The effect of a functional NOS1 promoter polymorphism on impulsivity is moderated by platelet MAO activity

Laas, Kariina; Reif, Andreas; Herterich, Sabine; Eensoo, Diva; Lesch, Klaus‐Peter; Harro, Jaanus

doi:10.1007/s00213-010-1793-z

Cited by 35 publications

(31 citation statements)

References 39 publications

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“…Laas and colleagues compared genotype with platelet MAO activity and self-reported impulsivity scores, and reported that short variant NOS1 alleles are related to elevated impulsivity. Furthermore, if short variant individuals have mid range MAO activity, then they have the highest impulsivity scores (Laas et al 2010). Certainly using self-reports of impulsivity is one limitation of this study, but the interaction bears similarity to results in rodents previously described, making the notion of an NO-serotonin interaction in impulsive or aggressive traits among humans plausible.…”

Section: Serotonin-no Interactionssupporting

confidence: 54%

“…Lin and colleagues (Laas et al 2010) applied an optogenetic approach combined with in vivo electrophysiological recording to identify an aggression locus in the mouse hypothalamus. Stimulation with a fiber optic cable of neurons in the VMHvl expressing channelrhodopsin rapidly elicited attack behavior when the male mouse was presented with an intruder, regardless of whether it was a male, female, or castrated male intruder.…”

Section: Advanced Methods and Future Agendamentioning

confidence: 99%

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Nitric Oxide and Serotonin Interactions in Aggression

Bedrosian

Nelson

2013

Current Topics in Behavioral Neurosciences

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Violence is a significant public health problem worldwide. Neurobiological research on violence and aggression attempts to elucidate the cellular and molecular pathways that increase the propensity toward this behavior. Research over the past 40 years has implicated several brain regions and neurotransmitters in aggression, mainly using rodent models. Perhaps the strongest association is the link between serotonin and aggression, which has compelling interactions with the nitric oxide system. Recently, new insights into these relationships have been added as modern techniques allow more sophisticated analyses. This chapter will discuss current developments implicating serotonin and nitric oxide in aggressive behavior. Recently developed high-resolution methods for examining the neurobiological basis of aggression will be considered, with emphasis on future directions for the field.

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Section: Serotonin-no Interactionssupporting

confidence: 54%

Section: Advanced Methods and Future Agendamentioning

confidence: 99%

Nitric Oxide and Serotonin Interactions in Aggression

Bedrosian

Nelson

2013

Current Topics in Behavioral Neurosciences

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“…In the previous human studies, Reif et al (2009) found an association between a VNTR in the promoter region and many disorders characterized by impulsivity, such as attention deficit hyperactivity disorder, SCZ, and suicide attempt. They also found an association between the same VNTR and self-reported impulsiveness, venturesomeness, and empathy (Retz et al, 2010;Laas et al, 2010;Reif et al, 2011). They further found that the risk variant was associated with altered brain function related to working memory (in an fNIRS study with an N-back task) (Kopf et al, 2011) and attentional control (in both EEG and NIRS studies with the CPT and combined stop-signal and Go/No-Go task) (Kopf et al, 2012;Reif et al, 2006;Reif et al, 2009).…”

Section: Discussionmentioning

confidence: 88%

“…Most of these studies were conducted by Reif et al (2009;2011) and focused on the promoter VNTR. For example, they found that the VNTR had a significant role in impulsive behavior (Retz et al, 2010;Laas et al, 2010;Reif et al, 2011) and mental disorders characterized by impulsive behavior (Reif et al, 2009). They also conducted a series of functional near-infrared spectroscopy (NIRS) studies and found that the VNTR could affect prefrontal activity during a working memory (a letter N-back) task or an attentional control task (combining the stop-signal task with the Go/No-Go task) (Kopf et al, 2012;Kopf et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Evidence for the Contribution of NOS1 Gene Polymorphism (rs3782206) to Prefrontal Function in Schizophrenia Patients and Healthy Controls

Zhang¹,

Chen

et al. 2014

Neuropsychopharmacol

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Nitric oxide (NO), a gaseous neurotransmitter, has been implicated in the pathogenesis of schizophrenia. Accordingly, several polymorphisms of the gene that codes for the main NO-producing enzyme, the nitric oxide synthase 1 (NOS1), have been found to convey a risk for schizophrenia. This study examined the role of NOS1 gene polymorphisms in cognitive functions and related neural mechanism. First, with a sample of 580 schizophrenia patients and 720 healthy controls, we found that rs3782206 genotype had main effects on the 1-back task (P ¼ 0.005), the 2-back task (P ¼ 0.049), the AY condition of the dot-pattern expectancy (DPX) task (P ¼ 0.001), and the conflict effect of the attention network (ANT) test (Po0.001 for RT differences and P ¼ 0.002 for RT ratio) and interaction effects with diagnosis on the BX condition of the DPX (P ¼ 0.009), the AY condition of the DPX (Po0.001), and the Stroop conflict effect (P ¼ 0.003 for RT differences and P ¼ 0.038 for RT ratio). Simple effect analyses further showed that the schizophrenia risk allele (T) of rs3782206 was associated with poorer performance in five measures for the patients (1-back, P ¼ 0.025; BX, P ¼ 0.017; AY, Po0.001; ANT conflict effect (RT differences), P ¼ 0.005; Stroop conflict effect (RT differences), P ¼ 0.019) and three measures for the controls ( for the 2-back task, P ¼ 0.042; for the ANT conlict effect (RT differences), P ¼ 0.013; for the ANT conflict effect (RT ratios), P ¼ 0.028). Then, with a separate sample of 78 healthy controls, we examined the association between rs3782206 and brain activation patterns during the N-back task and the Stroop task. Whole brain analyses found that the risk allele carriers showed reduced activation at the right inferior frontal gyrus (IFG) during both tasks. Finally, we examined functional connectivity seeded from the right IFG to the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex under three conditions (the N-back task, the Stroop task, and the resting state). Results showed reduced connectivity with the DLPFC for the risk allele carriers mainly in the Stroop task and the resting state. Taken together, results of this study strongly suggested a link between NOS1 gene polymorphism at rs3782206 and cognitive functions and their neural underpinnings at the IFG. These results have important implications for our understanding of the neural mechanism underlying the association between NOS1 gene polymorphism and schizophrenia.

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“…Moreover, recently 3 independent studies of non-clinical samples reported an association between the NOS1 ex1f variable number tandem repeat (VNTR) -functional promoter polymorphismand impulsivity traits measured with different questionnaires [25][26][27] . Hence, it is plausible that NOS1 and NOS3 genes could be implicated in the modulation of impulsive and/or aggressive traits.…”

Section: Discussionmentioning

confidence: 99%

NCAM1, TACR1 and NOS Genes and Temperament: A Study on Suicide Attempters and Controls

et al. 2011

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Suicide, one of the leading causes of death among young adults, seems to be plausibly modulated by both genetic and personality factors. The aim of this study was to dissect the potential association between genetics and temperament in a sample of 111 suicide attempters and 289 healthy controls. We focused on 4 genes previously investigated in association with suicide on the same sample: the nitric oxide synthase 1 and 3 (NOS1 and NOS3), the neuronal cell adhesion molecule 1 (NCAM1), and the tachykinin receptor 1 (TACR1) genes. In particular, we investigated whether a set of genetic variants in these genes (NOS1: rs2682826, rs1353939, rs693534; NOS3: rs2070744, rs1799983, rs891512; NCAM1: rs2301228, rs1884, rs1245113, rs1369816, rs2196456, rs584427; TACR1: rs3771810, rs3771825, rs726506, rs1477157) were associated with temperamental traits at the Temperament and Character Inventory (TCI). No strong evidence was found for the association between TCI personality traits and the polymorphisms considered in the 4 genes, with the exception of an association between reward dependence trait and the rs2682826 SNP in NOS1 in the healthy sample. However, this result could be plausibly interpreted as a false-positive finding. In conclusion, our study did not support the thesis of a direct modulation of these genes on temperament; however, further studies on larger samples are clearly required in order to confirm our preliminary findings and to exclude any possible minor influence.

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The effect of a functional NOS1 promoter polymorphism on impulsivity is moderated by platelet MAO activity

Abstract: This study supports evidence for higher impulsivity in the NOS1 short/short genotype subjects and further suggests that this is present in the subset of subjects who have close to average platelet MAO activity.

Cited by 35 publications

References 39 publications

Nitric Oxide and Serotonin Interactions in Aggression

Nitric Oxide and Serotonin Interactions in Aggression

Evidence for the Contribution of NOS1 Gene Polymorphism (rs3782206) to Prefrontal Function in Schizophrenia Patients and Healthy Controls

<i>NCAM1</i>, <i>TACR1</i> and <i>NOS</i> Genes and Temperament: A Study on Suicide Attempters and Controls

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