The dopamine transporter and neuroimaging in attention deficit hyperactivity disorder

Krause, Klaus; Dresel, S.; Krause, J.; Fougère, Christian la; Ackenheil, Manfred

doi:10.1016/j.neubiorev.2003.08.012

Cited by 162 publications

(82 citation statements)

References 79 publications

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“…Given nicotine's ability to increase dopamine neurotransmission pathways, detrimental effects of nicotinic acetylcholine receptor (nAChR) stimulated dopamine release in 9R allele carriers can be presumed to reflect 'overdosing' of dopamine levels in relatively intact brain structures. Increasing dopamine levels with nicotine may be particularly relevant for 9Rs, as acute nicotine also lowers dopamine transporter activity, impairing the ability to remove dopamine from synapses in a rapid fashion and thus increasing dopamine above an optimal level (Krause et al, 2003). In mutant mice in which dopamine production or the dopamine transporter is inactivated, studies have evidenced a persistent extracellular hyperdopaminergic tone (Jones et al, 1998;Gainetdinov et al, 1999), altered neurocircuitry , and hypersensitivity to dopaminergic receptor agonists (Kim et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

The moderating role of the dopamine transporter 1 gene on P50 sensory gating and its modulation by nicotine

et al. 2011

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Although schizophrenia has been considered primarily a disease of dopaminergic neurotransmission, the role of dopamine in auditory sensory gating deficits in this disorder and their amelioration by smoking/nicotine is unclear. Hypothesizing that individual differences in striatal dopamine levels may moderate auditory gating and its modulation by nicotine, this preliminary study used the mid-latency (P50) auditory event-related potential (ERP) to examine the single dose (6 mg) effects of nicotine (vs. placebo) gum on sensory gating in 24 healthy nonsmokers varying in the genetic expression of the dopamine transporter (DAT). Consistent with an inverted-U relationship between dopamine level and the drug effects, individuals carrying the 9R (lower gene expression) allele, which is related to greater striatal dopamine levels, tended to evidence increased baseline gating compared to 10R (higher gene expression) allele carriers and showed a reduction in gating with acute nicotine. The present results may help to understand the link between excessive smoking and sensory gating deficits in schizophrenia and to explain the potential functional implications of genetic disposition on nicotinic treatment in schizophrenia. Keywords schizophrenia; P50; gating; dopamine transporter gene; nicotine; smoking Early theoretical models of information processing in schizophrenia postulated impairment in the preattentive, automatic processing of sensory input to be a contributing factor in the appearance of psychotic symptoms, perceptual disturbances, and various cognitive deficits that characterize this disorder (Venables, 1964). Meta-analyses and reviews of event-related potential (ERP) studies probing auditory sensory gating in a paired stimulus paradigm (involving the presentation two [ CIHR Author Manuscript CIHR Author Manuscript CIHR Author Manuscriptfound that ~90% of patients with schizophrenia as well as ~50% of their first-degree relatives exhibit insufficient inhibitory processing of repetitive, irrelevant acoustic stimuli (Bramon et al., 2004;De Wilde et al., 2007;Patterson et al., 2008). Typically assessed with the amplitude of the early (50 ms) positive ERP component, P50, abnormal auditory sensory gating has been evidenced by a relative inability to suppress P50 to S 2 , and is expressed by larger S 2 /S 1 ratio (rP50) and/or smaller S 1 minus S 2 difference (dP50) scores.Smoking and acute nicotine have transiently corrected deficient P50 processing in schizophrenia patients and their relatives, respectively (Adler et al., 1992(Adler et al., , 1993. In addition, in a rodent model of schizophrenia-like gating deficiency, studies assessing the P20-N40 ERP, which is an analogue of the human P50, have shown agonists and antagonists of the α7 nicotinic receptor to improve deficient S 2 inhibition and to block normal S 2 inhibition, respectively (Stevens et al., 1998(Stevens et al., , 1999Simosky et al., 2001). Other studies reporting gating improvements with nicotine in rodents and humans, however, have found increa...

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Section: Discussionmentioning

confidence: 99%

The moderating role of the dopamine transporter 1 gene on P50 sensory gating and its modulation by nicotine

et al. 2011

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“…In vivo studies using single photon emission computed tomography (SPECT) show an increased density of striatal DAT in ADHD subjects compared with controls (Dougherty et al, 1999;Dresel et al, 2000;Krause et al, 2000Krause et al, , 2003. Cheon et al (2005) found a higher DAT density in the Interaction BDNF-DAT influences anxiety-related traits R Hünnerkopf et al basal ganglia of ADHD children with VNTR 10/10 genotype, suggesting that there might be an association between the VNTR genotype and DAT density.…”

Section: Discussionmentioning

confidence: 99%

Interaction between BDNF Val66Met and Dopamine Transporter Gene Variation Influences Anxiety-Related Traits

Hünnerkopf

Strobel²,

Gutknecht

et al. 2007

Neuropsychopharmacol

117

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The involvement in neural plasticity and the mediation of effects of repeated stress exposure and long-term antidepressant treatment on hippocampal neurogenesis supports a critical role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of affective and other stress-related disorders. A previously reported valine to methionine substitution at amino-acid position 66 (BDNF Val66Met) seems to account for memory disturbance and hippocampal dysfunction. In the present study, we evaluated the impact of the BDNF Val66Met polymorphism on individual differences in personality traits in a sample of healthy volunteers in relation to other common gene variants thought to be involved in the pathophysiology of affective disorders, such as the serotonin transporter promoter polymorphism (5-HTTLPR) and a variable number of tandem repeat polymorphism of the dopamine transporter gene (DAT VNTR). Personality traits were assessed using the NEO personality inventory (NEO-PI-R) and Tridimensional Personality Questionnaire (TPQ). There was a significant DAT VNTR-dependent association between NEO-PI-R Neuroticism and the BDNF Val66Met polymorphism. Among individuals with at least one copy of the DAT 9-repeat allele, carriers of the BDNF Met allele exhibited significantly lower Neuroticism scores than noncarriers. This interaction was also observed for TPQ Harm Avoidance, a personality dimension related to Neuroticism. Our results support the notion that allelic variation at the BDNF locusFin interaction with other gene variantsFinfluences anxietyand depression-related personality traits.

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“…Interestingly, some human genetic studies suggest the involvement of a DAT gene polymorphism in ADHD (Cook et al, 1995;Gill et al, 1997;Waldman et al, 1998; for a review, see DiMaio et al, 2003), although recent meta-analyses do not confirm this association (Purper-Ouakil et al, 2005;Li et al, 2006). PET scan data have shown an increase of DAT density in the caudateputamen of ADHD patients, reversed by nicotine abuse (Krause et al, 2003) and by methylphenidate treatment (Krause et al, 2003;Vles et al, 2003). Furthermore, in vivo imaging studies have provided evidence for a loss of the right-left asymmetry of DAT in the caudate of schizophrenic patients (Hsiao et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Nicotine Improves Cognitive Deficits of Dopamine Transporter Knockout Mice without Long-Term Tolerance

Weiss

Nosten‐Bertrand

McIntosh

et al. 2007

Neuropsychopharmacol

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Various studies suggest a dysfunction of nicotinic neurotransmission in schizophrenia and establish that patients suffering from schizophrenia and attention deficit hyperactivity disorder (ADHD) have a high tobacco consumption, potentially for the purpose of selfmedication. Owing to its neuroprotective and procognitive effects, transdermal nicotine was proposed to be an effective treatment of some neurodegenerative and psychiatric diseases. Mice deficient in the dopamine transporter (DAT KO) exhibit a phenotype reminiscent of schizophrenia and ADHD, including hyperdopaminergia, hyperactivity, paradoxical calming by methylphenidate and cognitive deficits, some of which being improved by antipsychotic agents. We recently demonstrated that nicotinic receptor content and function were profoundly modified in DAT KO mice. In this study, we assessed the effects of a chronic nicotine treatment in the drinking water on the nicotine-induced locomotion, anxiety status and learning performance. Chronically nicotine-treated DAT KO mice were always hypersensitive to the hypolocomotor effect of nicotine without tolerance and did not exhibit the anxiogenic effect of nicotine treatment observed in WT mice. Very interestingly, both acute and chronic nicotine treatments greatly improved their deficits in the cued and spatial learning, without eliciting tolerance. We speculate that the procognitive effects of nicotine in DAT KO mice are related to the upregulation of a7 nicotinic receptors in the hippocampus, amygdala, and prelimbic cortex, all areas involved in cognition. Data from our studies on DAT KO mice shed light on the nicotine self-medication in psychiatric patients and suggest that nicotinic agonists could favorably lead to additional therapy of psychiatric diseases.

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The dopamine transporter and neuroimaging in attention deficit hyperactivity disorder

Cited by 162 publications

References 79 publications

The moderating role of the dopamine transporter 1 gene on P50 sensory gating and its modulation by nicotine

The moderating role of the dopamine transporter 1 gene on P50 sensory gating and its modulation by nicotine

Interaction between BDNF Val66Met and Dopamine Transporter Gene Variation Influences Anxiety-Related Traits

Nicotine Improves Cognitive Deficits of Dopamine Transporter Knockout Mice without Long-Term Tolerance

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