Hyperkinetic disorder. A review

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenAttention-deficit/hyperactivity disorder or hyperkinetic disorder is a clinically defined syndrome characterised by age inappropriate deficits in sustained attention, impulsivity and overactivity. Despite extensive investigation, a specific neuroanatomical, physiological, biochemical, or psychological origin has not been identified. Diagnosis is based on detailed medical and developmental history, symptom rating scales, psychological assessment and medical evaluation. Increases in diagnosis and treatment of the disorder have elicited public and professional concern. The main focus in this article is on this disorder in children and adolescents and includes practical information on assessment and treatment. Other disorders, which may be either comorbid with or mistaken for hyperkinetic disorder, are reviewed in less detail.Ofvirkniröskun er heilkenni einkenna á sviði hreyfiofvirkni, hvatvísi og athyglisbrests sem eru í ósamræmi við aldur og þroska. Þrátt fyrir aukna þekkingu á líffræðilegum og sálfræðilegum þáttum röskunarinnar hefur ekki tekist að finna sértæka orsök. Við greiningu er nákvæm sjúkrasaga mikilvæg en einnig er stuðst við staðlaða einkennamatskvarða, sálfræðilegt mat og læknisfræðilega skoðun. Aukning í greiningu og meðferð röskunarinnar hefur verið til umræðu, bæði meðal almennings og fagfólks. Í þessari yfirlitsgrein er reynt að gera röskuninni skil á sem hagnýtastan hátt, bæði varðandi greiningu og meðferð en ekki er farið nákvæmlega í fylgiraskanir eða mismunagreiningar

Medication use and treatment characteristics of children referred to the outpatient ADHD-clinic at the Department of Child and Adolescent Psychiatry, the National University Hospital

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenMaterial and methods: Data was accumulated by retrospectively looking at the records of 102 children of both sexes between 3 and 15 years of age, referred to the ADHD outpatient clinic during the period June 1, 1998 - May 31, 1999. A semi-structured diagnostic parent interview was used to assess childhood psychiatric disorders according to ICD-10. The ADHD Rating Scale- IV, the Home Situations Questionnaire and the Child Behavior Checklist were completed by the parents. Teachers filled out the ADHD Rating Scale and the Teacher Report Form as well as a form evaluating the child's academic progress. To assess intellectual functioning, WISC-III or WPPSI-R were administered. Medical evaluation was performed and drug treatment recorded. Results: Seventy-two children fulfilled ICD-10 diagnostic criteria of hyperkinetic disorder. High rates of other behavioural disorders, especially oppositional defiant disorder and a significant frequency of emotional disorders were recorded. Nearly two-thirds of the children had been started on medication prior to referral, most often amytryptiline and methylphenidate. Eleven children received combined pharmacotherapy but 35% had not received any drug treatment. Psychopharmacotherapy for most of the children was started between the age of four and eight years. Behaviour management counselling and parent training was recommended in most cases. Conclusions: Thirty children did not meet full hyperkinetic disorder diagnostic criteria, but these children may nonetheless have manifested high levels of symptoms. Most of the children were started on tricyclic antidepressants rather than stimulants which is unusual compared with international research and practice. The reason is unclear but may reflect the high rate of comorbidity but also doctors' preferences.Tilgangur: Greining og meðferð við ofvirkniröskun hefur aukist mjög á undanförnum árum. Lítið er vitað um meðferðarhefðir hér á landi. Rannsóknin lýsir lyfja- og sálfélagslegri meðferð hjá hópi barna sem vísað var til ofvirknimóttöku við göngudeild barna-og unglingageðdeildar Landspítalans (BUGL). Jafnframt voru greiningar og fylgiraskanir skoðaðar. Efniviður og aðferðir: Rannsóknin er afturskyggn og tekur til 102 barna og unglinga á aldrinum 3-15 ára sem komu til athugunar vegna ofvirkni eða gruns um ofvirkni á göngudeild BUGL á tímabilinu 1. júní 1998 til 31. maí 1999. Greiningarviðtal við foreldra var byggt á ICD-10 (International Statistical Classification of Diseases and Related Health Problems, 10th revision) greiningarskilmerkjum, stuðst var við staðlaða hegðunarmatskvarða sem útfylltir voru af foreldrum og kennurum, vitsmunaþroski barnsins var metinn og læknisskoðun gerð með tilliti til líkamlegs og andlegs ástands. Niðurstöður: Alls greindust 72 börn með ofvirkniröskun. Algengasta fylgiröskunin var mótþróaþrjóskuröskun bæði í þeim hópi barna sem greindist með ofvirkniröskun og þeim sem fengu aðra fyrstu greiningu. Hjá umtalsverðum hluta hópsins greindust einnig tilfinningaraskanir. Algengast var að lyfjameðferð væri hafin milli fjögurra og átta ára aldurs. Amitriptýlín og metýlfenýdat voru oftast valin sem fyrsta meðferð en önnur lyf voru mun sjaldnar notuð og hjá 35% barnanna hafði lyfjameðferð ekki verið reynd. Við komu voru 56 börn á lyfjameðferð og 11 þeirra fengu fleiri en eitt lyf. Algengasta sálfélagslega meðferðarúrræðið var að bjóða foreldrum upp á sérstök ráðgjafarviðtöl. Næst algengast var meðferðartilboð um þjálfunarnámskeið og fræðslunámskeið. Ályktanir: Umtalsverður hluti þeirra barna sem vísað var til göngudeildar BUGL vegna gruns um ofvirkni uppfyllti ekki greiningarskilmerki um ofvirkniröskun. Notkun þríhringlaga þunglyndislyfja í byrjun meðferðar virðist ennfremur mun algengari en víðast hvar erlendis. Ástæðan er óljós en kann að vera há tíðni fylgiraskana eða einstaklingsbundið val þeirra lækna sem í hlut eiga

The frequency of some factors in pregnancy and delivery for Icelandic children with ADHD

Hægt er að lesa greinina í heild sinni með því að smella á hlekkinn View/OpenOBJECTIVE: ADHD is a well known psychiatric disorder that begins in childhood and frequently persists into adulthood. In the last decade numerous studies have shown the importance of genetic factors in the etiology of ADHD. However other etiological factors seem to be involved. The aim of this study was to examine the frequency of some possible etiological factors for ADHD in Icelandic children diagnosed with ADHD. The study is descriptive. MATERIALS AND METHODS: The participants were 196 children referred for suspected ADHD to the outpatient unit of the Department of Child and Adolescent Psychiatry, Landspitali University Hospital during a 2 year period 1998-1999. The participants had either ICD-10 or DSM-IV hyperkinetic disorder and/or ADHD and the information was obtained from patient case notes. Information provided by parents in a questionnaire concerning health in pregnancy and the perinatal period was retrospectively analysed. RESULTS: The main results show statistically significant increased risk for ADHD associated with several factors such as low birthweight, young age of the mother at the time of the child's birth and Caesarean section, compared with reference groups such as mean values in all of the community. Other factors such as birthweight, alcohol or tobacco use in pregnancy, use of medication in pregnancy or vacuum extraction did not show statistically significant association with ADHD. CONCLUSION: The results indicate as some studies from other countries have suggested that an association exists between a number of factors in pregnancy, delivery and perinatal period and ADHD, even though there is still not enough evidence to confirm definite etiological factors.Tilgangur: Ofvirkniröskun (athyglisbrestur með ofvirkni) er vel þekkt klínískt heilkenni athyglisbrests, hreyfiofvirkni og hvatvísi. Einkenni heilkennisins koma fram á barnsaldri og geta haldist fram á fullorðinsár. Rannsóknir benda til að um samspil ýmissa orsakaþátta sé að ræða en að erfðaþátturinn vegi þyngst. Markmið þessarar rannsóknar var að kanna tengsl vissra þátta á meðgöngu og í fæðingu við ofvirkniröskun hjá börnum og unglingum á Íslandi. Um er að ræða lýsandi, afturvirka rannsókn. Efniviður og aðferðir: Upplýsingar voru fengnar úr sjúkraskrám þeirra barna sem komu til greiningar vegna gruns um ofvirkni á göngudeild Barna- og unglingageðdeildar Landspítala (BUGL) 1998 og 1999. Í rannsóknarhópnum voru 196 börn sem fengu ofvirknigreiningu samkvæmt greiningarkerfunum ICD-10 eða DSM-IV. Foreldrar fylltu út spurningalista þar sem meðal annars var spurt um heilsufar barnsins, meðgöngu og fæðingu og byggjast niðurstöðurnar á upplýsingum úr þessum listum. Niðurstöður: Fram komu marktæk tengsl milli ofvirkniröskunar hjá barni og þáttanna: aldur móður innan við tvítugt við fæðingu barns, að barnið hafi verið fyrirburi eða hafi verið tekið með keisaraskurði eða töngum. Einnig voru þættirnir: fæðingarþyngd barns, áfengisnotkun, reykingar, lyfjanotkun og sogklukkufæðingar athugaðir en ekki var hægt að sýna fram á marktæk tengsl þessa við ofvirkniröskun. Ályktanir: Niðurstöðurnar eru áþekkar niðurstöðum nokkurra erlendra rannsókna og benda til þess að tengsl séu milli nokkrurra þátta á meðgöngu og í fæðingu og þess að börn greinist með ofvirkni-röskun. Um er að ræða lýsandi rannsókn en enn eru ekki nægar forsendur til staðar til að draga ályktanir um orsakasamhengi áhættuþátta

Etiology of ADHD/hyperkinetic disorder--a review

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenHyperkinetic disorder or Attention Deficit Hyperactivity Disorder (ADHD) is a developmental syndrome that affects approximately 7% of children and can sustain into adulthood. In this review current research on the etiology of the syndrome is reviewed.Ofvirkniröskun eða athyglisbrestur með ofvirkni, kemur fram á barnsaldri og hefur algengi verið metið um 7 %. Heilkennið einkennist af einbeitingarerfiðleikum, hreyfiofvirkni og hvatvísi. Einkennin geta haldist fram á fullorðinsár og er algengi hjá fullorðnum talin um 4,5 %. Orsakir ofvirkniröskunar eru margþættar en áætlað er að erfðir skýri heilkennið í 70-95 % tilfella. Erfðafræðilegur breytileiki í ýmsum boðefnakerfum í heila er talinn hafa mikla þýðingu og hefur dópamínerga kerfið mest verið rannsakað. Þar hafa erfðarannsóknir sýnt fylgni ofvirkniröskunar við erfðabreytileika í genunum DR4, DR5 og DAT-1. Hlutverk annara boðefnakerfa í ofvirkniröskun eru óljósari svo sem hlutverk noradrenalíns og serotónins. Vísbendingar eru um að reykingar, áfengisneysla á meðgöngu, lág fæðingarþyngd og fæðingaráverkar eigi hlut að máli varðandi orsakir ofvirkniröskunar en frekari rannsókna er þörf. Fleiri þættir hafa verið nefndir til sögunnar, svo sem blýeitrun og heilaskaði. Eins og þekkingin stendur í dag eru erfðir sá orsakaþáttur sem hefur mest vægi. Í greininni er farið yfir stöðu rannsókna á orsökum ofvirkniröskunar

Electroencephalography as a clinical tool for diagnosing and monitoring attention deficit hyperactivity disorder: a cross-sectional study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The aim of this study was to develop and test, for the first time, a multivariate diagnostic classifier of attention deficit hyperactivity disorder (ADHD) based on EEG coherence measures and chronological age.The participants were recruited in two specialised centres and three schools in Reykjavik.The data are from a large cross-sectional cohort of 310 patients with ADHD and 351 controls, covering an age range from 5.8 to 14 years. ADHD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) criteria using the K-SADS-PL semistructured interview. Participants in the control group were reported to be free of any mental or developmental disorders by their parents and had a score of less than 1.5 SDs above the age-appropriate norm on the ADHD Rating Scale-IV. Other than moderate or severe intellectual disability, no additional exclusion criteria were applied in order that the cohort reflected the typical cross section of patients with ADHD.Diagnostic classifiers were developed using statistical pattern recognition for the entire age range and for specific age ranges and were tested using cross-validation and by application to a separate cohort of recordings not used in the development process. The age-specific classification approach was more accurate (76% accuracy in the independent test cohort; 81% cross-validation accuracy) than the age-independent version (76%; 73%). Chronological age was found to be an important classification feature.The novel application of EEG-based classification methods presented here can offer significant benefit to the clinician by improving both the accuracy of initial diagnosis and ongoing monitoring of children and adolescents with ADHD. The most accurate possible diagnosis at a single point in time can be obtained by the age-specific classifiers, but the age-independent classifiers are also useful as they enable longitudinal monitoring of brain function.Icelandic Technology Development Fund 071201007 Landspitali University Hospital Research Fun

COPA syndrome in an Icelandic family caused by a recurrent missense mutation in COPA

Background: Rare missense mutations in the gene encoding coatomer subunit alpha (COPA) have recently been shown to cause autoimmune interstitial lung, joint and kidney disease, also known as COPA syndrome, under a dominant mode of inheritance. Case presentation: Here we describe an Icelandic family with three affected individuals over two generations with a rare clinical presentation of lung and joint disease and a histological diagnosis of follicular bronchiolitis. We performed whole-genome sequencing (WGS) of the three affected as well as three unaffected members of the family, and searched for rare genotypes associated with disease using 30,067 sequenced Icelanders as a reference population. We assessed all coding and splicing variants, prioritizing variants in genes known to cause interstitial lung disease. We detected a heterozygous missense mutation, p.Glu241Lys, in the COPA gene, private to the affected family members. The mutation occurred de novo in the paternal germline of the index case and was absent from 30,067 Icelandic genomes and 141,353 individuals from the genome Aggregation Database (gnomAD). The mutation occurs within the conserved and functionally important WD40 domain of the COPA protein. Conclusions: This is the second report of the p.Glu241Lys mutation in COPA, indicating the recurrent nature of the mutation. The mutation was reported to co-segregate with COPA syndrome in a large family from the USA with five affected members, and classified as pathogenic. The two separate occurrences of the p.Glu241Lys mutation in cases and its absence from a large number of sequenced genomes confirms its role in the pathogenesis of the COPA syndrome. Keywords: COPA syndrome, Lung disease, Arthritis, Immune dysregulation, Case reportPeer Reviewe

Whole genome characterization of sequence diversity of 15,220 Icelanders

Understanding of sequence diversity is the cornerstone of analysis of genetic disorders, population genetics, and evolutionary biology. Here, we present an update of our sequencing set to 15,220 Icelanders who we sequenced to an average genome-wide coverage of 34X. We identified 39,020,168 autosomal variants passing GATK filters: 31,079,378 SNPs and 7,940,790 indels. Calling de novo mutations (DNMs) is a formidable challenge given the high false positive rate in sequencing datasets relative to the mutation rate. Here we addressed this issue by using segregation of alleles in three-generation families. Using this transmission assay, we controlled the false positive rate and identified 108,778 high quality DNMs. Furthermore, we used our extended family structure and read pair tracing of DNMs to a panel of phased SNPs, to determine the parent of origin of 42,961 DNMs.Peer Reviewe

Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder

Publisher's version (útgefin grein).Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5–BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10−21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.We are grateful to the participants and we thank the staff at the Research Recruitment Center. We also thank the staff at deCODE genetics core facilities and all our colleagues for their important contribution to this work. We are grateful to the Benefit Society for Children with Disabilities (Styrktarfélag Lamaðra og Fatlaðra; SLF) for their participation. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreements’ no. 115008 (NEWMEDS) and no. 115300 (EUAIMS), of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (EU-FP7/2007–2013), from EU-FP7 grants no. 602450 (IMAGEMEND) and no. 502805 (Aggressotype), EU-FP7-People-2011-IAPP grant no. 286213 (PsychDPC), and The Research Council of Norway (#226971, 229129, 223273, 213694, 248778), the KG Jebsen Stiftelsen (SKGJ-MED-002 and SKGJ-MED-008), and The South-East Norway Health Authority (#2012–132).Peer Reviewe

The population genomic legacy of the second plague pandemic

Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%-40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th-19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics