCSO-524®) supplementation in children and adolescents with clinical and subclinical symptoms of attention-deficit hyperactivity disorder (ADHD): a randomised, double-blind, placebo-controlled trial.

    PubMed

    Kean, James D; Sarris, Jerome; Scholey, Andrew; Silberstein, Richard; Downey, Luke A; Stough, Con

    2017-02-01

    This study investigated the effects of a marine oil extract (PCSO-524®) on inattention, hyperactivity, mood and cognition in children and adolescents. PCSO-524® is a standardised lipid extract of the New Zealand green-lipped mussel and is an inflammatory modulator that inhibits the 5'-lipoxygenase and cyclooxygenase pathways and decreases concentrations of the pro-inflammatory arachidonic acid (AA). PCSO-524® or a matched placebo was administered for 14 weeks to 144 participants (123 males/21 females; mean age 8.7 years) with high hyperactivity and inattention in a randomised, double-blind, placebo-controlled study. The primary outcome was the Conners Parent Rating Scale assessing parental reports of behavioural problems. Secondary outcomes assessed changes in cognition and mood. The results of the present study did not support the hypothesis that PCSO-524® improves parental reports of hyperactivity, inattention and impulsivity in children ages 6 to 14 years over placebo. Repeated measures ANOVA on post hoc subsample analysis indicated significant improvements in hyperactivity (p = 0.04), attention (p = 0.02), learning (p = 0.05) and probability of ADHD (p = 0.04) with a medium to large average effect size (d = 0.65) in those children who did not meet criteria for combined hyperactivity and inattention. Furthermore, significant improvements in the PCSO-524® group were indicated in a whole sample repeated measures ANCOVA on recognition memory between baseline and week 8 over placebo (p = 0.02, d = 0.56); this difference was not sustained at week 14. The results presented indicate that PCSO-524® may be beneficial in reducing levels of hyperactivity and inattention in a population of children with clinical and subclinical symptoms of ADHD.

  10. B6eGFPChAT mice overexpressing the vesicular acetylcholine transporter exhibit spontaneous hypoactivity and enhanced exploration in novel environments

    PubMed Central

    Nagy, Paul M; Aubert, Isabelle

    2013-01-01

    Cholinergic innervation is extensive throughout the central and peripheral nervous systems. Among its many roles, the neurotransmitter acetylcholine (ACh) contributes to the regulation of motor function, locomotion, and exploration. Cholinergic deficits and replacement strategies have been investigated in neurodegenerative disorders, particularly in cases of Alzheimer's disease (AD). Focus has been on blocking acetylcholinesterase (AChE) and enhancing ACh synthesis to improve cholinergic neurotransmission. As a first step in evaluating the physiological effects of enhanced cholinergic function through the upregulation of the vesicular acetylcholine transporter (VAChT), we used the hypercholinergic B6eGFPChAT congenic mouse model that has been shown to contain multiple VAChT gene copies. Analysis of biochemical and behavioral paradigms suggest that modest increases in VAChT expression can have a significant effect on spontaneous locomotion, reaction to novel stimuli, and the adaptation to novel environments. These observations support the potential of VAChT as a therapeutic target to enhance cholinergic tone, thereby decreasing spontaneous hyperactivity and increasing exploration in novel environments. PMID:24381809

  11. Prevalence of Hyperactivity-Impulsivity and Inattention Among Canadian Children: Findings from the First Data Collection Cycle (1994-1995) of the National Longitudinal Survey of Children and Youth. Final Report

    ERIC Educational Resources Information Center

    Romano, Elisa; Baillargeon, Raymond H.; Tremblay, Richard E.

    2002-01-01

    Hyperactivity, impulsivity, and inattention are among the most common behaviour problems in children. The aim of this study was to estimate the prevalence of hyperactivity-impulsivity and inattention in the Canadian population of 2-11-year-old girls and boys, using data from the first National Longitudinal Survey of Children and Youth (NLSCY)…

  12. Hyperactivity, unexplained speech delay, and coarse facies--is it Sanfilippo syndrome?

    PubMed

    Saini, Arushi Gahlot; Singhi, Pratibha; Sahu, Jitendra Kumar; Ganesan, Saptharishi L; Vyas, Sameer; Rao, Sandeep; Sachdeva, Man Updesh Singh

    2014-08-01

    Mucopolysaccharidosis-IIIB or Sanfilippo-B syndrome is caused by deficiency of lysosomal α-N-acetylglucosaminidase that leads to accumulation of heparan-sulphate and degeneration of central nervous system with progressive dementia, hyperactivity, and aggressive behavior. Mucopolysaccharidosis-III remains underdiagnosed as a cause of developmental delay and hyperactivity both in adults and children because in contrast to other mucopolysaccharidoses, they have little somatic disease, coarse facial features, hepatosplenomegaly or skeletal changes, and a high incidence of false-negative results on the urinary screening tests. We describe here a girl with the classic phenotype of mucopolysaccharidosis-IIIB to alert pediatricians to the possibility of this disorder in children with unexplained speech delay and hyperactivity and prevent unnecessary investigations. © The Author(s) 2013.

  13. ADHD

    MedlinePlus

    ADHD Attention Deficit/Hyperactivity Disorder Fact Sheet Learn about ADHD and what to do if you have concerns. What is ADHD? Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioral ...

  14. Nutrition and Hyperactivity.

    ERIC Educational Resources Information Center

    Hammond, Janice M.

    1980-01-01

    Reviews information suggesting that chemical additives in food can cause hyperactivity and learning problems in young children. Suggests approaches that teachers can take to improve the diet of their pupils. (GC)

  15. Do early internalizing and externalizing problems predict later irritability in adolescents with attention-deficit/hyperactivity disorder?

    PubMed

    Mulraney, Melissa; Zendarski, Nardia; Mensah, Fiona; Hiscock, Harriet; Sciberras, Emma

    2017-04-01

    Irritable mood is common in children with attention-deficit/hyperactivity disorder. Research to date has primarily comprised cross-sectional studies; thus, little is known about the antecedents of irritability. Furthermore, existing cross-sectional studies generally focus on the association between irritability and comorbidities and do not examine broader aspects of functioning. Finally, previous research has neglected to include child-report of irritability. This study aimed to address these gaps using data from a longitudinal study of children with attention-deficit/hyperactivity disorder. Children aged 5-13 years (mean = 10.2; standard deviation = 1.9) with attention-deficit/hyperactivity disorder were recruited from pediatric practices across Victoria, Australia. This study reports on those who had reached adolescence (12 years or older, mean = 13.8; standard deviation = 1.2) at the 3-year follow-up ( n = 140). Internalizing and externalizing problems were measured using the Strengths and Difficulties Questionnaire. At follow-up, parent-reported and adolescent self-reported irritability was assessed using the Affective Reactivity Index. Parent and adolescent outcomes measured at follow-up included attention-deficit/hyperactivity disorder symptom severity, sleep, behavior and parent mental health. Children with externalizing problems at age 10 had higher parent-reported irritability (β = 0.31, 95% confidence interval = [0.17,-0.45], p = 0.001) in adolescence. Cross-sectional analyses found that irritability was associated with increased attention-deficit/hyperactivity disorder symptom severity and sleep problems; poorer emotional, behavioral and social functioning; and poorer parent mental health. Our findings highlight the importance of assessing for and managing early conduct problems in children with attention-deficit/hyperactivity disorder, as these predict ongoing irritability which, in turn, is associated with poorer functioning across a number of domains.

  16. The effects of a double blind, placebo controlled, artificial food colourings and benzoate preservative challenge on hyperactivity in a general population sample of preschool children

    PubMed Central

    Bateman, B; Warner, J; Hutchinson, E; Dean, T; Rowlandson, P; Gant, C; Grundy, J; Fitzgerald, C; Stevenson, J

    2004-01-01

    Aims: To determine whether artificial food colourings and a preservative in the diet of 3 year old children in the general population influence hyperactive behaviour. Methods: A sample of 1873 children were screened in their fourth year for the presence of hyperactivity at baseline (HA), of whom 1246 had skin prick tests to identify atopy (AT). Children were selected to form the following groups: HA/AT, not-HA/AT, HA/not-AT, and not-HA/not-AT (n = 277). After baseline assessment, children were subjected to a diet eliminating artificial colourings and benzoate preservatives for one week; in the subsequent three week within subject double blind crossover study they received, in random order, periods of dietary challenge with a drink containing artificial colourings (20 mg daily) and sodium benzoate (45 mg daily) (active period), or a placebo mixture, supplementary to their diet. Behaviour was assessed by a tester blind to dietary status and by parents' ratings. Results: There were significant reductions in hyperactive behaviour during the withdrawal phase. Furthermore, there were significantly greater increases in hyperactive behaviour during the active than the placebo period based on parental reports. These effects were not influenced by the presence or absence of hyperactivity, nor by the presence or absence of atopy. There were no significant differences detected based on objective testing in the clinic. Conclusions: There is a general adverse effect of artificial food colouring and benzoate preservatives on the behaviour of 3 year old children which is detectable by parents but not by a simple clinic assessment. Subgroups are not made more vulnerable to this effect by their prior levels of hyperactivity or by atopy. PMID:15155391

  17. Ice-binding proteins that accumulate on different ice crystal planes produce distinct thermal hysteresis dynamics

    PubMed Central

    Drori, Ran; Celik, Yeliz; Davies, Peter L.; Braslavsky, Ido

    2014-01-01

    Ice-binding proteins that aid the survival of freeze-avoiding, cold-adapted organisms by inhibiting the growth of endogenous ice crystals are called antifreeze proteins (AFPs). The binding of AFPs to ice causes a separation between the melting point and the freezing point of the ice crystal (thermal hysteresis, TH). TH produced by hyperactive AFPs is an order of magnitude higher than that produced by a typical fish AFP. The basis for this difference in activity remains unclear. Here, we have compared the time dependence of TH activity for both hyperactive and moderately active AFPs using a custom-made nanolitre osmometer and a novel microfluidics system. We found that the TH activities of hyperactive AFPs were time-dependent, and that the TH activity of a moderate AFP was almost insensitive to time. Fluorescence microscopy measurement revealed that despite their higher TH activity, hyperactive AFPs from two insects (moth and beetle) took far longer to accumulate on the ice surface than did a moderately active fish AFP. An ice-binding protein from a bacterium that functions as an ice adhesin rather than as an antifreeze had intermediate TH properties. Nevertheless, the accumulation of this ice adhesion protein and the two hyperactive AFPs on the basal plane of ice is distinct and extensive, but not detectable for moderately active AFPs. Basal ice plane binding is the distinguishing feature of antifreeze hyperactivity, which is not strictly needed in fish that require only approximately 1°C of TH. Here, we found a correlation between the accumulation kinetics of the hyperactive AFP at the basal plane and the time sensitivity of the measured TH. PMID:25008081

  18. Validity of DSM-IV attention–deficit/hyperactivity disorder symptom dimensions and subtypes

    PubMed Central

    Willcutt, Erik G.; Nigg, Joel T.; Pennington, Bruce F.; Solanto, Mary V.; Rohde, Luis A.; Tannock, Rosemary; Loo, Sandra K.; Carlson, Caryn L.; McBurnett, Keith; Lahey, Benjamin B.

    2013-01-01

    DSM-IV criteria for ADHD specify two dimensions of inattention and hyperactivity-impulsivity symptoms that are used to define three nominal subtypes: predominantly hyperactive-impulsive type (ADHD-H), predominantly inattentive type (ADHD-I), and combined type (ADHD-C). To aid decision-making for DSM-5 and other future diagnostic systems, a comprehensive literature review and meta-analysis of 546 studies was completed to evaluate the validity of the DSM-IV model of ADHD. Results indicated that DSM-IV criteria identify individuals with significant and persistent impairment in social, academic, occupational, and adaptive functioning when intelligence, demographic factors, and concurrent psychopathology are controlled. Available data overwhelmingly support the concurrent, predictive, and discriminant validity of the distinction between inattention and hyperactivity-impulsivity symptoms, and indicate that nearly all differences among the nominal subtypes are consistent with the relative levels of inattention and hyperactivity-impulsivity symptoms that define the subtypes. In contrast, the validity of the DSM-IV subtype model is compromised by weak evidence for the validity of ADHD-H after first grade, minimal support for the distinction between ADHD-I and ADHD-C in studies of etiological influences, academic and cognitive functioning, and treatment response, and the marked longitudinal instability of all three subtypes. Overall, it is concluded that the DSM-IV ADHD subtypes provide a convenient clinical shorthand to describe the functional and behavioral correlates of current levels of inattention and hyperactivity-impulsivity symptoms, but do not identify discrete subgroups with sufficient long-term stability to justify the classification of distinct forms of the disorder. Empirical support is stronger for an alternative model that would replace the subtypes with dimensional modifiers that reflect the number of inattention and hyperactivity-impulsivity symptoms at the time of assessment. PMID:22612200

  19. Increase or Decrease of fMRI Activity in Adult Attention Deficit/ Hyperactivity Disorder: Does It Depend on Task Difficulty?

    PubMed

    Biehl, Stefanie C; Merz, Christian J; Dresler, Thomas; Heupel, Julia; Reichert, Susanne; Jacob, Christian P; Deckert, Jürgen; Herrmann, Martin J

    2016-05-27

    Attention deficit/hyperactivity disorder has been shown to affect working memory, and fMRI studies in children and adolescents with attention deficit/hyperactivity disorder report hypoactivation in task-related attentional networks. However, studies with adult attention deficit/hyperactivity disorder patients addressing this issue as well as the effects of clinically valid methylphenidate treatment are scarce. This study contributes to closing this gap. Thirty-five adult patients were randomized to 6 weeks of double-blind placebo or methylphenidate treatment. Patients completed an fMRI n-back working memory task both before and after the assigned treatment, and matched healthy controls were tested and compared to the untreated patients. There were no whole-brain differences between any of the groups. However, when specified regions of interest were investigated, the patient group showed enhanced BOLD responses in dorsal and ventral areas before treatment. This increase was correlated with performance across all participants and with attention deficit/hyperactivity disorder symptoms in the patient group. Furthermore, we found an effect of treatment in the right superior frontal gyrus, with methylphenidate-treated patients exhibiting increased activation, which was absent in the placebo-treated patients. Our results indicate distinct activation differences between untreated adult attention deficit/hyperactivity disorder patients and matched healthy controls during a working memory task. These differences might reflect compensatory efforts by the patients, who are performing at the same level as the healthy controls. We furthermore found a positive effect of methylphenidate on the activation of a frontal region of interest. These observations contribute to a more thorough understanding of adult attention deficit/hyperactivity disorder and provide impulses for the evaluation of therapy-related changes. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  20. [Classification of Children with Attention-Deficit/Hyperactivity Disorder and Typically Developing Children Based on Electroencephalogram Principal Component Analysis and k-Nearest Neighbor].

    PubMed

    Yang, Jiaojiao; Guo, Qian; Li, Wenjie; Wang, Suhong; Zou, Ling

    2016-04-01

    This paper aims to assist the individual clinical diagnosis of children with attention-deficit/hyperactivity disorder using electroencephalogram signal detection method.Firstly,in our experiments,we obtained and studied the electroencephalogram signals from fourteen attention-deficit/hyperactivity disorder children and sixteen typically developing children during the classic interference control task of Simon-spatial Stroop,and we completed electroencephalogram data preprocessing including filtering,segmentation,removal of artifacts and so on.Secondly,we selected the subset electroencephalogram electrodes using principal component analysis(PCA)method,and we collected the common channels of the optimal electrodes which occurrence rates were more than 90%in each kind of stimulation.We then extracted the latency(200~450ms)mean amplitude features of the common electrodes.Finally,we used the k-nearest neighbor(KNN)classifier based on Euclidean distance and the support vector machine(SVM)classifier based on radial basis kernel function to classify.From the experiment,at the same kind of interference control task,the attention-deficit/hyperactivity disorder children showed lower correct response rates and longer reaction time.The N2 emerged in prefrontal cortex while P2 presented in the inferior parietal area when all kinds of stimuli demonstrated.Meanwhile,the children with attention-deficit/hyperactivity disorder exhibited markedly reduced N2 and P2amplitude compared to typically developing children.KNN resulted in better classification accuracy than SVM classifier,and the best classification rate was 89.29%in StI task.The results showed that the electroencephalogram signals were different in the brain regions of prefrontal cortex and inferior parietal cortex between attention-deficit/hyperactivity disorder and typically developing children during the interference control task,which provided a scientific basis for the clinical diagnosis of attention-deficit/hyperactivity disorder individuals.

  1. A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831)

    PubMed Central

    Kean, James D.; Kaufman, Jordy; Lomas, Justine; Goh, Antionette; White, David; Simpson, David; Scholey, Andrew; Singh, Hemant; Sarris, Jerome; Zangara, Andrea; Stough, Con

    2015-01-01

    Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6–14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners’ Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831. PMID:26633481

  2. Attention deficit/hyperactivity disorder blame game: a study on the positioning of professionals, teachers and parents.

    PubMed

    Frigerio, Alessandra; Montali, Lorenzo; Fine, Michelle

    2013-11-01

    Attention deficit/hyperactivity disorder is currently the most debated childhood psychiatric diagnosis. Given the circulation of competing perspectives about the 'real' causes of children's behaviour and the 'best' way to treat them, we aim to analyse the interactions of the central social actors' discourses about attention deficit/hyperactivity disorder children within the Italian context. Adopting a multi-method approach, we focus on the polyphonic chorus of voices surrounding the child, studying the discourses of mental health professionals, teachers and parents. These actors are representative of three contexts that are deeply engaged with attention deficit/hyperactivity disorder: medical institutions, schools and families. Our theoretical and methodological approach integrates positioning theory, the Bakhtinian notion of dialogical thinking and discourse analysis to study stakeholders' reflexive and interactive positioning in terms of the attribution of rights, duties, responsibilities and power issues. The results show that mutual blame is a constitutive element of relational dynamics among the key adults surrounding attention deficit/hyperactivity disorder children. We argue that these conflicting relationships are not merely related to the debate regarding the validity of the attention deficit/hyperactivity disorder diagnosis. Rather, the mutual blame centres on questions of compliance, recognition of authority and morality. Through the blame game, adults negotiate their own and others' subjectivity in ways that simultaneously (re)produce power relationships and resistance efforts.

  3. A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831).

    PubMed

    Kean, James D; Kaufman, Jordy; Lomas, Justine; Goh, Antionette; White, David; Simpson, David; Scholey, Andrew; Singh, Hemant; Sarris, Jerome; Zangara, Andrea; Stough, Con

    2015-12-02

    Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6-14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners' Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831.

  4. Hyperactivity in the Gunn rat model of neonatal jaundice: age-related attenuation and emergence of gait deficits

    PubMed Central

    Stanford, John A.; Shuler, Jeffrey M.; Fowler, Stephen C.; Stanford, Kimberly G.; Ma, Delin; Bittel, Douglas C.; Le Pichon, Jean-Baptiste; Shapiro, Steven M.

    2014-01-01

    Background Neonatal jaundice resulting from elevated unconjugated bilirubin (UCB) occurs in 60–80% of newborn infants. Although mild jaundice is generally considered harmless, little is known about its long-term consequences. Recent studies have linked mild bilirubin-induced neurological dysfunction (BIND) with a range of neurological syndromes, including attention deficit-hyperactivity disorder. The goal of this study was to measure BIND across the lifespan in the Gunn rat model of BIND. Methods Using a sensitive force plate actometer, we measured locomotor activity and gait in jaundiced (jj) Gunn rats versus their non-jaundiced (Nj) littermates. Data were analyzed for young adult (3–4 months), early middle-aged (9–10 months), and late middle-aged (17–20 months) male rats. Results jj rats exhibited lower body weights at all ages and a hyperactivity that resolved at 17–20 months of age. Increased propulsive force and gait velocity accompanied hyperactivity during locomotor bouts at 9–10 months in jj rats. Stride length did not differ between the two groups at this age. Hyperactivity normalized and gait deficits, including decreased stride length, propulsive force, and gait velocity, emerged in the 17–20-month-old jj rats. Conclusions These results demonstrate that, in aging, hyperactivity decreases with the onset of gait deficits in the Gunn rat model of BIND. PMID:25518009

  5. Memory-guided saccades in youth-onset psychosis and attention deficit hyperactivity disorder (ADHD).

    PubMed

    White, Tonya; Mous, Sabine; Karatekin, Canan

    2014-08-01

    Working memory deficits have been shown to be present in children and adolescents with schizophrenia and attention deficit hyperactivity disorder. Considering the differences in clinical characteristics between these disorders, it was the goal of this study to assess differences in the specific components of working memory in children and adolescents with psychosis and attention deficit hyperactivity disorder. Children and adolescents (age range 8-20 years) with either a non-affective psychotic disorder (n = 25), attention deficit hyperactivity disorder (n = 33) and controls (n = 58) were administered an oculomotor delayed-response task using both a recall and a control condition. Memory-guided saccades were measured during delay periods of 2, 8 and 20 s. Although both clinical groups were less accurate than controls, there was no evidence of a disproportionate impairment in recall. In addition, there was no evidence of a delay-dependent impairment in psychosis; however, there was a delay-dependent impairment in attention deficit hyperactivity disorder when corrective saccades were included. Speed of information processing was correlated with distance errors in psychosis, suggesting that speed of encoding the stimulus location may have constrained the accuracy of the saccades. Our findings support impairments during encoding in the psychosis group and a delay-dependent deficit in the attention deficit hyperactivity disorder group. © 2013 Wiley Publishing Asia Pty Ltd.

  6. Prevalence of parent-rated attention deficit hyperactivity disorder and associated parent-related factors in primary school children of Navi Mumbai--a school based study.

    PubMed

    Ajinkya, Shaunak; Kaur, Darpan; Gursale, Akshay; Jadhav, Pradeep

    2013-03-01

    To study the prevalence of parent-rated attention deficit hyperactivity disorder and associated parent-related factors in primary school children of Navi Mumbai. One hundred twenty two children including both boys and girls aged between 6 y and 11 y were selected from a school at Navi Mumbai and their parents were given the National Innovative for Children's Healthcare Quality (NICHQ) Vanderbilt Assessment Scale to be filled and returned, which was subsequently analyzed using SPSS (version 16). The prevalence of attention deficit hyperactivity disorder was 12.3 % with boy to girl ratio of 3:2. It was more prevalent in nuclear type of family and in families where a single parent was working especially where the father was the sole breadwinner and doing semi-skilled or unskilled type of work. No significant relation was found between the numbers of work-related hours when parents were away from children and attention deficit hyperactivity disorder. Attention deficit hyperactivity disorder is prevalent in the primary school-going population of Navi Mumbai, especially in boys. The increased prevalence in nuclear families and families with single working parent should further be explored. Further studies with larger sample size and longer period of follow up may be recommended. The study also recommends screening of school children for symptoms of attention deficit hyperactivity disorder (ADHD) for early diagnosis and treatment.

  7. Working memory arrest in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder: results from a 2-year longitudinal study.

    PubMed

    Andersen, Per N; Skogli, Erik W; Hovik, Kjell T; Geurts, Hilde; Egeland, Jens; Øie, Merete

    2015-05-01

    The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically developing children (age 9-16 years) were included at baseline and followed up approximately 25 months later. The children were given a letter/number sequencing task to assess verbal working memory. The performance of children with high-functioning autism on verbal working memory did not improve after 2 years, while improvement was observed in children with attention-deficit/hyperactivity disorder and typically developing children. The results indicate a different developmental trajectory for verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. More research is needed to construct a developmental framework more suitable for children with autism spectrum disorder. © The Author(s) 2014.

  8. Early Visual Foraging in Relationship to Familial Risk for Autism and Hyperactivity/Inattention.

    PubMed

    Gliga, Teodora; Smith, Tim J; Likely, Noreen; Charman, Tony; Johnson, Mark H

    2015-12-04

    Information foraging is atypical in both autism spectrum disorders (ASDs) and ADHD; however, while ASD is associated with restricted exploration and preference for sameness, ADHD is characterized by hyperactivity and increased novelty seeking. Here, we ask whether similar biases are present in visual foraging in younger siblings of children with a diagnosis of ASD with or without additional high levels of hyperactivity and inattention. Fifty-four low-risk controls (LR) and 50 high-risk siblings (HR) took part in an eye-tracking study at 8 and 14 months and at 3 years of age. At 8 months, siblings of children with ASD and low levels of hyperactivity/inattention (HR/ASD-HI) were more likely to return to previously visited areas in the visual scene than were LR and siblings of children with ASD and high levels of hyperactivity/inattention (HR/ASD+HI). We show that visual foraging is atypical in infants at-risk for ASD. We also reveal a paradoxical effect, in that additional family risk for ADHD core symptoms mitigates the effect of ASD risk on visual information foraging. © The Author(s) 2015.

  9. Guanfacine Use in Children With Down Syndrome and Comorbid Attention-Deficit Hyperactivity Disorder (ADHD) With Disruptive Behaviors.

    PubMed

    Capone, George T; Brecher, Liza; Bay, Mihee

    2016-07-01

    The purpose of this study was to characterize children with Down syndrome and attention-deficit hyperactivity disorder (ADHD) with disruptive behaviors using the Aberrant Behavior Checklist (ABC), and to measure the treatment effects of guanfacine on maladaptive behaviors. Subjects were enrolled from a group of outpatients who visited our clinic between 2002 and 2007. Subjects (N = 23) were children with Down syndrome ages 4 to 12 years (mean 7.4 ± 4.1), who met criteria for ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition The Aberrant Behavior Checklist Irritability and Hyperactivity subscales each showed a significant decrease (P < .0001) at follow-up. The mean decline on Hyperactivity was 25% (-7.8 points), and for Irritability, 25% (-3.5 points). The mean composite score also declined by 24% (-12 points). Effect size differences on Irritability were moderate, whereas differences on Hyperactivity and composite score appeared large. Clinically important target behaviors were reduced. Medication was generally well tolerated and the incidence of treatment emergent side effects remained low. © The Author(s) 2016.

  10. Phenotypic and genetic associations between reading and attention-deficit/hyperactivity disorder dimensions in adolescence.

    PubMed

    Plourde, Vickie; Boivin, Michel; Brendgen, Mara; Vitaro, Frank; Dionne, Ginette

    2017-10-01

    Multiple studies have shown that reading abilities and attention-deficit/hyperactivity disorder symptoms, mainly inattention symptoms, are phenotypically and genetically associated during childhood. However, few studies have looked at these associations during adolescence to investigate possible developmental changes. The aim of the study is to examine the genetic and environmental etiology of the associations between inattention and hyperactivity reported by parents, and reading accuracy, reading speed, and word reading in a population-based twin sample (Quebec Newborn Twin Study). Participants were between 14 and 15 years of age at the time of testing (N = 668-837). Phenotypic results showed that when nonverbal and verbal abilities were controlled, inattention, but not hyperactivity/impulsivity, was a modest and significant predictor of reading accuracy, reading speed, and word reading. The associations between inattention and all reading abilities were partly explained by genetic and unique environmental factors. However, the genetic correlations were no longer significant after controlling for verbal abilities. In midadolescence, inattention is the attention-deficit/hyperactivity disorder dimension associated with reading abilities, but they could also share genetic factors with general verbal skills.

  11. Antisocial violent offenders with attention deficit hyperactivity disorder demonstrate akathisia-like hyperactivity in three-channel actometry.

    PubMed

    Tuisku, Katinka; Virkkunen, Matti; Holi, Matti; Lauerma, Hannu; Naukkarinen, Hannu; Rimon, Ranan; Wahlbeck, Kristian

    2003-01-01

    Actometry enables quantitative and qualitative analysis of various hyperactivity disorders. Antisocial violent offenders have demonstrated diurnal increases in motor activity that may be related to attention deficit hyperactivity disorder (ADHD) that often precedes antisocial development. Motor restlessness in ADHD has common features with neuroleptic-induced akathisia. In this study, three-channel actometry was used to compare 15 antisocial violent offenders who had a history of ADHD with 15 healthy control subjects and 10 akathisia patients. The Barnes Akathisia Rating Scale (BARS) was used for clinical evaluation of akathisia symptoms. Ankle movement indices and the ankle-waist ratio differentiated the antisocial patients from the healthy controls significantly, with no overlap, and the same parameters expectedly differentiated the akathisia patients from the healthy controls. The repetitive, rhythmic pattern of akathisia was found in 13 of the 15 antisocial patients. Nine of the antisocial patients scored 2 or 3 (mild to moderate akathisia) on the BARS. Thus, the motor hyperactivity of antisocial ADHD patients has common features with mild akathisia. This may be due to a common hypodopaminergic etiology of ADHD and akathisia.

  12. Successful child psychotherapy of attention deficit/hyperactive disorder: an agitated depression explanation.

    PubMed

    Seitler, Burton Norman

    2008-09-01

    Science tries to explain phenomena in ways that are demonstrable and replicable to develop logical, coherent, parsimonious, and predictive theoretical systems. Yet hyperactive children are given stimulants to "calm" them down, despite the fact that science would predict stimulants would increase hyperactivity. Bradley (1937, 1950) observed that half of the behavior-problem children to whom he administered a stimulant for one week became subdued. He called this finding paradoxical, speculating that inhibitory centers of the central nervous system were stimulated. While Bradley's assertion of a paradoxical reverse effect in children may be an empirical observation, it is not an explanation. The Attention Deficit/Hyperactive Disorder (ADHD) is inferred to exist from hyperactive behavior, which in turn, is inferred to be neurological in origin, a circular argument. An inevitable consequence of the belief in the hypothetical neurological etiology of ADHD is that children are typically given stimulants. Using the case of a seven-year old child, described as experiencing ADHD, who was treated successfully without medication as an illustration, the author provides an alternative, more parsimonious explanation of the etiology, suggesting that ADHD is related to agitated depression.

  13. Attention Deficit Hyperactivity Disorder

    MedlinePlus

    ... finish things? If so, your child may have attention deficit hyperactivity disorder (ADHD). Nearly everyone shows some of these behaviors at times, but ADHD lasts more than 6 months and causes problems ...

  14. Blood-Bourne MicroRNA Biomarker Evaluation in Attention-Deficit/Hyperactivity Disorder of Han Chinese Individuals: An Exploratory Study.

    PubMed

    Wang, Liang-Jen; Li, Sung-Chou; Lee, Min-Jing; Chou, Miao-Chun; Chou, Wen-Jiun; Lee, Sheng-Yu; Hsu, Chih-Wei; Huang, Lien-Hung; Kuo, Ho-Chang

    2018-01-01

    Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly genetic neurodevelopmental disorder, and its dysregulation of gene expression involves microRNAs (miRNAs). The purpose of this study was to identify potential miRNAs biomarkers and then use these biomarkers to establish a diagnostic panel for ADHD. Design and methods: RNA samples from white blood cells (WBCs) of five ADHD patients and five healthy controls were combined to create one pooled patient library and one control library. We identified 20 candidate miRNAs with the next-generation sequencing (NGS) technique (Illumina). Blood samples were then collected from a Training Set (68 patients and 54 controls) and a Testing Set (20 patients and 20 controls) to identify the expression profiles of these miRNAs with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). We used receiver operating characteristic (ROC) curves and the area under the curve (AUC) to evaluate both the specificity and sensitivity of the probability score yielded by the support vector machine (SVM) model. Results: We identified 13 miRNAs as potential ADHD biomarkers. The ΔCt values of these miRNAs in the Training Set were integrated to create a biomarker model using the SVM algorithm, which demonstrated good validity in differentiating ADHD patients from control subjects (sensitivity: 86.8%, specificity: 88.9%, AUC: 0.94, p < 0.001). The results of the blind testing showed that 85% of the subjects in the Testing Set were correctly classified using the SVM model alignment (AUC: 0.91, p < 0.001). The discriminative validity is not influenced by patients' age or gender, indicating both the robustness and the reliability of the SVM classification model. Conclusion: As measured in peripheral blood, miRNA-based biomarkers can aid in the differentiation of ADHD in clinical settings. Additional studies are needed in the future to clarify the ADHD-associated gene functions and biological mechanisms modulated by miRNAs.

  15. Significant association between rare IPO11-HTR1A variants and attention deficit hyperactivity disorder in Caucasians

    PubMed Central

    Zuo, Lingjun; Saba, Laura; Lin, Xiandong; Tan, Yunlong; Wang, Kesheng; Krystal, John H.; Tabakoff, Boris; Luo, Xingguang

    2016-01-01

    Objective We comprehensively examined the rare variants in the IPO11-HTR1A region to explore their roles in neuropsychiatric disorders. Method Five hundred seventy-three to 1,181 rare SNPs in subjects of European descent and 1,234-2,529 SNPs in subjects of African descent (0 < minor allele frequency (MAF) < 0.05) were analyzed in a total of 49,268 subjects in 21 independent cohorts with 11 different neuropsychiatric disorders. Associations between rare variant constellations and diseases and associations between individual rare variants and diseases were tested. RNA expression changes of this region were also explored. Results We identified a rare variant constellation across the entire IPO11-HTR1A region that was associated with attention deficit hyperactivity disorder (ADHD) in Caucasians (T5: p=7.9×10−31; Fp: p=1.3×10−32), but not with any other disorder examined; association signals mainly came from IPO11 (T5: p=3.6×10−10; Fp: p=3.2×10−10) and the intergenic region between IPO11 and HTR1A (T5: p=4.1×10−30; Fp: p=5.4×10−32). One association between ADHD and an intergenic rare variant, i.e., rs10042956, exhibited region- and cohort-wide significance (p=5.2×10−6) and survived correction for false discovery rate (q=0.006). Cis-eQTL analysis showed that, 29 among the 41 SNPs within or around IPO11 had replicable significant regulatory effects on IPO11 exon expression (1.5×10−17≤p<0.002) in human brain or peripheral blood mononuclear cell tissues. Conclusion We concluded that IPO11-HTR1A was a significant risk gene region for ADHD in Caucasians. PMID:26079129

  16. Effect of Methylphenidate on Cardiorespiratory Responses in Hyperactive Children

    ERIC Educational Resources Information Center

    Boileau, Richard A.; And Others

    1976-01-01

    Recognition by the physical education teacher that the cardiovascular dynamics of the hyperactive child are augmented during methylphenidate (Ritalin) medication is warranted when planning strenuous physical activity. (JD)

  17. Treatment of the Hyperactive Child

    ERIC Educational Resources Information Center

    Wunderlich, Ray C.

    1973-01-01

    Described individually are the following forms of medical treatment for the hyperactive child: stimulants, tranquilizers, megavitamins, corticosteroids, antihistamines, anticonvulsants, food elimination, air filtration, allergic desensitization, perceptual motor training, and behavioral counseling. (DB)

  18. Oxidative Stress and Erythrocyte Membrane Alterations in Children with Autism: Correlation with Clinical Features

    PubMed Central

    Visconti, Paola; Bolotta, Alessandra; Ferreri, Carla; Gobbi, Giuseppe; Malisardi, Gemma; Manfredini, Stefano; Marini, Marina; Nanetti, Laura; Pipitone, Emanuela; Raffaelli, Francesca; Resca, Federica; Mazzanti, Laura

    2013-01-01

    It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na+/K+-ATPase activity (−66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-ω3 with a consequent increase in ω6/ω3 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD. PMID:23840462

  19. Bladder pain induced by prolonged peripheral alpha 1A adrenoceptor stimulation involves the enhancement of transient receptor potential vanilloid 1 activity and an increase of urothelial adenosine triphosphate release.

    PubMed

    Matos, R; Cordeiro, J M; Coelho, A; Ferreira, S; Silva, C; Igawa, Y; Cruz, F; Charrua, A

    2016-12-01

    Pathophysiological mechanisms of chronic visceral pain (CVP) are unknown. This study explores the association between the sympathetic system and bladder nociceptors activity by testing the effect of a prolonged adrenergic stimulation on transient receptor potential vanilloid 1 (TRPV1) activity and on urothelial adenosine triphosphate (ATP) release. Female Wistar rats received saline, phenylephrine (PHE), PHE + silodosin, PHE + naftopidil or PHE + prazosin. TRPV1 knockout and wild-type mice received saline or PHE. Visceral pain behaviour tests were performed before and after treatment. Cystometry was performed, during saline and capsaicin infusion. Fos immunoreactivity was assessed in L6 spinal cord segment. Human urothelial ATP release induced by mechanical and thermal stimulation was evaluated. Subcutaneous, but not intrathecal, PHE administration induced pain, which was reversed by silodosin, a selective alpha 1A adrenoceptor antagonist, but not by naftopidil, a relatively selective antagonist for alpha 1D adrenoceptor. Silodosin also reversed PHE-induced bladder hyperactivity and L6 spinal cord Fos expression. Thus, in subsequent experiments, only silodosin was used. Wild-type, but not TRPV1 knockout, mice exhibited phenylephrine-induced pain. Capsaicin induced a greater increase in voiding contractions in PHE-treated rats than in control animals, and silodosin reversed this effect. When treated with PHE, ATP release from human urothelial cells was enhanced either by mechanical stimulation or by lowering the thermal threshold of urothelial TRPV1, which becomes abnormally responsive at body temperature. This study suggests that the activation of peripheral alpha 1A adrenoceptors induces CVP, probably through its interaction with TRPV1 and ATP release. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  20. Neutrophils in chronic and aggressive periodontitis in interaction with Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans

    PubMed Central

    Guentsch, Arndt; Puklo, Magdalena; Preshaw, Philip M.; Glockmann, Eike; Pfister, Wolfgang; Potempa, Jan; Eick, Sigrun

    2014-01-01

    AIM The aim of this in vitro study was to study phagocytosis and killing of Porphyromonas gingivalis ATCC 33277 and Aggregatibacter actinomycetemcomitans Y4 by peripheral blood PMNs taken from aggressive and chronic periodontitis patients. Also, the release of reactive oxygen species (ROS) and human neutrophil elastase (HNE) upon the interaction of PMNs with bacteria was measured. METHODS Peripheral blood PMNs obtained from 12 chronic periodontitis patients, 6 aggressive periodontitis patients and 12 healthy controls were exposed to Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans following opsonisation of the bacteria using the patient’s own serum. Phagocytosis and killing of the bacteria as well as the extracellular HNE activity were quantified for up to 2 hours. The total amount and the extracellular release of ROS were measured by luminol and isoluminol dependent chemiluminescence. RESULTS PMNs from chronic (62.16 ± 19.39 %) and aggressive periodontitis (43.26 ± 26.63 %) patients phagocytosed more P. gingivalis than the healthy controls (24.43 ± 19.87 %) at 30 mins after exposure to the bacteria (p < 0.05). PMNs from subjects with chronic and aggressive periodontitis released significantly more ROS and demonstrated greater HNE activity in the absence of any stimulus than PMNs from healthy controls (p < 0.05). The total release of ROS increased in chronic periodontitis PMNs and in the control group PMNs after interaction with P. gingivalis. The interaction with A. actinomycetemcomitans resulted in greater total ROS release in chronic periodontitis PMNs and in the control group PMNs than P. gingivalis. CONCLUSION PMNs in aggressive and chronic periodontitis are hyperactive even without any particular stimulus. The extracellular release of ROS and neutrophil elastase by PMNs may not only affect bacterial virulence and/or viability, but also contribute to damage of the surrounding periodontal tissues. PMID:19210340

  1. Information Technology Administrator’s Instruction Manual for the Personal Academic Strategies for Success (PASS) Tool, With Subcomponent Academic Class Composite Tool (AC2T)

    DTIC Science & Technology

    2013-12-01

    Attention Deficit / Hyperactivity Disorder Symptom Score 20. Parental Marital Status – Parents Divorced 21. Home Until Enlisted 22. High School...FL, 2012; pp 86–96. Rice, V. J. B.; Butler, J.; Marra, D. Neuro-Cognitive Assessment, Symptoms of Attention Deficit and Hyperactivity Disorder , and...V. J.; Butler, J.; Marra, D. The Relationship Between Symptoms of Attention Deficit and Hyperactivity Disorder and Oppositional Defiant Disorder

  2. Stimulant Drugs and Activity Level in Hyperactive Children.

    ERIC Educational Resources Information Center

    Barkley, Russell A.; Cunningham, Charles E.

    1979-01-01

    Results of the study involving 14 hyperactive boys (5-12 years old) indicated that activity and attention span are affected by methylphenidate even in highly stimulating, informal settings. (Author/SBH)

  3. ADHD Diet: Do Food Additives Cause Hyperactivity?

    MedlinePlus

    ... additives and their possible effects is controversial. Some studies indicate that certain food colorings and preservatives may increase hyperactive behavior in some children. But the Food and Drug Administration (FDA) Food ...

  4. A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment

    PubMed Central

    Fryer, Tim D.; Hong, Young T.; Smith, Rob; Brichard, Laurent; Acosta-Cabronero, Julio; Chamberlain, Samuel R.; Tait, Roger; Izquierdo, David; Regenthal, Ralf; Dowson, Jonathan; Suckling, John; Baron, Jean-Claude; Aigbirhio, Franklin I.; Robbins, Trevor W.; Sahakian, Barbara J.; Müller, Ulrich

    2013-01-01

    Through the combined use of 18F-fallypride positron emission tomography and magnetic resonance imaging this study examined the neural mechanisms underlying the attentional deficits associated with attention deficit/hyperactivity disorder and their potential reversal with a single therapeutic dose of methylphenidate. Sixteen adult patients with attention deficit/hyperactivity disorder and 16 matched healthy control subjects were positron emission tomography and magnetic resonance imaging scanned and tested on a computerized sustained attention task after oral methylphenidate (0.5 mg/kg) and placebo administration in a within-subject, double-blind, cross-over design. Although patients with attention deficit/hyperactivity disorder as a group showed significant attentional deficits and reduced grey matter volume in fronto-striato-cerebellar and limbic networks, they had equivalent D2/D3 receptor availability and equivalent increases in endogenous dopamine after methylphenidate treatment to that observed in healthy control subjects. However, poor attentional performers drawn from both the attention deficit/hyperactivity disorder and the control groups had significantly reduced left caudate dopamine activity. Methylphenidate significantly increased dopamine levels in all nigro-striatal regions, thereby normalizing dopamine levels in the left caudate in low performers. Behaviourally, methylphenidate improved sustained attention in a baseline performance-dependent manner, irrespective of diagnosis. This finding was accompanied by an equally performance-dependent effect of the drug on dopamine release in the midbrain, whereby low performers showed reduced dopamine release in this region. Collectively, these findings support a dimensional model of attentional deficits and underlying nigro-striatal dopaminergic mechanisms of attention deficit/hyperactivity disorder that extends into the healthy population. Moreover, they confer midbrain dopamine autoreceptors a hitherto neglected role in the therapeutic effects of oral methylphenidate in attention deficit/hyperactivity disorder. The absence of significant case–control differences in D2/D3 receptor availability (despite the observed relationships between dopamine activity and attention) suggests that dopamine dysregulation per se is unlikely to be the primary cause underlying attention deficit/hyperactivity disorder pathology in adults. This conclusion is reinforced by evidence of neuroanatomical changes in the same set of patients with attention deficit/hyperactivity disorder. PMID:24163364

  5. l-Theanine inhibits proinflammatory PKC/ERK/ICAM-1/IL-33 signaling, apoptosis, and autophagy formation in substance P-induced hyperactive bladder in rats.

    PubMed

    Tsai, Wen-Hsin; Wu, Chung-Hsin; Yu, Hong-Jeng; Chien, Chiang-Ting

    2017-02-01

    Upregulation of substance P (SP) and neurokinin-1 receptor (NK1R) activation induces pro-inflammatory bladder hyperactivity through the PKC/ERK/NF-κB/ICAM-1/IL-33 signaling pathways to increase the leukocyte infiltration and adhesion leading to reactive oxygen species (ROS) production, autophagy, and apoptosis. l-Theanine is a unique non-protein-forming amino acid present in tea (Camellia sinensis [L.] O. Kuntze) with its antioxidant, anti-inflammatory, and relaxation effects to improve cognition, mood, gastric ulcer injury, and cerebral ischemia/reperfusion injury, and posttraumatic stress disorder. We explored the protective effect of l-theanine on SP-induced bladder hyperactivity. In urethane-anesthetized female Wistar rats, we explored the transcystometrogram, pelvic nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, apoptosis-related Caspase 3/poly-(ADP-ribose)-polymerase (PARP), and autophagy-mediated LC3 II expression by Western blot, electrophoretic-mobility shift assay and immunohistochemistry, bladder ROS amount by a ultrasensitive chemiluminescence method, and possible ROS sources from the different leukocytes by specific stains in SP-evoked hyperactive bladder. l-Theanine dose-dependently depressed H 2 O 2 and HOCl activity in vitro. In urethane-anesthetized female Wistar rats, intra-arterial SP through NK1R activation increased voiding frequency (shortened intercontraction intervals) associated with the increase in bladder nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, Caspase 3/PARP-mediated apoptosis, LC3 II-mediated autophagy, ROS amount, neutrophils adhesion, CD68 (monocyte/macrophage) infiltration, and mast cells degranulation in the hyperactive bladder. Intragastrical l-theanine (15 mg/kg) twice daily for 2 weeks efficiently ameliorated all the enhanced parameters in the SP-treated hyperactive bladder. In conclusion, l-theanine through antioxidant and anti-inflammatory actions ameliorates SP-induced bladder hyperactivity via the inhibition of proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, oxidative stress, bladder nerve hyperactivity, apoptosis, and autophagy. Neurourol. Urodynam. 36:297-307, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Neurotoxicity of misonidazole in rats following intravenous administration.

    PubMed

    Graziano, M J; Henck, J W; Meierhenry, E F; Gough, A W

    1996-06-01

    Misonidazole is a hypoxic cell radiosensitizer that induces a peripheral neuropathy in humans after exceeding a schedule-dependent cumulative threshold dose. Clinical studies of misonidazole have been conducted using oral administration, whereas most other radiosensitizers have been administered intravenously. Since route of exposure can potentially influence the toxicity of xenobiotics, the objective of this study was to assess the neurotoxicity of misonidazole in rats following intravenous dosing using a battery of routine clinical, neurofunctional, biochemical, and histopathologic screening methods. Male Sprague-Dawley rats were administered intravenous doses of misonidazole at 0 (vehicle control), 100, 200, 300, or 400 mg kg-1 once per day, 5 days per week, for 2 weeks. Animals were evaluated for neurofunctional and pathological changes following termination of treatment (Days 15-17) and at the end of a 4 week observation period (Days 43-45). During the dosing phase, hypoactivity, salivation, rhinorrhea, chromodacryorrhea, rough pelage and ataxia were observed at 400 mg kg-1, and body weight gain of the 300 and 400 mg kg-1 groups was significantly decreased relative to the vehicle controls by 24% and 49%, respectively. Corresponding reductions in food consumption were 8% and 23%, respectively. Although most 400 mg kg-1 animals appeared normal on Day 15 prior to the neurofunctional evaluations, rotorod testing precipitated a number of clinical signs including: ataxia, impaired righting reflex, excessive rearing, tremors, vocalization, circling, head jerking, excessive sniffing and hyperactivity. All of these animals recovered and appeared normal from Day 17 through study termination. There were no treatment-related effects on motor activity, acoustic startle response, rotorod performance, forelimb group strength, toe and tail pinch reflexes, tibial nerve beta-glucuronidase activity or tail nerve conduction velocity. Although hindlimb grip strength of the 400 mg kg-1 group was significantly decreased by 17% relative to the vehicle controls on Day 15, this finding appeared related to the reduced food consumption and body weight gain in these animals. No microscopic changes were detected in peripheral nerves. Necrosis and proliferation of fibrillary astrocytes (gliosis) were seen in the cerebellum and medulla of the 400 mg kg-1 animals on Day 16. Gliosis in these same brain regions was observed in the 300 and 400 mg kg-1 groups on Day 44. The results show that intravenous administration of misonidazole to rats causes dose-limiting central nervous system toxicity without effects on peripheral nervous tissue. The lack of peripheral neurotoxicity was most likely due to a combination of several interrelated factors including route of administration, duration and intensity of the dosing regimen, and total cumulative dose.

  7. Attention-Deficit Hyperactivity Disorder.

    ERIC Educational Resources Information Center

    Barkley, Russell A.

    1998-01-01

    Attention deficit hyperactivity disorder (ADHD) may arise when key brain circuits do not develop properly, perhaps due to an altered gene or genes. Describes ADHD in detail and introduces a psychological model of ADHD. (ASK)

  8. Mental Illness Statistics

    MedlinePlus

    ... Top ı cs Mental Illness Any Anxiety Disorder Attention-Deficit/Hyperactivity Disorder (ADHD) Autism Spectrum Disorder (ASD) Bipolar ... Anorexia Nervosa Any Anxiety Disorder Any Mood Disorder Attention-Deficit/Hyperactivity Disorder (ADHD) Autism Spectrum Disorder (ASD) Binge ...

  9. Hyperactivity and children

    MedlinePlus

    ... are very active. They also have a short attention span. This type of behavior is normal for their age. Providing lots of healthy active play for your child can ... deficit hyperactivity disorder (ADHD) or another mental health ...

  10. Attention Deficit/Hyperactivity Disorder (ADHD): The Basics

    MedlinePlus

    ... Signs Treating ADHD Reprints For More Information Share Attention-Deficit/Hyperactivity Disorder (ADHD): The Basics Download PDF ... Overview Do you find it hard to pay attention? Do you feel the need to move constantly ...

  11. Faststats: Attention Deficit Hyperactivity Disorder (ADHD)

    MedlinePlus

    ... this? Submit What's this? Submit Button NCHS Home Attention Deficit Hyperactivity Disorder (ADHD)* Recommend on Facebook Tweet ... visits Number of visits to physician offices with attention deficit disorder as the primary diagnosis: 10.9 ...

  12. Genetics Home Reference: monoamine oxidase A deficiency

    MedlinePlus

    ... may have features of other behavioral disorders, including autism spectrum disorder and attention deficit-hyperactivity disorder (ADHD). ... Health Topic: Attention Deficit Hyperactivity Disorder Health Topic: Autism Spectrum Disorder Health Topic: Developmental Disabilities Genetic and ...

  13. The Role of Academic Failure in Hyperactive Behavior

    ERIC Educational Resources Information Center

    Cunningham, Charles E.; Barkley, Russell A.

    1978-01-01

    A model and supporting research are presented which suggest that academic failure resulting from a variety of etiological factors is sufficient to generate the behavioral patterns observed in many hyperactive children. (CL)

  14. Methamphetamine/Dextroamphetamine and Pregnancy

    MedlinePlus

    ... d-amphetamine is a prescription medication used for attention deficit hyperactivity disorder (ADHD) and narcolepsy (extreme daytime sleepiness). ... of dexamphetamine into breast milk during treatment for attention deficit hyperactivity disorder. Br J Clin Pharmacol. 63(3): ...

  15. Varieties of preschool hyperactivity: multiple pathways from risk to disorder.

    PubMed

    Sonuga-Barke, Edmund J S; Auerbach, Judith; Campbell, Susan B; Daley, David; Thompson, Margaret

    2005-03-01

    In this paper we examine the characteristics of preschool attention deficit hyperactivity disorder (ADHD) from both mental disorder and developmental psychopathology points of view. The equivalence of preschool and school-aged hyperactivity as a behavioral dimension is highlighted together with the potential value of extending the use of the ADHD diagnostic category to the preschool period where these behaviours take an extreme and impairing form (assuming age appropriate diagnostic items and thresholds can be developed). At the same time, the importance of identifying pathways between risk and later ADHD is emphasized. Developmental discontinuity and heterogeneity are identified as major characteristics of these pathways. We argue that models that distinguish among different developmental types of early-emerging problems are needed. An illustrative taxonomy of four developmental pathways implicating preschool hyperactivity is presented to provide a framework for future research.

  16. Affect Recognition in Adults with Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Miller, Meghan; Hanford, Russell B.; Fassbender, Catherine; Duke, Marshall; Schweitzer, Julie B.

    2014-01-01

    Objective This study compared affect recognition abilities between adults with and without Attention-Deficit/Hyperactivity Disorder (ADHD). Method The sample included 51 participants (34 men, 17 women) divided into 3 groups: ADHD-Combined Type (ADHD-C; n = 17), ADHD-Predominantly Inattentive Type (ADHD-I; n = 16), and controls (n = 18). The mean age was 34 years. Affect recognition abilities were assessed by the Diagnostic Analysis of Nonverbal Accuracy (DANVA). Results Analyses of Variance showed that the ADHD-I group made more fearful emotion errors relative to the control group. Inattentive symptoms were positively correlated while hyperactive-impulsive symptoms were negatively correlated with affect recognition errors. Conclusion These results suggest that affect recognition abilities may be impaired in adults with ADHD and that affect recognition abilities are more adversely affected by inattentive than hyperactive-impulsive symptoms. PMID:20555036

  17. Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter

    PubMed Central

    Gainetdinov, Raul R.; Mohn, Amy R.; Bohn, Laura M.; Caron, Marc G.

    2001-01-01

    In the brain, dopamine exerts an important modulatory influence over behaviors such as emotion, cognition, and affect as well as mechanisms of reward and the control of locomotion. The dopamine transporter (DAT), which reuptakes the released neurotransmitter into presynaptic terminals, is a major determinant of the intensity and duration of the dopaminergic signal. Knockout mice lacking the dopamine transporter (DAT-KO mice) display marked changes in dopamine homeostasis that result in elevated dopaminergic tone and pronounced locomotor hyperactivity. A feature of DAT-KO mice is that their hyperactivity can be inhibited by psychostimulants and serotonergic drugs. The pharmacological effect of these drugs occurs without any observable changes in dopaminergic parameters, suggesting that other neurotransmitter systems in addition to dopamine might contribute to the control of locomotion in these mice. We report here that the hyperactivity of DAT-KO mice can be markedly further enhanced when N-methyl-d-aspartate receptor-mediated glutamatergic transmission is blocked. Conversely, drugs that enhance glutamatergic transmission, such as positive modulators of l-α-amino-3-hydroxy-5-methylisoxazole-4-propionate glutamate receptors, suppress the hyperactivity of DAT-KO mice. Interestingly, blockade of N- methyl-d-aspartate receptors prevented the inhibitory effects of both psychostimulant and serotonergic drugs on hyperactivity. These findings support the concept of a reciprocal functional interaction between dopamine and glutamate in the basal ganglia and suggest that agents modulating glutamatergic transmission may represent an approach to manage conditions associated with dopaminergic dysfunction. PMID:11572967

  18. [Analysis of Applying Chinese Medical Clinical Pathway for Treating Attention-deficit Hyperactivity Disorder].

    PubMed

    Guo, Yu-qing; Han, Xin-min; Zhu, Xian-kang; Zhou, Zheng; Ma, Bing-xiang; Zhang, Bao-qing; Li, Yan-ning; Feng, Yu-lin; Xue, Zheng; Wang, Yong-hong; Li, Yi-min; Jiang, Zhi-mei; Xu, Jin-xing; Yue, Wei-zhen; Xiang, Xi-xiong

    2015-12-01

    To evaluate the application effect of Chinese medical clinical pathway for treating attention-deficit hyperactivity disorder (ADHD), and to provide evidence for further improving clinical pathways. Totally 270 ADHD children patients were recruited and treated at pediatrics clinics of 9 cooperative hospitals from December 2011 to December 2012. The treatment course for all was 3 months. Scores of attention deficit and hyperactivity rating scale, scores of behavior, Conners index of hyperactivity (CIH), and Chinese medical syndrome scores were compared between before and after treatment. The efficacy difference in various sexes, ages, and disease courses were evaluated by judging standards for Chinese medical syndrome and ADHD. Fifteen children patients who entered clinical pathway dropped out, and the rest 255 completed this trial. Compared with before treatment, total scores of attention deficit and hyperactivity rating scale, scores of attention deficit and hyperactivity rating scale, CIH, and Chinese medical syndrome scores obviously decreased (all P < 0.01). The total effective rate in disease efficacy was 87.8% (224/255 cases), and the total effective rate in Chinese medical syndrome curative effect was 87.5% (223/255 cases). The clinical curative effect was not influenced by age, gender, or course of disease when statistically analyzed from judging standards for Chinese medical syndrome or for disease efficacy. Intervention by Chinese medical clinical pathway could improve ADHD patients' symptoms, and its efficacy was not influenced by sex, age, or course of disease.

  19. Teachers' reporting of behavioural problems and cognitive-academic performances in children aged 5-7 years.

    PubMed

    Giannopulu, I; Escolano, S; Cusin, F; Citeau, H; Dellatolas, G

    2008-03-01

    The behavioural and academic performance of young children with teachers' reported hyperactivity, conduct problems or inattention is under debate. This study investigates the associations between teachers' reported behavioural difficulties and academic and cognitive performances in two large samples of preschool and school children in France. SAMPLES AND METHOD: Behavioural data relating to two large samples of preschool (N=475) and first grade (N=465) children were collected from their teachers by means of a questionnaire. A factorial analysis of the questionnaire revealed a four-factor structure ('hyperactivity', 'inattention', 'conduct problems' and 'unsociability') that was similar in both age groups. Cognitive tests were used for each age group. Teachers' reporting of 'inattention' was associated with significantly lower performances in all tests in both the preschool and first grade samples. 'Hyperactivity' or 'conduct problems' were not consistently associated with the test results, when the effect of 'inattention' was taken into account. Preschool 'inattention', but not 'hyperactivity' or 'conduct/sociability problems', was related to poor performances at reading tasks in first grade. These findings question the pathological significance of teachers' report of 'hyperactivity' in young children without associated attention problems.

  20. Possible neuronal mechanisms of sleep disturbances in patients with autism spectrum disorders and attention-deficit/hyperactivity disorder.

    PubMed

    Kohyama, Jun

    2016-12-01

    The most common form of sleep disturbance among both patients with autism spectrum disorders and patients with attention-deficit/hyperactivity disorder is sleep-onset insomnia, but the neuronal mechanisms underlying it have yet to be elucidated and no specific treatment strategy has been proposed. This means that many caregivers struggle to manage this problem on a daily basis. This paper presents a hypothesis about the neuronal mechanisms underlying insomnia in patients with autism spectrum disorders and attention-deficit/hyperactivity disorder based on recent clinical and basic research. It is proposed that three neuronal mechanisms (increased orexinergic system activity, reduced 5-hydroxytryptamine and melatonergic system activity, rapid eye movement sleep reduction) are involved in insomnia in both autism spectrum disorders and attention-deficit/hyperactivity disorder. This suggests that antagonists against the orexin receptors may have beneficial effects on insomnia in patients with autism spectrum disorders or attention-deficit/hyperactivity disorder. To the best of the author's knowledge there has been no research into the effects of this agent on insomnia in these patient groups. Large, controlled trials should be carried out. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The Structure of Adult ADHD

    PubMed Central

    Adler, Lenard A.; Faraone, Stephen V.; Spencer, Thomas J.; Berglund, Patricia; Alperin, Samuel; Kessler, Ronald C.

    2017-01-01

    Although DSM-5 stipulates that symptoms of attention-deficit/hyperactivity disorder (ADHD) are the same for adults as children, clinical observations suggest that adults have more diverse deficits than children in higher-level executive functioning and emotional control. Previous psychometric analyses to evaluate these observations have been limited in ways addressed in the current study, which analyzes the structure of an expanded set of adult ADHD symptoms in 3 pooled U.S. samples: a national household sample, a sample of health plan members, and a sample of adults referred for evaluation at an adult ADHD clinic. Exploratory factor analysis found 4 factors representing executive dysfunction/inattention (including, but not limited to, all the DSM-5 inattentive symptoms, with non-DSM symptoms having factor loadings comparable to those of DSM symptoms), hyperactivity, impulsivity, and emotional dyscontrol. Empirically-derived multivariate symptom profiles were broadly consistent with the DSM-5 inattentive-only, hyperactive/impulsive-only, and combined presentations, but with inattention including executive dysfunction/inattention and hyperactivity-only limited to hyperactivity without high symptoms of impulsivity. These results show that executive dysfunction is as central as DSM-5 symptoms to adult ADHD, while emotional dyscontrol is more distinct but prominent resent in the combined presentation of adult ADHD. PMID:28211596

  2. Atomoxetine reduces hyperactive/impulsive behaviours in neurokinin-1 receptor 'knockout' mice.

    PubMed

    Pillidge, Katharine; Porter, Ashley J; Vasili, Temis; Heal, David J; Stanford, S Clare

    2014-12-01

    Mice with functional ablation of the neurokinin-1 receptor gene (NK1R(-/-)) display behavioural abnormalities which resemble the hyperactivity, inattention and impulsivity seen in Attention Deficit Hyperactivity Disorder (ADHD). Here, we investigated whether the established ADHD treatment, atomoxetine, alleviates these abnormalities when tested in the light/dark exploration box (LDEB) and 5-Choice Serial Reaction-Time Task (5-CSRTT). Separate cohorts of mice were tested in the 5-CSRTT and LDEB after treatment with no injection, vehicle or atomoxetine (5-CSRTT: 0.3, 3 or 10mg/kg; LDEB: 1, 3 or 10mg/kg). Atomoxetine reduced the hyperactivity displayed by NK1R(-/-) mice in the LDEB at a dose (3mg/kg) which did not affect the locomotor activity of wildtypes. Atomoxetine (10mg/kg) also reduced impulsivity in NK1R(-/-) mice, but not wildtypes, in the 5-CSRTT. No dose of drug affected attention in either genotype. This evidence that atomoxetine reduces hyperactive/impulsive behaviours in NK1R(-/-) mice consolidates the validity of using NK1R(-/-) mice in research of the aetiology and treatment of ADHD. Copyright © 2014. Published by Elsevier Inc.

  3. Atomoxetine reduces hyperactive/impulsive behaviours in neurokinin-1 receptor ‘knockout’ mice

    PubMed Central

    Pillidge, Katharine; Porter, Ashley J.; Vasili, Temis; Heal, David J.; Stanford, S. Clare

    2014-01-01

    Background Mice with functional ablation of the neurokinin-1 receptor gene (NK1R−/−) display behavioural abnormalities which resemble the hyperactivity, inattention and impulsivity seen in Attention Deficit Hyperactivity Disorder (ADHD). Here, we investigated whether the established ADHD treatment, atomoxetine, alleviates these abnormalities when tested in the light/dark exploration box (LDEB) and 5-Choice Serial Reaction-Time Task (5-CSRTT). Methods Separate cohorts of mice were tested in the 5-CSRTT and LDEB after treatment with no injection, vehicle or atomoxetine (5-CSRTT: 0.3, 3 or 10 mg/kg; LDEB: 1, 3 or 10 mg/kg). Results Atomoxetine reduced the hyperactivity displayed by NK1R−/− mice in the LDEB at a dose (3 mg/kg) which did not affect the locomotor activity of wildtypes. Atomoxetine (10 mg/kg) also reduced impulsivity in NK1R−/− mice, but not wildtypes, in the 5-CSRTT. No dose of drug affected attention in either genotype. Conclusions This evidence that atomoxetine reduces hyperactive/impulsive behaviours in NK1R−/− mice consolidates the validity of using NK1R−/− mice in research of the aetiology and treatment of ADHD. PMID:25450119

  4. Focusing on ADHD - Attention Deficit Hyperactivity Disorder

    MedlinePlus

    ... September 2014 Print this issue Focusing on ADHD Attention Deficit Hyperactivity Disorder En español Send us your ... kid. But some kids have such trouble paying attention, staying focused, and finishing tasks that it interferes ...

  5. Attention-Deficit / Hyperactivity Disorder (ADHD): Symptoms and Diagnosis

    MedlinePlus

    ... Search Form Controls Cancel Submit Search the CDC Attention-Deficit / Hyperactivity Disorder (ADHD) Note: Javascript is disabled ... for developmental level: Often fails to give close attention to details or makes careless mistakes in schoolwork, ...

  6. Effects of Combining Methylphenidate and a Classroom Token System in Modifying Hyperactive Behavior

    ERIC Educational Resources Information Center

    Christensen, Donald E.

    1975-01-01

    The combined effects of methylphenidate (Ritalin) and a token reinforcement program in controlling the classroom behavior of 16 hyperactive, institutionalized retarded youngsters (9- to 15-years-old) was investigated. (Author)

  7. Hyperkinesis and Chemotherapy.

    ERIC Educational Resources Information Center

    Calhoun, George

    1979-01-01

    The article discusses several criticisms of the use of drugs in the treatment of hyperactivity, and suggests some nondrug procedures for parents and teachers to use in the home and classroom to minimize and control a child's hyperactive behavior. (DLS)

  8. Attention Deficit Hyperactivity Disorder: Strategies for the Classroom.

    ERIC Educational Resources Information Center

    Purvis, Johnny R.; And Others

    1992-01-01

    This article discusses classroom strategies used with students with attention deficit hyperactivity disorder (ADHD), methods for controlling the ADHD child's behavior, and the need for consistency and collaboration between the school and home. (Author/JDD)

  9. Attention deficit and hyperactivity disorder: a therapeutic option

    PubMed Central

    Topczewski, Abram

    2014-01-01

    Objective To evaluate the use of a therapeutic regimen to treat attention deficit hyperactivity disorder patients. Methods A total of 140 patients initially underwent physical, neurological and laboratory evaluation. Thereafter, treatment was initiated with a compounding product consisting of a tricyclic antidepressant and an anxiolytic. Results The response was positive in 71.43% of patients in controlling hyperactivity and improving dispersion and attention deficit. Conclusion The therapeutic regimen utilized proved to be an effective therapeutic alternative, especially for patients who do not adapt to psychostimulant drugs. PMID:25295451

  10. Sons and daughters beyond your control: episodes in the prehistory of the attention deficit/hyperactivity syndrome.

    PubMed

    Foley, Paul Bernard

    2014-09-01

    Hyperactive and inattentive children have been discussed in both the pedagogic and medical literature since the nineteenth century, and many controversies associated with attention deficit and hyperactivity disorder (ADHD) have been repeatedly analyzed in different contexts. The 'prehistory' of the ADHD concept-that is, up to the definition of ADHD in DSM-III and of the corresponding 'hyperkinetic disorder' in ICD-9-is outlined, with an emphasis on the literature not previously discussed in English language reviews of the subject.

  11. Parenting of children with ADHD in South Korea: the role of socio-emotional development of children with ADHD.

    PubMed

    Oh, Won-Oak; Park, Eun Sook; Suk, Min Hyun; Song, Dong Ho; Im, Yeojin

    2012-07-01

    The aim was to investigate the factors affecting the self-esteem and social competence of children with attention deficit hyperactivity disorder. Many studies have reported parenting variables such as parenting attitude and sense of competence have been suggested as significant determinants of socio-emotional development of children with attention deficit hyperactivity disorder. In South Korean society, the traditional culture of Confucianism is a strong influence on parenting practices and children's behaviour. However, there have been few studies that examined the relative significance of the parenting and other associated factors for self-esteem and social competence in children with attention deficit hyperactivity disorder in Korea living in a strict parenting environment. This study was designed as a cross-sectional and descriptive survey. The subjects were 124 pairs of mothers and their children with attention deficit hyperactivity disorder, recruited from local paediatric psychiatric clinics in South Korea. Data collection was conducted through the use of questionnaires. Affectionate parenting attitude and co-morbid condition of the child were the most important predictors of self-esteem. Rejecting parenting attitude was the most important predictor of social competence. Higher levels of affectionate parenting attitude of mothers and non-co-morbid status of children both contributed unique variance to the overall prediction of higher self-esteem of children. Higher levels of rejecting parenting attitude of mothers contributed unique variance to the overall prediction of lower social competence in children with attention deficit hyperactivity disorder. Parenting attitude is the most important factor to contribute to the healthy socio-emotional development in children with attention deficit hyperactivity disorder. Health care providers need to develop and apply a parenting skills improvement program to improve positive parenting attitudes, which will benefit self-esteem and social competence in children with attention deficit hyperactivity disorder. © 2012 Blackwell Publishing Ltd.

  12. Shortened Conditioned Eyeblink Response Latency in Male but not Female Wistar-Kyoto Hyperactive Rats

    PubMed Central

    Thanellou, Alexandra; Schachinger, Kira M.; Green, John T.

    2014-01-01

    Reductions in the volume of the cerebellum and impairments in cerebellar-dependent eyeblink conditioning have been observed in attention-deficit/hyperactivity disorder (ADHD). Recently, it was reported that subjects with ADHD as well as male spontaneously hypertensive rats (SHR), a strain that is frequently employed as an animal model in the study of ADHD, exhibit a parallel pattern of timing deficits in eyeblink conditioning. One criticism that has been posed regarding the validity of the SHR strain as an animal model for the study of ADHD is that SHRs are not only hyperactive but also hypertensive. It is conceivable that many of the behavioral characteristics seen in SHRs that seem to parallel the behavioral symptoms of ADHD are not solely due to hyperactivity but instead are the net outcome of the interaction between hyperactivity and hypertension. We used Wistar-Kyoto Hyperactive (WKHA) and Wistar-Kyoto Hypertensive (WKHT) rats (males and females), strains generated from recombinant inbreeding of SHRs and their progenitor strain, Wistar-Kyoto (WKY) rats, to compare eyeblink conditioning in strains that are exclusively hyperactive or hypertensive. We used a long-delay eyeblink conditioning task in which a tone conditioned stimulus was paired with a periorbital stimulation unconditioned stimulus (750-ms delay paradigm). Our results showed that WKHA and WKHT rats exhibited similar rates of conditioned response (CR) acquisition. However, WKHA males displayed shortened CR latencies (early onset and peak latency) in comparison to WKHT males. In contrast, female WKHAs and WKHTs did not differ. In subsequent extinction training, WKHA rats extinguished at similar rates in comparison to WKHT rats. The current results support the hypothesis of a relationship between cerebellar abnormalities and ADHD in an animal model of ADHD-like symptoms that does not also exhibit hypertension, and suggest that cerebellar-related timing deficits are specific to males. PMID:19485572

  13. NEONATAL CEREBRAL MORPHOMETRY AND LATER RISK OF PERSISTENT INATTENTION/HYPERACTIVITY IN CHILDREN BORN VERY PRETERM

    PubMed Central

    Bora, Samudragupta; Pritchard, Verena E.; Chen, Zhe; Inder, Terrie E.; Woodward, Lianne J.

    2014-01-01

    Background Attention problems are among the most prevalent neurobehavioral morbidities affecting very preterm (VPT) born children. The first study aim was to document rates of persistent attention/hyperactivity problems from ages 4 to 9 years in a regional cohort of VPT born children. The second aim was to examine the extent to which persistent problems were related to cerebral white matter abnormality and structural development on neonatal MRI. Methods Data were drawn from a prospective longitudinal study of 110 VPT (≤32 weeks’ gestation) and 113 full-term (FT) children born from 1998 to 2000. At term equivalent, all VPT and 10 FT children underwent cerebral structural MRI, with scans analyzed qualitatively for white matter abnormalities and quantitatively for cortical and subcortical gray matter, myelinated and unmyelinated white matter, and cerebrospinal fluid volumes. At ages 4, 6, and 9 years, each child’s parent and teacher completed the Inattention/Hyperactivity subscale of the Strengths and Difficulties Questionnaire. Results VPT born children had a 5-fold increased risk of persistent attention/hyperactivity problems compared to FT children (13.1% vs. 2.8%; p=.002). No association was found between neonatal white matter abnormalities and later persistent inattention/hyperactivity risk (p≥.24). In contrast, measures of cerebral structural development including volumetric estimates of total cerebral tissue and cerebrospinal fluid relative to intracranial volume were associated with an increased risk of persistent attention/hyperactivity problems in VPT born children (p=.001). The dorsal prefrontal region showed the largest volumetric reduction (↓3.2–8.2ml). These brain-behavior associations persisted and in some cases, strengthened after covariate adjustment for postmenstrual age at MRI, sex, and family socioeconomic status. Conclusions Just over one in 10 VPT born children are subject to early onset and persistent attention/hyperactivity problems during childhood. These problems appear to reflect, at least in part, neonatal disturbances in cerebral growth and development rather than the effects of white matter injury. PMID:24438003

  14. Learning, Attention/Hyperactivity, and Conduct Problems as Sequelae of Excessive Daytime Sleepiness in a General Population Study of Young Children

    PubMed Central

    Calhoun, Susan L.; Fernandez-Mendoza, Julio; Vgontzas, Alexandros N.; Mayes, Susan D.; Tsaoussoglou, Marina; Rodriguez-Muñoz, Alfredo; Bixler, Edward O.

    2012-01-01

    Study Objectives: Although excessive daytime sleepiness (EDS) is a common problem in children, with estimates of 15%; few studies have investigated the sequelae of EDS in young children. We investigated the association of EDS with objective neurocognitive measures and parent reported learning, attention/hyperactivity, and conduct problems in a large general population sample of children. Design: Cross-sectional. Setting: Population based. Participants: 508 children from The Penn State Child Cohort. Interventions: N/A. Measurements and Results: Children underwent a 9-h polysomnogram, comprehensive neurocognitive testing, and parent rating scales. Children were divided into 2 groups: those with and without parent-reported EDS. Structural equation modeling was used to examine whether processing speed and working memory performance would mediate the relationship between EDS and learning, attention/hyperactivity, and conduct problems. Logistic regression models suggest that parent-reported learning, attention/hyperactivity, and conduct problems, as well as objective measurement of processing speed and working memory are significant sequelae of EDS, even when controlling for AHI and objective markers of sleep. Path analysis demonstrates that processing speed and working memory performance are strong mediators of the association of EDS with learning and attention/hyperactivity problems, while to a slightly lesser degree are mediators from EDS to conduct problems. Conclusions: This study suggests that in a large general population sample of young children, parent-reported EDS is associated with neurobehavioral (learning, attention/hyperactivity, conduct) problems and poorer performance in processing speed and working memory. Impairment due to EDS in daytime cognitive and behavioral functioning can have a significant impact on children's development. Citation: Calhoun SL; Fernandez-Mendoza J; Vgontzas AN; Mayes SD; Tsaoussoglou M; Rodriguez-Muñoz A; Bixler EO. Learning, attention/hyperactivity, and conduct problems as sequelae of excessive daytime sleepiness in a general population study of young children. SLEEP 2012;35(5):627-632. PMID:22547888

  15. The Effects of Caffeine on Hyperactive Children

    ERIC Educational Resources Information Center

    Firestone, Philip; And Others

    1978-01-01

    The psychological, physiological, and behavioral effects of a 2-week regimen of 300 mg of caffeine on 20 hyperactive males between the ages of 5 and 12 years were examined, using a double-blind crossover format. (Author)

  16. Hyperactivity, Learning Disabilities, and Alcohol.

    ERIC Educational Resources Information Center

    Gold, Sandra; Sherry, Lee

    1984-01-01

    A review of research on the effects of alcohol consumption by pregnant women supports the U.S. Food and Drug Administration's warning about the possible negative effects (learning disabilities, hyperactivity, short attention span, and emotional liability) of children. (Author/CL)

  17. The Assessment of Hyperactivity in Preschool Populations: A Multidisciplinary Perspective.

    ERIC Educational Resources Information Center

    Rosenberg, Michael S.; And Others

    1989-01-01

    The variety of methods available for the assessment of hyperactivity in preschool populations is reviewed. Specific procedures for assessment are presented from a multidisciplinary perspective, integrating biophysical, behavioral, cognitive, and ecological models. (Author/JDD)

  18. Motivational deficit in childhood depression and hyperactivity.

    PubMed

    Layne, C; Berry, E

    1983-07-01

    A recent theory states that the immediate cause of adult depression is low motivation, where motivation is the multiplicative product of a person's expectation for a reward times his value for that reward. The present experiment supported the extension of this theory to childhood depression. The expectations, values, and motivations of three groups of children (Ns = 18; mean ages = 10) were measured: A depressed group and a hyperactive control group were selected from a population of clinically disturbed children, while normal controls were selected from regular classrooms. As predicted, the depressed children exhibited reduced motivation, primarily because their expectations were pessimistic. Unexpected findings were that the depressives' expectations were not abnormally irrational; and that hyperactives exhibited optimistic expectations, inflated values, and, hence, inflated motivation--especially for tangible rewards. Cognitive therapy techniques that focus upon expectations were recommended for the treatment of both depressed and hyperactive children.

  19. Teachers' ratings of disruptive behaviors: the influence of halo effects.

    PubMed

    Abikoff, H; Courtney, M; Pelham, W E; Koplewicz, H S

    1993-10-01

    This study evaluated the accuracy of teachers' ratings and examined whether these ratings are influenced by halo effects. One hundred thirty-nine elementary school teachers viewed videotapes of what they believed were children in regular fourth-grade classrooms. In fact, the children were actors who followed prepared scripts that depicted a child engaging in behaviors characteristic of an attention-deficit hyperactivity disorder (ADHD), an oppositional defiant disorder or a normal youngster. The findings provide support for a bias that was unidirectional in nature. Specifically, teachers rated hyperactive behaviors accurately when the child behaved like an ADHD youngster. However, ratings of hyperactivity and of ADHD symptomatic behaviors were spuriously inflated when behaviors associated with oppositional defiant disorder occurred. In contrast, teachers rated oppositional and conduct problem behaviors accurately, regardless of the presence of hyperactive behaviors. The implications of these findings regarding diagnostic practices and rating scale formats are discussed.

  20. [Parenting styles and their relationship with hyperactivity].

    PubMed

    Raya Trenas, Antonio Félix; Herreruzo Cabrera, Javier; Pino Osuna, María José

    2008-11-01

    The present study aims to determine the relationship among factors that make up the parenting styles according to the PCRI (Parent-Child Relationship Inventory) and hyperactivity reported by parents through the BASC (Behaviour Assessment System for Children). We selected a sample of 32 children between 3 and 14 years old (23 male and 9 female) with risk scores in hyperactivity and another similar group with low scores in hyperactivity. After administering both instruments to the parents, we carried out a binomial logistic regression analysis which resulted in a prediction model for 84.4% of the sample, made up of the PCRI factors: fathers' involvement, communication and role orientation, mothers' parental support, and both parents' limit-setting and autonomy. Moreover, our analysis of the variance produced significant differences in the support perceived by the fathers and mothers of both groups. Lastly, the utility of results to propose intervention strategies within the family based on an authoritative style is discussed.

  1. Attention-deficit/hyperactivity disorder symptom levels and romantic relationship quality in college students.

    PubMed

    Bruner, Michael R; Kuryluk, Amanda D; Whitton, Sarah W

    2015-01-01

    The purpose of this study was to examine whether attention-deficit/hyperactivity disorder (ADHD) symptom levels in college undergraduates are associated with poorer romantic relationship quality, and to test whether emotion regulation difficulties, perceived stress, and hostile relationship conflict mediate this association. The sample consisted of 189 undergraduate students aged 18 to 25. Self-report measures of ADHD symptoms, relationship quality, and the proposed mediators were collected via online survey from May through August 2011. Participants who reported clinically significant levels of both hyperactivity-impulsivity and inattentiveness (consistent with ADHD-C) had lower relationship quality than those whose self-reported symptoms indicated no ADHD diagnosis. Further, for women only, both hyperactive-impulsive and inattentive symptom levels were negatively associated with relationship quality. Emotion regulation problems and hostile relationship conflict mediated this association. Findings suggest that ADHD impairs relationship quality among young adults and suggest mechanisms through which this impairment might occur.

  2. Does Sluggish Cognitive Tempo Fit within a Bi-factor Model of Attention-Deficit/Hyperactivity Disorder?

    PubMed Central

    Garner, Annie A.; Peugh, James; Becker, Stephen P.; Kingery, Kathleen M.; Tamm, Leanne; Vaughn, Aaron J.; Ciesielski, Heather; Simon, John O.; Loren, Richard E. A.; Epstein, Jeffery N.

    2014-01-01

    Objective Studies demonstrate sluggish cognitive tempo (SCT) symptoms to be distinct from inattentive and hyperactive-impulsive dimensions of Attention-Deficit/Hyperactivity Disorder (ADHD). No study has examined SCT within a bi-factor model of ADHD whereby SCT may form a specific factor distinct from inattention and hyperactivity/impulsivity while still fitting within a general ADHD factor, which was the purpose of the current study. Method 168 children were recruited from an ADHD clinic. Most (92%) met diagnostic criteria for ADHD. Parents and teachers completed measures of ADHD and SCT. Results Although SCT symptoms were strongly associated with inattention they loaded onto a factor independent of ADHD ‘g’. Results were consistent across parent and teacher ratings. Conclusions SCT is structurally distinct from inattention as well as from the general ADHD latent symptom structure. Findings support a growing body of research suggesting SCT to be distinct and separate from ADHD. PMID:25005039

  3. Does mindfulness meditation improve attention in attention deficit hyperactivity disorder?

    PubMed

    Modesto-Lowe, Vania; Farahmand, Pantea; Chaplin, Margaret; Sarro, Lauren

    2015-12-22

    Attention deficit hyperactivity disorder (ADHD) manifests by high levels of inattention, impulsiveness and hyperactivity. ADHD starts in childhood and results in impairments that continue into adulthood. While hyperactivity declines over time, inattention and executive function difficulties persist, leading to functional deficits. Adolescents and adults with ADHD have pervasive impairment in interpersonal and family relationships. They may develop addiction, delinquent behavior and comorbid psychiatric disorders. Despite advances in diagnosis and treatment, persistent residual symptoms are common, highlighting the need for novel treatment strategies. Mindfulness training, derived from Eastern meditation practices, may improve self-regulation of attention. It may also be a useful strategy to augment standard ADHD treatments and may be used as a potential tool to reduce impairments in patients with residual symptoms of ADHD. Clinically, this would manifest by an increased ability to suppress task-unrelated thoughts and distractions resulting in improved attention, completion of tasks and potential improvement in occupational and social function.

  4. ADHD in school-aged youth: Management and special treatment considerations in the primary care setting.

    PubMed

    Weed, Elizabeth D

    Attention-deficit/hyperactivity disorder is considered one of the most common neurodevelopmental disorders of childhood. Primary care providers are in the unique position of providing comprehensive care-routine care, well child visits, immunizations, and other healthcare needs-to a majority of children and adolescents with attention-deficit/hyperactivity disorder. As such, primary care providers are pivotal in the diagnosis, management, and treatment of this population. This article will address special treatment considerations to aid in the management of attention-deficit/hyperactivity disorder in the primary care setting, including substance use disorders and diversion, cardiac issues and stimulant medication, medication holidays and follow-up monitoring. The database of PubMed was searched using keywords that included attention-deficit/hyperactivity disorder, children, prevalence, medication holidays, safety, cardiovascular, cardiac, blood pressure, substance use, diversion, adverse drug reactions; inclusion dates were January 1, 2011 to September 30, 2015. © The Author(s) 2016.

  5. Neural basis of reward anticipation and its genetic determinants.

    PubMed

    Jia, Tianye; Macare, Christine; Desrivières, Sylvane; Gonzalez, Dante A; Tao, Chenyang; Ji, Xiaoxi; Ruggeri, Barbara; Nees, Frauke; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia J; Dove, Rachel; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny A; Heinz, Andreas; Ittermann, Bernd; Lathrop, Mark; Lemaitre, Hervé; Martinot, Jean-Luc; Paus, Tomáš; Pausova, Zdenka; Poline, Jean-Baptiste; Rietschel, Marcella; Robbins, Trevor; Smolka, Michael N; Müller, Christian P; Feng, Jianfeng; Rothenfluh, Adrian; Flor, Herta; Schumann, Gunter

    2016-04-05

    Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A (VPS4A) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila Our data provide a neurobehavioral model explaining the heterogeneity of reward-related behaviors and generate a hypothesis accounting for their enduring nature.

  6. The impact of a model-based clinical regional registry for attention-deficit hyperactivity disorder.

    PubMed

    Zanetti, Michele; Cartabia, Massimo; Didoni, Anna; Fortinguerra, Filomena; Reale, Laura; Mondini, Matteo; Bonati, Maurizio

    2017-09-01

    This article describes the development and clinical impact of the Italian Regional ADHD Registry, aimed at collecting and monitoring diagnostic and therapeutic pathways of care for attention-deficit hyperactivity disorder children and adolescents, launched by the Italian Lombardy Region in June 2011. In particular, the model-based software used to run the registry and manage clinical care data acquisition and monitoring, is described. This software was developed using the PROSAFE programme, which is already used for data collection in many Italian intensive care units, as a stand-alone interface case report form. The use of the attention-deficit hyperactivity disorder regional registry led to an increase in the appropriateness of the clinical management of all patients included in the registry, proving to be an important instrument in ensuring an appropriate healthcare strategy for children and adolescents with attention-deficit/hyperactivity disorder.

  7. Neural basis of reward anticipation and its genetic determinants

    PubMed Central

    Jia, Tianye; Macare, Christine; Desrivières, Sylvane; Gonzalez, Dante A.; Tao, Chenyang; Ji, Xiaoxi; Ruggeri, Barbara; Nees, Frauke; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L. W.; Bromberg, Uli; Büchel, Christian; Conrod, Patricia J.; Dove, Rachel; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny A.; Heinz, Andreas; Ittermann, Bernd; Lathrop, Mark; Lemaitre, Hervé; Martinot, Jean-Luc; Paus, Tomáš; Pausova, Zdenka; Poline, Jean-Baptiste; Rietschel, Marcella; Robbins, Trevor; Müller, Christian P.; Feng, Jianfeng; Rothenfluh, Adrian; Flor, Herta; Schumann, Gunter

    2016-01-01

    Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A (VPS4A) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila. Our data provide a neurobehavioral model explaining the heterogeneity of reward-related behaviors and generate a hypothesis accounting for their enduring nature. PMID:27001827

  8. Anxiety and methylphenidate in attention deficit hyperactivity disorder: a double-blind placebo-drug trial.

    PubMed

    Moshe, Keren; Karni, Avi; Tirosh, Emanuel

    2012-09-01

    To examine the relationship between attention and anxiety and the response to methylphenidate in children with attention deficit hyperactivity disorder (ADHD), a total of 57 boys, between the ages of 7-12 years, were assessed for their attention and level of anxiety. Methylphenidate was administered for a week in a randomized double-blind drug/placebo-drug cross-over design. The levels of anxiety were evenly distributed between the inattentive and hyperactive/impulsive types. Anxiety was significantly correlated with the attention as reported by both teachers and parents. The response to methylphenidate was inversely correlated with the reported anxiety level only in boys with the hyperactive/impulsive and combined types. The higher the level of anxiety, the lower level of response to methylphenidate was observed. In the assessment and treatment of children with ADHD, the level of anxiety should be evaluated and taken into account while planning and monitoring treatment regiment.

  9. Adult attention deficit hyperactivity disorder symptoms and five-factor model traits in a clinical sample: a structural equation modeling approach.

    PubMed

    Knouse, Laura E; Traeger, Lara; O'Cleirigh, Conall; Safren, Steven A

    2013-10-01

    Relationships among attention deficit hyperactivity disorder (ADHD) symptoms and adult personality traits have not been examined in larger clinically diagnosed samples. We collected multisource ADHD symptom and self-report NEO Five-Factor Inventory (Costa and McCrae [Odessa, FL: Psychological Assessment Resources, Inc, 1992) data from 117 adults with ADHD and tested symptom-trait associations using structural equation modeling. The final model fit the data. Inattention was positively associated with neuroticism and negatively associated with conscientiousness. On the basis of ADHD expression in adulthood, hyperactivity and impulsivity were estimated as separate constructs and showed differential relationships to extraversion and agreeableness. A significant positive relationship between hyperactivity and conscientiousness arose in the context of other pathways. ADHD symptoms are reliably associated with personality traits, suggesting a complex interplay across development that warrants prospective study into adulthood.

  10. Association between sleep problems and symptoms of attention-deficit/hyperactivity disorder in young adults.

    PubMed

    Gau, Susan S F; Kessler, Ronald C; Tseng, Wan-Ling; Wu, Yu-Yu; Chiu, Yen-Nan; Yeh, Chin-Bin; Hwu, Hai-Gwo

    2007-02-01

    To examine the association between sleep-related problems and symptoms of attention-deficit/hyperactivity disorder (ADHD) in a community sample of young adults in Taiwan. A college-based cross-sectional survey. Two thousand two hundred eighty-four first-year college students (aged 18-20) in a university in Taiwan. Each student completed a questionnaire regarding sleep schedule (self-estimated total sleep duration and sleep need), sleep problems (dyssomnia, parasomnia, and snoring), and the Chinese version of the Adult ADHD Self-Report Scale. Subjects were grouped separately for the inattention and hyperactivity subscales into highly likely ADHD (2.3%, 0.7%), probable ADHD (21.3%, 5.7%), and probably non-ADHD (76.4%, 93.6%) groups according to the scoring scheme of the subscales of the Adult ADHD Self-Report Scale. Results showed that, for both inattention and hyperactivity symptoms, the highly likely ADHD and probable ADHD groups were more likely than the non-ADHD group to have a variety of current and lifetime sleep problems. No significant difference in sleep problems was found between the highly likely ADHD and probable ADHD groups. Inattention, but not hyperactivity, was associated with greater sleep need and greater difference between sleep need and self-estimated nocturnal sleep duration. Hyperactivity, but not inattention, was associated with decreased nocturnal sleep duration. Consistent with prior findings from children and adolescents, ADHD symptoms in young adults are related to sleep problems. Further studies on adults with ADHD should help to refine our understanding of the causal basis for any implications of this association.

  11. Antecedents of Attention-Deficit/Hyperactivity Disorder symptoms in children born extremely preterm

    PubMed Central

    Johnson, Samantha; Kochhar, Puja; Hennessy, Enid; Marlow, Neil; Wolke, Dieter; Hollis, Chris

    2016-01-01

    Objective To investigate antecedents of Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in children born extremely preterm (EP; <26 weeks gestation). Method The EPICure Study recruited all babies born EP in the UK and Ireland in March-December 1995. Neurodevelopmental outcomes were assessed at 2.5 (n=283; 90%), 6 (n=160; 78%) and 11 (n=219; 71%) years of age. Parents and teachers completed the Du Paul Rating Scale-IV to assess inattention and hyperactivity/impulsivity symptoms at 11 years. Regression analyses were used to explore the association of neonatal, neurodevelopmental and behavioral outcomes to 6 years with ADHD symptoms at 11 years. Results EP children had significantly more inattention (mean difference 1.2 SD; 95% CI 0.9, 1.5) and hyperactivity/impulsivity (0.5 SD; 0.2, 0.7) than controls, with a significantly greater effect size for inattention than hyperactivity/impulsivity. Significant independent predictors of inattention at 11 years included smaller head circumference, lower IQ and pervasive peer relationship problems at 6 years, and motor development at 2.5 years. In contrast, significant independent predictors of hyperactivity/impulsivity included lower IQ, pervasive conduct problems and ADHD symptoms at 6 years, externalizing problems at 2.5 years and non-white maternal ethnicity. Conclusions EP children are at increased risk for ADHD symptoms, predominantly inattention, for which the antecedents differ by symptom domain. Attention deficits following EP birth were associated with poor brain growth and neurological function. Cognitive and behavioral assessments in early and middle childhood to identify neurodevelopmental and peer relationship problems may be beneficial for identifying EP children at risk for inattention. PMID:27096570

  12. Distinct dimensions defining the Adult ADHD Self-Report Scale: Implications for assessing inattentive and hyperactive/impulsive symptoms.

    PubMed

    Stanton, Kasey; Forbes, Miriam K; Zimmerman, Mark

    2018-06-07

    There has been growing interest in studying attention-deficit/hyperactivity disorder (ADHD) in adulthood as a result of research indicating that ADHD often persists into adulthood and frequently is comorbid with other psychiatric disorders. Adult ADHD symptoms are most commonly assessed via self-report, but prior research examining the structure of self-reported adult ADHD symptoms has yielded discrepant results. Explicating the factor structure of ADHD symptom measures is essential to determine if such self-report measures assess symptom dimensions showing distinctive relations with other psychopathology and psychosocial functioning. Consequently, we examined the structure of adult ADHD symptoms in a large sample of adult outpatients (N = 1,094). Symptoms were assessed via the Adult ADHD Self-Report Scale (ASRS; Kessler et al., 2005), which has become the most widely used self-report ADHD measure. Additionally, we extended prior research by examining the relations for emergent ADHD dimensions with other psychopathology and psychosocial impairment. Results indicated that the ASRS's items define a bifactor structure with specific dimensions of inattentiveness, motor hyperactivity/impulsivity, and verbal hyperactivity/impulsivity. Our results indicate that specific ADHD factors show distinctive relations in some ways. For example, verbal hyperactivity/impulsivity showed negative relations with major depressive disorder, whereas inattentiveness showed positive relations with major depression. These results highlight the need for future research determining the extent to which making distinctions among various ADHD symptom types (i.e., distinguishing motor and verbal hyperactivity/impulsivity) is empirically warranted and clinically useful. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  13. Bupropion hydrochloride produces conditioned hyperactivity in rats.

    PubMed

    Wilkinson, Jamie L; Bevins, Rick A

    2007-04-23

    Bupropion is marketed as an antidepressant, Wellbutrin and smoking cessation aid, Zyban. Although the therapeutic neurological mechanisms of bupropion have not been fully elucidated, bupropion shares some behavioral similarities with classic psychomotor stimulants. The present study sought to further investigate these psychomotor stimulant effects of bupropion by assessing whether repeated administration of bupropion in a distinct environment produced conditioned hyperactivity. Paired rats received 10 daily i.p. injections of bupropion (2.5-30 mg/kg) before placement in locomotor chambers for 30 min. Bupropion (10-30 mg/kg) produced acute locomotor hyperactivity compared to Unpaired controls. After repeated administration, there was no progressive increase or decrease in bupropion-induced activity. In a subsequent drug-free session conditioned hyperactivity was observed at 5-30 mg/kg doses. In a follow-up experiment, we examined whether responsiveness to novelty predicted the subsequent unconditioned and conditioned locomotor effect of bupropion. Reactivity to inescapable novelty, novel environment approach, and novel-object interaction were measured before locomotor conditioning with 30 mg/kg bupropion. We replicated the previous experiment, but scores on the novelty screens did not predict locomotor response to bupropion. This study extends the literature by demonstrating that environmental cues repeatedly paired with the stimulant effects of bupropion come to evoke elevated activity in the absence of drug (i.e., conditioned hyperactivity). This finding is consistent with the literature suggesting that bupropion shares many behavioral similarities with other psychomotor stimulants which also produce conditioned hyperactivity. However, a predictive relation between reactivity to forced novelty and the subsequent locomotor effect of bupropion may not be one of these similarities.

  14. Energy drinks and youth self-reported hyperactivity/inattention symptoms.

    PubMed

    Schwartz, Deborah L; Gilstad-Hayden, Kathryn; Carroll-Scott, Amy; Grilo, Stephanie A; McCaslin, Catherine; Schwartz, Marlene; Ickovics, Jeannette R

    2015-01-01

    To describe patterns in sweetened beverage consumption by race/ethnicity and sex, documenting both the amount and types of sweetened beverages consumed; and to examine the association of sweetened beverage consumption with hyperactivity/inattention symptoms among middle school students in a single urban school district. Middle school students (n = 1649; 47% Hispanic and 38% black, non-Hispanic) from 12 schools, randomly selected out of 27 district schools, completed health behavior surveys in fall 2011. Students reported quantity and types of sweetened beverages consumed in the past 24 hours and completed the 5-item Hyperactivity/Inattention subscale of the Strengths and Difficulties Questionnaire to measure symptoms. Amount and variety of reported sweetened beverage consumption (including energy drinks) were greater among boys versus girls and among black and Hispanic versus white students. Risk of hyperactivity/inattention increased by 14% for each additional sweetened beverage consumed, adjusting for age, race/ethnicity, sex, school lunch eligibility, family structure, and sugary food consumption. Students reporting consumption of energy drinks were 66% more likely to be at risk for hyperactivity/inattention after adjusting for number of drinks, other types of drinks consumed, and other potential confounders. Results support recommendations to limit consumption of sweetened beverages and to avoid consumption of energy drinks among children. Interventions to reduce sweetened beverage consumption should explicitly focus on energy drinks and other emerging sweetened beverages such as sports and sweetened coffee drinks. More research is needed to understand the direction of effects and the mechanisms behind the association between sweetened beverages and hyperactivity/inattention symptoms. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  15. Childhood attention-deficit/hyperactivity disorder symptoms and the development of adolescent alcohol problems: A prospective, population-based study of Swedish twins.

    PubMed

    Quinn, Patrick D; Pettersson, Erik; Lundström, Sebastian; Anckarsäter, Henrik; Långström, Niklas; Gumpert, Clara Hellner; Larsson, Henrik; Lichtenstein, Paul; D'Onofrio, Brian M

    2016-10-01

    Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of problematic alcohol and other substance use in adolescence. This study used data from an ongoing, prospective, population-based twin study of Swedish children and adolescents to evaluate the extent to which the association between ADHD symptoms and alcohol problems reflects a unique source of genetic or environmental risk related to ADHD versus a broader predisposition to youth externalizing behavior. We used all available data from same-sex monozygotic (MZ) and dizygotic (DZ) twins on ADHD symptoms in childhood (age 9/12; N = 15,549) and alcohol problems in late adolescence (age 18; N = 2,564). Consistent with prior longitudinal studies, the phenotypic association between hyperactive/impulsive ADHD symptoms and alcohol problems was small in magnitude, whereas the association for inattentive symptoms was even weaker. Additive genetic influences explained 99.8% of the association between hyperactive/impulsive symptoms and alcohol problems. Furthermore, we found that the genetic risk specifically associated with hyperactive/impulsive symptoms was attenuated when estimated in the context of externalizing behavior liability during childhood, of which ADHD symptoms were specific expressions. In sensitivity analyses exploring hyperactivity in mid-adolescence, we found a similar pattern of genetic associations. These results are consistent with previous findings of genetically driven overlap in the etiology of ADHD and problematic alcohol use. At least some of this co-occurrence may result from a general predisposition to externalizing behaviors in youth. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  16. Dopamine Transporter Genotype Conveys Familial Risk of Attention-Deficit/Hyperactivity Disorder through Striatal Activation

    ERIC Educational Resources Information Center

    Durston, Sarah; Fossella, John A.; Mulder, Martijn J.; Casey B. J.; Ziermans, Tim B.; Vessaz, M. Nathalie; Van Engeland, Herman

    2008-01-01

    The study examines the effect of the dopamine transporter (DAT1) genotype in attention-deficit/hyperactivity disorder (ADHD). The results confirm that DAT1 translates the genetic risk of ADHD through striatal activation.

  17. Research: Hyperactivity, Placement Centers

    ERIC Educational Resources Information Center

    Nation's Schools and Colleges, 1975

    1975-01-01

    A diet that emphasizes the elimination of food containing artificial coloring and flavoring from meals served to hyperactive children has met with success in preliminary studies; college placement centers are advised to shift their emphasis from job research and counseling. (Author/MLF)

  18. Narrative Intervention: A School-Based Counseling Strategy for Students with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Kamali, Khosrow; Yoosefi Looyeh, Majid

    2013-01-01

    This article describes a group narrative intervention for improving the behavior of 8- to 11-year-old children with attention-deficit/hyperactivity disorder at home and school. (Contains 2 tables and 1 note.)

  19. Spider wrapping silk fibre architecture arising from its modular soluble protein precursor

    NASA Astrophysics Data System (ADS)

    Tremblay, Marie-Laurence; Xu, Lingling; Lefèvre, Thierry; Sarker, Muzaddid; Orrell, Kathleen E.; Leclerc, Jérémie; Meng, Qing; Pézolet, Michel; Auger, Michèle; Liu, Xiang-Qin; Rainey, Jan K.

    2015-06-01

    Spiders store spidroins in their silk glands as high concentration aqueous solutions, spinning these dopes into fibres with outstanding mechanical properties. Aciniform (or wrapping) silk is the toughest spider silk and is devoid of the short amino acid sequence motifs characteristic of the other spidroins. Using solution-state NMR spectroscopy, we demonstrate that the 200 amino acid Argiope trifasciata AcSp1 repeat unit contrasts with previously characterized spidroins, adopting a globular 5-helix bundle flanked by intrinsically disordered N- and C-terminal tails. Split-intein-mediated segmental NMR-active isotope-enrichment allowed unambiguous demonstration of modular and malleable “beads-on-a-string” concatemeric behaviour. Concatemers form fibres upon manual drawing with silk-like morphology and mechanical properties, alongside secondary structuring and orientation consistent with native AcSp1 fibres. AcSp1 structural stability varies locally, with the fifth helix denaturing most readily. The structural transition of aciniform spidroin from a mostly α-helical dope to a mixed α-helix/β-sheet-containing fibre can be directly related to spidroin architecture and stability.

  20. Conditional genomic rearrangement by designed meiotic recombination using VDE (PI-SceI) in yeast.

    PubMed

    Fukuda, Tomoyuki; Ohya, Yoshikazu; Ohta, Kunihiro

    2007-10-01

    Meiotic recombination plays critical roles in the acquisition of genetic diversity and has been utilized for conventional breeding of livestock and crops. The frequency of meiotic recombination is normally low, and is extremely low in regions called "recombination cold domains". Here, we describe a new and highly efficient method to modulate yeast meiotic gene rearrangements using VDE (PI-SceI), an intein-encoded endonuclease that causes an efficient unidirectional meiotic gene conversion at its recognition sequence (VRS). We designed universal targeting vectors, by use of which the strain that inserts the VRS at a desired site is acquired. Meiotic induction of the strains provided unidirectional gene conversions and frequent genetic rearrangements of flanking genes with little impact on cell viability. This system thus opens the way for the designed modulation of meiotic gene rearrangements, regardless of recombinational activity of chromosomal domains. Finally, the VDE-VRS system enabled us to conduct meiosis-specific conditional knockout of genes where VDE-initiated gene conversion disrupts the target gene during meiosis, serving as a novel approach to examine the functions of genes during germination of resultant spores.

  1. Behavioral Approach in ADHD: Testing a Motivational Dysfunction Hypothesis

    ERIC Educational Resources Information Center

    Mitchell, John T.

    2010-01-01

    Objective: Etiological models of attention-deficit hyperactivity disorder (ADHD) increasingly support the role of a motivational dysfunction pathway, particularly for hyperactive-impulsive symptoms. Overactive behavioral approach tendencies are implicated among these motivational accounts. However, other externalizing disorder symptoms, such as…

  2. Exercise: Applications to Childhood ADHD

    ERIC Educational Resources Information Center

    Wigal, Sharon B.; Emmerson, Natasha; Gehricke, Jean-G.; Galassetti, Pietro

    2013-01-01

    ADHD is the most common neurobehavioral disorder of childhood, presenting with pervasive and impairing symptoms of inattention, hyperactivity, impulsivity, or a combination. The leading hypothesis of the underlying physiology of this disorder of inattention and/or hyperactivity-impulsivity is based on catecholamine dysfunction. Pharmacotherapy…

  3. 77 FR 3275 - Government-Owned Inventions; Availability for Licensing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-23

    ... Predict Attention Deficit Hyperactivity Disorder Outcome and Severity Description of Technology: Genotyping of attention deficit hyperactivity disorder (ADHD) linked chromosomal regions containing single... storage disorder--murine Pompe disease. Autophagy. 2010 Nov;6(8):1078-1089. [PMID 20861693]. 2. Raben N...

  4. Did goethe describe attention deficit hyperactivity disorder?

    PubMed

    Bonazza, Sara; Scaglione, Cesa; Poppi, Massimo; Rizzo, Giovanni

    2011-01-01

    As early as 1846, the typical symptoms of attention deficit hyperactivity disorder (ADHD) were described by Heinrich Hoffmann (1809-1894). However, in Goethe's masterpiece Faust (1832), the character of Euphorion strongly suggests ADHD diagnosis. Copyright © 2011 S. Karger AG, Basel.

  5. Marijuana use is associated with inattention in men and sleep quality in women with Attention-Deficit/Hyperactivity Disorder: a preliminary study.

    PubMed

    Ly, Christine; Gehricke, Jean-G

    2013-12-30

    The study examined the association between marijuana use, Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms, and sleep quality in 56 men and 20 women with ADHD. Participants, ages 18-45, were assessed with the Assessment of Hyperactivity and Attention, drug use survey, and Pittsburgh Sleep Quality Index. Moderate to strong correlations were found between marijuana use and inattentive symptoms in men, and marijuana use and decreased sleep quality in women. Men and women with ADHD may use marijuana for different reasons. © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Management of a hyperactive teen and cardiac safety.

    PubMed

    Sowinski, Heather; Karpawich, Peter P

    2014-02-01

    Since the earliest descriptions of the condition, controversy has prevailed as to the existence of as well as appropriate management of attention deficit hyperactivity disorder. Often diagnosed in childhood, symptoms of attention deficit hyperactivity disorder can continue into adolescence and adulthood, requiring lifelong therapy. Effective therapeutic interventions include stimulant medications with all their respective potential side effects, including the cardiovascular system. However, although initial studies raised concerns for an increase in serious adverse cardiovascular effects among children receiving these drugs, more recent and extensive reports have failed to substantiate those findings among young patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Pharmacological analysis of zebrafish lphn3.1 morphant larvae suggests that saturated dopaminergic signaling could underlie the ADHD-like locomotor hyperactivity.

    PubMed

    Lange, Merlin; Froc, Cynthia; Grunwald, Hannah; Norton, William H J; Bally-Cuif, Laure

    2018-06-08

    Polymorphisms in the gene coding for the adhesion G-protein coupled receptor LPHN3 are a risk factor for attention-deficit/hyperactivity disorder (ADHD). Transient down-regulation of latrophilin3.1 (lphn3.1), the zebrafish LPHN3 homologue, causes hyperactivity. Zebrafish injected with a lphn3.1-specific morpholino are hyperactive and display an impairment in dopaminergic neuron development. In the present study we used lphn3.1 morphants to further characterize the changes to dopaminergic signaling that trigger hyperactivity. We applied dopamine agonists (Apomorphine, Quinpirole, SKF-38393) and antagonists (Haloperidol, Eticlopride, SCH-23390) to Lphn3.1 morpholino-injected or control-injected animals. The percentage of change in locomotor activity was then determined at three different time periods (10-20 min, 30-40 min and 60-70 min). Our results show that drugs targeting dopamine receptors appear to elicit similar effects on locomotion in zebrafish larvae and mammals. In addition, we observed that lphn3.1 morphants have an overall hyposensitivity to dopamine agonists and antagonists compared to control fish. These results are compatible with a model whereby dopaminergic neurotransmission is saturated in lphn3.1 morphants. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Personality profiles in adults with attention deficit hyperactivity disorder (ADHD).

    PubMed

    Perroud, Nader; Hasler, Roland; Golay, Nicolas; Zimmermann, Julien; Prada, Paco; Nicastro, Rosetta; Aubry, Jean-Michel; Ardu, Stefano; Herrmann, François R; Giannakopoulos, Panteleimon; Baud, Patrick

    2016-06-14

    Previous studies suggested that the presence of ADHD in children and young adolescents may affect the development of personality. Whether or not the persistence of ADHD in adult life is associated with distinct personality patterns is still matter for debate. To address this issue, we compared the profiles of the Temperament and Character Inventory (TCI) that assesses personality dimensions in 119 adults ADHD and 403 controls. ANCOVA were used to examine group differences (controls vs. ADHD and ADHD inattentive type vs. ADHD combined + hyperactive/impulsive types) in Temperaments and Characters. Partial correlation coefficients were used to assess correlation between TCI and expression and severity of symptoms of ADHD. High novelty seeking (NS), harm avoidance (HA) and self-transcendence (ST) scores as well as low self-directedness (SD) and cooperativeness (C) scores were associated with ADHD diagnosis. Low SD was the strongest personality trait associated with adult ADHD. Cases with the ADHD inattentive type showed higher HA and lower SD scores compared to the combined and hyperactive/impulsive types. High HA scores correlated with inattention symptoms whereas high NS and ST scores were related to hyperactive symptoms. Finally low SD and high NS were associated with increased ADHD severity. Distinct temperaments were associated with inattentive versus hyperactive/impulsive symptoms supporting the heterogeneous nature of the disorder.

  9. Deficiency of tumor suppressor NDRG2 leads to attention deficit and hyperactive behavior.

    PubMed

    Li, Yan; Yin, Anqi; Sun, Xin; Zhang, Ming; Zhang, Jianfang; Wang, Ping; Xie, Rougang; Li, Wen; Fan, Ze; Zhu, Yuanyuan; Wang, Han; Dong, Hailong; Wu, Shengxi; Xiong, Lize

    2017-12-01

    Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder in children. Although an imbalance of excitatory and inhibitory inputs has been proposed as contributing to this disorder, the mechanisms underlying this highly heterogeneous disease remain largely unknown. Here, we show that N-myc downstream-regulated gene 2 (NDRG2) deficiency is involved in the development of ADHD in both mice and humans. Ndrg2-knockout (Ndrg2-/-) mice exhibited ADHD-like symptoms characterized by attention deficits, hyperactivity, impulsivity, and impaired memory. Furthermore, interstitial glutamate levels and excitatory transmission were markedly increased in the brains of Ndrg2-/- mice due to reduced astroglial glutamate clearance. We developed an NDRG2 peptide that rescued astroglial glutamate clearance and reduced excitatory glutamate transmission in NDRG2-deficient astrocytes. Additionally, NDRG2 peptide treatment rescued ADHD-like hyperactivity in the Ndrg2-/- mice, while routine methylphenidate treatment had no effect on hyperactivity in these animals. Finally, children who were heterozygous for rs1998848, a SNP in NDRG2, had a higher risk of ADHD than children who were homozygous for rs1998848. Our results indicate that NDRG2 deficiency leads to ADHD phenotypes and that impaired astroglial glutamate clearance, a mechanism distinct from the well-established dopamine deficit hypothesis for ADHD, underlies the resultant behavioral abnormalities.

  10. The ataxic mouse as a model for studying downbeat nystagmus.

    PubMed

    Stahl, John S; Thumser, Zachary C; Oommen, Brian S

    2012-01-01

    Downbeat nystagmus (DBN) is a common eye movement complication of cerebellar disease. Use of mice to study pathophysiology of vestibulocerebellar disease is increasing, but it is unclear if mice can be used to study DBN; it has not been reported in this species. We determined whether DBN occurs in the ataxic mutant tottering, which carries a mutation in the Cacna1a gene for P/Q calcium channels. Spontaneous DBN occurred only rarely, and its magnitude did not exhibit the relationship to head tilt seen in human patients. DBN during yaw rotation was more common and shares some properties with the tilt-independent, gaze-independent component of human DBN, but differs in its dependence on vision. Hyperactivity of otolith circuits responding to pitch tilts is hypothesized to contribute to the gaze-independent component of human DBN. Mutants exhibited hyperactivity of the tilt maculo-ocular reflex (tiltMOR) in pitch. The hyperactivity may serve as a surrogate for DBN in mouse studies. TiltMOR hyperactivity correlates with hyperdeviation of the eyes and upward deviation of the head during ambulation; these may be alternative surrogates. Muscimol inactivation of the cerebellar flocculus suggests a floccular role in the tiltMOR hyperactivity and provides insight into the rarity of frank DBN in ataxic mice.

  11. The ataxic mouse as a model for studying downbeat nystagmus

    PubMed Central

    Stahl, John S.; Thumser, Zachary C.; Oommen, Brian S.

    2016-01-01

    Downbeat nystagmus (DBN) is a common eye movement complication of cerebellar disease. Use of mice to study pathophysiology of vestibulocerebellar disease is increasing, but it is unclear if mice can be used to study DBN; it has not been reported in this species. We determined whether DBN occurs in the ataxic mutant tottering, which carries a mutation in the Cacna1a gene for P/Q calcium channels. Spontaneous DBN occurred only rarely, and its magnitude did not exhibit the relationship to head tilt seen in human patients. DBN during yaw rotation was more common and shares some properties with the tilt-independent, gaze-independent component of human DBN, but differs in its dependence on vision. Hyperactivity of otolith circuits responding to pitch tilts is hypothesized to contribute to the gaze-independent component of human DBN. Mutants exhibited hyperactivity of the tilt maculo-ocular reflex (tiltMOR) in pitch. The hyperactivity may serve as a surrogate for DBN in mouse studies. TiltMOR hyperactivity correlates with hyperdeviation of the eyes and upward deviation of the head during ambulation; these may be alternative surrogates. Muscimol inactivation of the cerebellar flocculus suggests a floccular role in the tiltMOR hyperactivity and provides insight into the rarity of frank DBN in ataxic mice. PMID:23302704

  12. Hyperactivity induced by stimulation of separate dopamine D-1 and D-2 receptors in rats with bilateral 6-OHDA lesions.

    PubMed

    Arnt, J

    1985-08-26

    The effects of DA agonists and antagonists with different dopamine (DA) D-1 and D-2 receptor selectivity have been studied in rats with bilateral 6-OHDA lesions. The D-1 agonist SK & F 38393, the D-2 agonist pergolide and the mixed agonist apomorphine all induced marked hyperactivity in lesioned rats in doses which were without stimulant effect in sham-operated animals. The hyperactivity induced by SK & F 38393 was blocked by the DA D-1 antagonist SCH 23390, but unaffected by the D-2 antagonists spiroperidol or clebopride. Pergolide-induced hyperactivity showed the reverse selectivity. The mixed D-1/D-2 antagonists, cis(Z)-flupentixol and cis(Z)-clopenthixol, however blocked the effect of both agonists. Apomorphine-induced hyperactivity was neither blocked by selective D-1 nor D-2 antagonists, but was dose-dependently inhibited by cis(Z)-flupentixol and cis(Z)-clopenthixol. Potent blockade was also obtained by combined treatment with SCH 23390 and spiroperidol, indicating the need of blocking both D-1 and D-2 receptors simultaneously. The results indicate that D-1 and D-2 receptor function can be independently manipulated in denervated rats and they confirm similar results obtained in rats with unilateral 6-OHDA lesions using circling behaviour.

  13. Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.

    PubMed

    Goldstein, Jill M; Lancaster, Katie; Longenecker, Julia M; Abbs, Brandon; Holsen, Laura M; Cherkerzian, Sara; Whitfield-Gabrieli, Susan; Makris, Nicolas; Tsuang, Ming T; Buka, Stephen L; Seidman, Larry J; Klibanski, Anne

    2015-06-30

    Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. The association between attention-deficit/hyperactivity (ADHD) symptoms and self-employment.

    PubMed

    Verheul, Ingrid; Rietdijk, Wim; Block, Joern; Franken, Ingmar; Larsson, Henrik; Thurik, Roy

    2016-08-01

    Attention-deficit/hyperactivity (ADHD) symptoms have been associated with the decision to become self-employed. Although these symptoms are generally regarded as disadvantageous, there may also be a bright side. To our knowledge, however, there has been no systematic, epidemiological evidence to support this claim. This paper examines the association between ADHD symptoms and self-employment in a population-based sample from the STAGE cohort of the Swedish Twin Registry (N = 7208). For replication, we used a sample of Dutch students who participated in the Global University Entrepreneurial Spirit Students' Survey (N = 13,112). In the Swedish sample, we found a positive association with self-employment for both general ADHD symptoms [odds ratio (OR) 1.13; 95 % confidence intervals (CI) 1.04-1.23] and hyperactivity symptoms [OR 1.19; 95 % CI 1.08-1.32], whereas no association was found for attention-deficit symptoms [OR 0.99; 95 % CI 0.89-1.10]. The positive association between hyperactivity and self-employment was replicated in the Dutch student sample [OR 1.09; 95 % CI 1.03-1.15]. Our results show that certain aspects of ADHD, in particular hyperactivity, can have a bright side, as they are positively associated with self-employment.

  15. INCLEN diagnostic tool for attention deficit hyperactivity disorder (INDT-ADHD): development and validation.

    PubMed

    Mukherjee, Sharmila; Aneja, Satinder; Russell, Paul S S; Gulati, Sheffali; Deshmukh, Vaishali; Sagar, Rajesh; Silberberg, Donald; Bhutani, Vinod K; Pinto, Jennifer M; Durkin, Maureen; Pandey, Ravindra M; Nair, M K C; Arora, Narendra K

    2014-06-01

    To develop and validate INCLEN Diagnostic Tool for Attention Deficit Hyperactivity Disorder (INDT-ADHD). Diagnostic test evaluation by cross sectional design. Tertiary care pediatric centers. 156 children aged 65-117 months. After randomization, INDT-ADHD and Connors 3 Parent Rating Scale (C3PS) were administered, followed by an expert evaluation by DSM-IV-TR diagnostic criteria. Psychometric evaluation of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency. INDT-ADHD had 18 items that quantified symptoms and impairment. Attention deficit hyperactivity disorder was identified in 57, 87 and 116 children by expert evaluation, INDT-ADHD and C3PS, respectively. Psychometric parameters of INDT-ADHD for differentiating attention deficit hyperactivity disorder and normal children were: sensitivity 87.7%, specificity 97.2%, positive predictive value 98.0% and negative predictive value 83.3%, whereas for differentiating from other neuro-developmental disorders were 87.7%, 42.9%, 58.1% and 79.4%, respectively. Internal consistency was 0.91. INDT-ADHD has a 4-factor structure explaining 60.4% of the variance. Convergent validity with Conner's Parents Rating Scale was moderate (r =0.73, P= 0.001). INDT-ADHD is suitable for diagnosing attention deficit hyperactivity disorder in Indian children between the ages of 6 to 9 years.

  16. Disagreeing about development: An analysis of parent-teacher agreement in ADHD symptom trajectories across the elementary school years.

    PubMed

    Murray, Aja Louise; Booth, Tom; Ribeaud, Denis; Eisner, Manuel

    2018-05-30

    It is well-known that in cross-sectional analyses, agreement between informants is modest as best when rating attention-deficit/hyperactivity disorder and other disruptive behaviour disorder symptoms. We here aimed to develop recommendations for the use of multi-informant data in the context of longitudinal developmental analyses that examine symptom trajectories over time. Using parallel process modelling, we estimated parent-teacher agreement in inattention and hyperactivity/impulsivity symptom initial levels and slopes across the elementary school years (ages 7, 9, and 11) for a community sample of n = 1,388 youth. We also used these models to examine whether initial levels and slopes differed significantly across informants. Informant agreement was low to moderate and higher for inattention slopes (r = .47) than for hyperactivity/impulsivity slopes (r = .23). Parents and teachers reported opposite developmental trends for inattention with teachers reporting declines and parents reporting increases over time. Parents reported overall higher levels of hyperactivity/impulsivity, but there were no average informant differences in slopes. Of the options available, we recommend specifying separate but correlated factors for different informants in developmental analyses of attention-deficit/hyperactivity disorder. This can be achieved within latent growth curve and growth mixture models. Copyright © 2018 John Wiley & Sons, Ltd.

  17. Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spices

    PubMed Central

    Pezzoli, Maurizio; Elhamdani, Abdeladim; Camacho, Susana; Meystre, Julie; González, Stephanie Michlig; le Coutre, Johannes; Markram, Henry

    2014-01-01

    Active ingredients of spices (AIS) modulate neural response in the peripheral nervous system, mainly through interaction with TRP channel/receptors. The present study explores how different AIS modulate neural response in layer 5 pyramidal neurons of S1 neocortex. The AIS tested are agonists of TRPV1/3, TRPM8 or TRPA1. Our results demonstrate that capsaicin, eugenol, menthol, icilin and cinnamaldehyde, but not AITC dampen the generation of APs in a voltage- and time-dependent manner. This effect was further tested for the TRPM8 ligands in the presence of a TRPM8 blocker (BCTC) and on TRPM8 KO mice. The observable effect was still present. Finally, the influence of the selected AIS was tested on in vitro gabazine-induced seizures. Results coincide with the above observations: except for cinnamaldehyde, the same AIS were able to reduce the number, duration of the AP bursts and increase the concentration of gabazine needed to elicit them. In conclusion, our data suggests that some of these AIS can modulate glutamatergic neurons in the brain through a TRP-independent pathway, regardless of whether the neurons are stimulated intracellularly or by hyperactive microcircuitry. PMID:25359561

  18. Serum protein profiling and proteomics in autistic spectrum disorder using magnetic bead-assisted mass spectrometry.

    PubMed

    Taurines, Regina; Dudley, Edward; Conner, Alexander C; Grassl, Julia; Jans, Thomas; Guderian, Frank; Mehler-Wex, Claudia; Warnke, Andreas; Gerlach, Manfred; Thome, Johannes

    2010-04-01

    The pathophysiology of autistic spectrum disorder (ASD) is not fully understood and there are no diagnostic or predictive biomarkers. Proteomic profiling has been used in the past for biomarker research in several non-psychiatric and psychiatric disorders and could provide new insights, potentially presenting a useful tool for generating such biomarkers in autism. Serum protein pre-fractionation with C8-magnetic beads and protein profiling by matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-ToF-MS) were used to identify possible differences in protein profiles in patients and controls. Serum was obtained from 16 patients (aged 8-18) and age-matched controls. Three peaks in the MALDI-ToF-MS significantly differentiated the ASD sample from the control group. Sub-grouping the ASD patients into children with and without comorbid Attention Deficit and Hyperactivity Disorder, ADHD (ASD/ADHD+ patients, n = 9; ASD/ADHD- patients, n = 7), one peak distinguished the ASD/ADHD+ patients from controls and ASD/ADHD- patients. Our results suggest that altered protein levels in peripheral blood of patients with ASD might represent useful biomarkers for this devastating psychiatric disorder.

  19. Clock Genes and Altered Sleep–Wake Rhythms: Their Role in the Development of Psychiatric Disorders

    PubMed Central

    Charrier, Annaëlle; Olliac, Bertrand; Roubertoux, Pierre; Tordjman, Sylvie

    2017-01-01

    In mammals, the circadian clocks network (central and peripheral oscillators) controls circadian rhythms and orchestrates the expression of a range of downstream genes, allowing the organism to anticipate and adapt to environmental changes. Beyond their role in circadian rhythms, several studies have highlighted that circadian clock genes may have a more widespread physiological effect on cognition, mood, and reward-related behaviors. Furthermore, single nucleotide polymorphisms in core circadian clock genes have been associated with psychiatric disorders (such as autism spectrum disorder, schizophrenia, anxiety disorders, major depressive disorder, bipolar disorder, and attention deficit hyperactivity disorder). However, the underlying mechanisms of these associations remain to be ascertained and the cause–effect relationships are not clearly established. The objective of this article is to clarify the role of clock genes and altered sleep–wake rhythms in the development of psychiatric disorders (sleep problems are often observed at early onset of psychiatric disorders). First, the molecular mechanisms of circadian rhythms are described. Then, the relationships between disrupted circadian rhythms, including sleep–wake rhythms, and psychiatric disorders are discussed. Further research may open interesting perspectives with promising avenues for early detection and therapeutic intervention in psychiatric disorders. PMID:28468274

  20. Clock Genes and Altered Sleep-Wake Rhythms: Their Role in the Development of Psychiatric Disorders.

    PubMed

    Charrier, Annaëlle; Olliac, Bertrand; Roubertoux, Pierre; Tordjman, Sylvie

    2017-04-29

    In mammals, the circadian clocks network (central and peripheral oscillators) controls circadian rhythms and orchestrates the expression of a range of downstream genes, allowing the organism to anticipate and adapt to environmental changes. Beyond their role in circadian rhythms, several studies have highlighted that circadian clock genes may have a more widespread physiological effect on cognition, mood, and reward-related behaviors. Furthermore, single nucleotide polymorphisms in core circadian clock genes have been associated with psychiatric disorders (such as autism spectrum disorder, schizophrenia, anxiety disorders, major depressive disorder, bipolar disorder, and attention deficit hyperactivity disorder). However, the underlying mechanisms of these associations remain to be ascertained and the cause-effect relationships are not clearly established. The objective of this article is to clarify the role of clock genes and altered sleep-wake rhythms in the development of psychiatric disorders (sleep problems are often observed at early onset of psychiatric disorders). First, the molecular mechanisms of circadian rhythms are described. Then, the relationships between disrupted circadian rhythms, including sleep-wake rhythms, and psychiatric disorders are discussed. Further research may open interesting perspectives with promising avenues for early detection and therapeutic intervention in psychiatric disorders.

  1. Helping the Hyperactive Child.

    ERIC Educational Resources Information Center

    Texas State Dept. of Mental Health and Mental Retardation, Austin.

    This brief booklet discusses the characteristics, causes, and treatments of attention deficit disorders with hyperactivity. Although children with this condition may be overly active, fidgety, distractible, aggressive, impulsive, and have difficulty learning, the primary problem is their inability to concentrate and pay attention. The exact origin…

  2. Language Impairment in the Attention-Deficit/Hyperactivity Disorder Context

    ERIC Educational Resources Information Center

    Redmond, Sean M.

    2016-01-01

    Purpose: Attention-deficit/hyperactivity disorder (ADHD) is a ubiquitous designation that affects the identification, assessment, treatment, and study of pediatric language impairments (LIs). Method: Current literature is reviewed in 4 areas: (a) the capacity of psycholinguistic, neuropsychological, and socioemotional behavioral indices to…

  3. Validation of the Classroom Behavior Inventory

    ERIC Educational Resources Information Center

    Blunden, Dale; And Others

    1974-01-01

    Factor-analytic methods were used toassess contruct validity of the Classroom Behavior Inventory, a scale for rating behaviors associated with hyperactivity. The Classroom Behavior Inventory measures three dimensions of behavior: Hyperactivity, Hostility, and Sociability. Significant concurrent validity was obtained for only one Classroom Behavior…

  4. What Exactly Are the Benefits of Stimulants for ADHD?

    ERIC Educational Resources Information Center

    Advokat, Claire

    2009-01-01

    Stimulant drugs (methylphenidate and amphetamine) have been used successfully for decades to improve the behavioral impairments of hyperactivity, impulsivity, and inattention in children diagnosed with attention-deficit/hyperactivity disorder (ADHD). A voluminous literature supports the benefits of stimulants for improving classroom manageability…

  5. Assessment and Classification of Attention Deficit Hyperactive Disorders.

    ERIC Educational Resources Information Center

    Schaughency, Elizabeth A.; Rothlind, Johannes

    1991-01-01

    Issues concerning evaluation, assessment, and classification of Attention-Deficit Hyperactive Disorders (ADHD) are discussed. The diagnosis of ADHD should be a best-estimate diagnosis, based on a behavioral assessment strategy with multimethod assessment. The selection and use of assessment techniques are discussed. (SLD)

  6. A Support Group Offers Help for Parents of Hyperactive Children.

    ERIC Educational Resources Information Center

    Pond, Elizabeth F.; Gilbert, Charlotte M.

    1987-01-01

    Describes the development of a parents' support group in Augusta, Georgia which offers parents of hyperactive and Attention Deficit Disorder (ADD) children an opportunity to share experiences and explore problem-solving strategies for coping with and managing their children. (Author/BB)

  7. Relative benefits of stimulant therapy with OROS methylphenidate versus mixed amphetamine salts extended release in improving the driving performance of adolescent drivers with attention-deficit/hyperactivity disorder.

    PubMed

    Cox, Daniel J; Merkel, R Lawrence; Moore, Melissa; Thorndike, Frances; Muller, Carrie; Kovatchev, Boris

    2006-09-01

    Automobile accidents are the leading cause of death among adolescents, and collisions are 2 to 4 times more likely to occur among adolescents with attention-deficit/hyperactivity disorder. Studies have demonstrated that stimulants improve driving performance. This study compared 2 long-acting stimulant medications during daytime and evening driving evaluations. Adolescent drivers with attention-deficit/hyperactivity disorder were compared on a driving simulator after taking 72 mg of OROS methylphenidate, 30 mg of mixed amphetamine salts extended release, or placebo in a randomized, double-blind, placebo-controlled, crossover study design. During laboratory testing, adolescents drove a driving simulator at 5:00 pm, 8:00 pm, and 11:00 pm. Driving performance was rated by adolescents and investigators. The study included 35 adolescent drivers with attention-deficit/hyperactivity disorder (19 boys/16 girls). The mean age was 17.8 years. The overall Impaired Driving Score demonstrated that OROS methylphenidate led to better driving performance compared with placebo and mixed amphetamine salts extended release, whereas mixed amphetamine salts extended release demonstrated no statistical improvement over placebo. Specifically, relative to placebo, OROS methylphenidate resulted in less time driving off the road, fewer instances of speeding, less erratic speed control, more time executing left turns, and less inappropriate use of brakes. OROS methylphenidate and mixed amphetamine salts extended release worked equally well for male and female adolescents and equally as well with teenagers who have combined and inattentive subtypes of attention-deficit/hyperactivity disorder. This study validates the use of stimulants to improve driving performance in adolescents with attention-deficit/hyperactivity disorder. In the study, OROS methylphenidate promoted significantly improved driving performance compared with placebo and mixed amphetamine salts extended release.

  8. Role of Prefrontal Serotonergic and Dopaminergic Systems in Encounter-Induced Hyperactivity in Methamphetamine-Sensitized Mice.

    PubMed

    Tanaka, Tatsunori; Ago, Yukio; Umehara, Chiaki; Imoto, Emina; Hasebe, Shigeru; Hashimoto, Hitoshi; Takuma, Kazuhiro; Matsuda, Toshio

    2017-05-01

    Isolation-reared mice show social encounter-induced hyperactivity with activation of prefrontal serotonergic and dopaminergic systems, but it is not known whether this stress response is observed in other pathological conditions. Here we examined whether the social encounter stimulation induces abnormal behavior during withdrawal in chronic methamphetamine-treated mice. To induce methamphetamine-induced behavioral sensitization, male mice were injected with methamphetamine (1 mg/kg) once daily for 7 days. The encounter with an intruder elicited hyperactivity 24 h after the last injection of methamphetamine in methamphetamine-sensitized mice. This response was observed even as long as 2 weeks after withdrawal of methamphetamine. The encounter increased c-Fos expression in the prefrontal cortex, dorsal raphe nucleus and ventral tegmental area in methamphetamine-sensitized mice, while it did not in control mice. Furthermore, the encounter increased extracellular serotonin (5-HT) and dopamine, but not noradrenaline, levels in the prefrontal cortex in methamphetamine-sensitized mice. Local injection of 5,7-dihydroxytryptamine and 6-hydroxydopamine into the prefrontal cortex attenuated encounter-induced hyperactivity in methamphetamine-sensitized mice and it markedly decreased prefrontal 5-HT and dopamine levels, respectively. Pharmacological analysis showed that the encounter-induced hyperactivity is mediated by dopamine D1 receptors and 5-HT2A receptors and attenuated by anxiolytics and antidepressants such as diazepam, osemozotan and selective 5-HT reuptake inhibitors. The effect of paroxetine was blocked by the 5-HT3 receptor antagonist azasetron. The present study shows that psychological stress elicits hyperactivity with activation of prefrontal 5-HT and dopamine systems in methamphetamine-dependent mice and suggests that the abnormal behavior is associated with anxiety and depression. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  9. Attention-Deficit/Hyperactivity Disorder subtypes and substance use and use disorders in NESARC

    PubMed Central

    De Alwis, Duneesha; Lynskey, Michael T.; Reiersen, Angela M.; Agrawal, Arpana

    2014-01-01

    Background Attention-deficit /hyperactivity disorder (ADHD) is associated with substance use and substance use disorders (SUD). However, relatively little is known about the relationship between DSM-IV ADHD subtypes and substance use or DSM-IV abuse/dependence in epidemiological samples. Methods Data were obtained from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC, N=33,588). Respondents reported on ADHD symptoms (DSM-IV) for the period of time when they were 17 years or younger. Lifetime use and DSM-IV abuse/dependence of alcohol, nicotine, cannabis, cocaine, sedatives, stimulants and heroin/opiates were compared across those with ADHD symptoms but no diagnosis (ADHDsx; N=17,009), the Combined (ADHD-C; N=361), Predominantly Inattentive (ADHD-I; N=325), and the Predominantly Hyperactive-Impulsive (ADHD-HI; N=279) ADHD subtypes. Taking a more dimensional approach, inattentive and hyperactive-impulsive symptom counts and their associations with substance use and misuse were also examined. Results After adjustments for conduct disorder, major depressive disorder, any anxiety disorder and other socio-demographic covariates, substance use and SUD were associated with ADHDsx, ADHD-C, ADHD-I and ADHD-HI. Overall, substance use and SUD were more weakly associated with the ADHDsx group compared to the three ADHD diagnostic groups. Statistically significant differences were not evident across the three diagnostic groups. Hyperactive-impulsive symptoms were more consistently associated with substance use and SUD compared to inattentive symptoms. Conclusions ADHD subtypes are consistently associated with substance use and SUD. The relatively stronger association of hyperactive/impulsive symptoms with substance use and abuse/dependence is consistent with the extant literature noting impulsivity as a precursor of substance use and SUD. PMID:24821471

  10. Inattention and hyperactivity in association with autism spectrum disorders in the CHARGE study

    PubMed Central

    Lyall, Kristen; Schweitzer, Julie B.; Schmidt, Rebecca J.; Hertz-Picciotto, Irva; Solomon, Marjorie

    2017-01-01

    Background Attention deficits in young children with autism spectrum disorder (ASD) are not well understood. This study sought to determine: 1) the prevalence of ADHD symptoms in young children with ASD, typical development (TD), and developmental delay (DD) and 2) the association between ADHD symptoms and cognitive and behavioral functioning in children with ASD. Method ADHD symptoms, defined according to Aberrant Behavior Checklist (ABC) hyperactivity subscale scores, were compared across children aged 2–5 from a large case-control study with ASD (n=548), TD (n=423), and DD (n=180). Inattention and hyperactivity items within this subscale were also explored. Within the ASD group, linear and logistic regression were used to examine how ADHD symptoms were associated with cognition as assessed by the Mullen Scales of Early Learning and adaptive functioning as assessed by the Vineland Adaptive Behavior Scales. Results Mean hyperactivity subscale scores were lowest in children with TD (mean=3.19), higher in children with DD (12.3), and highest in children with ASD (18.2; between-group p<0.001). Among children with ASD, significant associations were observed with higher ADHD symptoms and poorer adaptive and cognitive functioning (adjusted beta for hyperactivity score in association with: Vineland composite = −5.63, p=0.0005; Mullen visual reception scale = −2.94, p=0.02; for the highest vs. lowest quartile of hyperactivity score, odds of lowest quintile of these scores was approximately doubled). Exploratory analyses highlighted associations with inattention-related items specifically. Conclusion These results suggest ADHD symptoms may play a key role in the functioning of young children with ASD. PMID:29276530

  11. The Associations between Callous-unemotional Traits and Symptoms of Conduct Problems, Hyperactivity and Emotional Problems: A Study of Adolescent Twins Screened for Neurodevelopmental Problems.

    PubMed

    Saunders, Marie Claire; Anckarsäter, Henrik; Lundström, Sebastian; Hellner, Clara; Lichtenstein, Paul; Fontaine, Nathalie M G

    2018-05-05

    Callous-unemotional (CU) traits (e.g., lack of empathy, lack of guilt, shallow affect) are associated with severe and persistent conduct problems in youth. There is evidence showing a substantial genetic correlation between CU traits and conduct problems. The etiological associations between CU traits and other psychopathological symptoms, including symptoms of hyperactivity and emotional problems (such as anxiety and depression symptoms), have been less explored. To examine the etiological associations between CU traits and symptoms of conduct problems, hyperactivity and emotional problems separately through the use of a twin design. Participants were same-sex twin pairs (n = 426 twins; 42% female; 43% MZ; age = 15) drawn from the Child and Adolescents Twin Study in Sweden, a longitudinal study of twins born in Sweden. The sample was mainly composed of children who screenpositive on neurodevelopmental problems/mental health problems or at-risk children (i.e., screen-negative children considered to be genetically at-risk siblings). We used self-report measures of CU traits, conduct problems, hyperactivity and emotional problems. Model-fitting analyses were conducted using structural equation modeling. We found a strong positive genetic correlation between CU traits and conduct problems and a moderate genetic correlation between CU traits and hyperactivity. We also found a relatively modest, but significant negative genetic correlation between CU traits and emotional problems. Using a sample of adolescent twins screened for neurodevelopmental problems, we replicated previous findings that showed a strong genetic correlation between CU traits and conduct problems and we extended research by examining further the etiological associations between CU traits and symptoms of hyperactivity and emotional problems.

  12. Double-dissociation between the mechanism leading to impulsivity and inattention in Attention Deficit Hyperactivity Disorder: A resting-state functional connectivity study.

    PubMed

    Sanefuji, Masafumi; Craig, Michael; Parlatini, Valeria; Mehta, Mitul A; Murphy, Declan G; Catani, Marco; Cerliani, Leonardo; Thiebaut de Schotten, Michel

    2017-01-01

    Two core symptoms characterize Attention Deficit Hyperactivity Disorder (ADHD) subtypes: inattentiveness and hyperactivity-impulsivity. While previous brain imaging research investigated ADHD as if it was a homogenous condition, its two core symptoms may originate from different brain mechanisms. We, therefore, hypothesized that the functional connectivity of cortico-striatal and attentional networks would be different between ADHD subtypes. We studied 165 children (mean age 10.93 years; age range, 7-17 year old) diagnosed as having ADHD based on their revised Conner's rating scale score and 170 typical developing individuals (mean age 11.46 years; age range, 7-17 year old) using resting state functional fMRI. Groups were matched for age, IQ and head motion during the MRI acquisition. We fractionated the ADHD group into predominantly inattentive, hyperactive-impulsive and combined subtypes based on their revised Conner's rating scale score. We then analyzed differences in resting state functional connectivity of the cortico-striatal and attentional networks between these subtypes. We found a double dissociation of functional connectivity in the cortico-striatal and ventral attentional networks, reflecting the subtypes of the ADHD participants. Particularly, the hyperactive-impulsive subtype was associated with increased connectivity in cortico-striatal network, whereas the inattentive subtype was associated with increased connectivity in the right ventral attention network. Our study demonstrated for the first time a right lateralized, double dissociation between specific networks associated with hyperactivity-impulsivity and inattentiveness in ADHD children, providing a biological basis for exploring symptom dimensions and revealing potential targets for more personalized treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. [Adrenal protein expressions after Pinggan Qianyang Formula treatment in hypertensive rats with liver-yang hyperactivity: a comparative proteomic analysis].

    PubMed

    Zhang, Ying; Chen, Ze-qi; Zhong, Guang-wei

    2008-07-01

    To explore the pathogenic mechanism of liver-yang hyperactivity type of hypertension and to observe the effects of Pinggan Qianyang Formula (PGQYF), a compound of traditional Chinese herbals for calming the liver and suppressing yang, so as to provide experimental evidence for new marker proteins of drug therapy. A rat model of liver-yang hyperactivity was prepared with spontaneous hypertensive rats (SHRs) by administration of Aconiti Praeparatae Decoction. Adrenal proteins were separated by 2D gel electrophoresis (2-DE). The differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and database analysis. The rat model of liver-yang hyperactivity was successfully reproduced, and the PGQYF could decrease the grades of irritability, conjunctival congestion and systolic blood pressure of the rats (P<0.05, P<0.01). After analysis, twelve obviously differentially expressed proteins were found, eight of which were identified. The expression levels of isocitrate dehydrogenase and steroidogenic acute regulatory protein in the untreated group were up-regulated as compared with those in the normal control group, and down-regulated in the treatment group. The expression levels of ferritin light chain, elongation factor Tu, Rho GDP disassociation inhibitor 1, flavin reductase and basic transcription factor 3 in the untreated group were down-regulated as compared with those in the normal control group, and up-regulated in the treatment group. Differentially expressed adrenal proteins in SHRs with live-yang hyperactivity are successfully identified. This approach may lay a foundation for the further investigation of pathogenic mechanisms in hypertension with liver-yang hyperactivity and the mechanisms of PGQYF treatment.

  14. GABAA overactivation potentiates the effects of NMDA blockade during the brain growth spurt in eliciting locomotor hyperactivity in juvenile mice.

    PubMed

    Oliveira-Pinto, Juliana; Paes-Branco, Danielle; Cristina-Rodrigues, Fabiana; Krahe, Thomas E; Manhães, Alex C; Abreu-Villaça, Yael; Filgueiras, Cláudio C

    2015-01-01

    Both NMDA receptor blockade and GABAA receptor overactivation during the brain growth spurt may contribute to the hyperactivity phenotype reminiscent of attention-deficit/hyperactivity disorder. Here, we evaluated the effects of exposure to MK801 (a NMDA antagonist) and/or to muscimol (a GABAA agonist) during the brain growth spurt on locomotor activity of juvenile Swiss mice. This study was carried out in two separate experiments. In the first experiment, pups received a single i.p. injection of either saline solution (SAL), MK801 (MK, 0.1, 0.3 or 0.5 mg/kg) or muscimol (MU, 0.02, 0.1 or 0.5 mg/kg) at the second postnatal day (PND2), and PNDs 4, 6 and 8. In the second experiment, we investigated the effects of a combined injection of MK (0.1 mg/kg) and MU (doses: 0.02, 0.1 or 0.5 mg/kg) following the same injection schedule of the first experiment. In both experiments, locomotor activity was assessed for 15 min at PND25. While MK promoted a dose-dependent increase in locomotor activity, exposure to MU failed to elicit significant effects. The combined exposure to the highest dose of MU and the lowest dose of MK induced marked hyperactivity. Moreover, the combination of the low dose of MK and the high dose of MU resulted in a reduced activity in the center of the open field, suggesting an increased anxiety-like behavior. These findings suggest that, during the brain growth spurt, the blockade of NMDA receptors induces juvenile locomotor hyperactivity whereas hyperactivation of GABAA receptors does not. However, GABAA overactivation during this period potentiates the effects of NMDA blockade in inducing locomotor hyperactivity. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Developmental exposure to acetaminophen does not induce hyperactivity in zebrafish larvae.

    PubMed

    Reuter, Isabel; Knaup, Sabine; Romanos, Marcel; Lesch, Klaus-Peter; Drepper, Carsten; Lillesaar, Christina

    2016-08-01

    First line pain relief medication during pregnancy relies nearly entirely on the over-the-counter analgesic acetaminophen, which is generally considered safe to use during gestation. However, recent epidemiological studies suggest a risk of developing attention-deficit/hyperactivity disorder (ADHD)-like symptoms in children if mothers use acetaminophen during pregnancy. Currently, there are no experimental proofs that prenatal acetaminophen exposure causes developmental brain alterations of progeny. Exposure to high acetaminophen concentrations causes liver toxicity, which is well investigated in different model organisms. However, sub-liver-toxic concentrations have not been experimentally investigated with respect to ADHD endophenotypes such as hyperactivity. We used zebrafish to investigate the potential impact of acetaminophen exposure on locomotor activity levels, and compared it to the established zebrafish Latrophilin 3 (Lphn3) ADHD-model. We determined the sub-liver-toxic concentration of acetaminophen in zebrafish larvae and treated wild-type and lphn3.1 knockdown larvae with increasing concentrations of acetaminophen. We were able to confirm that lphn3.1 knockdown alone causes hyperactivity, strengthening the implication of Lphn3 dysfunction as an ADHD risk factor. Neither acute nor chronic exposure to acetaminophen at sub-liver-toxic concentrations in wild-type or lphn3.1 knock-downs increases locomotor activity levels. Together our findings show that embryonic to larval exposure to acetaminophen does not cause hyperactivity in zebrafish larvae. Furthermore, there are no additive and/or synergistic effects of acetaminophen exposure in a susceptible background induced by knock-down of lphn3.1. Our experimental study suggests that there is, at least in zebrafish larvae, no direct link between embryonic acetaminophen exposure and hyperactivity. Further work is necessary to clarify this issue in humans.

  16. Infant brain structures, executive function, and attention deficit/hyperactivity problems at preschool age. A prospective study.

    PubMed

    Ghassabian, Akhgar; Herba, Catherine M; Roza, Sabine J; Govaert, Paul; Schenk, Jacqueline J; Jaddoe, Vincent W; Hofman, Albert; White, Tonya; Verhulst, Frank C; Tiemeier, Henning

    2013-01-01

    Neuroimaging findings have provided evidence for a relation between variations in brain structures and attention deficit/hyperactivity disorder (ADHD). However, longitudinal neuroimaging studies are typically confined to children who have already been diagnosed with ADHD. In a population-based study, we aimed to characterize the prospective association between brain structures measured during infancy and executive function and attention deficit/hyperactivity problems assessed at preschool age. In the Generation R Study, the corpus callosum length, the gangliothalamic ovoid diameter (encompassing the basal ganglia and thalamus), and the ventricular volume were measured in 784 6-week-old children using cranial postnatal ultrasounds. Parents rated executive functioning at 4 years using the behavior rating inventory of executive function-preschool version in five dimensions: inhibition, shifting, emotional control, working memory, and planning/organizing. Attention deficit/hyperactivity problems were assessed at ages 3 and 5 years using the child behavior checklist. A smaller corpus callosum length during infancy was associated with greater deficits in executive functioning at 4 years. This was accounted for by higher problem scores on inhibition and emotional control. The corpus callosum length during infancy did not predict attention deficit/hyperactivity problem at 3 and 5 years, when controlling for the confounders. We did not find any relation between gangliothalamic ovoid diameter and executive function or Attention deficit/hyperactivity problem. Variations in brain structures detectible in infants predicted subtle impairments in inhibition and emotional control. However, in this population-based study, we could not demonstrate that early structural brain variations precede symptoms of ADHD. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

  17. Attention-deficit/hyperactivity disorder subtypes and substance use and use disorders in NESARC.

    PubMed

    De Alwis, Duneesha; Lynskey, Michael T; Reiersen, Angela M; Agrawal, Arpana

    2014-08-01

    Attention-deficit/hyperactivity disorder (ADHD) is associated with substance use and substance use disorders (SUD). However, relatively little is known about the relationship between DSM-IV ADHD subtypes and substance use or DSM-IV abuse/dependence in epidemiological samples. Data were obtained from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC, N = 33,588). Respondents reported on ADHD symptoms (DSM-IV) for the period of time when they were 17 years or younger. Lifetime use and DSM-IV abuse/dependence of alcohol, nicotine, cannabis, cocaine, sedatives, stimulants and heroin/opiates were compared across those with ADHD symptoms but no diagnosis (ADHDsx; N = 17,009), the Combined (ADHD-C; N = 361), Predominantly Inattentive (ADHD-I; N = 325), and the Predominantly Hyperactive-Impulsive (ADHD-HI; N = 279) ADHD subtypes. Taking a more dimensional approach, inattentive and hyperactive-impulsive symptom counts and their associations with substance use and misuse were also examined. After adjustments for conduct disorder, major depressive disorder, any anxiety disorder and other socio-demographic covariates, substance use and SUD were associated with ADHDsx, ADHD-C, ADHD-I and ADHD-HI. Overall, substance use and SUD were more weakly associated with the ADHDsx group compared to the three ADHD diagnostic groups. Statistically significant differences were not evident across the three diagnostic groups. Hyperactive-impulsive symptoms were more consistently associated with substance use and SUD compared to inattentive symptoms. ADHD subtypes are consistently associated with substance use and SUD. The relatively stronger association of hyperactive/impulsive symptoms with substance use and abuse/dependence is consistent with the extant literature noting impulsivity as a precursor of substance use and SUD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Stimulant Medication and the Hyperactive Adolescent: Myths and Facts.

    ERIC Educational Resources Information Center

    Clampit, M. K.; Pirkle, Jane B.

    1983-01-01

    Reviews literature that describes the rational and nonrational factors sustaining the myth that stimulant medication is ineffective for hyperactive adolescents. Discusses methodological problems and factors--such as increasing size, misbehavior and misattribution, and perceived relationship to drug abuse--that influence treatment decisions. (JAC)

  19. Attention Deficit Hyperactivity Disorder: ADHD Task Force Report.

    ERIC Educational Resources Information Center

    Michigan State Dept. of Education, Lansing. Special Education Services.

    A Michigan task force examined existing and needed services for students with attention deficit hyperactivity disorder (ADHD), to assist school districts in developing services and to create a systematic plan for statewide information dissemination regarding referral, assessment, identification, intervention strategies, and legal mandates.…

  20. Oculomotor Anomalies in Attention-Deficit/Hyperactivity Disorder: Evidence for Deficits in Response Preparation and Inhibition

    ERIC Educational Resources Information Center

    Mahone, E. Mark; Mostofsky, Stewart H.; Lasker, Adrian G.; Zee, David; Denckla, Martha B.

    2009-01-01

    Girls, but not boys, with attention deficit hyperactivity disorder (ADHD) have significantly longer visually guided saccades latencies. It is found that sex differences in children with ADHD extend beyond symptom presentation to the development of oculomotor control.

  1. Kids Who Can't Sit Still.

    ERIC Educational Resources Information Center

    Black, Susan

    1992-01-01

    Little advanced research exists on the causes, diagnosis, and treatment of hyperactivity disorders in children. This article debates the pros and cons of ritalin and other medical treatments and defines the principal's role in studying recent research on attention deficit hyperactivity disorder, examining current identification policies,…

  2. Altered White Matter Microstructure in Children with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Nagel, Bonnie J.; Bathula, Deepti; Herting, Megan; Schmitt, Colleen; Kroenke, Christopher D.; Fair, Damien; Nigg, Joel T.

    2011-01-01

    Objective: Identification of biomarkers is a priority for attention-deficit/hyperactivity disorder (ADHD). Studies have documented macrostructural brain alterations in ADHD, but few have examined white matter microstructure, particularly in preadolescent children. Given dramatic white matter maturation across childhood, microstructural differences…

  3. Structural Brain Abnormalities in Adolescents with Autism Spectrum Disorder and Patients with Attention Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Brieber, Sarah; Neufang, Susanne; Bruning, Nicole; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Fink, Gereon R.; Konrad, Kerstin

    2007-01-01

    Background: Although autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are two distinct neurodevelopmental diseases, they share behavioural, neuropsychological and neurobiological characteristics. For the identification of endophenotypes across diagnostic categories, further investigations of phenotypic overlap…

  4. Understanding Tourette Syndrome: An Educators' Guide for the Inclusive Classroom.

    ERIC Educational Resources Information Center

    Knight, Diane

    1999-01-01

    This guide to Tourette Syndrome addresses prevalence and etiology, associated behaviors (such as obsessive-compulsive disorder and attention deficit hyperactivity disorder), treatment approaches and medication, and classroom management techniques (such as handling tic release/stress and managing hyperactivity/controlling attentional impulses). (DB)

  5. Study shows that young adults diagnosed with severe attention deficit hyperactivity disorder as children have more driving risks

    DOT National Transportation Integrated Search

    1996-07-01

    The National Highway Traffic Safety Administration sponsored a study to assess whether Attention Deficit Hyperactivity Disorder (ADHD) diagnosed during childhood would be a risk factor for poorer driving performance during early adulthood. This Traff...

  6. Dealing with Abnormal Behavior in the Classroom. Fastback 245.

    ERIC Educational Resources Information Center

    Romney, David M.

    This booklet discusses four of the more common classroom behavior disorders with which teachers must deal: hyperactivity, childhood depression, extreme shyness, and aggressive behavior. In the section on hyperactivity, three characteristics--excessive motor activity, inattentiveness, and impulsiveness--are listed as constituting the hyperactivity…

  7. Attention Deficit Hyperactivity Disorder: The Differential Diagnosis.

    ERIC Educational Resources Information Center

    Weinberg, Warren A.; Emslie, Graham J.

    This paper presents information on the diagnostic criteria and management of disorders that may be wrongly identified as Attention Deficit Hyperactivity Disorder (ADHD) or may coexist with ADHD thus complicating identification and treatment. The disorders discussed are: depression, mania, primary disorder of vigilance, narcolepsy, developmental…

  8. Hyperactivity with Agitative-Like Behavior in a Mouse Tauopathy Model.

    PubMed

    Jul, Pia; Volbracht, Christiane; de Jong, Inge E M; Helboe, Lone; Elvang, Anders Brandt; Pedersen, Jan Torleif

    2016-01-01

    Tauopathies, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), are characterized by formation of neurofibrillary tangles consisting of hyperphosphorylated tau. In addition to memory loss, patients experience behavioral symptoms such as agitation, aggression, depression, and insomnia. We explored the behavioral phenotype of a mouse model (rTg4510) carrying the human tau P301L mutation found in a familial form of FTD. We tested these mice in locomotor activity assays as well as in the Morris water maze to access spatial memory. In addition to cognitive impairments, rTg4510 mice exhibited a hyperactivity phenotype which correlated with progression of tau pathology and was dependent on P301L tau transgene expression. The hyperactive phenotype was characterized by significantly increased locomotor activity in a novel and in a simulated home cage environment together with a disturbed day/night cycle. The P301L-tau-dependent hyperactivity and agitative-like phenotype suggests that these mice may form a correlate to some of the behavioral disturbances observed in advanced AD and FTD.

  9. Hyperactivity and impaired response habituation in hyperdopaminergic mice

    PubMed Central

    Zhuang, Xiaoxi; Oosting, Ronald S.; Jones, Sara R.; Gainetdinov, Raul R.; Miller, Gary W.; Caron, Marc G.; Hen, René

    2001-01-01

    Abnormal dopaminergic transmission is implicated in schizophrenia, attention deficit hyperactivity disorder, and drug addiction. In an attempt to model aspects of these disorders, we have generated hyperdopaminergic mutant mice by reducing expression of the dopamine transporter (DAT) to 10% of wild-type levels (DAT knockdown). Fast-scan cyclic voltammetry and in vivo microdialysis revealed that released dopamine was cleared at a slow rate in knockdown mice, which resulted in a higher extracellular dopamine concentration. Unlike the DAT knockout mice, the DAT knockdown mice do not display a growth retardation phenotype. They have normal home cage activity but display hyperactivity and impaired response habituation in novel environments. In addition, we show that both the indirect dopamine receptor agonist amphetamine and the direct agonists apomorphine and quinpirole inhibit locomotor activity in the DAT knockdown mice, leading to the hypothesis that a shift in the balance between dopamine auto and heteroreceptor function may contribute to the therapeutic effect of psychostimulants in attention deficit hyperactivity disorder. PMID:11172062

  10. The Latent Structure of Attention Deficit/Hyperactivity Disorder in an Adult Sample

    PubMed Central

    Marcus, David K.; Norris, Alyssa L.; Coccaro, Emil F.

    2012-01-01

    The vast majority of studies that have examined the latent structure of attention deficit/hyperactivity disorder (ADHD) in children and adolescents have concluded that ADHD has a dimensional latent structure. In other words, ADHD symptomatology exists along a continuum and there is no natural boundary or qualitative distinction (i.e., taxon) separating youth with ADHD from those with subclinical inattention or hyperactivity/impulsivity problems. Although adult ADHD appears to be less prevalent than ADHD in youth (which could suggest a more severe adult ADHD taxon), researchers have yet to examine the latent structure of ADHD in adults. The present study used a sample (N = 600) of adults who completed a self-report measure of ADHD symptoms. The taxometric analyses revealed a dimensional latent structure for inattention, hyperactivity/impulsivity, and ADHD. These findings are consistent with previous taxometric studies that examined ADHD in children and adolescents, and with contemporary polygenic and multifactorial models of ADHD. PMID:22480749

  11. Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

    PubMed

    Bock, J; Breuer, S; Poeggel, G; Braun, K

    2017-03-01

    In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using ( 14 C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

  12. Prenatal Exposure to Maternal and Paternal Smoking on Attention Deficit Hyperactivity Disorders Symptoms and Diagnosis in Offspring

    PubMed Central

    Nomura, Yoko; Marks, David J.; Halperin, Jeffrey M.

    2011-01-01

    The study examined the effect of maternal and paternal smoking during pregnancy on the child’s inattention and hyperactivity/impulsivity symptoms, and the risk for attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). Generalized estimating equations, incorporating data from multiple informants (parents and teachers), was used to evaluate levels of ADHD as a function of parental smoking. The risk for ADHD, ODD, and comorbid ADHD and ODD was evaluated using polytomous logistic regression. We found that maternal, but not paternal, smoking was significantly associated with elevated inattention, hyperactivity/impulsivity, and total ADHD symptoms in children. Children of smoking, relative to nonsmoking, mothers had a significant increased risk for comorbid ADHD and ODD and ADHD, but not ODD. Although father’s smoking was not associated with an increased risk, as it strongly influenced mothers’ smoking, intervention for both parents may be most effective in preventing the pathway to ADHD-related problems in the children. PMID:20823730

  13. Implications of parental affiliate stigma in families of children with ADHD.

    PubMed

    Mikami, Amori Yee; Chong, Gua Khee; Saporito, Jena M; Na, Jennifer Jiwon

    2015-01-01

    This study examined parents' perceptions/awareness and internalization of public courtesy stigma (affiliate stigma) about their children's inattentive and hyperactive/impulsive symptoms, and associations between parental affiliate stigma, parental negativity expressed toward the child, and child social functioning. Participants were families of 63 children (ages 6-10; 42 boys) with attention-deficit/hyperactivity disorder, assessed in a cross-sectional design. After statistical control of children's severity of inattentive and hyperactive/impulsive symptoms (as reported by parents and teachers), parents' self-reports of greater affiliate stigma were associated with more observed negative parenting. The associations between high parental affiliate stigma and children's poorer adult informant-rated social skills and greater observed aggression were partially mediated by increased parental negativity. As well, the positive association between children's adult informant-rated aggressive behavior and parental negativity was partially mediated by parents' increased affiliate stigma. Parental affiliate stigma about their children's inattentive and hyperactive/impulsive symptoms may have negative ramifications for parent-child interactions and children's social functioning. Clinical implications for parent training interventions are discussed.

  14. Attention deficit hyperactivity disorder and sensory modulation disorder: a comparison of behavior and physiology.

    PubMed

    Miller, Lucy Jane; Nielsen, Darci M; Schoen, Sarah A

    2012-01-01

    Children with attention deficit hyperactivity disorder (ADHD) are impulsive, inattentive and hyperactive, while children with sensory modulation disorder (SMD), one subtype of Sensory Processing Disorder, have difficulty responding adaptively to daily sensory experiences. ADHD and SMD are often difficult to distinguish. To differentiate these disorders in children, clinical ADHD, SMD, and dual diagnoses were assessed. All groups had significantly more sensory, attention, activity, impulsivity, and emotional difficulties than typical children, but with distinct profiles. Inattention was greater in ADHD compared to SMD. Dual diagnoses had more sensory-related behaviors than ADHD and more attentional difficulties than SMD. SMD had more sensory issues, somatic complaints, anxiety/depression, and difficulty adapting than ADHD. SMD had greater physiological/electrodermal reactivity to sensory stimuli than ADHD and typical controls. Parent-report measures identifying sensory, attentional, hyperactive, and impulsive difficulties varied in agreement with clinician's diagnoses. Evidence suggests ADHD and SMD are distinct diagnoses. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. DNA Electrochemistry Shows DNMT1 Methyltransferase Hyperactivity in Colorectal Tumors.

    PubMed

    Furst, Ariel L; Barton, Jacqueline K

    2015-07-23

    DNMT1, the most abundant human methyltransferase, is responsible for translating the correct methylation pattern during DNA replication, and aberrant methylation by DNMT1 has been linked to tumorigenesis. We have developed a sensitive signal-on electrochemical assay for the measurement of DNMT1 activity in crude tissue lysates. We have further analyzed ten tumor sets and have found a direct correlation between DNMT1 hyperactivity and tumorous tissue. In the majority of samples analyzed, the tumorous tissue has significantly higher DNMT1 activity than the healthy adjacent tissue. No such correlation is observed in measurements of DNMT1 expression by qPCR, DNMT1 protein abundance by western blotting, or DNMT1 activity using a radiometric DNA labeling assay. DNMT1 hyperactivity can result from both protein overexpression and enzyme hyperactivity. DNMT1 activity measured electrochemically provides a direct measure of activity in cell lysates and, as a result, provides a sensitive and early indication of cancerous transformation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Multi-Method Assessment of ADHD Characteristics in Preschool Children: Relations between Measures

    PubMed Central

    Sims, Darcey M.; Lonigan, Christopher J.

    2011-01-01

    Several forms of assessment tools, including behavioral rating scales and objective tests such as the Continuous Performance Test (CPT), can be used to measure inattentive and hyperactive/impulsive behaviors associated with Attention-Deficit/Hyperactivity Disorder (ADHD). However, research with school-age children has shown that the correlations between parent ratings, teacher ratings, and scores on objective measures of ADHD-characteristic behaviors are modest at best. In this study, we examined the relations between parent and teacher ratings of ADHD and CPT scores in a sample of 65 preschoolers ranging from 50 to 72 months of age. No significant associations between teacher and parent ratings of ADHD were found. Parent-ratings of both inattention and hyperactivity/impulsivity accounted for variance in CPT omission errors but not CPT commission errors. Teacher ratings showed evidence of convergent and discriminant validity when entered simultaneously in a hierarchical regression. These tools may be measuring different aspects of inattention and hyperactivity/impulsivity. PMID:22518069

  17. The latent structure of attention deficit/hyperactivity disorder in an adult sample.

    PubMed

    Marcus, David K; Norris, Alyssa L; Coccaro, Emil F

    2012-06-01

    The vast majority of studies that have examined the latent structure of attention deficit/hyperactivity disorder (ADHD) in children and adolescents have concluded that ADHD has a dimensional latent structure. In other words, ADHD symptomatology exists along a continuum and there is no natural boundary or qualitative distinction (i.e., taxon) separating youth with ADHD from those with subclinical inattention or hyperactivity/impulsivity problems. Although adult ADHD appears to be less prevalent than ADHD in youth (which could suggest a more severe adult ADHD taxon), researchers have yet to examine the latent structure of ADHD in adults. The present study used a sample (N = 600) of adults who completed a self-report measure of ADHD symptoms. The taxometric analyses revealed a dimensional latent structure for inattention, hyperactivity/impulsivity, and ADHD. These findings are consistent with previous taxometric studies that examined ADHD in children and adolescents, and with contemporary polygenic and multifactorial models of ADHD. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Jordan-3: measuring visual reversals in children as symptoms of learning disability and attention-deficit/hyperactivity disorder.

    PubMed

    Jordan, Brian T; Martin, Nancy; Austin, J Sue

    2012-12-01

    The purpose of this research was to establish new norms for the Jordan-3 for children ages 5 to 18 years. The research also investigated the frequency of visual reversals in children previously identified as having reading disability, attention-deficit/hyperactivity disorder, and broader learning disabilities. Participants were regular education students, ages 5 through 18 years, and special education students previously diagnosed with attention-deficit/hyperactivity disorder, reading disability, or broader learning disability. Jordan-3 Accuracy and Error raw scores were compared to assess if there was a significant difference between the two groups. Mean Accuracy and Error scores were compared for males and females. Children with learning disability and attention-deficit/hyperactivity disorder had higher reversals when compared to regular education children, which lends continued support to the Jordan-3 as a valid and reliable measure of visual reversals in children and adolescents. This study illustrates the utility of the Jordan-3 when assessing children who may require remediation to reach their academic potential.

  19. Evaluating relationships among clinical working memory assessment and inattentive and hyperactive/impulsive behaviors in a community sample of children.

    PubMed

    Colbert, Alison M; Bo, Jin

    2017-07-01

    This study examined relationships between inattentive and hyperactive/impulsive behaviors and working memory (WM) functioning, and the utility of WM in categorical diagnosis of ADHD versus considering ADHD symptoms on a continuum. The study included 50 male children (6-12 years). Inattentive and hyperactive/impulsive behaviors were measured by the Conners-3P parent report, and WM was assessed by the WISC-IV WM subtests and Working Memory Index (WMI). WISC-IV Arithmetic and Digit Span Backward were most consistently related to inattentive behaviors, and no WM measure was consistently related to ADHD hyperactive/impulsive behaviors. Arithmetic and Digit Span Backward also accounted for significant variance in inattentive behaviors and ADHD inattention symptoms, respectively. Neither the WMI nor the Arithmetic subtest correctly classified individuals diagnosed with ADHD. Measurement of inattentive behaviors on a continuum best characterized relationships between symptoms of ADHD and WM functioning; WM functioning did not have utility in categorical understanding of ADHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Efficacy of Guanfacine Extended Release in the Treatment of Combined and Inattentive Only Subtypes of Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Kollins, Scott H.; Wigal, Timothy L.

    2012-01-01

    Abstract Background Extended-release guanfacine (GXR) is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6–17 years. This post-hoc analysis further examines the effects of GXR on hyperactivity-impulsivity and inattentiveness. Method Data from two large double-blind placebo-controlled pivotal trials of GXR in the treatment of ADHD were analyzed. Using the pooled population to provide sufficient sample size and associated statistical power, the impact of GXR treatment on core ADHD symptoms was examined by comparing ADHD Rating Scale IV (ADHD-RS-IV) total scores in the overall GXR and placebo groups in subjects with each of the three ADHD subtypes. ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores in the overall study population by randomized dose group (vs. placebo) were also examined. Results The full analysis set included 631 subjects aged 6–17 years (GXR: n=490; placebo: n=141). Among subjects with the predominantly inattentive subtype of ADHD, differences in least squares (LS) mean reductions from baseline in ADHD-RS-IV total scores were significantly greater in GXR-treated subjects (n=127) than in placebo-treated subjects (n=38) at treatment weeks 3 through 5 and end point (p≤0.020). Among subjects with combined type ADHD, differences in LS mean ADHD-RS-IV total score reductions from baseline were significantly greater in the GXR group (n=354) than in the placebo group (n=100) at treatment weeks 1 through 5 and end point (p≤0.011). The dearth of predominantly hyperactive-impulsive type subjects (n=12) precluded analysis of this subgroup. Each randomized GXR dose group in each trial demonstrated significantly greater reductions from baseline in ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores than did the respective placebo group at end point (p≤0.05 for all). Conclusions The results support the use of GXR in the treatment of core ADHD symptoms as defined in the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision, including hyperactivity, impulsivity, and inattention. PMID:22612526

Top