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

Identification of genetic overlap and novel risk loci for attention-deficit/hyperactivity disorder and bipolar disorder

Differential diagnosis between childhood onset attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) remains a challenge, mainly due to overlapping symptoms and high rates of comorbidity. Despite this, genetic correlation reported for these disorders is low and non-significant. Here we aimed to better characterize the genetic architecture of these disorders utilizing recent large genome-wide association studies (GWAS). We analyzed independent GWAS summary statistics for ADHD (19,099 cases and 34,194 controls) and BD (20,352 cases and 31,358 controls) applying the conditional/conjunctional false discovery rate (condFDR/conjFDR) statistical framework that increases the power to detect novel phenotype-specific and shared loci by leveraging the combined power of two GWAS. We observed cross-trait polygenic enrichment for ADHD conditioned on associations with BD, and vice versa. Leveraging this enrichment, we identified 19 novel ADHD risk loci and 40 novel BD risk loci at condFDR <0.05. Further, we identified five loci jointly associated with ADHD and BD (conjFDR < 0.05). Interestingly, these five loci show concordant directions of effect for ADHD and BD. These results highlight a shared underlying genetic risk for ADHD and BD which may help to explain the high comorbidity rates and difficulties in differentiating between ADHD and BD in the clinic. Improving our understanding of the underlying genetic architecture of these disorders may aid in the development of novel stratification tools to help reduce these diagnostic difficulties.acceptedVersio

Identification of genetic loci shared between ADHD, intelligence and educational attainment

Background Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is consistently associated with lower levels of educational attainment. A recent large genome-wide association study identified common gene variants associated with ADHD, but most of the genetic architecture remains unknown. Methods We analyzed independent genome-wide association study summary statistics for ADHD (19,099 cases and 34,194 controls), educational attainment ( N = 842,499), and general intelligence ( N = 269,867) using a conditional/conjunctional false discovery rate (FDR) statistical framework that increases power of discovery by conditioning the FDR on overlapping associations. The genetic variants identified were characterized in terms of function, expression, and biological processes. Results We identified 58 linkage disequilibrium–independent ADHD-associated loci (conditional FDR < 0.01), of which 30 were shared between ADHD and educational attainment or general intelligence (conjunctional FDR < 0.01) and 46 were novel risk loci for ADHD. Conclusions These results expand on previous genetic and epidemiological studies and support the hypothesis of a shared genetic basis between these phenotypes. Although the clinical utility of the identified loci remains to be determined, they can be used as resources to guide future studies aiming to disentangle the complex etiologies of ADHD, educational attainment, and general intelligence