Influence of Functional Variant of Neuronal Nitric Oxide Synthase on Impulsive Behaviors in Humans

Reif, Andreas; Jacob, Christian; Rujescu, Dan; Herterich, Sabine; Lang, S; Gutknecht, Lise; Baehne, Christina G.; Strobel, Alexander; Freitag, Christine M.; Giegling, Ina; Romanos, Marcel; Hartmann, Annette M.; Rösler, Michael; Renner, Tobias; Fallgatter, Andreas J.; Retz, Wolfgang; Ehlis, Ann‐Christine; Lesch, Klaus‐Peter

doi:10.1001/archgenpsychiatry.2008.510

Cited by 136 publications

(161 citation statements)

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“…Targeted disruption of Nos1 in mice increased impulsivity and aggressiveness, reduced anxiety, and impaired learning (19,20). Human behavioral and imaging studies have shown NOS1 exon 1f-VNTR to be associated with hyperactive, impulsive, and aggressive behavior as well as hypofunctioning of the anterior cingulate cortex (15,21,22).Although the NOS1 gene has been linked to ADHD, impulsivity, and modification of neurotransmitter levels in the striatum, effects of NOS1 genetic variation on striatal activity have not been investigated. The objective of the present study was to better understand the effect of this gene on neurobiological dysfunctioning in adult ADHD by exploring the influence of the exon 1f-VNTR on impulsivity and reward-related striatal activity in a large sample of adult ADHD patients (N=87) and healthy comparison subjects (N=49).…”

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confidence: 99%

Nitric Oxide Synthase Genotype Modulation of Impulsivity and Ventral Striatal Activity in Adult ADHD Patients and Healthy Comparison Subjects

Hoogman¹,

Aarts²,

Zwiers³

et al. 2011

AJP

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(5), as evidenced by steeper temporal discounting rates, altered decision making, and an aversion to delay of gratification in reward-related tests (6-9). Temporal discounting is the patient's preference to receive smaller rewards sooner rather than larger rewards later and is postulated to be an intermediate phenotype for impulsivity. Neuroimaging studies have shown engagement of alternative brain regions in decision making in ADHD patients (10). A prominent feature is hypoactivation of the ventral striatum, a brain area with an important role in reward processing (11,12), during reward anticipation (13,14). Ventral striatal activity is also associated with impulsivity, a hallmark of ADHD (12,13). Recently, the NOS1 gene was identified as a candidate gene for ADHD and other impulsivity disorders (15). A variant in this gene was also among the top findings of a genome-wide association study in ADHD (3). NOS1 encodes nitric oxide synthase 1. Nitric oxide, the product of this enzyme's activity, acts as the second messenger downstream of the N-methyl-d-aspartate receptor and interacts with both the dopaminergic and serotonergic systems in the human brain. Nitric oxide inhibits monoamine transporters, thereby modulating the dopamine and noradrenalin concentration in the extracellular space (16). In addi-(A m J P sy c h ia try 2 0 1 1 ; 1 6 8 :1 0 9 9 -1 1 0 6 ) N itric O x id e S y n th a se G e n o ty p e M o d u la tio n o f Im p u lsiv ity a n d Ve n tra l S tria ta l A c tiv ity in A d u lt A D H D P a tie n ts a n d H e a lth y C o m p a riso n S u b je c ts O b je c tiv e : Attention deficit hyperactivity disorder (AD HD ) is a highly heritable disorder. The NO S1 gene encoding nitric oxide synthase is a candidate gene for AD HD and has been previously linked w ith im pulsivity. In the present study, the authors investigated the effect of a functional variable num ber of tandem repeats (VNTR ) polym orphism in NO S1 (NO S1 exon 1f-VNTR ) on the processing of rew ards, one of the cognitive deficits in AD HD. M e th o d :A sam ple of 136 participants, consisting of 87 adult AD HD patients and 49 healthy com parison subjects, completed a rew ard-related im pulsivity task. A total of 104 participants also underw ent functional m agnetic resonance im aging during a rew ard anticipation task. The effect of the NO S1 exon 1f-VNTR genotype on rew ard-related im pulsivity and rew ard-related ventral striatal activity w as exam ined.R e s u lts : AD HD patients had higher impulsivity scores and low er ventral striatal activity than healthy com parison subjects. The association betw een the short allele and increased im pulsivity w as confirm ed. How ever, independent of disease status, hom ozygous carriers of the short allele of NO S1, the AD HD risk genotype, dem onstrated higher ventral striatal activity than carriers of the other NO S1 VNTR genotypes.C o n c lu s io n s : The authors suggest that the NO S1 genotype influences im pulsivity and its relation w ith AD HD is m ediated through effects on this behavioral tr...

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mentioning

confidence: 99%

Nitric Oxide Synthase Genotype Modulation of Impulsivity and Ventral Striatal Activity in Adult ADHD Patients and Healthy Comparison Subjects

Hoogman¹,

Aarts²,

Zwiers³

et al. 2011

AJP

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“…Reif et al (2006; have observed a polymorphic promoter dinucleotide repeat length variation of the NOS1 gene (NOS1 Ex1f-VNTR), which may potentially be related to clinical characteristics of impulsive behaviors (Reif et al, 2009). Retz et al (2010) have examined the association between self-reported impulsiveness, venturesomeness and empathy in 182 adult males (young to middle-aged) Caucasian offenders referred to forensic psychiatric medicine; impulsiveness and venturesomeness presenting closely related facets (Eysenck et al, 1990) and empathy involving moral reasoning, prosocial behavior and control of aggression (Eisenberg, 2000;Eysenck et al, 1990).…”

Section: Epigenetic Implications Modulating Impulsiveness: a Case Formentioning

confidence: 99%

Neuroquantum Theories of Psychiatric Genetics: Can Physical Forces Induce Epigenetic Influence on Future Genomes?

Blum

Braverman

Waite³

et al. 2015

Neuroquantology

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This paper serves to encourage quantum physicists to engage in psychiatric based research on the brain and its functions (i.e., consciousness, memory, attention). By using physics theorems such as Einstein's theory of relativity and the string theory, both physicists and geneticists alike may be able to elucidate potential links between components of the universe and their effects on the human brain. We have outlined some interesting posits including the cosmos' role in evolutionary biology, alpha bonding in biological molecules, and environmentally induced epigenetic effects on genetics. We also explore how physical forces can influence human memory, behavioral traits, and rates of addiction. Impulsiveness is used to exemplify how environmental changes can contribute to epigenetics and its hereditary alterations. We propose the idea of the presence of a "mental universe," where brain functionality like consciousness is a continuum of physically altered pathways. The realization that the universe and all of its precepts remains a mystery is reflected in the lack of a standardized "unified" physics theorem and mathematical equation that can explain universal dimensions (physical and mental), and as such, so is the complex nature of the functionality of the human brain. We provide herein a suggestion to remedy possible confusion, whereby we attempt to show the relationship of brain as a complex quantum-like organ and the impact of epigenetics on behavioral expression.

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“…[81] Reif ve arkadaşlarının yaptığı çalışmada ise DEHB'li hastalarda anormal NOS-1 varyantı tespit edilmiştir. [82] Ceylan ve arkadaşlarının yaptığı bir çalışmada DEHB ile kontrol grubu karşılaştırıldığında nitrik oksit (NO) seviyesi yüksek bulunmuştur. [83] Aynı çalışmada aile hikayesinde DEHB'li bireylerin çok olduğu hasta grubuyla ailesinde DEHB hikayesi negatif olan grupla karşılaştı-rıldığında anlamlılığa yakın olarak (NO) seviyesinin yükselmiş olduğu bulundu.…”

Section: Alfa 1c Noradrenerjik Reseptör Geniunclassified

Candidate Gene Studies of Attention Deficit Hyperactivity Disorder

Güney¹,

Ceylan²,

İşeri³

2011

Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychia

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Dikkat eksikliği hiperaktivite bozukluğu (DEHB) çocuklarda %5-10 oranında görülen yaygın bir psikiyatrik rahatsızlıktır. Bu hastalık dikkat eksikliği ve hiperaktivite/dürtüsellik belirtilerinin bileşimi olarak tanımlanmıştır. İkiz çalışmalarında DEHB'nin yüksek derecede kalıtılabirliğinin kanıtlanmış, yapılan moleküler genetik çalışmalarda da DEHB'de karmaşık bir genetik yapı olduğu tespit edilmiştir. Moleküler genetik çalışmalar, bu kompleks hastalığın etyolojisinde dopaminerjik, serotonerjik ve noradrenerjik nörotransmisyondaki sorunlardan kaynaklandığını göstermektedir. Bu çalış-mada DEHB'nin moleküler genetiği ile ilgili en son bulgular kapsamlı olarak gözden geçirilmiştir. Anahtar Sözcükler: DEHB, genetik, aday gen çalışmaları, etyoloji ABSTRACT Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric condition that affects approximately 5-10% of children worldwide. This disorder is defined by a combination of symptoms of inattention and hyperactivity/impulsivity. Although twin studies demonstrate that ADHD is a highly heritable condition, molecular genetic studies suggest that the genetic architecture of ADHD is complex. Molecular genetic studies support the thesis that dopaminergic, serotonergic, and noradrenergic neurotransmission pathways account for the etiology of this complex disease. This article reviews the latest findings on the molecular genetics of ADHD.

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Influence of Functional Variant of Neuronal Nitric Oxide Synthase on Impulsive Behaviors in Humans

Abstract: These findings implicate deficits in neuronal signaling via nitric oxide in moderation of prefrontal circuits underlying impulsivity-related behavior in humans.

Cited by 136 publications

References 58 publications

Nitric Oxide Synthase Genotype Modulation of Impulsivity and Ventral Striatal Activity in Adult ADHD Patients and Healthy Comparison Subjects

Nitric Oxide Synthase Genotype Modulation of Impulsivity and Ventral Striatal Activity in Adult ADHD Patients and Healthy Comparison Subjects

Neuroquantum Theories of Psychiatric Genetics: Can Physical Forces Induce Epigenetic Influence on Future Genomes?

Candidate Gene Studies of Attention Deficit Hyperactivity Disorder

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