Strengths and limitations of genetic models of ADHD

Gainetdinov, Raul R.

doi:10.1007/s12402-010-0021-3

Cited by 24 publications

(30 citation statements)

References 77 publications

(132 reference statements)

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“…Human genetics and mouse models suggest dopamine deregulation as causative for ADHD (3,4). Normal locomotion on blockade of dopamine receptors revealed a dopamine deregulation in ACC mice as well.…”

Section: Discussionmentioning

confidence: 99%

“…The dopamine/norepinephrine reuptake inhibitor methylphenidate is widely used for ADHD treatment and normalizes locomotion in ADHD mouse models (1,4,27,30,31). We analyzed whether methylphenidate has similar effects in ACC mice.…”

Section: Adhd Medication Normalizes Locomotion In Acc Micementioning

confidence: 99%

“…Twin, adoption, and segregation studies have revealed a high heritability of ADHD, and molecular genetics associated ADHD with dopamine-related genes, including the dopamine transporter (DAT) and dopamine receptors (3). Defects reminiscent of ADHD are displayed by DAT mutant mice, underlining the implication of dopamine dysfunction in the etiology of ADHD (4). Several ADHD susceptibility loci do not contain dopamine-related genes (5)(6)(7)(8)(9), and an increasing number of studies implicate corticostriatal network abnormalities in ADHD (10).…”

mentioning

confidence: 99%

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Attention-Deficit/Hyperactivity Disorder–like Phenotype in a Mouse Model with Impaired Actin Dynamics

Zimmermann

Jene

Wolf

et al. 2015

Biological Psychiatry

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BACKGROUND: Actin depolymerizing proteins of the actin depolymerizing factor (ADF)/cofilin family are essential for actin dynamics, which is critical for synaptic function. Two ADF/cofilin family members, ADF and n-cofilin, are highly abundant in the brain, where they are present in excitatory synapses. Previous studies demonstrated the relevance of n-cofilin for postsynaptic plasticity, associative learning, and anxiety. These studies also suggested overlapping functions for ADF and n-cofilin. METHODS: We performed pharmacobehavioral, electrophysiologic, and electron microscopic studies on ADF and n-cofilin single mutants and double mutants (named ACC mice) to characterize the importance of ADF/cofilin activity for synapse physiology and mouse behavior. RESULTS: The ACC mice, but not single mutants, exhibited hyperlocomotion, impulsivity, and impaired working memory. Hyperlocomotion and impulsive behavior were reversed by methylphenidate, a psychostimulant commonly used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Also, ACC mice displayed a disturbed morphology of striatal excitatory synapses, accompanied by strongly increased glutamate release. Blockade of dopamine or glutamate transmission resulted in normal locomotion. CONCLUSIONS: Our study reveals that ADHD can result from a disturbed balance between excitation and inhibition in striatal circuits, providing novel insights into the mechanisms underlying this neurobehavioral disorder. Our results link actin dynamics to ADHD, suggesting that mutations in actin regulatory proteins may contribute to the etiology of ADHD in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Adhd Medication Normalizes Locomotion In Acc Micementioning

confidence: 99%

mentioning

confidence: 99%

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Attention-Deficit/Hyperactivity Disorder–like Phenotype in a Mouse Model with Impaired Actin Dynamics

Zimmermann

Jene

Wolf

et al. 2015

Biological Psychiatry

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“…Mice lacking DAT have increased dopaminergic tone and represent a genetic animal model in which certain endophenotypes of ADHD can be recapitulated [443]. In DAT knockout mice, DA is cleared very slowly from the synaptic cleft, causing a five fold elevation of extracellular DA in the striatum (that is, a hyperdopaminergic state).…”

Section: Reviewmentioning

confidence: 99%

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Dichter

Damiano

Allen

2012

J Neurodevelop Disord

253

207

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This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

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“…Bu modelde aşırı hiperaktivite gözlenmektedir, perseveratif davranışlar artmaktadır, BDNF ve postsinaptik nöronun iskelet yoğunluğunda azalma olmaktadır (Gainetdinov 2010). Postsinaptik ve presinaptikdopamin reseptörlerinde aşağı-regulasyon ve duyarsızlaşma gözlenmiştir.…”

Section: Hayvan çAlışmaları Ve Dehb Modelleriunclassified

Dikkat Eksikliği Hiperaktivite Bozukluğu ve Genetik

Çetin¹,

Işık²

2018

Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry

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ÖzDikkat Eksikliği Hiperaktivite Bozukluğu (DEHB) üç temel özelliği çocukluk döneminde başlayan dikkatsizlik, gelişimsel düzeye uygun olmayan aşırı hareketlilik ve dürtüsellik olan nörogelişimsel bir bozukluktur. Dünya çapında yaygınlığı çocuklarda %5-12 ve yetişkinlerde %4.4 kadardır. DEHB hem birey hem de aile ve toplum açısından önemli sorunlara zemin hazırlamaktadır ve bu nedenle bozukluğun erken tanınması ve aynı zamanda bozukluğa yatkınlık oluşturan faktörlerin anlaşılması önemlidir. DEHB, etyolojisinde genetik ve çevresel faktörlerin rol oynadığı multifaktöriyel bir bozukluktur. Yapılan tüm çalışmalar DEHB'nin kalıtılabilirlik oranının %76 gibi hayli yüksek bir oranda olduğunu göstermiştir. Bu yazıda DEHB genetiği ikiz çalışmaları, evlat edinme çalışmaları, aile çalışmaları, segregasyon analizleri ve moleküler genetik çalışmalar şeklinde sınıflandırılarak anlatılmış ve DEHB'nin genetik yönünün gözden geçirilmesi amaçlanmıştır.Anahtar sözcükler: Genetik, dikkat eksikliği hiperaktivite bozukluğu, dopamin. AbstractAttention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder of which three basic symptoms are lack of attention, over-activity that is improper to the age and impulsivity, all of which appear in childhood. Its incidence is 5-12% in children and 4.4% in adults throughout the world. ADHD provides a basis for important problems for both patient, family and society and thus it is important to diagnose the disorder early and understand the factors that create predisposition to the disorder. ADHD is a multifactorial disorder with an etiology of genetic and environmental components. The importance of genetic factors first implied by Cantwell and Morrison is supported by many studies ever since. All these studies showed that inheritance rate of ADHD is as high as 76%. The aim of this article is to explain ADHD genetics in categorization of twin studies, adoption studies, family studies, segregation analyzes and molecular genetic researches and to review the genetic component of ADHD.

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Strengths and limitations of genetic models of ADHD

Cited by 24 publications

References 77 publications

Attention-Deficit/Hyperactivity Disorder–like Phenotype in a Mouse Model with Impaired Actin Dynamics

Attention-Deficit/Hyperactivity Disorder–like Phenotype in a Mouse Model with Impaired Actin Dynamics

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Dikkat Eksikliği Hiperaktivite Bozukluğu ve Genetik

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