Dissociation of impulsivity and aggression in mice deficient for the ADHD risk gene Adgrl3: Evidence for dopamine transporter dysregulation

Mortimer, Niall; Ganster, Tatjana; O’Leary, Aet; Popp, Sandy; Freudenberg, Florian; Reif, Andreas; Artigas, María Soler; Ribasés, Marta; Ramos-Quiroga, Josep Antoni; Lesch, Klaus‐Peter; Rivero, Olga

doi:10.1016/j.neuropharm.2019.02.039

Cited by 35 publications

(39 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ADGRL3 was confirmed as an ADHD candidate locus in two other independent casecontrol studies, by association of one haplotype in ADGRL3 [21] and single associations of several SNPs [22]. In the zebrafish model, the loss of adgrl3 leads to a reduction of dopaminergic neurons in the ventral diencephalon and a hyperactive/impulsive phenotype [23], whereas in Adgrl3knockout mice, an increase in reward motivation and activity level as well as other ADHD-analogous behaviors was observed-parallel to dysregulation of the dopamine transporter [24,25]. This suggests that the biological validation of an ADHD candidate gene from a GWAS in an animal model can elucidate potential mechanisms of pathogenesis.…”

Section: Genome-wide Association Studies (Gwas)mentioning

confidence: 78%

Genetics of ADHD: What Should the Clinician Know?

Grimm

Kranz

Reif

2020

Curr Psychiatry Rep

Self Cite

View full text Add to dashboard Cite

Purpose of Review Attention deficit hyperactivity disorder (ADHD) shows high heritability in formal genetic studies. In our review article, we provide an overview on common and rare genetic risk variants for ADHD and their link to clinical practice. Recent findings The formal heritability of ADHD is about 80% and therefore higher than most other psychiatric diseases. However, recent studies estimate the proportion of heritability based on singlenucleotide variants (SNPs) at 22%. It is a matter of debate which genetic mechanisms explain this huge difference. While frequent variants in first mega-analyses of genomewideassociation study data containing several thousand patients give the first genome-wide results, explaining only little variance, the methodologically more difficult analyses of rare variants are still in their infancy. Some rare genetic syndromes show higher prevalence for ADHD indicating a potential role for a small number of patients. In contrast, polygenic risk scores (PRS) could potentially be applied to every patient. We give an overview how PRS explain different behavioral phenotypes in ADHD and how they could be used for diagnosis and therapy prediction. Summary Knowledge about a patient's genetic makeup is not yet mandatory for ADHD therapy or diagnosis. PRS however have been introduced successfully in other areas of clinical medicine, and their application in psychiatry will begin within the next years. In order to ensure competent advice for patients, knowledge of the current state of research is useful forpsychiatrists.

show abstract

Section: Genome-wide Association Studies (Gwas)mentioning

confidence: 78%

Genetics of ADHD: What Should the Clinician Know?

Grimm

Kranz

Reif

2020

Curr Psychiatry Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Variation has been shown in the concentration of DA metabolites like Homovanillic acid (HVA) level is elevated, while 3,4‐dihydroxyphenylacetic acid (DOPAC) remains the same (Efimova et al., 2016). Changes in the postsynaptic side include a decrease in mRNA and D1 and D2 receptor protein in the basal ganglia (Mortimer et al., 2019). Paradoxically, compounds having a direct action on DA transporter lead to inhibit hyperactivity and such compounds includes amphetamine, methylphenidate, and cocaine (Somkuwar et al., 2016).…”

Section: Animal Models Of Adhdmentioning

confidence: 99%

Animal models of attention‐deficit hyperactivity disorder (ADHD)

Rahi

Kumar

2021

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

Attention‐deficit hyperactivity disorder (ADHD) is a heterogeneous neuropsychiatric disorder characterized by three primary symptoms hyperactivity, attention deficit, and impulsiveness, observed in both children and adults. In childhood, this disorder is more common in boys than in girls, and at least 75% will continue to suffer from the disorder until adulthood. Individuals with ADHD generally have poor academic, occupational, and social functioning resulting from developmentally inappropriate levels of hyperactivity and impulsivity, as well as impaired ability to maintain attention on motivationally relevant tasks. Very few drugs available in clinical practice altogether abolish the symptoms of ADHD, therefore, to find new drugs and target it is essential to understand the neuropathological, neurochemical, and genetic alterations that lead to the progression of ADHD. With this contrast, an animal study is the best approach because animal models provide relatively fast invasive manipulation, rigorous hypothesis testing, as well as it provides a better angle to understand the pathological mechanisms involved in disease progression. Moreover, animal models, especially for ADHD, serve with good predictive validity would allow the assessment and development of new therapeutic interventions, with this aim, the present review collect the various animal models on a single platform so that the research can select an appropriate model to pursue his study.

show abstract

“…Dysregulationen im dopaminergen System liefern wichtige Erklärungsansätze für die Entstehung von ADHS. Störungen im dopaminergen System stehen im Zusammenhang mit Dysregulationen im Belohnungssystem, motorischer Hyperaktivität, Impulsivität, aggressivem Verhalten, Aufmerksamkeitsdefizit und einem Defizit in den exekutiven Funktionen [19][20][21].…”

Section: Zusammenspiel Zwischen Dopaminergem Und Endocannabinoidsystemunclassified

Endocannabinoidsystem und Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung im Erwachsenenalter

Brunkhorst-Kanaan¹,

Kittel‐Schneider²

2019

Nervenheilkunde

View full text Add to dashboard Cite

ZUSAMMENFASSUNGADHS ist eine entwicklungspsychiatrische Erkrankung, die im Erwachsenenalter häufig unerkannt und unbehandelt bleibt. Die Folgen für die Betroffenen sind neben häufigeren Arbeitsplatzverlusten, ein erhöhtes Unfallrisiko und Schwierigkeiten in der sozialen Interaktion. Häufig präsentiert sich die ADHS im Erwachsenenalter sehr heterogen und ist in ca. 80 % der Fälle mit psychiatrischen Komorbiditäten, wie Depressionen, bipolare Störung, Angststörung, Borderline- und dissoziale Persönlichkeitsstörung sowie Suchterkrankungen vergesellschaftet. Letztere führt zu der hohen Inzidenz von Cannabismissbrauch von Patienten mit ADHS. Auf der anderen Seite wird vermutet, dass Cannabis von den Betroffenen als leichtes Sedativum im Sinne einer Selbstmedikation gegen einige Symptome des ADHS wie innere Unruhe, Rastlosigkeit und Schlafstörungen eingesetzt wird. Seit den frühen 1990er-Jahren sind zahlreiche Studien erschienen, die den Zusammenhang zwischen einer Störung des physiologischen endogenen Cannabinoidsystems und der Genese psychiatrischer Erkrankungen wie Depressionen, Angststörungen, posttraumatischer Belastungsstörung (PTBS), Schizophrenie, Suchterkrankungen und Schlafstörungen beschreiben und im Endocannabinoidsystem eine potenzielle Möglichkeit neuer pharmakologischer Behandlungsmöglichkeiten, z. B. durch den Einsatz von synthetischen Cannabinoiden, sehen. In diesem Artikel sollen grundlegende Mechanismen des Endocannabinoidsystems erklärt und die Zusammenhänge mit der Genese des ADHS anhand der Studienlage beleuchtet werden. Zudem soll ein Ausblick auf mögliche Therapieoptionen mit Cannabinoiden gegeben werden.

show abstract

Dissociation of impulsivity and aggression in mice deficient for the ADHD risk gene Adgrl3: Evidence for dopamine transporter dysregulation

Cited by 35 publications

References 91 publications

Genetics of ADHD: What Should the Clinician Know?

Genetics of ADHD: What Should the Clinician Know?

Animal models of attention‐deficit hyperactivity disorder (ADHD)

Endocannabinoidsystem und Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung im Erwachsenenalter

Contact Info

Product

Resources

About