Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder.

PubMed

Wang, Gene-Jack; Volkow, Nora D; Wigal, Timothy; Kollins, Scott H; Newcorn, Jeffrey H; Telang, Frank; Logan, Jean; Jayne, Millard; Wong, Christopher T; Han, Hao; Fowler, Joanna S; Zhu, Wei; Swanson, James M

2013-01-01

Brain dopamine dysfunction in attention deficit/hyperactivity disorder (ADHD) could explain why stimulant medications, which increase dopamine signaling, are therapeutically beneficial. However while the acute increases in dopamine induced by stimulant medications have been associated with symptom improvement in ADHD the chronic effects have not been investigated. We used positron emission tomography and [(11)C]cocaine (dopamine transporter radioligand) to measure dopamine transporter availability in the brains of 18 never-medicated adult ADHD subjects prior to and after 12 months of treatment with methylphenidate and in 11 controls who were also scanned twice at 12 months interval but without stimulant medication. Dopamine transporter availability was quantified as non-displaceable binding potential using a kinetic model for reversible ligands. Twelve months of methylphenidate treatment increased striatal dopamine transporter availability in ADHD (caudate, putamen and ventral striatum: +24%, p<0.01); whereas there were no changes in control subjects retested at 12-month interval. Comparisons between controls and ADHD participants revealed no significant difference in dopamine transporter availability prior to treatment but showed higher dopamine transporter availability in ADHD participants than control after long-term treatment (caudate: p<0.007; putamen: p<0.005). Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories.

Association of dopamine gene variants, emotion dysregulation and ADHD in autism spectrum disorder.

PubMed

Gadow, Kenneth D; Pinsonneault, Julia K; Perlman, Greg; Sadee, Wolfgang

2014-07-01

The aim of the present study was to evaluate the association of dopaminergic gene variants with emotion dysregulation (EMD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD). Three dopamine transporter gene (SLC6A3/DAT1) polymorphisms (intron8 5/6 VNTR, 3'-UTR 9/10 VNTR, rs27072 in the 3'-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on à priori evidence of regulatory activity or, in the case of DAT1 9/10 VNTR, commonly reported associations with ADHD. A sample of 110 children with ASD was assessed with a rigorously validated DSM-IV-referenced rating scale. Global EMD severity (parents' ratings) was associated with DAT1 intron8 (ηp(2)=.063) and rs2283265 (ηp(2)=.044). Findings for DAT1 intron8 were also significant for two EMD subscales, generalized anxiety (ηp(2)=.065) and depression (ηp(2)=.059), and for DRD2 rs2283265, depression (ηp(2)=.053). DRD2 rs2283265 was associated with teachers' global ratings of ADHD (ηp(2)=.052). DAT1 intron8 was associated with parent-rated hyperactivity (ηp(2)=.045) and both DAT1 9/10 VNTR (ηp(2)=.105) and DRD2 rs2283265 (ηp(2)=.069) were associated with teacher-rated inattention. These findings suggest that dopaminergic gene polymorphisms may modulate EMD and ADHD symptoms in children with ASD but require replication with larger independent samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dysfunctions in Dopamine Systems and ADHD: Evidence From Animals and Modeling

PubMed Central

Viggiano, Davide; Vallone, Daniela; Sadile, Adolfo

2004-01-01

Animal models are useful for characterizing neural substrates of neuropsychiatric disorders. Several models have been proposed for the study of Attention Deficit Hyperactivity Disorder (ADHD). The models can be divided into various groups: (i) genetically derived hyperactivity/ inattention, (ii) animal models showing symptoms after pharmacological intervention, and (iii) those based on spontaneous variations in a random population. Spontaneously hypertensive (SHR) and Naples High Excitability (NHE) rats show behavioral traits featuring the main aspects of ADHD in humans but show different changes in dopamine (DA) systems. In fact, the enzyme tyrosine hydroxylase is hyperexpressed in NHE rats and hypoexpressed in SHR. The DA transporter is hyperexpressed in both lines, although in the SHR, DAT activity is low (reduced DA uptake). The DA levels in the striatum and prefrontal cortex are increased in the juvenile SHR, but are decreased in handled young and non-handled older animals. The mRNA of the D1 DA receptor is upregulated in the prefrontal cortex of SHR and downregulated in NHE. The D2 DA receptors are likely to be hypofunctioning in SHR, although the experimental evidence is not univocal, whereas their mRNA is hyperexpressed in NHE. Thus, in SHR both the mesocortical and mesolimbic DA pathways appear to be involved, whereas in NHE only the mesocortical system. To understand the effects of methylphenidate, the elective ADHD drug treatment in humans, in a dysfunctioning DA system, we realized a simple mathematical model of DA regulation based on experimental data from electrophysiological, cyclic voltammetry, and microdialysis studies. This model allows the estimation of a higher firing frequency of DA neurons in SHR rats and suggests that methylphenidate increases attentive processes by regulating the firing rate of DA neurons. PMID:15303308

Stimulus-Dependent Dopamine Release in Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Sikstrom, Sverker; Soderlund, Goran

2007-01-01

Attention-deficit/hyperactivity disorder (ADHD) is related to an attenuated and dysfunctional dopamine system. Normally, a high extracellular dopamine level yields a tonic dopaminergic input that down-regulates stimuli-evoked phasic dopamine responses through autoreceptors. Abnormally low tonic extracellular dopamine in ADHD up-regulates the…

Low-Resolution Electromagnetic Tomography (LORETA) of changed Brain Function Provoked by Pro-Dopamine Regulator (KB220z) in one Adult ADHD case.

PubMed

Steinberg, Bruce; Blum, Kenneth; McLaughlin, Thomas; Lubar, Joel; Febo, Marcelo; Braverman, Eric R; Badgaiyan, Rajendra D

Attention Deficit-Hyperactivity Disorder (ADHD) often continues into adulthood. Recent neuroimaging studies found lowered baseline dopamine tone in the brains of affected individuals that may place them at risk for Substance Use Disorder (SUD). This is an observational case study of the potential for novel management of Adult ADHD with a non-addictive glutaminergic-dopaminergic optimization complex KB200z. Low-resolution electromagnetic tomography (LORETA) was used to evaluate the effects of KB220z on a 72-year-old male with ADHD, at baseline and one hour following administration. The resultant z-scores, averaged across Eyes Closed, Eyes Open and Working Memory conditions, increased for each frequency band, in the anterior, dorsal and posterior cingulate regions, as well as the right dorsolateral prefrontal cortex during Working Memory, with KB220z. These scores are consistent with other human and animal neuroimaging studies that demonstrated increased connectivity volumes in reward circuitry and may offer a new approach to ADHD treatment. However, larger randomized trials to confirm these results are required.

Low-Resolution Electromagnetic Tomography (LORETA) of changed Brain Function Provoked by Pro-Dopamine Regulator (KB220z) in one Adult ADHD case

PubMed Central

Steinberg, Bruce; Blum, Kenneth; McLaughlin, Thomas; Lubar, Joel; Febo, Marcelo; Braverman, Eric R.; Badgaiyan, Rajendra D

2016-01-01

Attention Deficit-Hyperactivity Disorder (ADHD) often continues into adulthood. Recent neuroimaging studies found lowered baseline dopamine tone in the brains of affected individuals that may place them at risk for Substance Use Disorder (SUD). This is an observational case study of the potential for novel management of Adult ADHD with a non-addictive glutaminergic-dopaminergic optimization complex KB200z. Low-resolution electromagnetic tomography (LORETA) was used to evaluate the effects of KB220z on a 72-year-old male with ADHD, at baseline and one hour following administration. The resultant z-scores, averaged across Eyes Closed, Eyes Open and Working Memory conditions, increased for each frequency band, in the anterior, dorsal and posterior cingulate regions, as well as the right dorsolateral prefrontal cortex during Working Memory, with KB220z. These scores are consistent with other human and animal neuroimaging studies that demonstrated increased connectivity volumes in reward circuitry and may offer a new approach to ADHD treatment. However, larger randomized trials to confirm these results are required. PMID:27610420

Moderator Effects of Working Memory on the Stability of ADHD Symptoms by Dopamine Receptor Gene Polymorphisms during Development

ERIC Educational Resources Information Center

Trampush, Joey W.; Jacobs, Michelle M.; Hurd, Yasmin L.; Newcorn, Jeffrey H.; Halperin, Jeffrey M.

2014-01-01

We tested the hypothesis that dopamine D1 and D2 receptor gene (DRD1 and DRD2, respectively) polymorphisms and the development of working memory skills can interact to influence symptom change over 10 years in children with attention-deficit/hyperactivity disorder (ADHD). Specifically, we examined whether improvements in working memory maintenance…

Dopamine and serotonin genetic risk scores predicting substance and nicotine use in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Groenman, Annabeth P.; Greven, Corina U.; van Donkelaar, Marjolein M.J.; Schellekens, Arnt; van Hulzen, Kimm J.E.; Rommelse, Nanda; Hartman, Catharina A.; Hoekstra, Pieter J.; Luman, Marjolein; Franke, Barbara; Faraone, Stephen V.; Oosterlaan, Jaap; Buitelaar, Jan K.

2015-01-01

Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence. The co-occurrence of ADHD and SUDs/nicotine dependence may in part be mediated by shared genetic liability. Several neurobiological pathways have been implicated in both ADHD and SUDs, including dopamine and serotonin pathways. We hypothesized that variations in dopamine and serotonin neurotransmission genes were involved in the genetic liability to develop SUDs/nicotine dependence in ADHD. The current study included participants with ADHD (n=280) who were originally part of the Dutch International Multicenter ADHD Genetics study. Participants were aged 5–15 years and attending outpatient clinics at enrollment in the study. Diagnoses of ADHD, SUDs, nicotine dependence, age of first nicotine and substance use, and alcohol use severity were based on semi-structured interviews and questionnaires. Genetic risk scores were created for both serotonergic and dopaminergic risk genes previously shown to be associated with ADHD and SUDs and/or nicotine dependence. The serotonin genetic risk score significantly predicted alcohol use severity. No significant serotonin*dopamine risk score or effect of stimulant medication was found. The current study adds to literature by providing insight into genetic underpinnings of the comorbidity of ADHD and SUDs. While the focus of the literature so far has been mostly on dopamine, our study suggests that serotonin may also play a role in the relationship between these disorders. PMID:25752199

ADHD-Derived Coding Variation in the Dopamine Transporter Disrupts Microdomain Targeting and Trafficking Regulation

PubMed Central

Sakrikar, Dhananjay; Mazei-Robison, Michelle S.; Mergy, Marc A.; Richtand, Nathan W.; Han, Qiao; Hamilton, Peter J.; Bowton, Erica; Galli, Aurelio; Veenstra-VanderWeele, Jeremy; Gill, Michael; Blakely, Randy D.

2012-01-01

Attention-Deficit Hyperactivity Disorder (ADHD) is the most commonly diagnosed disorder of school-age children. Although genetic and brain imaging studies suggest a contribution of altered dopamine (DA) signaling in ADHD, evidence of signaling perturbations contributing to risk is largely circumstantial. The presynaptic, cocaine and amphetamine (AMPH)-sensitive DA transporter (DAT) constrains DA availability at pre- and post-synaptic receptors following vesicular release and is targeted by the most commonly prescribed ADHD therapeutics. Using polymorphism discovery approaches with an ADHD cohort, we identified a human DAT (hDAT) coding variant, R615C, located in the transporter’s distal C-terminus, a region previously implicated in constitutive and regulated transporter trafficking. Here we demonstrate that whereas wildtype DAT proteins traffic in a highly regulated manner, DAT 615C proteins recycle constitutively, and demonstrate insensitivity to the endocytic effects of AMPH and protein kinase C (PKC) activation. The disrupted regulation of DAT 615C parallels a redistribution of the transporter variant away from GM1 ganglioside- and flotillin1-enriched membranes, and is accompanied by altered calcium/calmodulin-dependent protein kinase II (CaMKII) and flotillin-1 interactions. Using C-terminal peptides derived from wildtype DAT and the R615C variant, we establish that the DAT 615C C-terminus can act dominantly to preclude AMPH regulation of wildtype DAT. Mutagenesis of DAT C-terminal sequences suggest that phosphorylation of T613 may be important in sorting DAT between constitutive and regulated pathways. Together, our studies support a coupling of DAT microdomain localization with transporter regulation and provide evidence of perturbed DAT activity and DA signaling as a risk determinant for ADHD. PMID:22514303

Dopamine D4 Receptor Gene Polymorphism in a Sample of Egyptian Children With Attention-Deficit Hyperactivity Disorder (ADHD).

PubMed

ElBaz Mohamed, Farida; Kamal, Tarek Mostafa; Zahra, Sally Soliman; Khfagy, Mona Abdel Hakiem; Youssef, Azza Mohamed

2017-02-01

This study aimed to detect DRD4 receptor gene polymorphisms in attention-deficit hyperactivity disorder (ADHD) children and to correlate their phenotype-genotype. Fifty children with ADHD were diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria and were subjected to Conners Parent Rating Scale. All cases and controls were subjected to history taking, physical examination, IQ assessment, and dopamine receptor D4 (DRD4) exon 3 genotyping. The 7-repeat allele was present only in controls, whereas 2-repeat allele was present in the ADHD children (heterozygous 2-repeat allele in 16% and homozygous in 26% of cases). Eight percent of cases had homozygous 4-repeat allele vs 28% of controls, whereas 10% of cases had heterozygous 4-repeat allele vs 6% of controls, with its predominance in controls. The 2-repeat and 4-repeat alleles have been associated with more inattention, hyperactivity, and impulsivity phenotypes. In conclusion, children with ADHD had a significant presence of the 2-repeat allele and absence of the 7-repeat allele.

Low dopamine transporter occupancy by methylphenidate as a possible reason for reduced treatment effectiveness in ADHD patients with cocaine dependence.

PubMed

Crunelle, Cleo L; van den Brink, Wim; Veltman, Dick J; van Emmerik-van Oortmerssen, Katelijne; Dom, Geert; Schoevers, Robert A; Booij, Jan

2013-12-01

Methylphenidate (MPH) occupies brain striatal dopamine transporters (DATs) and is an effective treatment for attention deficit hyperactivity disorder (ADHD). However, patients with ADHD and comorbid cocaine dependence do not benefit significantly from treatment with MPH. To better understand the neurobiology of this phenomenon, we examined DAT availability and the effects of MPH treatment on DAT occupancy in ADHD patients with and without cocaine dependence. ADHD patients without a comorbid substance use disorder (N=16) and ADHD patients with comorbid cocaine dependence (N=8) were imaged at baseline and after two weeks MPH treatment using single photon emission computed tomography (SPECT) with the DAT tracer [(123)I]FP-CIT. Changes in ADHD symptoms were measured with the ADHD symptom rating scale (ASRS). At baseline, we observed lower striatal DAT availability in ADHD patients with cocaine dependence. Following fixed MPH treatment, MPH occupied significantly less striatal DATs in cocaine-dependent than in non-cocaine dependent ADHD patients. There were no significant correlations between baseline DAT availability or DAT occupancy by MPH and ADHD symptom improvement. However, we did find significant correlations between DAT occupancy by MPH and decreases in impulsivity scores and years of cocaine use. These preliminary findings suggest that low DAT occupancy is not the reason why ADHD patients with cocaine dependence do not benefit from MPH treatment. It also suggests that higher dosages of MPH in these patients are probably not the solution and that medications directed at other pharmacological targets should be considered in these comorbid ADHD patients. This trial is registered at the Dutch Trial Register, www.trialregister.nl, under Trial ID number NTR3127. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Dopamine D4 Receptor Gene Associated with the Frontal-Striatal-Cerebellar Loop in Children with ADHD: A Resting-State fMRI Study.

PubMed

Qian, Andan; Wang, Xin; Liu, Huiru; Tao, Jiejie; Zhou, Jiejie; Ye, Qiong; Li, Jiance; Yang, Chuang; Cheng, Jingliang; Zhao, Ke; Wang, Meihao

2018-06-01

Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamine D4 receptor (DRD4) on functional brain activity during the resting state in ADHD children using the methods of regional homogeneity (ReHo) and functional connectivity (FC). Resting-state functional magnetic resonance imaging data were analyzed in 49 children with ADHD. All participants were classified as either carriers of the DRD4 4-repeat/4-repeat (4R/4R) allele (n = 30) or the DRD4 2-repeat (2R) allele (n = 19). The results showed that participants with the DRD4 2R allele had decreased ReHo bilaterally in the posterior lobes of the cerebellum, while ReHo was increased in the left angular gyrus. Compared with participants carrying the DRD4 4R/4R allele, those with the DRD4 2R allele showed decreased FC to the left angular gyrus in the left striatum, right inferior frontal gyrus, and bilateral lobes of the cerebellum. The increased FC regions included the left superior frontal gyrus, medial frontal gyrus, and rectus gyrus. These data suggest that the DRD4 polymorphisms are associated with localized brain activity and specific functional connections, including abnormality in the frontal-striatal-cerebellar loop. Our study not only enhances the understanding of the correlation between the cerebellar lobes and ADHD, but also provides an imaging basis for explaining the neural mechanisms underlying ADHD in children.

Adolescent Atomoxetine Treatment in a Rodent Model of ADHD: Effects on Cocaine Self-Administration and Dopamine Transporters in Frontostriatal Regions

PubMed Central

Somkuwar, Sucharita S; Jordan, Chloe J; Kantak, Kathleen M; Dwoskin, Linda P

2013-01-01

Cocaine abuse and attention deficit/hyperactivity disorder (ADHD) are often comorbid. Preclinical research indicates that medial prefrontal (mPFC) and orbitofrontal (OFC) cortices are important neural substrates for both disorders. Using the spontaneously hypertensive rat (SHR) model of ADHD, we reported that adolescent treatment with the stimulant methylphenidate, a dopamine (DAT) and norepinephrine (NET) transporter inhibitor, enhanced cocaine self-administration during adulthood, and was associated with increased DAT function in mPFC. This study investigates the effects of atomoxetine ((R)-N-methyl-γ-(2-methylphenoxy)-benzenepropanamine hydrochloride) treatment, a selective NET inhibitor, during adolescence on cocaine self-administration and on DAT function and cell-surface expression in mPFC and OFC during adulthood. SHR acquired cocaine self-administration faster than Wistar–Kyoto and Wistar. Across cocaine doses, SHR earned more cocaine infusions and had higher progressive-ratio breakpoints than Wistar–Kyoto and Wistar, demonstrating that the SHR phenotype models comorbid ADHD and cocaine abuse. Prior atomoxetine treatment did not augment cocaine self-administration in SHR, but acquisition was enhanced in Wistar–Kyoto. No strain differences were found for DAT kinetic parameters or cellular localization in the vehicle controls. Atomoxetine did not alter DAT kinetic parameters or localization in SHR mPFC. Rather, atomoxetine decreased Vmax and DAT cell surface expression in SHR OFC, indicating that inhibition of NET by atomoxetine treatment during adolescence indirectly reduced DAT function and trafficking to the cell surface in OFC, specifically in the ADHD model. Thus, atomoxetine, unlike methylphenidate, does not enhance vulnerability to cocaine abuse in SHR and may represent an important alternative for teens with ADHD when drug addiction is a concern. PMID:23822950

Circadian Modulation of Dopamine Levels and Dopaminergic Neuron Development Contributes to Attention Deficiency and Hyperactive Behavior

PubMed Central

Huang, Jian; Zhong, Zhaomin; Wang, Mingyong; Chen, Xifeng; Tan, Yicheng; Zhang, Shuqing; He, Wei; He, Xiong; Huang, Guodong; Lu, Haiping; Wu, Ping; Che, Yi; Yan, Yi-Lin; Postlethwait, John H.; Chen, Wenbiao

2015-01-01

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children and adults. While ADHD patients often display circadian abnormalities, the underlying mechanisms are unclear. Here we found that the zebrafish mutant for the circadian gene period1b (per1b) displays hyperactive, impulsive-like, and attention deficit-like behaviors and low levels of dopamine, reminiscent of human ADHD patients. We found that the circadian clock directly regulates dopamine-related genes monoamine oxidase and dopamine β hydroxylase, and acts via genes important for the development or maintenance of dopaminergic neurons to regulate their number and organization in the ventral diencephalic posterior tuberculum. We then found that Per1 knock-out mice also display ADHD-like symptoms and reduced levels of dopamine, thereby showing highly conserved roles of the circadian clock in ADHD. Our studies demonstrate that disruption of a circadian clock gene elicits ADHD-like syndrome. The circadian model for attention deficiency and hyperactive behavior sheds light on ADHD pathogenesis and opens avenues for exploring novel targets for diagnosis and therapy for this common psychiatric disorder. PMID:25673850

Infant acetylcholine, dopamine, and melatonin dysregulation: Neonatal biomarkers and causal factors for ASD and ADHD phenotypes.

PubMed

Hellmer, Kahl; Nyström, Pär

2017-03-01

Autism spectrum disorders (ASD) and ADHD are common neurodevelopmental disorders that benefit from early intervention but currently suffer from late detection and diagnosis: neurochemical dysregulations are extant already at birth but clinical phenotypes are not distinguishable until preschool age or later. The vast heterogeneity between subjects' phenotypes relates to interaction between multiple unknown factors, making research on factor causality insurmountable. To unlock this situation we pose the hypothesis that atypical pupillary light responses from rods, cones, and the recently discovered ipRGC system reflect early acetylcholine, melatonin, and dopamine dysregulation that are sufficient but not necessary factors for developing ASD and/or ADHD disorders. Current technology allows non-invasive cost-efficient assessment already from the first postnatal month. The benefits of the current proposal are: identification of clinical subgroups based on cause rather than phenotypes; facilitation of research on other causal factors; neonatal prediction of later diagnoses; and guidance for targeted therapeutical intervention. Copyright © 2017 Elsevier Ltd. All rights reserved.

Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD

PubMed Central

Furukawa, Emi; Bado, Patricia; Tripp, Gail; Mattos, Paulo; Wickens, Jeff R.; Bramati, Ivanei E.; Alsop, Brent; Ferreira, Fernanda Meireles; Lima, Debora; Tovar-Moll, Fernanda; Sergeant, Joseph A.; Moll, Jorge

2014-01-01

Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD. PMID:24586543

Dopamine D4 receptor, but not the ADHD-associated D4.7 variant, forms functional heteromers with the dopamine D2S receptor in the brain

PubMed Central

González, Sergio; Rangel-Barajas, Claudia; Peper, Marcela; Lorenzo, Ramiro; Moreno, Estefanía; Ciruela, Francisco; Borycz, Janusz; Ortiz, Jordi; Lluís, Carme; Franco, Rafael; McCormick, Peter J.; Volkow, Nora D.; Rubinstein, Marcelo; Floran, Benjamin; Ferré, Sergi

2011-01-01

Polymorphic variants of the dopamine D4 receptor have been consistently associated with attention-deficit hyperactivity disorder (ADHD). However the functional significance of the risk polymorphism (variable number of tandem repeats in exon 3) is still unclear. Here we show that whereas the most frequent 4-repeat (D4.4) and the 2-repeat (D4.2) variants form functional heteromers with the short isoform of the dopamine D2 receptor (D2S), the 7-repeat risk allele (D4.7) does not. D2 receptor activation in the D2S-D4 receptor heteromer potentiates D4 receptor-mediated MAPK signaling in transfected cells and in the striatum, which did not occur in cells expressing D4.7 or in the striatum of knock-in mutant mice carrying the 7 repeats of the human D4.7 in the third intracellular loop of the D4 receptor. In the striatum D4 receptors are localized in cortico-striatal glutamatergic terminals, where they selectively modulate glutamatergic neurotransmission by interacting with D2S receptors. This interaction shows the same qualitative characteristics than the D2S-D4 receptor heteromer-mediated MAPK signaling and D2S receptor activation potentiates D4 receptor-mediated inibition of striatal glutamate release. It is therefore postulated that dysfunctional D2S-D4.7 heteromers may impair presynaptic dopaminergic control of corticostriatal glutamatergic neurotransmission and explain functional deficits associated with ADHD. PMID:21844870

ADHD Candidate Gene Study in a Population-Based Birth Cohort: Association with DBH and DRD2

ERIC Educational Resources Information Center

Nyman, Emma S.; Ogdie, Matthew N.; Loukola, Anu; Varilo, Teppo; Taanila, Anja; Hurtig, Tuula; Moilanen, Irma K.; Loo, Sandra K.; McGough, James J.; Jarvelin, Marjo-Riitta; Smalley, Susan L.

2007-01-01

A study aims to examine the genetic contribution if any to attention-deficit/hyperactivity disorder (ADHD). The results confirm the hypothesis and the association of dopamine [beta]-hydroxylase and dopamine receptor D2 genes with ADHD.

Candidate genetic pathways for attention-deficit/hyperactivity disorder (ADHD) show association to hyperactive/impulsive symptoms in children with ADHD.

PubMed

Bralten, Janita; Franke, Barbara; Waldman, Irwin; Rommelse, Nanda; Hartman, Catharina; Asherson, Philip; Banaschewski, Tobias; Ebstein, Richard P; Gill, Michael; Miranda, Ana; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph A; Oosterlaan, Jaap; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; Faraone, Stephen V; Buitelaar, Jan K; Arias-Vásquez, Alejandro

2013-11-01

Because multiple genes with small effect sizes are assumed to play a role in attention-deficit/hyperactivity disorder (ADHD) etiology, considering multiple variants within the same analysis likely increases the total explained phenotypic variance, thereby boosting the power of genetic studies. This study investigated whether pathway-based analysis could bring scientists closer to unraveling the biology of ADHD. The pathway was described as a predefined gene selection based on a well-established database or literature data. Common genetic variants in pathways involved in dopamine/norepinephrine and serotonin neurotransmission and genes involved in neuritic outgrowth were investigated in cases from the International Multicentre ADHD Genetics (IMAGE) study. Multivariable analysis was performed to combine the effects of single genetic variants within the pathway genes. Phenotypes were DSM-IV symptom counts for inattention and hyperactivity/impulsivity (n = 871) and symptom severity measured with the Conners Parent (n = 930) and Teacher (n = 916) Rating Scales. Summing genetic effects of common genetic variants within the pathways showed a significant association with hyperactive/impulsive symptoms ((p)empirical = .007) but not with inattentive symptoms ((p)empirical = .73). Analysis of parent-rated Conners hyperactive/impulsive symptom scores validated this result ((p)empirical = .0018). Teacher-rated Conners scores were not associated. Post hoc analyses showed a significant contribution of all pathways to the hyperactive/impulsive symptom domain (dopamine/norepinephrine, (p)empirical = .0004; serotonin, (p)empirical = .0149; neuritic outgrowth, (p)empirical = .0452). The present analysis shows an association between common variants in 3 genetic pathways and the hyperactive/impulsive component of ADHD. This study demonstrates that pathway-based association analyses, using quantitative measurements of ADHD symptom domains, can increase the power of genetic analyses to

Alterations in pain response are partially reversed by methylphenidate (Ritalin) in adults with attention deficit hyperactivity disorder (ADHD).

PubMed

Treister, Roi; Eisenberg, Elon; Demeter, Naor; Pud, Dorit

2015-01-01

Attention deficit hyperactivity disorder (ADHD) is characterized by dysregulation of sensory processing and neurobiology of dopamine. Although cumulative evidence suggests that dopamine is involved in pain processing, pain perception in ADHD subjects and the effect of dopamine agonists such as methylphenidate (MP, Ritalin) on it have rarely been studied. The aims of this study were to (1) psychophysically assess sensitivity to pain in ADHD subjects as compared to controls and (2) examine the effects of MP on pain response in ADHD subjects. Thirty subjects with ADHD and 30 age- and gender-matched controls participated in a preliminary trial. Pain threshold, intensity, and tolerance in response to cold pain stimulation were measured for both groups (ADHD with no treatment). In addition, the ADHD group was reassessed following a single dose of MP treatment. The ADHD subjects "without MP" in comparison with controls displayed significantly shorter cold pain threshold (2.8 ± 2.1 vs. 5.8 ± 2.5 seconds, respectively, P < 0.001) and cold tolerance (21.8 ± 22.3 vs. 62.8 ± 59.8 seconds, respectively P < 0.001). No differences in pain intensities between the groups were found. Following MP treatment, both cold threshold and tolerance in the ADHD subjects increased significantly compared to those with no treatment (3.6 ± 2.5 seconds, P = 0.011, and 46.4 ± 53.3 seconds, P < 0.001, respectively). These results suggest that adults with ADHD are more sensitive to pain compared with controls and that MP may exert antinociceptive properties in these subjects. Randomized, controlled trials are warranted to verify these findings. © 2013 World Institute of Pain.

[Substance use disorders and ADHD: an overview of recent Dutch research].

PubMed

van Emmerik-van Oortmerssen, K; Crunelle, C L; Carpentier, P J

2013-01-01

ADHD is an important risk factor for the development of substance use disorders (SUD). To provide an overview of recent Dutch research into the prevalence of ADHD in SUD populations and the neurobiological substrate of the reduced effect of pharmacological treatment of this patient group. We describe three studies: a meta-analysis and meta-regression analysis of the prevalence of ADHD in 6689 SUD patients; a cross-sectional study of the prevalence of ADHD and several other psychiatric disorders in 193 methadon maintenance patients, and finally a study in which the availability and occupation of dopamine transporters before and after methylphenidate treatment were measured using SPECT scans in 24 ADHD patients with and without cocaine addiction. The prevalence of ADHD in SUD patients is estimated to be 23.1% (95% confidence interval 19.4-27.2). This prevalence is influenced by the diagnostic instrument for ADHD and by the substance of abuse: cocaine is associated with a lower ADHD prevalence than other substances. The prevalence found among methadone maintenance patients was similar, namely 24.9%; additional comorbid psychiatric disorders were also frequently present. In the imaging study, lower availability of dopamine transporters and lower occupation by methylphenidate were found in cocaine-dependent ADHD patients than in ADHD patients without SUD. These studies confirm the high prevalence of ADHD in SUD patients, and provide a possible explanation for the reduced efficacy of methylphenidate in this patient population.

Molecular imaging genetics of methylphenidate response in ADHD and substance use comorbidity.

PubMed

Szobot, Claudia M; Roman, Tatiana; Hutz, Mara H; Genro, Júlia P; Shih, Ming Chi; Hoexter, Marcelo Q; Júnior, Neivo; Pechansky, Flávio; Bressan, Rodrigo A; Rohde, Luis A P

2011-02-01

Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) are highly comorbid and may share a genetic vulnerability. Methylphenidate (MPH), a dopamine transporter (DAT) blocker, is an effective drug for most ADHD patients. Although dopamine D4 receptor (DRD4) and dopamine transporter (DAT1) genes have a role in both disorders, little is known about how these genes influence brain response to MPH in individuals with ADHD/SUDs. The goal of this study was to evaluate whether ADHD risk alleles at DRD4 and DAT1 genes could predict the change in striatal DAT occupancy after treatment with MPH in adolescents with ADHD/SUDs. Seventeen adolescents with ADHD/SUDs underwent a SPECT scan with [Tc(99m) ]TRODAT-1 at baseline and after three weeks on MPH. Caudate and putamen DAT binding potential was calculated. Comparisons on DAT changes were made according to the subjects' genotype. The combination of both DRD4 7-repeat allele (7R) and homozygosity for the DAT1 10-repeat allele (10/10) was significantly associated with a reduced DAT change after MPH treatment in right and left caudate and putamen, even adjusting the results for potential confounders (P ≤ 0.02; R² from 0.50 to 0.56). In patients with ADHD/SUDs, combined DRD4 7R and DAT1 10/10 could index MPH reduced DAT occupancy. This might be important for clinical trials, in terms of better understanding individual variability in treatment response. Copyright © 2010 Wiley-Liss, Inc.

Dopaminergic and Noradrenergic Contributions to Functionality in ADHD: The Role of Methylphenidate

PubMed Central

Engert, Veronika; Pruessner, Jens C

2008-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood psychiatric condition characterized by severe impulsiveness, inattention and overactivity. Methylphenidate (MPH), a psychostimulant affecting both the dopaminergic and the noradrenergic systems, is one of the most frequently prescribed treatments for ADHD. Despite the widespread use of MPH and its proven effectiveness, its precise neurochemical mechanisms of action are under debate. For the most part, MPH’s influence on subcortical dopamine neurotransmission is thought to play a crucial role in its behavioral and cognitive effects. In their hypothesis of biphasic MPH action, Seeman and Madras [42, 43] suggest that therapeutic doses of MPH elevate tonic dopamine while inhibiting phasic transmitter release in subcortical structures, leading to reduced postsynaptic receptor stimulation and psychomotor activation in response to salient stimuli. Volkow and colleagues [56] suggest that by amplifying a weak striatal dopamine signal, MPH increases the perception of a stimulus or task as salient. The enhanced interest for the task is thought to increase attention and improve performance. Recent animal studies have however shown that when administered at doses producing clinically relevant drug plasma levels and enhancing cognitive function, MPH preferentially activates dopamine and noradrenaline efflux within the prefrontal cortex relative to the subcortical structures [5]. Overall, we suggest that the delineated theories of MPH therapeutic action should not be discussed as exclusive. Studies are outlined that allow integrating the different findings and models. PMID:19587853

Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

PubMed Central

Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

2014-01-01

Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

Increased Striatal Dopamine Synthesis Capacity in Gambling Addiction.

PubMed

van Holst, Ruth J; Sescousse, Guillaume; Janssen, Lieneke K; Janssen, Marcel; Berry, Anne S; Jagust, William J; Cools, Roshan

2018-06-15

The hypothesis that dopamine plays an important role in the pathophysiology of pathological gambling is pervasive. However, there is little to no direct evidence for a categorical difference between pathological gamblers and healthy control subjects in terms of dopamine transmission in a drug-free state. Here we provide evidence for this hypothesis by comparing dopamine synthesis capacity in the dorsal and ventral parts of the striatum in 13 pathological gamblers and 15 healthy control subjects. This was achieved using [ 18 F]fluoro-levo-dihydroxyphenylalanine dynamic positron emission tomography scans and striatal regions of interest that were hand-drawn based on visual inspection of individual structural magnetic resonance imaging scans. Our results show that dopamine synthesis capacity was increased in pathological gamblers compared with healthy control subjects. Dopamine synthesis was 16% higher in the caudate body, 17% higher in the dorsal putamen, and 17% higher in the ventral striatum in pathological gamblers compared with control subjects. Moreover, dopamine synthesis capacity in the dorsal putamen and caudate head was positively correlated with gambling distortions in pathological gamblers. Taken together, these results provide empirical evidence for increased striatal dopamine synthesis in pathological gambling. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Maternal separation affects dopamine transporter function in the spontaneously hypertensive rat: an in vivo electrochemical study.

PubMed

Womersley, Jacqueline S; Hsieh, Jennifer H; Kellaway, Lauriston A; Gerhardt, Greg A; Russell, Vivienne A

2011-12-01

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR) is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT) in ways that distinguish SHR from control rat strains. SHR and control Wistar-Kyoto (WKY) rats were subjected to maternal separation for 3 hours per day from postnatal day 2 to 14. Rats were tested for separation-induced anxiety-like behaviour followed by in vivo chronoamperometry to determine whether changes had occurred in striatal clearance of dopamine by DAT. The rate of disappearance of ejected dopamine was used as a measure of DAT function. Consistent with a model for ADHD, SHR were more active than WKY in the open field. SHR entered the inner zone more frequently and covered a significantly greater distance than WKY. Maternal separation increased the time that WKY spent in the closed arms and latency to enter the open arms of the elevated plus maze, consistent with other rat strains. Of note is that, maternal separation failed to produce anxiety-like behaviour in SHR. Analysis of the chronoamperometric data revealed that there was no difference in DAT function in the striatum of non-separated SHR and WKY. Maternal separation decreased the rate of dopamine clearance (k-1) in SHR striatum. Consistent with this observation, the dopamine clearance time (T100) was increased in SHR. These results suggest that the chronic mild stress of maternal separation impaired the function of striatal

Plugging the attention deficit: perceptual load counters increased distraction in ADHD.

PubMed

Forster, Sophie; Robertson, David J; Jennings, Alistair; Asherson, Philip; Lavie, Nilli

2014-01-01

Increased vulnerability to extraneous distraction is a key symptom of Attention-Deficit Hyperactivity Disorder (ADHD), which may have particularly disruptive consequences. Here we apply Load Theory of attention to increase understanding of this symptom, and to explore a potential method for ameliorating it. Previous research in nonclinical populations has highlighted increased perceptual load as a means of improving the ability to focus attention and avoid distraction. The present study examines whether adults with ADHD can also benefit from conditions of high perceptual load to improve their focused attention abilities. We tested adults with ADHD and age- and IQ-matched controls on a novel measure of irrelevant distraction under load, designed to parallel the form of distraction that is symptomatic of ADHD. During a letter search task, in which perceptual load was varied through search set size, participants were required to ignore salient yet entirely irrelevant distractors (colorful images of cartoon characters) presented infrequently (10% of trials). The presence of these distractors produced a significantly greater interference effect on the search RTs for the adults with ADHD compared with controls, p = .005, ηp² = .231. Perceptual load, however, significantly reduced distractor interference for the ADHD group and was as effective in reducing the elevated distractor interference in ADHD as it was for controls. These findings clarify the nature of the attention deficit underlying increased distraction in ADHD, and demonstrate a tangible method for overcoming it.

Plugging the Attention Deficit: Perceptual Load Counters Increased Distraction in ADHD

PubMed Central

2013-01-01

Objective: Increased vulnerability to extraneous distraction is a key symptom of Attention-Deficit Hyperactivity Disorder (ADHD), which may have particularly disruptive consequences. Here we apply Load Theory of attention to increase understanding of this symptom, and to explore a potential method for ameliorating it. Previous research in nonclinical populations has highlighted increased perceptual load as a means of improving the ability to focus attention and avoid distraction. The present study examines whether adults with ADHD can also benefit from conditions of high perceptual load to improve their focused attention abilities. Method: We tested adults with ADHD and age- and IQ-matched controls on a novel measure of irrelevant distraction under load, designed to parallel the form of distraction that is symptomatic of ADHD. During a letter search task, in which perceptual load was varied through search set size, participants were required to ignore salient yet entirely irrelevant distractors (colorful images of cartoon characters) presented infrequently (10% of trials). Results: The presence of these distractors produced a significantly greater interference effect on the search RTs for the adults with ADHD compared with controls, p = .005, ηp2 = .231. Perceptual load, however, significantly reduced distractor interference for the ADHD group and was as effective in reducing the elevated distractor interference in ADHD as it was for controls. Conclusions: These findings clarify the nature of the attention deficit underlying increased distraction in ADHD, and demonstrate a tangible method for overcoming it. PMID:24219607

Acute fasting increases somatodendritic dopamine release in the ventral tegmental area

PubMed Central

2015-01-01

Fasting and food restriction alter the activity of the mesolimbic dopamine system to affect multiple reward-related behaviors. Food restriction decreases baseline dopamine levels in efferent target sites and enhances dopamine release in response to rewards such as food and drugs. In addition to releasing dopamine from axon terminals, dopamine neurons in the ventral tegmental area (VTA) also release dopamine from their soma and dendrites, and this somatodendritic dopamine release acts as an autoinhibitory signal to inhibit neighboring VTA dopamine neurons. It is unknown whether acute fasting also affects dopamine release, including the local inhibitory somatodendritic dopamine release in the VTA. In these studies, I have tested whether fasting affects the inhibitory somatodendritic dopamine release within the VTA by examining whether an acute 24-h fast affects the inhibitory postsynaptic current mediated by evoked somatodendritic dopamine release (D2R IPSC). Fasting increased the contribution of the first action potential to the overall D2R IPSC and increased the ratio of repeated D2R IPSCs evoked at short intervals. Fasting also reduced the effect of forskolin on the D2R IPSC and led to a significantly bigger decrease in the D2R IPSC in low extracellular calcium. Finally, fasting resulted in an increase in the D2R IPSCs when a more physiologically relevant train of D2R IPSCs was used. Taken together, these results indicate that fasting caused a change in the properties of somatodendritic dopamine release, possibly by increasing dopamine release, and that this increased release can be sustained under conditions where dopamine neurons are highly active. PMID:26084913

Searching for a neurobiological basis for self-medication theory in ADHD comorbid with substance use disorders: an in vivo study of dopamine transporters using (99m)Tc-TRODAT-1 SPECT.

PubMed

Silva, Neivo; Szobot, Claudia M; Shih, Ming C; Hoexter, Marcelo Q; Anselmi, Carlos Eduardo; Pechansky, Flavio; Bressan, Rodrigo A; Rohde, Luis Augusto

2014-02-01

Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) frequently co-occur. Although several studies have shown changes in striatal dopamine transporter (DAT) density in these disorders, little is known about the neurobiological basis of the comorbidity. The aim of this study was to evaluate striatal DAT density in treatment-naive ADHD adolescents with SUD (ADHD + SUD) and without SUD (ADHD), compared to SUD adolescents without ADHD (SUD) and healthy control subjects (HC). Sixty-two male age-matched subjects diagnosed with DSM-IV criteria were included: ADHD + SUD (n = 18), SUD (n = 14), HC (n = 19), and ADHD (n = 11). Urine tests confirmed participants' drug use. All subjects performed SPECT scans with Tc-TRODAT-1 to evaluate DAT density in the striatum. The mean right striatum specific binding were 1.68 (ADHD), 1.38 (ADHD + SUD), 1.19 (HC), 1.17 (SUD), and in left striatum 1.65 (ADHD), 1.39 (ADHD + SUD), 1.19 (HC), and 1.17 (SUD). The ADHD group presented significantly higher striatal DAT density compared with ADHD + SUD, SUD, and HC groups. Adolescents with ADHD + SUD had significantly lower DAT density than those with ADHD, but significantly higher DAT density than those with SUD only and no significant difference from the healthy control group. The ADHD + SUD group had lower striatal DAT density in comparison with ADHD without SUD. It is possible to speculate that the use of cannabis and cocaine is responsible for the lower striatal DAT density in this group which would help in understanding the neurobiological basis for the self-medication theory in ADHD adolescents.

Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT

PubMed Central

Aguilar, Jenny I.; Dunn, Matthew; Mingote, Susana; Karam, Caline S.; Farino, Zachary J.; Sonders, Mark S.; Choi, Se Joon; Grygoruk, Anna; Zhang, Yuchao; Cela, Carolina; Choi, Ben Jiwon; Flores, Jorge; Freyberg, Robin J.; McCabe, Brian D.; Mosharov, Eugene V.; Krantz, David E.; Javitch, Jonathan A.; Sulzer, David; Sames, Dalibor; Rayport, Stephen; Freyberg, Zachary

2017-01-01

SUMMARY The ability of presynaptic dopamine terminals to tune neurotransmitter release to meet the demands of neuronal activity is critical to neurotransmission. Although vesicle content has been assumed to be static, in vitro data increasingly suggest that cell activity modulates vesicle content. Here, we use a coordinated genetic, pharmacological, and imaging approach in Drosophila to study the presynaptic machinery responsible for these vesicular processes in vivo. We show that cell depolarization increases synaptic vesicle dopamine content prior to release via vesicular hyperacidification. This depolarization-induced hyperacidification is mediated by the vesicular glutamate transporter (VGLUT). Remarkably, both depolarization-induced dopamine vesicle hyperacidification and its dependence on VGLUT2 are seen in ventral midbrain dopamine neurons in the mouse. Together, these data suggest that in response to depolarization, dopamine vesicles utilize a cascade of vesicular transporters to dynamically increase the vesicular pH gradient, thereby increasing dopamine vesicle content. PMID:28823729

Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT.

PubMed

Aguilar, Jenny I; Dunn, Matthew; Mingote, Susana; Karam, Caline S; Farino, Zachary J; Sonders, Mark S; Choi, Se Joon; Grygoruk, Anna; Zhang, Yuchao; Cela, Carolina; Choi, Ben Jiwon; Flores, Jorge; Freyberg, Robin J; McCabe, Brian D; Mosharov, Eugene V; Krantz, David E; Javitch, Jonathan A; Sulzer, David; Sames, Dalibor; Rayport, Stephen; Freyberg, Zachary

2017-08-30

The ability of presynaptic dopamine terminals to tune neurotransmitter release to meet the demands of neuronal activity is critical to neurotransmission. Although vesicle content has been assumed to be static, in vitro data increasingly suggest that cell activity modulates vesicle content. Here, we use a coordinated genetic, pharmacological, and imaging approach in Drosophila to study the presynaptic machinery responsible for these vesicular processes in vivo. We show that cell depolarization increases synaptic vesicle dopamine content prior to release via vesicular hyperacidification. This depolarization-induced hyperacidification is mediated by the vesicular glutamate transporter (VGLUT). Remarkably, both depolarization-induced dopamine vesicle hyperacidification and its dependence on VGLUT2 are seen in ventral midbrain dopamine neurons in the mouse. Together, these data suggest that in response to depolarization, dopamine vesicles utilize a cascade of vesicular transporters to dynamically increase the vesicular pH gradient, thereby increasing dopamine vesicle content. Copyright © 2017 Elsevier Inc. All rights reserved.

Reward modulation of cognitive function in adult attention-deficit/hyperactivity disorder: a pilot study on the role of striatal dopamine.

PubMed

Aarts, Esther; van Holstein, Mieke; Hoogman, Martine; Onnink, Marten; Kan, Cornelis; Franke, Barbara; Buitelaar, Jan; Cools, Roshan

2015-02-01

Attention-deficit/hyperactivity disorder (ADHD) is accompanied by impairments in cognitive control, such as task-switching deficits. We investigated whether such problems, and their remediation by medication, reflect abnormal reward motivation and associated striatal dopamine transmission in ADHD. We used functional genetic neuroimaging to assess the effects of dopaminergic medication and reward motivation on task-switching and striatal BOLD signal in 23 adults with ADHD, ON and OFF methylphenidate, and 26 healthy controls. Critically, we took into account interindividual variability in striatal dopamine by exploiting a common genetic polymorphism (3'-UTR VNTR) in the DAT1 gene coding for the dopamine transporter. The results showed a highly significant group by genotype interaction in the striatum. This was because a subgroup of patients with ADHD showed markedly exaggerated effects of reward on the striatal BOLD signal during task-switching when they were OFF their dopaminergic medication. Specifically, patients carrying the 9R allele showed a greater striatal signal than healthy controls carrying this allele, whereas no effect of diagnosis was observed in 10R homozygotes. Aberrant striatal responses were normalized when 9R-carrying patients with ADHD were ON medication. These pilot data indicate an important role for aberrant reward motivation, striatal dopamine and interindividual genetic differences in cognitive processes in adult ADHD.

Reward modulation of cognitive function in adult attention-deficit/hyperactivity disorder: a pilot study on the role of striatal dopamine

PubMed Central

Aarts, Esther; Hoogman, Martine; Onnink, Marten; Kan, Cornelis; Franke, Barbara; Buitelaar, Jan; Cools, Roshan

2015-01-01

Attention-deficit/hyperactivity disorder (ADHD) is accompanied by impairments in cognitive control, such as task-switching deficits. We investigated whether such problems, and their remediation by medication, reflect abnormal reward motivation and associated striatal dopamine transmission in ADHD. We used functional genetic neuroimaging to assess the effects of dopaminergic medication and reward motivation on task-switching and striatal BOLD signal in 23 adults with ADHD, ON and OFF methylphenidate, and 26 healthy controls. Critically, we took into account interindividual variability in striatal dopamine by exploiting a common genetic polymorphism (3′-UTR VNTR) in the DAT1 gene coding for the dopamine transporter. The results showed a highly significant group by genotype interaction in the striatum. This was because a subgroup of patients with ADHD showed markedly exaggerated effects of reward on the striatal BOLD signal during task-switching when they were OFF their dopaminergic medication. Specifically, patients carrying the 9R allele showed a greater striatal signal than healthy controls carrying this allele, whereas no effect of diagnosis was observed in 10R homozygotes. Aberrant striatal responses were normalized when 9R-carrying patients with ADHD were ON medication. These pilot data indicate an important role for aberrant reward motivation, striatal dopamine and interindividual genetic differences in cognitive processes in adult ADHD. PMID:25485641

Dopamine Transporter Genotype Conveys Familial Risk of Attention-Deficit/Hyperactivity Disorder through Striatal Activation

ERIC Educational Resources Information Center

Durston, Sarah; Fossella, John A.; Mulder, Martijn J.; Casey B. J.; Ziermans, Tim B.; Vessaz, M. Nathalie; Van Engeland, Herman

2008-01-01

The study examines the effect of the dopamine transporter (DAT1) genotype in attention-deficit/hyperactivity disorder (ADHD). The results confirm that DAT1 translates the genetic risk of ADHD through striatal activation.

Piloting a mobile health intervention to increase physical activity for adolescents with ADHD.

PubMed

Schoenfelder, Erin; Moreno, Megan; Wilner, Molly; Whitlock, Kathryn B; Mendoza, Jason A

2017-06-01

Physical activity (PA) reduces symptoms of Attention Deficit Hyperactivity Disorder (ADHD); interventions to increase PA may improve functioning and health for adolescents with ADHD. Mobile health (mHealth) technology and social media constitute promising interactive modalities for engaging adolescents-who are at highest risk for ADHD treatment drop-out-in interventions to increase PA. The current pilot study evaluated feasibility and acceptability of an innovative intervention incorporating an mHealth-linked wearable activity tracker (Fitbit Flex) and a Facebook group to increase PA among adolescents with ADHD. 11 adolescents diagnosed with ADHD (age 14-18, m = 15.5; 54% female) participated in a 4-week trial utilizing the Fitbit Flex in conjunction with (1) weekly personalized step count goals (2) social support through a Facebook group and (3) daily text messages about PA. The study took place in the greater Seattle, Washington area in the fall of 2015. Adolescents completed online surveys twice per week to rate their ADHD symptoms and positive and negative mood states, and parents rated adolescent ADHD symptoms weekly. Participants were adherent to the study protocol and acceptability of the intervention was high. Linear mixed models indicated that participants significantly increased their average weekly steps over the course of the study and demonstrated improvements in both adolescent and parent-reported ADHD Inattentive symptoms. Results indicate that this mHealth intervention is engaging and promising for increasing PA among adolescents with ADHD, and warrant further study. Implications for improving ADHD symptoms and overall functioning for this undertreated population are discussed.

The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant-induced dopamine release in the prefrontal cortex.

PubMed

Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Bini, Valentina; Gessa, Gian Luigi

2014-07-01

The dopamine-beta-hydroxylase inhibitor nepicastat has been shown to reproduce disulfiram ability to suppress the reinstatement of cocaine seeking after extinction in rats. To clarify its mechanism of action, we examined the effect of nepicastat, given alone or in association with cocaine or amphetamine, on catecholamine release in the medial prefrontal cortex and the nucleus accumbens, two key regions involved in the reinforcing and motivational effects of cocaine and in the reinstatement of cocaine seeking. Nepicastat effect on catecholamines was evaluated by microdialysis in freely moving rats. Nepicastat reduced noradrenaline release both in the medial prefrontal cortex and in the nucleus accumbens, and increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. Moreover, nepicastat markedly potentiated cocaine- and amphetamine-induced extracellular dopamine accumulation in the medial prefrontal cortex but not in the nucleus accumbens. Extracellular dopamine accumulation produced by nepicastat alone or by its combination with cocaine or amphetamine was suppressed by the α2 -adrenoceptor agonist clonidine. It is suggested that nepicastat, by suppressing noradrenaline synthesis and release, eliminated the α2 -adrenoceptor mediated inhibitory mechanism that constrains dopamine release and cocaine- and amphetamine-induced dopamine release from noradrenaline or dopamine terminals in the medial prefrontal cortex. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

Putative therapeutic targets for symptom subtypes of adult ADHD: D4 receptor agonism and COMT inhibition improve attention and response inhibition in a novel translational animal model.

PubMed

Tomlinson, Anneka; Grayson, Ben; Marsh, Samuel; Hayward, Andrew; Marshall, Kay M; Neill, Joanna C

2015-04-01

Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attention and response inhibition; the core deficits in ADHD. We have previously shown that methylphenidate and atomoxetine differentially improve these deficits dependent on baseline performance. The present study extends this work to investigate the effects of putative therapeutic targets in our model. A selective dopamine D4 receptor agonist (A-412997) and the catechol-O-methyl-transferase (COMT) inhibitor; tolcapone, were investigated in the combined subtype of adult ADHD (ADHD-C). Adult female rats were trained to criterion in the 5C-CPT (5-Choice Continuous Performance Task) and then separated into subgroups according to baseline levels of sustained attention, vigilance, and response disinhibition. The subgroups included: high-attentive (HA) and low-attentive with high response disinhibition (ADHD-C). The ADHD-C subgroup was selected to represent the combined subtype of adult ADHD. Effects of tolcapone (3.0, 10.0, 15.0mg/kg) and A-412997 (0.1, 0.3, 1.0µmol/kg) were tested by increasing the variable inter-trial-interval (ITI) duration in the 5C-CPT. Tolcapone (15mg/kg) significantly increased sustained attention, vigilance and response inhibition in ADHD-C animals, and impaired attention in HA animals. A-412997 (1.0µmol/kg) significantly increased vigilance and response inhibition in ADHD-C animals only, with no effect in HA animals. This is the first study to use the translational 5C-CPT to model the adult ADHD-C subtype in rats and to study new targets in this model. Both tolcapone and A-412997 increased vigilance and response inhibition in the ADHD-C subgroup. D4 and COMT are emerging as important potential therapeutic targets in adult ADHD that warrant further investigation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Dopamine-dependent periadolescent maturation of corticostriatal functional connectivity in mouse.

PubMed

Galiñanes, Gregorio L; Taravini, Irene R E; Murer, M Gustavo

2009-02-25

Altered corticostriatal information processing associated with early dopamine systems dysfunction may contribute to attention deficit/hyperactivity disorder (ADHD). Mice with neonatal dopamine-depleting lesions exhibit hyperactivity that wanes after puberty and is reduced by psychostimulants, reminiscent of some aspects of ADHD. To assess whether the maturation of corticostriatal functional connectivity is altered by early dopamine depletion, we examined preadolescent and postadolescent urethane-anesthetized mice with or without dopamine-depleting lesions. Specifically, we assessed (1) synchronization between striatal neuron discharges and oscillations in frontal cortex field potentials and (2) striatal neuron responses to frontal cortex stimulation. In adult control mice striatal neurons were less spontaneously active, less responsive to cortical stimulation, and more temporally tuned to cortical rhythms than in infants. Striatal neurons from hyperlocomotor mice required more current to respond to cortical input and were less phase locked to ongoing oscillations, resulting in fewer neurons responding to refined cortical commands. By adulthood some electrophysiological deficits waned together with hyperlocomotion, but striatal spontaneous activity remained substantially elevated. Moreover, dopamine-depleted animals showing normal locomotor scores exhibited normal corticostriatal synchronization, suggesting that the lesion allows, but is not sufficient, for the emergence of corticostriatal changes and hyperactivity. Although amphetamine normalized corticostriatal tuning in hyperlocomotor mice, it reduced horizontal activity in dopamine-depleted animals regardless of their locomotor phenotype, suggesting that amphetamine modified locomotion through a parallel mechanism, rather than that modified by dopamine depletion. In summary, functional maturation of striatal activity continues after infancy, and early dopamine depletion delays the maturation of core functional

Dopamine-dependent periadolescent maturation of corticostriatal functional connectivity in mouse

PubMed Central

Galiñanes, Gregorio L.; Taravini, Irene R.E.; Murer, M. Gustavo

2009-01-01

Altered corticostriatal information processing associated with early dopamine systems dysfunction may contribute to attention deficit/hyperactivity disorder (ADHD). Mice with neonatal dopamine-depleting lesions exhibit hyperactivity that wanes after puberty and is reduced by psychostimulants, reminiscent of some aspects of ADHD. To assess whether the maturation of corticostriatal functional connectivity is altered by early dopamine depletion, we examined pre- and post-adolescent urethane-anesthetized mice with or without dopamine-depleting lesions. Specifically, we assessed (1) synchronization between striatal neuron discharges and oscillations in frontal cortex field potentials and (2) striatal neuron responses to frontal cortex stimulation. In adult control mice striatal neurons were less spontaneously active, less responsive to cortical stimulation and more temporally tuned to cortical rhythms than in infants. Striatal neurons from hyperlocomotor mice required more current to respond to cortical input and were less phase-locked to ongoing oscillations, resulting in fewer neurons responding to refined cortical commands. By adulthood some electrophysiological deficits waned together with hyperlocomotion, but striatal spontaneous activity remained substantially elevated. Moreover, dopamine-depleted animals showing normal locomotor scores exhibited normal corticostriatal synchronization, suggesting that the lesion allows, but is not sufficient, for the emergence of corticostriatal changes and hyperactivity. Although amphetamine normalized corticostriatal tuning in hyperlocomotor mice, it reduced horizontal activity in dopamine-depleted animals irrespective of their locomotor phenotype, suggesting that amphetamine modified locomotion through a parallel mechanism, rather than that modified by dopamine depletion. In summary, functional maturation of striatal activity continues after infancy, and early dopamine depletion delays the maturation of core functional

The interactions among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of dopamine receptor D4 increase the risk of attention deficit/hyperactivity disorder in children.

PubMed

Chang, Chia-Huang; Yu, Ching-Jung; Du, Jung-Chieh; Chiou, Hsien-Chih; Chen, Hsin-Chang; Yang, Winnie; Chung, Ming-Yi; Chen, Ying-Sheue; Hwang, Betau; Mao, I-Fang; Chen, Mei-Lien

2018-01-01

The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified. Children with ADHD had significantly higher dimethylphosphate (DMP, 236.69nmol/g cre. vs. 186.84nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95µg/g cre. vs. 16.55µg/g cre., p value<0.01) concentrations than control children. Children who carried DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4 GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24-0.84). The estimated value of the AP (attributable proportion due to interaction) was 0.59 (95% CI: 0.13-1.05), indicating that 59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD (OR = 11.74, 95% CI: 2.12-65.04). This study indicated a gene-environment interaction in the risk of ADHD in children. The association between DMP and ADHD in children might relate to the mechanism of lipid peroxidation. Dose-response relationships and the combined effects of OPs, oxidative stress, and genetic polymorphism on ADHD should not be neglected. Copyright © 2017 Elsevier Inc. All rights reserved.

The Control of Responsiveness in ADHD by Catecholamines: Evidence for Dopaminergic, Noradrenergic and Interactive Roles

ERIC Educational Resources Information Center

Oades, Robert D.; Sadile, Adolfo G.; Sagvolden, Terje; Viggiano, Davide; Zuddas, Alessandro; Devoto, Paola; Aase, Heidi; Johansen, Espen B.; Ruocco, Lucia A.; Russell, Vivienne A.

2005-01-01

We explore the neurobiological bases of attention deficit hyperactivity disorder (ADHD) from the viewpoint of the neurochemistry and psychopharmacology of the catecholamine-based behavioural systems. The contributions of dopamine (DA) and noradrenaline (NA) neurotransmission to the motor and cognitive symptoms of ADHD (e.g. hyperactivity, variable…

Do firstborn children have an increased risk of ADHD?

PubMed

Marín, Adela Masana; Seco, Fernando Lopez; Serrano, Susana Martí; García, Silvia Acosta; Gaviria Gómez, Ana Milena; Ney, Inti

2014-10-01

Although previous reports have found no birth-order influence on ADHD risk, the authors hypothesize that being the firstborn is a risk factor for developing ADHD. They selected all of the currently treated ADHD outpatients (n = 748) from our database. Families with adopted sons, nonnuclear families, and families with only one child and with sons (affected or unaffected) younger than 6 or older than 18 years were excluded. A total of 181 families with 213 ADHD sons met the inclusion criteria. We used all siblings without a clinical diagnosis of ADHD and who had no contact with our service as our unaffected controls (n = 173). The bivariate analysis showed that ADHD was associated with birth order and that firstborn children had nearly twice the ADHD risk of children with other birth orders. birth order can be an ADHD risk factor in clinical samples. © 2012 SAGE Publications.

Cognitive Functioning in Affected Sibling Pairs with ADHD: Familial Clustering and Dopamine Genes

ERIC Educational Resources Information Center

Loo, Sandra K.; Rich, Erika Carpenter; Ishii, Janeen; McGough, James; McCracken, James; Nelson, Stanley; Smalley, Susan L.

2008-01-01

Background: This paper examines familiality and candidate gene associations of cognitive measures as potential endophenotypes in attention-deficit/hyperactivity disorder (ADHD). Methods: The sample consists of 540 participants, aged 6 to 18, who were diagnosed with ADHD from 251 families recruited for a larger genetic study of ADHD. All members of…

Dopamine transporter gene polymorphism in children with ADHD: A pilot study in Indonesian samples.

PubMed

Wiguna, Tjhin; Ismail, Raden Irawati; Winarsih, Noorhana Setyawati; Kaligis, Fransiska; Hapsari, Anggia; Budiyanti, Lina; Sekartini, Rini; Rahayu, Susan; Guerrero, Anthony P S

2017-10-01

Several studies showed that DAT1 polymorphism closed related with ADHD although the results were not consistently found. Studies in China, South Korea, Japan revealed that 10-repeat allele gave a risk for ADHD. Based on that understanding, this study tried to identify whether the similar polymorphism of DAT1 was also apparent in Indonesian children with ADHD. This was a case - control study. Case was 50 Indonesian origin children with ADHD and without any other mental disorders and metal retardation. Control is Indonesian origin children without ADHD, other mental disorders and mental retardation. ADHD diagnosis was taken after doing the psychiatric interview and observation based on the DSM-IV TR diagnostic criteria for ADHD at the Child and Adolescent Psychiatry Out-patient Clinic, Dr. Cipto Mangunkusumo National Referral Hospital - Faculty of Medicine Universitas Indonesia. DNA isolation, DNA purity and concentration were measured. PCR was done by using a primer based on Homo sapiens solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3), RefSeq Gene on chromosome 5 with accession number NG_015885.1. To identify the serial of repeated allele, we used the sequencing technique. There were 47 children with ADHD and 48 children without ADHD that involved in the final analysis. The mean of age amongst ADHD group was 9.18 (2.42) and 8.10 (2.46) years old in non-ADHD group. The 10-repeated allele of DAT1 was the highest proportion in both. This finding was apparently similar with other studies on DAT1 polymorphism across Asian. Copyright © 2017 Elsevier B.V. All rights reserved.

The Contribution of Maternal ADHD Symptomatology, Maternal DAT1, and Home Atmosphere to Child ADHD Symptomatology at 7 Years of Age.

PubMed

Auerbach, Judith G; Zilberman-Hayun, Yael; Atzaba-Poria, Naama; Berger, Andrea

2017-04-01

Children of mothers with attention-deficit/hyperactivity disorder (ADHD) have an increased genetic and environmental risk for ADHD. The unique and interactive contributions of a maternal dopamine receptor gene (DAT1), maternal ADHD symptoms (hyperactive- impulsive, inattentive), and home atmosphere to the prediction of ADHD symptoms (hyperactive- impulsive, inattentive) in 7- year-old boys (N = 96) were examined using data from a longitudinal study of familial risk for ADHD. During the first 6 months of the study, mothers and their spouses completed a questionnaire about the mother's ADHD symptoms. Home atmosphere questionnaire data were collected 4 years later. At the 7-year assessment, mothers reported on their child's ADHD symptoms. Negative home atmosphere was significantly associated with child hyperactive-impulsive and inattentive symptoms. Maternal inattentive symptoms were significantly correlated with both child symptom dimensions. Regression models, with child genotype and maternal education controlled, showed main effects for maternal inattentive symptoms, maternal DAT1 10/10 genotype, and home atmosphere in the prediction of child inattentive symptoms. Only home atmosphere predicted child hyperactive-impulsive symptoms. There was a significant home atmosphere x maternal hyperactive-impulsive symptoms interaction in the prediction of child hyperactive-impulsive symptoms. Boys with higher levels of symptoms came from homes characterized by higher levels of negative atmosphere and had mothers with higher levels of hyperactive-impulsive symptoms. There was also a trend (p = 0.075) for a maternal DAT1 x home atmosphere interaction. Boys with higher levels of inattentive symptoms came from homes with higher levels of negative atmosphere and had mothers with the homozygous 10/10 genotype. The maternal heterozygous 9/10 genotype did not predict child symptoms.

Pharmacological and therapeutic directions in ADHD: Specificity in the PFC.

PubMed

Levy, Florence

2008-02-28

Recent directions in the treatment of ADHD have involved both a broadening of pharmacological perspectives to include nor-adrenergic as well as dopaminergic agents. A review of animal and human studies of pharmacological and therapeutic directions in ADHD suggests that the D1 receptor is a specific site for dopaminergic regulation of the PFC, but optimal levels of dopamine (DA) are required for beneficial effects on working memory. Animal and human studies indicate that the alpha-2A receptor is also important for prefrontal regulation, leaving open the question of the relative importance of these receptor sites. The therapeutic effects of ADHD medications in the prefrontal cortex have focused attention on the development of working memory capacity in ADHD. The actions of dopaminergic vs noradrenergic agents, currently available for the treatment of ADHD have overlapping, but different actions in the prefrontal cortex (PFC) and subcortical centers. While stimulants act on D1 receptors in the dorsolateral prefrontal cortex, they also have effects on D2 receptors in the corpus striatum and may also have serotonergic effects at orbitofrontal areas. At therapeutic levels, dopamine (DA) stimulation (through DAT transporter inhibition) decreases noise level acting on subcortical D2 receptors, while NE stimulation (through alpha-2A agonists) increases signal by acting preferentially in the PFC possibly on DAD1 receptors. On the other hand, alpha-2A noradrenergic transmission is more limited to the prefrontal cortex (PFC), and thus less likely to have motor or stereotypic side effects, while alpha-2B and alpha-2C agonists may have wider cortical effects. The data suggest a possible hierarchy of specificity in the current medications used in the treatment of ADHD, with guanfacine likely to be most specific for the treatment of prefrontal attentional and working memory deficits. Stimulants may have broader effects on both vigilance and motor impulsivity, depending on dose

The Role of D2-Autoreceptors in Regulating Dopamine Neuron Activity and Transmission

PubMed Central

Ford, Christopher P

2014-01-01

Dopamine D2-autoreceptors play a key role in regulating the activity of dopamine neurons and control the synthesis, release and uptake of dopamine. These Gi/o-coupled inhibitory receptors play a major part in shaping dopamine transmission. Found at both somatodendritic and axonal sites, autoreceptors regulate the firing patterns of dopamine neurons and control the timing and amount of dopamine released from their terminals in target regions. Alterations in the expression and activity of autoreceptors are thought to contribute to Parkinson’s disease as well as schizophrenia, drug addiction and attention deficit hyperactivity disorder (ADHD), which emphasizes the importance of D2-autoreceptors in regulating the dopamine system. This review will summarize the cellular actions of dopamine autoreceptors and discuss recent advances that have furthered our understanding of the mechanisms by which D2-receptors control dopamine transmission. PMID:24463000

Top-Down Dysregulation—From ADHD to Emotional Instability

PubMed Central

Petrovic, Predrag; Castellanos, F. Xavier

2016-01-01

Deficient cognitive top-down executive control has long been hypothesized to underlie inattention and impulsivity in attention-deficit/hyperactivity disorder (ADHD). However, top-down cognitive dysfunction explains a modest proportion of the ADHD phenotype whereas the salience of emotional dysregulation is being noted increasingly. Together, these two types of dysfunction have the potential to account for more of the phenotypic variance in patients diagnosed with ADHD. We develop this idea and suggest that top-down dysregulation constitutes a gradient extending from mostly non-emotional top-down control processes (i.e., “cool” executive functions) to mainly emotional regulatory processes (including “hot” executive functions). While ADHD has been classically linked primarily to the former, conditions involving emotional instability such as borderline and antisocial personality disorder are closer to the other. In this model, emotional subtypes of ADHD are located at intermediate levels of this gradient. Neuroanatomically, gradations in “cool” processing appear to be related to prefrontal dysfunction involving dorsolateral prefrontal cortex (dlPFC) and caudal anterior cingulate cortex (cACC), while “hot” processing entails orbitofrontal cortex and rostral anterior cingulate cortex (rACC). A similar distinction between systems related to non-emotional and emotional processing appears to hold for the basal ganglia (BG) and the neuromodulatory effects of the dopamine system. Overall we suggest that these two systems could be divided according to whether they process non-emotional information related to the exteroceptive environment (associated with “cool” regulatory circuits) or emotional information related to the interoceptive environment (associated with “hot” regulatory circuits). We propose that this framework can integrate ADHD, emotional traits in ADHD, borderline and antisocial personality disorder into a related cluster of mental

Gray Matter Increase in Motor Cortex in Pediatric ADHD: A Voxel-Based Morphometry Study.

PubMed

Sutcubasi Kaya, Bernis; Metin, Baris; Tas, Zeynep Cubukcuoglu; Buyukaslan, Ayse; Soysal, Aysegul; Hatiloglu, Deniz; Tarhan, Nevzat

2018-05-01

Several studies report that ADHD is associated with reduced gray matter (GM), whereas others report no differences in GM volume between ADHD patients and controls, and some even report more GM volume in individuals with ADHD. These conflicting findings suggest that reduced GM is not a universal finding in ADHD, and that more research is needed to delineate with greater accuracy the range of GM alterations. The present study aimed to identify GM alterations in ADHD using pediatric templates. 19 drug-naïve ADHD patients and 18 controls, all aged 7 to 14 years, were scanned using magnetic resonance imaging. Relative to the controls, the ADHD patients had more GM, predominantly in the precentral and supplementary motor areas. Moreover, there were positive correlations between GM volume in these areas and ADHD scale scores. The clinical and pathophysiological significance of increased GM in the motor areas remains to be elucidated by additional research.

Consequences of Variations in Genes that affect Dopamine in Prefrontal Cortex

PubMed Central

Diamond, Adele

2008-01-01

Patricia Goldman-Rakic played a groundbreaking role in investigating the cognitive functions subserved by dorsolateral prefrontal cortex and the key role of dopamine in that. The work discussed here builds on that including: 1) Studies of children predicted to have lower levels of prefrontal dopamine but otherwise basically normal brains (children treated for phenylketonuria [PKU]). Those studies changed medical guidelines, improving the children’s lives. 2) Studies of visual impairments (in contrast sensitivity and motion perception) in PKU children due to reduced retinal dopamine and due to excessive phenylalanine during the first postnatal weeks. Those studies, too, changed medical guidelines. 3) Studies of working memory and inhibitory control differences in typically developing children due to differences in catechol-O-methyltransferase (COMT) genotype, which selectively affect prefrontal dopamine levels. 4) Studies of gender differences in the effect of COMT genotype on cognitive performance in older adults. 5) A hypothesis about fundamental differences between attention deficit hyperactivity disorder (ADHD) that includes hyperactivity and ADHD of the inattentive type. Those disorders are hypothesized to differ in the affected neural system, underlying genetics, responsiveness to medication, comorbidities, and cognitive and behavioral profiles. These sound quite disparate but they all grew systematically out the base laid down by Patricia Goldman-Rakic. PMID:17725999

Hypothyroidism leads to increased dopamine receptor sensitivity and concentration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crocker, A.D.; Overstreet, D.H.; Crocker, J.M.

1986-06-01

Rats treated with iodine-131 were confirmed to be hypothyroid by their reduced baseline core body temperatures, reduced serum thyroxine concentrations and elevated serum thyroid stimulating hormone concentrations. When hypothyroid rats were compared to euthyroid controls they were more sensitive to the effects of apomorphine (1.0 mumol/kg) on stereotypy, operant responding and body temperature and showed a smaller reduction in locomotor activity after injection of haloperidol (0.25 mumol/kg). Receptor binding studies on striatal homogenates indicated that hypothyroid rats had increased concentrations of D2 dopamine receptors but there was no change in the affinity. It is concluded that hypothyroidism increases dopamine receptormore » sensitivity by increasing receptor concentration.« less

Mice lacking cyclin-dependent kinase-like 5 manifest autistic and ADHD-like behaviors.

PubMed

Jhang, Cian-Ling; Huang, Tzyy-Nan; Hsueh, Yi-Ping; Liao, Wenlin

2017-10-15

Neurodevelopmental disorders frequently share common clinical features and appear high rate of comorbidity, such as those present in patients with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). While characterizing behavioral phenotypes in the mouse model of cyclin-dependent kinase-like 5 (CDKL5) disorder, a neurodevelopmental disorder caused by mutations in the X-linked gene encoding CDKL5, we found that these mice manifested behavioral phenotypes mimicking multiple key features of ASD, such as impaired social interaction and communication, as well as increased stereotypic digging behaviors. These mice also displayed hyper-locomotion, increased aggressiveness and impulsivity, plus deficits in motor and associative learning, resembling primary symptoms of ADHD. Through brain region-specific biochemical analysis, we uncovered that loss of CDKL5 disrupts dopamine synthesis and the expression of social communication-related key genes, such as forkhead-box P2 and mu-opioid receptor, in the corticostriatal circuit. Together, our findings support that CDKL5 plays a role in the comorbid features of autism and ADHD, and mice lacking CDKL5 may serve as an animal model to study the molecular and circuit mechanisms underlying autism-ADHD comorbidity. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Association analysis of norepinephrine transporter polymorphisms and methylphenidate response in ADHD patients.

PubMed

Angyal, Nora; Horvath, Erzsebet Zsofia; Tarnok, Zsanett; Richman, Mara J; Bognar, Emese; Lakatos, Krisztina; Sasvari-Szekely, Maria; Nemoda, Zsofia

2018-06-08

Methylphenidate (MPH) is the most frequently prescribed drug in Attention Deficit Hyperactivity Disorder (ADHD). Hitherto mostly the dopamine transporter gene has been studied in MPH-response and only a few studies analyzed the norepinephrine transporter (NET, SLC6A2) gene, although MPH is a potent inhibitor of both dopamine and norepinephrine transporters. We aimed to analyze this monoamine transporter gene in relation to ADHD per se and MPH-response in particular to gain further knowledge in ADHD pharmacogenetics using a Caucasian sample. Six single nucleotide polymorphisms (rs28386840, rs2242446, rs3785143, rs3785157, rs5569, rs7194256 SNP) were studied across the NET gene in 163 ADHD children (age: 9.3±2.6; 86.5% male) using ADHD-RS hyperactivity-impulsivity and inattention scales. For case-control analysis 486 control subjects were also genotyped. At the MPH-response analysis responders had minimum 25% decrease of ADHD-RS total score after 2months of treatment, and chi-square test compared 90 responders and 32 non-responders, whereas ANOVA was used to assess symptom improvement after the first month among the 122 ADHD patients. The classical case-control analysis did not yield any association with ADHD diagnosis, which was supported by meta-analysis conducted on the available genetic data (combining previously published and the present studies). On the other hand, the intronic rs3785143 showed nominal association with inattention symptoms (p=0.01). The haplotype analysis supported this association, and indicated the importance of the first haploblock encompassing the intronic and 2 promoter SNPs. With MPH-response only the promoter rs28386840 showed nominal association: Those with at least one T-allele were overrepresented in the responder group (42% vs 19%, p=0.08), and they had better improvement on the hyperactivity-impulsivity scale compared to the AA genotype (p=0.04). Although none of our single SNP findings remained significant after correcting for

Symptoms of Attention-Deficit/Hyperactivity Disorder in Down Syndrome: Effects of the Dopamine Receptor D4 Gene

ERIC Educational Resources Information Center

Mason, Gina Marie; Spanó, Goffredina; Edgin, Jamie

2015-01-01

This study examined individual differences in ADHD symptoms and executive function (EF) in children with Down syndrome (DS) in relation to the dopamine receptor D4 (DRD4) gene, a gene often linked to ADHD in people without DS. Participants included 68 individuals with DS (7-21 years), assessed through laboratory tasks, caregiver reports, and…

Dopamine Transporter Genotype Predicts Attentional Asymmetry in Healthy Adults

ERIC Educational Resources Information Center

Newman, Daniel P.; O'Connell, Redmond G.; Nathan, Pradeep J.; Bellgrove, Mark A.

2012-01-01

A number of recent studies suggest that DNA variation in the dopamine transporter gene (DAT1) influences spatial attention asymmetry in clinical populations such as ADHD, but confirmation in non-clinical samples is required. Since non-spatial factors such as attentional load have been shown to influence spatial biases in clinical conditions, here…

Interactions among attention-deficit hyperactivity disorder (ADHD) and problem gambling in a probabilistic reward-learning task.

PubMed

Abouzari, Mehdi; Oberg, Scott; Gruber, Aaron; Tata, Matthew

2015-09-15

Problem gambling is thought to be highly comorbid with attention-deficit hyperactivity disorder (ADHD). We propose that the neurobiological pathologies underlying problem gambling overlap with those in ADHD. In this study, we used a simplified computerized version of the Iowa Gambling Task (IGT) to assess differences in reinforcement-driven choice adaptation among participants with pathological gambling and/or ADHD. The task contained two choice options with different net payouts over the session; a good bet that resulted in a win of +50 points on 60% of trials (and -50 points on 40%), and a bad bet that resulted in +100 points on 40% of the trials (and -100 points on 60%). We quantified participants' preference for the good bet over the session and their sensitivity to reinforcement. Both the control subjects and medicated ADHD nongamblers significantly increased the proportion of good bets over the 400-trial session. Subjects with problem gambling performed worse than controls and ADHD nongamblers, but better than our limited sample of unmedicated ADHD gamblers. Control subjects, medicated ADHD nongamblers, and unmedicated ADHD nongamblers tended to tolerate losses following good bets, whereas unmedicated ADHD gamblers tended to tolerate losses following bad bets. These data reveal that ADHD, particularly when treated with medication, is not associated with poor choices on the IGT, but may exacerbate pathological choices in problem gamblers. It seems that stabilization of dopamine signaling that occurs when ADHD is treated is itself also a treatment for certain forms of problem gambling. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Deficiency of Sustained Attention in ADHD and Its Potential Genetic Contributor MAOA.

PubMed

Liu, Lu; Cheng, Jia; Su, Yi; Ji, Ning; Gao, Qian; Li, Haimei; Yang, Li; Sun, Li; Qian, Qiujin; Wang, Yufeng

2015-03-17

To investigate the genetic contributors to ADHD sustained attention deficit among noradrenergic genes responsible for the synthesis (dopamine-β-hydroxylase gene, DBH), transport (norepinephrine transporter gene, NET1), reception (alpha-2A adrenergic receptor gene, ADRA2A), and metabolism (monoamine oxidase A gene, MAOA) of noradrenalin (NE). A total of 456 children with ADHD and 108 normal controls were included in a digit cancellation test (DCT). DNA was collected from 242 participants and genotyped for 14 single nucleotide polymorphisms (SNPs) of noradrenergic genes. Compared with normal controls, children with ADHD showed a lower total score and higher mean error rate in the DCT, indicating poorer sustained attention function. Analysis of covariance showed an association between MAOA genotypes and ADHD performance in DCT, with poorer performance in risk allele carriers. No association was found for other noradrenergic genes. Children with ADHD presented with a sustained attention deficit compared with normal controls. The sustained attention deficit of children with ADHD may be associated with genetic variant of MAOA. © 2015 SAGE Publications.

β-Phenylethylamine requires the dopamine transporter to increase extracellular dopamine in Caenorhabditis elegans dopaminergic neurons.

PubMed

Hossain, Murad; Wickramasekara, Rochelle N; Carvelli, Lucia

2014-07-01

β-Phenylethylamine (βPEA) is an endogenous amine that has been shown to increase the synaptic levels of dopamine (DA). A number of in vitro and behavioral studies suggest the dopamine transporter (DAT) plays a role in the effects generated by βPEA, however the mechanism through which βPEA affects DAT has not yet been elucidated. Here, we used Caenorhabditis (C.) elegans DAT (DAT-1) expressing LLC-pk1 cells and neuronal cultures to investigate whether the βPEA-induced increase of extracellular DA required DAT-1. Our data show that βPEA increases extracellular dopamine both in DAT-1 transfected cells and cultures of differentiated neurons. RTI-55, a cocaine homologue and DAT inhibitor, completely blocked the βPEA-induced effect in transfected cells. However in neuronal cultures, RTI-55 only partly inhibited the increase of extracellular DA generated by βPEA. These results suggest that βPEA requires DAT-1 and other, not yet identified proteins, to increase extracellular DA when tested in a native system. Furthermore, our results suggest that βPEA-induced increase of extracellular DA does not require functional monoamine vesicles as genetic ablation of the C. elegans homologue vesicular monoamine transporter, cat-1, did not compromise the ability of βPEA to increase extracellular DA. Finally, our electrophysiology data show that βPEA caused fast-rising and self-inactivating amperometric currents in a subset of wild-type DA neurons but not in neurons isolated from dat-1 knockout animals. Taken together, these data demonstrate that in both DA neurons and heterogeneous cultures of differentiated C. elegans neurons, βPEA releases cytoplasmic DA through DAT-1 to ultimately increase the extracellular concentration of DA. Copyright © 2013 Elsevier Ltd. All rights reserved.

β-phenylethylamine Requires the Dopamine Transporter to Increase Extracellular Dopamine in C. elegans Dopaminergic Neurons

PubMed Central

Hossain, Murad; Wickramasekara, Rochelle N.; Carvelli, Lucia

2013-01-01

β-phenylethylamine (βPEA) is an endogenous amine that has been shown to increase the synaptic levels of dopamine (DA). A number of in vitro and behavioral studies suggest the dopamine transporter (DAT) plays a role in the effects generated by βPEA, however the mechanism through which βPEA affects DAT has not yet been elucidated. Here, we used Caenorhabditis (C.) elegans DAT (DAT-1) expressing LLC-pk1 cells and neuronal cultures to investigate whether the βPEA-induced increase of extracellular DA required DAT-1. Our data show that βPEA increases extracellular dopamine both in DAT-1 transfected cells and cultures of differentiated neurons. RTI-55, a cocaine homologue and DAT inhibitor, completely blocked the βPEA-induced effect in transfected cells. However in neuronal cultures, RTI-55 only partly inhibited the increase of extracellular DA generated by βPEA. These results suggest that βPEA requires DAT-1 and other, not yet identified proteins, to increase extracellular DA when tested in a native system. Furthermore, our results suggest that βPEA-induced increase of extracellular DA does not require functional monoamine vesicles as genetic ablation of the C. elegans homologue vesicular monoamine transporter, cat-1, did not compromise the ability of βPEA to increase extracellular DA. Finally, our electrophysiology data show that βPEA caused fast-rising and self-inactivating amperometric currents in a subset of wild-type DA neurons but not in neurons isolated from dat-1 knockout animals. Taken together, these data demonstrate that in both DA neurons and heterogeneous cultures of differentiated C. elegans neurons, βPEA releases cytoplasmic DA through DAT-1 to ultimately increase the extracellular concentration of DA. PMID:24161617

The neurotropic parasite Toxoplasma gondii increases dopamine metabolism

USDA-ARS?s Scientific Manuscript database

The common parasite Toxoplasma gondii induces behavioral alterations in its hosts including phenotypes increasing the likelihood of its transmission in rodents and reports of psychobehavioral alterations in humans. We have found that elevated levels of dopamine are associated with the encysted stage...

Increased Intrasubject Variability in Boys with ADHD across Tests of Motor and Cognitive Control

ERIC Educational Resources Information Center

Rosch, Keri Shiels; Dirlikov, Benjamin; Mostofsky, Stewart H.

2013-01-01

Increased intrasubject variability (ISV), or short-term, within-person fluctuations in behavioral performance is consistently found in Attention-Deficit/Hyperactivity Disorder (ADHD). ADHD is also associated with impairments in motor control, particularly in boys. The results of the few studies that have examined variability in self-generated…

fMRI Activation during Response Inhibition and Error Processing: The Role of the DAT1 Gene in Typically Developing Adolescents and Those Diagnosed with ADHD

ERIC Educational Resources Information Center

Braet, Wouter; Johnson, Katherine A.; Tobin, Claire T.; Acheson, Ruth; McDonnell, Caroline; Hawi, Ziarah; Barry, Edwina; Mulligan, Aisling; Gill, Michael; Bellgrove, Mark A.; Robertson, Ian H.; Garavan, Hugh

2011-01-01

The DAT1 gene codes for the dopamine transporter, which clears dopamine from the synaptic cleft, and a variant of this gene has previously been associated with compromised response inhibition in both healthy and clinical populations. This variant has also been associated with ADHD, a disorder that is characterised by disturbed dopamine function as…

Role of aberrant striatal dopamine D1 receptor/cAMP/protein kinase A/DARPP32 signaling in the paradoxical calming effect of amphetamine.

PubMed

Napolitano, Francesco; Bonito-Oliva, Alessandra; Federici, Mauro; Carta, Manolo; Errico, Francesco; Magara, Salvatore; Martella, Giuseppina; Nisticò, Robert; Centonze, Diego; Pisani, Antonio; Gu, Howard H; Mercuri, Nicola B; Usiello, Alessandro

2010-08-18

Attention deficit/hyperactivity disorder (ADHD) is characterized by inattention, impulsivity, and motor hyperactivity. Several lines of research support a crucial role for the dopamine transporter (DAT) gene in this psychiatric disease. Consistently, the most commonly prescribed medications in ADHD treatment are stimulant drugs, known to preferentially act on DAT. Recently, a knock-in mouse [DAT-cocaine insensitive (DAT-CI)] has been generated carrying a cocaine-insensitive DAT that is functional but with reduced dopamine uptake function. DAT-CI mutants display enhanced striatal extracellular dopamine levels and basal motor hyperactivity. Herein, we showed that DAT-CI animals present higher striatal dopamine turnover, altered basal phosphorylation state of dopamine and cAMP-regulated phosphoprotein 32 kDa (DARPP32) at Thr75 residue, but preserved D(2) receptor (D(2)R) function. However, although we demonstrated that striatal D(1) receptor (D(1)R) is physiologically responsive under basal conditions, its stimulus-induced activation strikingly resulted in paradoxical electrophysiological, behavioral, and biochemical responses. Indeed, in DAT-CI animals, (1) striatal LTP was completely disrupted, (2) R-(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) treatment induced paradoxical motor calming effects, and (3) SKF 81297 administration failed to increase cAMP/protein kinase A (PKA)/DARPP32 signaling. Such biochemical alteration selectively affected dopamine D(1)Rs since haloperidol, by blocking the tonic inhibition of D(2)R, unmasked a normal activation of striatal adenosine A(2A) receptor-mediated cAMP/PKA/DARPP32 cascade in mutants. Most importantly, our studies highlighted that amphetamine, nomifensine, and bupropion, through increased striatal dopaminergic transmission, are able to revert motor hyperactivity of DAT-CI animals. Overall, our results suggest that the paradoxical motor calming effect induced by these

Pharmacology and pharmacogenetics of pediatric ADHD with associated aggression: a review.

PubMed

Patel, Bianca D; Barzman, Drew H

2013-12-01

Attention deficit hyperactivity disorder (ADHD) is often associated with symptoms of aggression in children and adolescents. Clinically, this is complex because aggression can be from hyperactivity and impulsivity, or could be a distinct symptom from a comorbid diagnosis. Past research has recommended first treating the primary disorder of ADHD. Stimulants are the most common treatment for pediatric ADHD, which can be helpful in decreasing aggressive behaviors. Alpha-adrenergic agonists and atomoxetine (ATX) are non-stimulant medications for ADHD and aggression, but more research is necessary to compare these drugs to stimulants. If aggressive symptoms do not improve from treating the primary disorder, aggression can be treated separately. Risperidone, lithium, valproic acid, clonidine, and guanfacine have shown positive results in reducing aggression, but studies including children with aggression and ADHD are limited. The variability in treatment tolerability in patients has stimulated research in pharmacogenetics for ADHD. Although this field is still emerging, research has found evidence supporting a link between the response rate of methylphenidate and the dopamine transporter (DAT1) and a link between the metabolism rate of atomoxetine and hepatic cytochrome 450 isozymes. Pharmacogenetics may be relevant to ADHD and associated aggression. Further research in pharmacogenetics will strive to identify patterns of genetic variations that can tailor individual treatments.

Cocaine Self-Administration Produces a Persistent Increase in Dopamine D2High Receptors

PubMed Central

Briand, Lisa A.; Flagel, Shelly B.; Seeman, Philip; Robinson, Terry E.

2008-01-01

Cocaine addicts are reported to have decreased numbers of striatal dopamine D2 receptors. However, in rodents, repeated cocaine administration consistently produces hypersensitivity to the psychomotor activating effects of both indirect dopamine agonists, such as cocaine itself, and importantly, to direct-acting D2 receptor agonists. The current study reports a possible resolution to this long-standing paradox. The dopamine D2 receptor exists in both a low and a high affinity state, and dopamine exerts its effects via the more functionally relevant high-affinity D2 receptor (D2High). We report here that cocaine self-administration experience produces a large (approximately 150%) increase in the proportion of D2High receptors in the striatum with no change in the total number of D2 receptors, and this effect is evident both 3 and 30 days after the discontinuation of cocaine self-administration. Changes in D2High receptors would not be evident with the probes used in human (and non-human primate) imaging studies. We suggest, therefore, that cocaine addicts and animals previously treated with cocaine may be hyper-responsive to dopaminergic drugs in part because an increase in D2High receptors results in dopamine supersensitivity. This may also help explain why stimuli that increase dopamine neurotransmission, including drugs themselves, are so effective in producing relapse in individuals with a history of exposure to cocaine. PMID:18284941

The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety.

PubMed

Heal, D J; Cheetham, S C; Smith, S L

2009-12-01

Results from in vivo techniques, especially intracerebral microdialysis in freely-moving rats, have provided insights into potential mechanisms responsible for the efficacy and safety of catecholaminergic drugs for ADHD treatment. The drugs reviewed come from distinct pharmacological classes: psychostimulant releasing agents, eg d-amphetamine; psychostimulant reuptake inhibitors, eg dl-threo-methylphenidate (dl-MPH), and non-stimulant reuptake inhibitors, eg atomoxetine. Psychostimulants, which currently deliver the best efficacy in treating ADHD, exhibit the following characteristics on extraneuronal catecholamine concentrations in rodent brain in vivo: 1) They enhance the efflux and function of both noradrenaline and dopamine in the central nervous system. 2) The increase of dopamine efflux that they produce is not limited to cortical regions. 3) They have a rapid onset of action with no ceiling on drug effect. d-Amphetamine has a mechanism independent of neuronal firing rate, displacing intraneuronal stores of catecholamines, delaying their reuptake and inhibiting catabolism by monoamine oxidase. dl-MPH has an enigmatic, extraneuronal action that is neuronal firing rate-dependent and reuptake transporter-mediated, yet paradoxically, almost as powerful as that of d-amphetamine. In safety terms, these powerful catecholaminergic effects also make the psychostimulants liable for abuse. Since efficacy and safety derive from the same pharmacological mechanisms, it has not yet been possible to separate these two components. However, the development of once-daily psychostimulant formulations and a prodrug, lisdexamfetamine, has improved patient compliance and markedly reduced scope for their diversion/abuse. This review will discuss the in vivo pharmacological profiles of approved catecholaminergic drugs for treatment of ADHD and implications for their clinical efficacy and abuse liability.

High Sibling Correlation on Methylphenidate Response but No Association with DAT1-10R Homozygosity in Dutch Sibpairs with ADHD

ERIC Educational Resources Information Center

van der Meulen, Emma M.; Bakker, Steven C.; Pauls, David L.; Oteman, Nicole; Kruitwagen, Cas L. J. J.; Pearson, Peter L.; Sinke, Richard J.; Buitelaar, Jan K.

2005-01-01

Background: A minority of patients with attention-deficit hyperactivity disorder (ADHD) do not respond favorably to methylphenidate. This has been partially associated with homozygosity for the Dopamine transporter (DAT1) 10-repeat allele and the presence of one or two Dopamine D4 receptor (DRD4) 7-repeat alleles. This study examined the sibling…

ADHD impacted by sulfotransferase (SULT1A) inhibition from artificial food colors and plant-based foods.

PubMed

Eagle, Ken

2014-08-01

Five recent reviews have analyzed trials on the association between artificial food colors and ADHD; the 50 underlying studies and the reviews in aggregate were inconclusive. Recent work has shown human in vivo SULT1A inhibition leading to incremental catecholamines, and an inverted-U relationship between brain catecholamines and proper functioning of the prefrontal cortex where ADHD behavior can arise. This study re-examined the same underlying trials for evidence that SULT1A inhibitors were in the placebos and other inactive foods, that these "inactive" materials were symptomatic, and that ADHD symptoms exhibited an inverted-U response to SULT1A inhibition. Nearly all the underlying diets, and many placebos and delivery vehicles, were found to contain SULT1A inhibitors. Eight publications provided evidence of ADHD symptoms caused by the "inactive" materials containing SULT1A inhibitors. Ten studies showed additional SULT1A inhibitors reducing the symptoms of some subjects. SULT1A inhibitors in foods, including natural substances and artificial food colors, have a role in ADHD that can both worsen or improve symptoms. Mechanistically, SULT1A enzymes normally deactivate catecholamines, especially dopamine formed in the intestines; SULT1A inhibition can influence brain catecholamines through the intermediary of plasma tyrosine levels, which are influenced by dopamine inhibition of intestinal tyrosine hydroxylase. Biochemical measurements focused on SULT1A activity and plasma tyrosine concentrations are proposed for future work. Copyright © 2014 Elsevier Inc. All rights reserved.

Intelligence in DSM-IV combined type attention-deficit/hyperactivity disorder is not predicted by either dopamine receptor/transporter genes or other previously identified risk alleles for attention-deficit/hyperactivity disorder.

PubMed

Sonuga-Barke, Edmund J S; Brookes, Keeley-Joanne; Buitelaar, Jan; Anney, Richard; Bitsakou, Paraskevi; Baeyens, Dieter; Buschgens, Cathelijne; Chen, Wai; Christiansen, Hanna; Eisenberg, Jacques; Kuntsi, Jonna; Manor, Iris; Meliá, Amanda; Mulligan, Aisling; Rommelse, Nanda; Müller, Ueli C; Uebel, Henrik; Banaschewski, Tobias; Ebstein, Richard; Franke, Barbara; Gill, Michael; Miranda, Ana; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Steinhausen, Hans Christoph; Thompson, Margaret; Taylor, Eric; Asherson, Philip; Faraone, Stephen V

2008-04-05

A major goal of genetic studies of attention deficit hyperactivity disorder (ADHD) is to identify individual characteristics that might help segregate the disorder's inherent heterogeneity. [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] recently reported a potentially important association between two dopamine-related risk polymorphisms (DRD4 variable number tandem repeat (VNTR) in exon 3 and DAT1 VNTR in the 3' UTR) and lowered IQ in ADHD. The objective of the current study was to replicate the [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] findings in a clinical sample and to extend the analysis to a large range of alternative SNP markers of putative ADHD risk alleles identified in a recent study [Brookes et al. (2006); Mol Genet 11:934-953]. Participants were 1081 children and adolescents with a research-confirmed combined type ADHD diagnosis and 1300 unaffected siblings who took part in the International Multi-centre ADHD Genetics (IMAGE) project. They were recruited from multiple settings from across Europe: Belgium, Britain, Germany, Ireland, Israel, Netherlands, Spain and Switzerland. The results were that ADHD was associated with reduced IQ. However, there was no association between the two dopamine-related risk polymorphisms and IQ in either the probands or their siblings. Furthermore, other selected genetic markers previously demonstrated to be associated with ADHD in this sample were not associated with IQ. This large scale study with a clinically ascertained and regorously diagnosed sample failed to replicate the association between genetic polymorphisms in the dopamine system and IQ in ADHD. We also observed no association of other SNPs with IQ in ADHD. Copyright 2007 Wiley-Liss, Inc.

Alternative pharmacological strategies for adult ADHD treatment: a systematic review.

PubMed

Buoli, Massimiliano; Serati, Marta; Cahn, Wiepke

2016-01-01

Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder.

The association between dopamine receptor (DRD4) gene polymorphisms and second language learning style and behavioral variability in undergraduate students in Turkey.

PubMed

Maras Atabay, Meltem; Safi Oz, Zehra; Kurtman, Elvan

2014-08-01

The dopamine D4 receptor gene (DRD4) encodes a receptor for dopamine, a chemical messenger used in the brain. One variant of the DRD4 gene, the 7R allele, is believed to be associated with attention deficit hyperactivity disorder (ADHD). The aim of this study was to investigate the relationships between repeat polymorphisms in dopamine DRD4 and second language learning styles such as visual (seeing), tactile (touching), auditory (hearing), kinesthetic (moving) and group/individual learning styles, as well as the relationships among DRD4 gene polymorphisms and ADHD in undergraduate students. A total of 227 students between the ages of 17-21 years were evaluated using the Wender Utah rating scale and DSM-IV diagnostic criteria for ADHD. Additionally, Reid's perceptual learning style questionnaire for second language learning style was applied. In addition, these students were evaluated for social distress factors using the list of Threatening Events (TLE); having had no TLE, having had just one TLE or having had two or more TLEs within the previous 6 months before the interview. For DRD4 gene polymorphisms, DNA was extracted from whole blood using the standard phenol/chloroform method and genotyped using polymerase chain reaction. Second language learners with the DRD4.7+ repeats showed kinaesthetic and auditory learning styles, while students with DRD4.7-repeats showed visual, tactile and group learning, and also preferred the more visual learning styles [Formula: see text]. We also demonstrated that the DRD4 polymorphism significantly affected the risk effect conferred by an increasing level of exposure to TLE.

Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children.

PubMed

Yu, C-J; Du, J-C; Chiou, H-C; Chung, M-Y; Yang, W; Chen, Y-S; Fuh, M-R; Chien, L-C; Hwang, B; Chen, M-L

2016-07-01

Attention-deficit/hyperactivity disorder (ADHD) is male predominated, and the etiology of this disorder remains unclear. Past studies have assessed the association of low-level organophosphate pesticide exposure with childhood ADHD cross-sectionally and prospectively. However, the results have been inconsistent. A first case-control study was performed to investigate the relationship between organophosphate pesticide exposure and ADHD with adjusted covariates. We recruited 97 doctor-diagnosed ADHD cases and 110 non-ADHD controls who were 4-15 years of age. Exposure was assessed using urinary levels of dialkylphosphate metabolites, which are biomarkers of OP pesticide exposure. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. The sociodemographics and lifestyles of the children and of the mothers during pregnancy were collected using a questionnaire. The blood lead levels of both groups were similar (1.57 ± 0.73 vs. 1.73 ± 0.77 μg/dL, p = 0.15). Significant urinary concentration differences in one of the six dialkylphosphate metabolites, dimethylphosphate (DMP), were found between ADHD and control subjects (322.92 ± 315.68 vs. 224.37 ± 156.58 nmol/g cr., p < 0.01). A dose-response relationship was found between urinary concentrations of DMP and ADHD in both crude and adjusted analyses (p for trend<0.05). Children with higher urinary DMP concentrations may have a twofold to threefold increased risk of being diagnosed with ADHD. We report a dose-response relationship between child DMP levels and ADHD. Organophosphate pesticide exposure may have deleterious effects on children's neurodevelopment, particularly the development of ADHD. © 2016 American Society of Andrology and European Academy of Andrology.

Effect of Dopamine Transporter Gene (SLC6A3) Variation on Dorsal Anterior Cingulate Function in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Brown, Ariel B.; Biederman, Joseph; Valera, Eve M.; Doyle, Alysa E.; Bush, George; Spencer, Thomas; Monuteaux, Michael C.; Mick, Eric; Whitfield-Gabrieli, Susan; Makris, Nikos; LaViolette, Peter S.; Oscar-Berman, Marlene; Faraone, Stephen V.; Seidman, Larry J.

2010-01-01

Objective - Although Attention-Deficit/Hyperactivity Disorder (ADHD) is associated both with brain alterations in attention and executive function (EF) circuitry and with genetic variations within the dopamine system (including the dopamine transporter gene [SLC6A3]), few studies have directly investigated how genetic variations are linked to brain alterations. We sought to examine how a polymorphism in the 3’ untranslated region (UTR) of SLC6A3, associated with ADHD in meta-analysis, might contribute to variation in dorsal anterior cingulate cortex (dACC) function in subjects with ADHD. Method - We collected fMRI scans of 42 individuals with ADHD, all of European descent and over the age of 17, while they performed the Multi-Source Interference Task (MSIT), a cognitive task shown to activate dACC. SLC6A3 3’ UTR variable number tandem repeat (VNTR) polymorphisms were genotyped and brain activity was compared for groups based on allele status. Results - ADHD individuals homozygous for the 10R allele showed significant hypoactivation in the left dACC compared to 9R-carriers. Exploratory analysis also showed trends toward hypoactivation in the 10R homozygotes in left cerebellar vermis and right lateral prefrontal cortex. Further breakdown of genotype groups showed similar activation in individuals heterozygous and homozygous for the 9R allele. Conclusions - Alterations in activation of attention and EF networks found previously to be involved in ADHD are likely influenced by SLC6A3 genotype. This genotype may contribute to heterogeneity of brain alterations found within ADHD samples. PMID:19676101

Dopamine Transporter Blockade Increases LTP in the CA1 Region of the Rat Hippocampus via Activation of the D3 Dopamine Receptor

ERIC Educational Resources Information Center

Swant, Jarod; Wagner, John J.

2006-01-01

Dopamine has been demonstrated to be involved in the modulation of long-term potentiation (LTP) in the CA1 region of the hippocampus. As monoamine transporter blockade will increase the actions of endogenous monoamine neurotransmitters, the effect of a dopamine transporter (DAT) antagonist on LTP was assessed using field excitatory postsynaptic…

Acute Stimulant Treatment and Reinforcement Increase the Speed of Information Accumulation in Children with ADHD.

PubMed

Fosco, Whitney D; White, Corey N; Hawk, Larry W

2017-07-01

The current studies utilized drift diffusion modeling (DDM) to examine how reinforcement and stimulant medication affect cognitive task performance in children with ADHD. In Study 1, children with (n = 25; 88 % male) and without ADHD (n = 33; 82 % male) completed a 2-choice discrimination task at baseline (100 trials) and again a week later under alternating reinforcement and no-reinforcement contingencies (400 trials total). In Study 2, participants with ADHD (n = 29; 72 % male) completed a double-blind, placebo-controlled trial of 0.3 and 0.6 mg/kg methylphenidate and completed the same task utilized in Study 1 at baseline (100 trials). Children with ADHD accumulated information at a much slower rate than controls, as evidenced by a lower drift rate. Groups were similar in nondecision time and boundary separation. Both reinforcement and stimulant medication markedly improved drift rate in children with ADHD (ds = 0.70 and 0.95 for reinforcement and methylphenidate, respectively); both treatments also reduced boundary separation (ds = 0.70 and 0.39). Reinforcement, which emphasized speeded accuracy, reduced nondecision time (d = 0.37), whereas stimulant medication increased nondecision time (d = 0.38). These studies provide initial evidence that frontline treatments for ADHD primarily impact cognitive performance in youth with ADHD by improving the speed/efficiency of information accumulation. Treatment effects on other DDM parameters may vary between treatments or interact with task parameters (number of trials, task difficulty). DDM, in conjunction with other approaches, may be helpful in clarifying the specific cognitive processes that are disrupted in ADHD, as well as the basic mechanisms that underlie the efficacy of ADHD treatments.

Colour vision in ADHD: part 1--testing the retinal dopaminergic hypothesis.

PubMed

Kim, Soyeon; Al-Haj, Mohamed; Chen, Samantha; Fuller, Stuart; Jain, Umesh; Carrasco, Marisa; Tannock, Rosemary

2014-10-24

To test the retinal dopaminergic hypothesis, which posits deficient blue color perception in ADHD, resulting from hypofunctioning CNS and retinal dopamine, to which blue cones are exquisitely sensitive. Also, purported sex differences in red color perception were explored. 30 young adults diagnosed with ADHD and 30 healthy young adults, matched on age and gender, performed a psychophysical task to measure blue and red color saturation and contrast discrimination ability. Visual function measures, such as the Visual Activities Questionnaire (VAQ) and Farnsworth-Munsell 100 hue test (FMT), were also administered. Females with ADHD were less accurate in discriminating blue and red color saturation relative to controls but did not differ in contrast sensitivity. Female control participants were better at discriminating red saturation than males, but no sex difference was present within the ADHD group. Poorer discrimination of red as well as blue color saturation in the female ADHD group may be partly attributable to a hypo-dopaminergic state in the retina, given that color perception (blue-yellow and red-green) is based on input from S-cones (short wavelength cone system) early in the visual pathway. The origin of female superiority in red perception may be rooted in sex-specific functional specialization in hunter-gather societies. The absence of this sexual dimorphism for red colour perception in ADHD females warrants further investigation.

Comparing ADHD in Velocardiofacial Syndrome to Idiopathic ADHD: A Preliminary Study

ERIC Educational Resources Information Center

Antshel, Kevin M.; Faraone, Stephen V.; Fremont, Wanda; Monuteaux, Michael C.; Kates, Wendy R.; Doyle, Alysa; Mick, Eric; Biederman, Joseph

2007-01-01

Objective: Background: Children with velocardiofacial syndrome (VCFS), a contiguous deletion syndrome, have an increased prevalence of attention deficit/hyperactivity disorder (ADHD). Method: The authors compared youth with VCFS+ADHD (from the SUNY Upstate VCFS Research Program) to those with ADHD but not VCFS (from the Massachusetts General…

The ADHD Concomitant Difficulties Scale (ADHD-CDS), a Brief Scale to Measure Comorbidity Associated to ADHD.

PubMed

Fenollar-Cortés, Javier; Fuentes, Luis J

2016-01-01

Although the critical feature of attention-deficit/hyperactivity disorder (ADHD) is a persistent pattern of inattention and/or hyperactivity/impulsivity behavior, the disorder is clinically heterogeneous, and concomitant difficulties are common. Children with ADHD are at increased risk for experiencing lifelong impairments in multiple domains of daily functioning. In the present study we aimed to build a brief ADHD impairment-related tool -ADHD concomitant difficulties scale (ADHD-CDS)- to assess the presence of some of the most important comorbidities that usually appear associated with ADHD such as emotional/motivational management, fine motor coordination, problem-solving/management of time, disruptive behavior, sleep habits, academic achievement and quality of life. The two main objectives of the study were (i) to discriminate those profiles with several and important ADHD functional difficulties and (ii) to create a brief clinical tool that fosters a comprehensive evaluation process and can be easily used by clinicians. The total sample included 399 parents of children with ADHD aged 6-18 years (M = 11.65; SD = 3.1; 280 males) and 297 parents of children without a diagnosis of ADHD (M = 10.91; SD = 3.2; 149 male). The scale construction followed an item improved sequential process. Factor analysis showed a 13-item single factor model with good fit indices. Higher scores on inattention predicted higher scores on ADHD-CDS for both the clinical sample (β = 0.50; p < 0.001) and the whole sample (β = 0.85; p < 0.001). The ROC curve for the ADHD-CDS (against the ADHD diagnostic status) gave an area under the curve (AUC) of.979 (95%, CI = [0.969, 0.990]). The ADHD-CDS has shown preliminary adequate psychometric properties, with high convergent validity and good sensitivity for different ADHD profiles, which makes it a potentially appropriate and brief instrument that may be easily used by clinicians, researchers, and health professionals in dealing with ADHD.

The ADHD Concomitant Difficulties Scale (ADHD-CDS), a Brief Scale to Measure Comorbidity Associated to ADHD

PubMed Central

Fenollar-Cortés, Javier; Fuentes, Luis J.

2016-01-01

Introduction: Although the critical feature of attention-deficit/hyperactivity disorder (ADHD) is a persistent pattern of inattention and/or hyperactivity/impulsivity behavior, the disorder is clinically heterogeneous, and concomitant difficulties are common. Children with ADHD are at increased risk for experiencing lifelong impairments in multiple domains of daily functioning. In the present study we aimed to build a brief ADHD impairment-related tool -ADHD concomitant difficulties scale (ADHD-CDS)- to assess the presence of some of the most important comorbidities that usually appear associated with ADHD such as emotional/motivational management, fine motor coordination, problem-solving/management of time, disruptive behavior, sleep habits, academic achievement and quality of life. The two main objectives of the study were (i) to discriminate those profiles with several and important ADHD functional difficulties and (ii) to create a brief clinical tool that fosters a comprehensive evaluation process and can be easily used by clinicians. Methods: The total sample included 399 parents of children with ADHD aged 6–18 years (M = 11.65; SD = 3.1; 280 males) and 297 parents of children without a diagnosis of ADHD (M = 10.91; SD = 3.2; 149 male). The scale construction followed an item improved sequential process. Results: Factor analysis showed a 13-item single factor model with good fit indices. Higher scores on inattention predicted higher scores on ADHD-CDS for both the clinical sample (β = 0.50; p < 0.001) and the whole sample (β = 0.85; p < 0.001). The ROC curve for the ADHD-CDS (against the ADHD diagnostic status) gave an area under the curve (AUC) of.979 (95%, CI = [0.969, 0.990]). Discussion: The ADHD-CDS has shown preliminary adequate psychometric properties, with high convergent validity and good sensitivity for different ADHD profiles, which makes it a potentially appropriate and brief instrument that may be easily used by clinicians, researchers, and

An increase in renal dopamine does not stimulate natriuresis after fava bean ingestion123

PubMed Central

Garland, Emily M; Cesar, Tericka S; Lonce, Suzanna; Ferguson, Marcus C; Robertson, David

2013-01-01

Background: Fava beans (Vicia faba) contain dihydroxyphenylalanine (dopa), and their ingestion may increase dopamine stores. Renal dopamine regulates blood pressure and blood volume via a natriuretic effect. Objective: The objective was to determine the relation between dietary fava beans, plasma and urinary catechols, and urinary sodium excretion in 13 healthy volunteers. Design: Catechol and sodium data were compared by using a longitudinal design in which all participants consumed a fixed-sodium study diet on day 1 and the fixed-sodium diet plus fava beans on day 2. Blood was sampled at 1, 2, 4, and 6 h after a meal, and 3 consecutive 4-h urine samples were collected. Results: Mean (±SD) plasma dopa was significantly greater 1 h after fava bean consumption (11,670 ± 5440 compared with 1705 ± 530 pg/mL; P = 0.001) and remained elevated at 6 h. Plasma dopamine increased nearly 15-fold during this period. Fava bean consumption also increased urinary dopamine excretion to 306 ± 116, 360 ± 235, and 159 ± 111 μg/4-h urine sample compared with 45 ± 21, 54 ± 29, and 44 ± 17 μg in the 3 consecutive 4-h samples after the control diet (P ≤ 0.005). These substantial increases in plasma and urinary dopa and dopamine were unexpectedly associated with decreased urinary sodium. Conclusion: The failure of fava bean consumption to provoke natriuresis may indicate that dopa concentrations in commercially available beans do not raise renal dopamine sufficiently to stimulate sodium excretion, at least when beans are added to a moderate-sodium diet in healthy volunteers. This trial was registered at clinicaltrials.gov as NCT01064739. PMID:23553159

Increase Academic Success for Children with ADHD Using Sticky Notes and Highlighters

ERIC Educational Resources Information Center

Stormont, Melissa A.

2008-01-01

Children with attention-deficit/hyperactivity disorder (ADHD) represent about 3% to 5% of the school-age population and are most often educated in the general education classroom. Unfortunately, general educators may not be prepared to provide supports for children with ADHD or other types of diverse learning needs. Children with ADHD have many…

Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA.

PubMed

Jiang, Xiaoliang; Zhang, Yanrong; Yang, Yu; Yang, Jian; Asico, Laureano D; Chen, Wei; Felder, Robin A; Armando, Ines; Jose, Pedro A; Yang, Zhiwei

2017-01-01

Gastrin is a peptide hormone that is involved in the regulation of sodium balance and blood pressure. Dopamine, which is also involved in the regulation of sodium balance and blood pressure, directly or indirectly interacts with other blood pressure-regulating hormones, including gastrin. This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane. The uptake of l-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. l-DOPA uptake in renal cortical slices is also lower in salt-sensitive C57Bl/6J than in salt-resistant BALB/c mice. The deficient renal cortical uptake of l-DOPA in C57Bl/6J mice may be due to decreased LAT-1 activity that is related to its decreased expression at the plasma membrane, relative to BALB/c mice. We also show that renal-selective silencing of Gast by the renal subcapsular injection of Gast siRNA in BALB/c mice decreases renal dopamine production and increases blood pressure. These results highlight the importance of renal gastrin in stimulating renal dopamine production, which may give a new perspective in the prevention and treatment of hypertension. Copyright © 2017 the American Physiological Society.

Dopamine Increases CD14+CD16+ Monocyte Migration and Adhesion in the Context of Substance Abuse and HIV Neuropathogenesis

PubMed Central

Coley, Jacqueline S.; Calderon, Tina M.; Gaskill, Peter J.; Eugenin, Eliseo A.; Berman, Joan W.

2015-01-01

Drug abuse is a major comorbidity of HIV infection and cognitive disorders are often more severe in the drug abusing HIV infected population. CD14+CD16+ monocytes, a mature subpopulation of peripheral blood monocytes, are key mediators of HIV neuropathogenesis. Infected CD14+CD16+ monocyte transmigration across the blood brain barrier mediates HIV entry into the brain and establishes a viral reservoir within the CNS. Despite successful antiretroviral therapy, continued influx of CD14+CD16+ monocytes, both infected and uninfected, contributes to chronic neuroinflammation and the development of HIV associated neurocognitive disorders (HAND). Drug abuse increases extracellular dopamine in the CNS. Once in the brain, CD14+CD16+ monocytes can be exposed to extracellular dopamine due to drug abuse. The direct effects of dopamine on CD14+CD16+ monocytes and their contribution to HIV neuropathogenesis are not known. In this study, we showed that CD14+CD16+ monocytes express mRNA for all five dopamine receptors by qRT-PCR and D1R, D5R and D4R surface protein by flow cytometry. Dopamine and the D1-like dopamine receptor agonist, SKF38393, increased CD14+CD16+ monocyte migration that was characterized as chemokinesis. To determine whether dopamine affected cell motility and adhesion, live cell imaging was used to monitor the accumulation of CD14+CD16+ monocytes on the surface of a tissue culture dish. Dopamine increased the number and the rate at which CD14+CD16+ monocytes in suspension settled to the dish surface. In a spreading assay, dopamine increased the area of CD14+CD16+ monocytes during the early stages of cell adhesion. In addition, adhesion assays showed that the overall total number of adherent CD14+CD16+ monocytes increased in the presence of dopamine. These data suggest that elevated extracellular dopamine in the CNS of HIV infected drug abusers contributes to HIV neuropathogenesis by increasing the accumulation of CD14+CD16+ monocytes in dopamine rich brain

Increasing Awareness and Understanding of Attention Deficit Hyperactivity Disorder (ADHD) in Education to Promote Better Academic Outcomes for Students with ADHD

ERIC Educational Resources Information Center

Martinussen, Rhonda L.; Tannock, Rosemary; Chaban, Peter; McInnes, Alison; Ferguson, Bruce

2006-01-01

In this paper we briefly review three areas of research on attention-deficit/hyperactivity disorder (ADHD) that have implications for the educational context. These areas are: (a) gender differences in ADHD, (b) inattention symptoms and academic risk, and (c) working memory and ADHD. We highlight the critical role that the school context plays in…

Association of ADHD, tics, and anxiety with dopamine transporter (DAT1) genotype in autism spectrum disorder

PubMed Central

Gadow, Kenneth D.; Roohi, Jasmin; DeVincent, Carla J.; Hatchwell, Eli

2015-01-01

Background Autism spectrum disorder (ASD) is associated with high rates of psychiatric disturbance to include attention-deficit/hyperactivity disorder (ADHD), tic disorder, and anxiety disorders. The aim of the present study was to examine the association between a variable number tandem repeat (VNTR) functional polymorphism located in the 3′-untranslated region of the dopamine transporter gene (DAT1) and the severity of these symptoms as well as the association between the DAT1 DdeI polymorphism and severity of tics. Methods Parents (n = 62) and teachers (n = 57) completed a DSM-IV-referenced rating scale for 67 children with ASD. Results According to parent ratings, children with the 10-10 repeat allele (versus a combined group of all other genotypes) exhibited less severe symptoms of hyperactivity and impulsivity as well as less severe language deficits. Teacher ratings indicated that social anxiety and tic symptoms were more severe for children with the 10-10 genotype versus all others. Exploratory analyses provided preliminary support for the notion that heterozygosity (9–10 repeat genotype) may be a risk/protective factor. There were no associations of tic severity with the DAT1 DdeI polymorphism. Conclusion Collectively, these results suggest that the extraordinary variability in ASD clinical phenotypes may be explained in part by the same genes that are implicated in a host of other psychiatric disorders in non-ASD populations. Nevertheless, replication with independent samples is necessary to confirm this preliminary finding. PMID:19120712

Association of ADHD, tics, and anxiety with dopamine transporter (DAT1) genotype in autism spectrum disorder.

PubMed

Gadow, Kenneth D; Roohi, Jasmin; DeVincent, Carla J; Hatchwell, Eli

2008-12-01

Autism spectrum disorder (ASD) is associated with high rates of psychiatric disturbance to include attention-deficit/hyperactivity disorder (ADHD), tic disorder, and anxiety disorders. The aim of the present study was to examine the association between a variable number tandem repeat (VNTR) functional polymorphism located in the 3'-untranslated region of the dopamine transporter gene (DAT1) and the severity of these symptoms as well as the association between the DAT1 DdeI polymorphism and severity of tics. Parents (n = 62) and teachers (n = 57) completed a DSM-IV-referenced rating scale for 67 children with ASD. According to parent ratings, children with the 10-10 repeat allele (versus a combined group of all other genotypes) exhibited less severe symptoms of hyperactivity and impulsivity as well as less severe language deficits. Teacher ratings indicated that social anxiety and tic symptoms were more severe for children with the 10-10 genotype versus all others. Exploratory analyses provided preliminary support for the notion that heterozygosity (9-10 repeat genotype) may be a risk/protective factor. There were no associations of tic severity with the DAT1 DdeI polymorphism. Collectively, these results suggest that the extraordinary variability in ASD clinical phenotypes may be explained in part by the same genes that are implicated in a host of other psychiatric disorders in non-ASD populations. Nevertheless, replication with independent samples is necessary to confirm this preliminary finding.

Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals

PubMed Central

Daberkow, DP; Brown, HD; Bunner, KD; Kraniotis, SA; Doellman, MA; Ragozzino, ME; Garris, PA; Roitman, MF

2013-01-01

Drugs of abuse hijack brain reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting non-exocytotic dopamine efflux via reverse transport. This mechanism of AMPH action, though, is inconsistent with its therapeutic effects and addictive properties - which are thought to be reliant on phasic dopamine signaling. Here we used fast-scan cyclic voltammetry in freely moving rats to interrogate principal neurochemical responses to AMPH in the striatum and relate these changes to behavior. First, we showed that AMPH dose-dependently enhanced evoked dopamine responses to phasic-like current pulse trains for up to two hours. Modeling the data revealed that AMPH inhibited dopamine uptake but also unexpectedly potentiated vesicular dopamine release. Second, we found that AMPH increased the amplitude, duration and frequency of spontaneous dopamine transients, the naturally occurring, non-electrically evoked, phasic increases in extracellular dopamine. Finally, using an operant sucrose reward paradigm, we showed that low-dose AMPH augmented dopamine transients elicited by sucrose-predictive cues. However, operant behavior failed at high-dose AMPH, which was due to phasic dopamine hyperactivity and the decoupling of dopamine transients from the reward predictive cue. These findings identify up-regulation of exocytotic dopamine release as a key AMPH action in behaving animals and support a unified mechanism of abused drugs to activate phasic dopamine signaling. PMID:23303926

Epigenetics in Developmental Disorder: ADHD and Endophenotypes

PubMed Central

Archer, Trevor; Oscar-Berman, Marlene; Blum, Kenneth

2011-01-01

Heterogeneity in attention-deficit/hyperactivity disorder (ADHD), with complex interactive operations of genetic and environmental factors, is expressed in a variety of disorder manifestations: severity, co-morbidities of symptoms, and the effects of genes on phenotypes. Neurodevelopmental influences of genomic imprinting have set the stage for the structural-physiological variations that modulate the cognitive, affective, and pathophysiological domains of ADHD. The relative contributions of genetic and environmental factors provide rapidly proliferating insights into the developmental trajectory of the condition, both structurally and functionally. Parent-of-origin effects seem to support the notion that genetic risks for disease process debut often interact with the social environment, i.e., the parental environment in infants and young children. The notion of endophenotypes, markers of an underlying liability to the disorder, may facilitate detection of genetic risks relative to a complex clinical disorder. Simple genetic association has proven insufficient to explain the spectrum of ADHD. At a primary level of analysis, the consideration of epigenetic regulation of brain signalling mechanisms, dopamine, serotonin, and noradrenaline is examined. Neurotrophic factors that participate in the neurogenesis, survival, and functional maintenance of brain systems, are involved in neuroplasticity alterations underlying brain disorders, and are implicated in the genetic predisposition to ADHD, but not obviously, nor in a simple or straightforward fashion. In the context of intervention, genetic linkage studies of ADHD pharmacological intervention have demonstrated that associations have fitted the “drug response phenotype,” rather than the disorder diagnosis. Despite conflicting evidence for the existence, or not, of genetic associations between disorder diagnosis and genes regulating the structure and function of neurotransmitters and brain-derived neurotrophic

A 40-bp VNTR polymorphism in the 3'-untranslated region of DAT1/SLC6A3 is associated with ADHD but not with alcoholism.

PubMed

Šerý, Omar; Paclt, Ivo; Drtílková, Ivana; Theiner, Pavel; Kopečková, Marta; Zvolský, Petr; Balcar, Vladimir J

2015-06-11

ADHD and alcoholism are psychiatric diseases with pathophysiology related to dopamine system. DAT1 belongs to the SLC6 family of transporters and is involved in the regulation of extracellular dopamine levels. A 40 bp variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1/SLC6A3 gene was previously reported to be associated with various phenotypes involving disturbed regulation of dopaminergic neurotransmission. A total of 1312 subjects were included and genotyped for 40 bp VNTR polymorphism of DAT1/SLC6A3 gene in this study (441 alcoholics, 400 non-alcoholic controls, 218 ADHD children and 253 non ADHD children). Using miRBase software, we have performed a computer analysis of VNTR part of DAT1 gene for presence of miRNA binding sites. We have found significant relationships between ADHD and the 40 bp VNTR polymorphisms of DAT1/SLC6A3 gene (P < 0.01). The 9/9 genotype appeared to reduce the risk of ADHD about 0.4-fold (p < 0.04). We also noted an occurrence of rare genotypes in ADHD (frequency different from controls at p < 0.01). No association between alcoholism and genotype frequencies of 40 bp VNTR polymorphism of DAT1/SLC6A3 gene has been detected. We have found an association between 40 bp VNTR polymorphism of DAT1/SLC6A3 gene and ADHD in the Czech population; in a broad agreement with studies in other population samples. Furthermore, we detected rare genotypes 8/10, 7/10 and 10/11 present in ADHD boys only and identified miRNAs that should be looked at as potential novel targets in the research on ADHD.

Increase of dopamine D2(High) receptors in the striatum of rats sensitized to caffeine motor effects.

PubMed

Simola, Nicola; Morelli, Micaela; Seeman, Philip

2008-05-01

It has been previously demonstrated how rats can develop behavioral dopamine supersensitivity after long-term administration of caffeine. Since behavioral dopamine supersensitivity in rats is usually accompanied by an elevation in striatal dopamine D2(High) receptors, we examined whether alterations in D2(High) receptors occurred in the striatum of rats administered caffeine according to a regimen capable of eliciting behavioral dopamine supersensitivity (15 mg/kg i.p. every other day for 14 days). An increase of 126% in striatal D2(High) receptors was found in caffeine-sensitized rats. This marked elevation in D2(High) receptors may account for the caffeine-induced behavioral dopamine supersensitivity and may help elucidate the interactions between caffeine and dopamine neurotransmission. (c) 2008 Wiley-Liss, Inc.

Beyond interference control impairment in ADHD: evidence from increased intraindividual variability in the color-stroop test.

PubMed

Borella, Erika; de Ribaupierre, Anik; Cornoldi, Cesare; Chicherio, Christian

2013-09-01

The present study investigates intraindividual variability (IIV) in the Color-Stroop test and in a simple reaction time (SRT) task. Performance level and variability in reaction times (RTs)-quantified with different measures such as individual standard deviation (ISD) and coefficient of variation (ICV), as well as ex-Gaussian parameters (mu, sigma, tau)-were analyzed in 24 children with attention deficit/hyperactivity disorder (ADHD) and 24 typically developing children (TDC). Children with ADHD and TDC presented equivalent Color-Stroop interference effects when mean RTs were considered, and the two groups did not differ in the SRT task. Interestingly, compared to TDC, children with ADHD were more variable in their responses, showing increased ISD and ICV in the Color-Stroop interference condition and in the SRT task. Moreover, children with ADHD exhibited higher tau values-that is, more frequent abnormally long RTs-in the Color-Stroop interference condition than did the TDC, but comparable tau values in the SRT, suggesting more variable responses. These results speak in favor of a general deficit in more basic and central processes that only secondarily may affect the efficiency of inhibitory processes in children with ADHD. Overall the present findings confirm the role of IIV as a cornerstone in the ADHD cognitive profile and support the search for fine-grained analysis of performance fluctuations.

European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD

PubMed Central

2010-01-01

Background Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that persists into adulthood in the majority of cases. The evidence on persistence poses several difficulties for adult psychiatry considering the lack of expertise for diagnostic assessment, limited treatment options and patient facilities across Europe. Methods The European Network Adult ADHD, founded in 2003, aims to increase awareness of this disorder and improve knowledge and patient care for adults with ADHD across Europe. This Consensus Statement is one of the actions taken by the European Network Adult ADHD in order to support the clinician with research evidence and clinical experience from 18 European countries in which ADHD in adults is recognised and treated. Results Besides information on the genetics and neurobiology of ADHD, three major questions are addressed in this statement: (1) What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be properly diagnosed? (3) How should ADHD in adults be effectively treated? Conclusions ADHD often presents as an impairing lifelong condition in adults, yet it is currently underdiagnosed and treated in many European countries, leading to ineffective treatment and higher costs of illness. Expertise in diagnostic assessment and treatment of ADHD in adults must increase in psychiatry. Instruments for screening and diagnosis of ADHD in adults are available and appropriate treatments exist, although more research is needed in this age group. PMID:20815868

Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND

PubMed Central

Gaskill, Peter J.; Calderon, Tina M.; Coley, Jacqueline S.; Berman, Joan W.

2013-01-01

Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers. PMID:23456305

ADHD

MedlinePlus

ADHD Attention Deficit/Hyperactivity Disorder Fact Sheet Learn about ADHD and what to do if you have concerns. What is ADHD? Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioral ...

A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD).

PubMed

Sharma, Alok; Couture, Justin

2014-02-01

To review the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). A literature search was conducted in PubMed and EMBASE using the terms attention deficit hyperactive disorder, ADHD, pathophysiology, etiology, and neurobiology. Limits applied were the following: published in the past 10 years (January 2003 to August 2013), humans, review, meta-analysis, and English language. These yielded 63 articles in PubMed and 74 in EMBASE. After removing duplicate/irrelevant articles, 86 articles and their relevant reference citations were reviewed. ADHD is a neurological disorder that affects children, but symptoms may persist into adulthood. Individuals suffering from this disorder exhibit hyperactivity, inattention, impulsivity, and problems in social interaction and academic performance. Medications used to treat ADHD such as methylphenidate, amphetamine, and atomoxetine indicate a dopamine/norepinephrine deficit as the neurochemical basis of ADHD, but the etiology is more complex. Moreover, these agents have poor adverse effect profiles and a multitude of drug interactions. Because these drugs are also dispensed to adults who may have concomitant conditions or medications, a pharmacist needs to be aware of these adverse events and drug interactions. This review, therefore, focuses on the pathophysiology, etiology, and treatment of ADHD and details the adverse effects and drug interaction profiles of the drugs used to treat it. Published research shows the benefit of drug therapy for ADHD in children, but given the poor adverse effect and drug interaction profiles, these must be dispensed with caution.

Increased Anterior Pelvic Angle Characterizes the Gait of Children with Attention Deficit/Hyperactivity Disorder (ADHD).

PubMed

Naruse, Hiroaki; Fujisawa, Takashi X; Yatsuga, Chiho; Kubota, Masafumi; Matsuo, Hideaki; Takiguchi, Shinichiro; Shimada, Seiichiro; Imai, Yuto; Hiratani, Michio; Kosaka, Hirotaka; Tomoda, Akemi

2017-01-01

Children with attention deficit/hyperactivity disorder (ADHD) frequently have motor problems. Previous studies have reported that the characteristic gait in children with ADHD is immature and that subjects demonstrate higher levels of variability in gait characteristics for the lower extremities than healthy controls. However, little is known about body movement during gait in children with ADHD. The purpose of this study was to identify the characteristic body movements associated with ADHD symptoms in children with ADHD. Using a three-dimensional motion analysis system, we compared gait variables in boys with ADHD (n = 19; mean age, 9.58 years) and boys with typical development (TD) (n = 21; mean age, 10.71 years) to determine the specific gait characteristics related to ADHD symptoms. We assessed spatiotemporal gait variables (i.e. speed, stride length, and cadence), and kinematic gait variables (i.e. angle of pelvis, hip, knee, and ankle) to measure body movement when walking at a self-selected pace. In comparison with the TD group, the ADHD group demonstrated significantly higher values in cadence (t = 3.33, p = 0.002) and anterior pelvic angle (t = 3.08, p = 0.004). In multiple regression analysis, anterior pelvic angle was associated with the ADHD rating scale hyperactive/impulsive scores (β = 0.62, t = 2.58, p = 0.025), but not other psychiatric symptoms in the ADHD group. Our results suggest that anterior pelvic angle represents a specific gait variable related to ADHD symptoms. Our kinematic findings could have potential implications for evaluating the body movement in boys with ADHD.

Examining Autistic Traits in Children with ADHD: Does the Autism Spectrum Extend to ADHD?

ERIC Educational Resources Information Center

Grzadzinski, Rebecca; Di Martino, Adriana; Brady, Emily; Mairena, Maria Angeles; O'Neale, Matthew; Petkova, Eva; Lord, Catherine; Castellanos, F. Xavier

2011-01-01

We examined to what extent increased parent reports of autistic traits in some children with Attention Deficit Hyperactivity Disorder (ADHD) are the result of ADHD-related symptoms or qualitatively similar to the core characteristics of autism spectrum disorders (ASD). Results confirm the presence of a subgroup of children with ADHD and elevated…

A Cooperative Learning Classroom Intervention for Increasing Peer's Acceptance of Children With ADHD.

PubMed

Capodieci, Agnese; Rivetti, Thomas; Cornoldi, Cesare

2016-08-31

The hypothesis behind this study was that trained teachers using cooperative learning procedures with children in their classroom (aged from 6 to 10 years) can influence the social skills of children with ADHD symptoms and their acceptance by their peers. The study involved 30 children with ADHD symptoms attending 12 different classes, where cooperative learning was adopted in some, and standard practices in others. ADHD children's symptoms, social skills, and cooperative behavior were assessed by means of a teacher's questionnaire, and the social preferences of the children in their class were collected. Changes emerged in teachers' assessments of the children's cooperative behavior in the experimental classes. Improvements in the sociometric status of children with ADHD symptoms were only seen in the cooperative learning classes. These results show the importance of well-structured intervention in classes that include children with ADHD symptoms. Implications of these findings for future intervention are discussed. © The Author(s) 2016.

Effects of Modafinil on Dopamine and Dopamine Transporters in the Male Human Brain: Clinical Implications

PubMed Central

Volkow, Nora D.; Fowler, Joanna S.; Logan, Jean; Alexoff, David; Zhu, Wei; Telang, Frank; Wang, Gene-Jack; Jayne, Millard; Hooker, Jacob M.; Wong, Christopher; Hubbard, Barbara; Carter, Pauline; Warner, Donald; King, Payton; Shea, Colleen; Xu, Youwen; Muench, Lisa; Apelskog-Torres, Karen

2009-01-01

Context Modafinil, a wake-promoting drug used to treat narcolepsy, is increasingly being used as a cognitive enhancer. Although initially launched as distinct from stimulants that increase extracellular dopamine by targeting dopamine transporters, recent preclinical studies suggest otherwise. Objective To measure the acute effects of modafinil at doses used therapeutically (200 mg and 400 mg given orally) on extracellular dopamine and on dopamine transporters in the male human brain. Design, Setting, and Participants Positron emission tomography with [11C]raclopride (D2/D3 radioligand sensitive to changes in endogenous dopamine) and [11C]cocaine (dopamine transporter radioligand) was used to measure the effects of modafinil on extracellular dopamine and on dopamine transporters in 10 healthy male participants. The study took place over an 8-month period (2007–2008) at Brookhaven National Laboratory. Main Outcome Measures Primary outcomes were changes in dopamine D2/D3 receptor and dopamine transporter availability (measured by changes in binding potential) after modafinil when compared with after placebo. Results Modafinil decreased mean (SD) [11C]raclopride binding potential in caudate (6.1% [6.5%]; 95% confidence interval [CI], 1.5% to 10.8%; P=.02), putamen (6.7% [4.9%]; 95% CI, 3.2% to 10.3%; P=.002), and nucleus accumbens (19.4% [20%]; 95% CI, 5% to 35%; P=.02), reflecting increases in extracellular dopamine. Modafinil also decreased [11C]cocaine binding potential in caudate (53.8% [13.8%]; 95% CI, 43.9% to 63.6%; P<.001), putamen (47.2% [11.4%]; 95% CI, 39.1% to 55.4%; P<.001), and nucleus accumbens (39.3% [10%]; 95% CI, 30% to 49%; P=.001), reflecting occupancy of dopamine transporters. Conclusions In this pilot study, modafinil blocked dopamine transporters and increased dopamine in the human brain (including the nucleus accumbens). Because drugs that increase dopamine in the nucleus accumbens have the potential for abuse, and considering the increasing

Occurrence of ADHD in parents of ADHD children in a clinical sample.

PubMed

Starck, Martina; Grünwald, Julia; Schlarb, Angelika A

2016-01-01

Despite the fact that there is a large amount of research on childhood attention deficit hyperactivity disorder (ADHD) treatment and an increasing amount of research on adult ADHD, little is known about the prevalence and influence of parental ADHD. Therefore, this study examined the frequency of parental ADHD in a clinical sample of German children suffering from ADHD. We also tried to find different levels of symptom severity for prognostic relevance. Furthermore, the association between subtypes of ADHD in children and their parents was investigated. In this study, parents of 79 ADHD children were screened for ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition and International Classification of Diseases, 10th edition. The Wender Utah Rating Scale and the ADHS-Self-Report were given to 75 mothers and 49 fathers for retrospective and current symptoms. Frequency of ADHD symptoms and severity groups was calculated and relationship between parental and children's ADHD was tested. ADHD occurrence for mothers of children with ADHD was 41.3%, for fathers 51.0%. About 16.0% of the mothers had a mixed type, 9.3% had a hyperactive-impulsive subtype, and 16.0% had an inattentive subtype. Of the fathers, 18.4% had a mixed type, 10.2% had a hyperactive-impulsive subtype, and 22.4% had an inattentive subtype; 61% of the mothers and 46.9% of the fathers had low symptom severity. Medium symptom severity was reported by 37.7% mothers and 46.9% fathers, while 1.3% of the mothers and 6.2% of the fathers showed severe symptoms. No significant correlation between parental and child diagnoses was observed. As nearly half of the parents suffered from ADHD, these results are a matter of concern in families with ADHD children. Besides parent-child interactions, parental ADHD symptoms might influence parental education style and also effects parent training as well as the child's therapy outcome. In the future, parents should be screened for ADHD

Increase in teachers' knowledge about ADHD after a week-long training program: a pilot study.

PubMed

Syed, Ehsan Ullah; Hussein, Sajida Abdul

2010-01-01

ADHD affects 3% to 5% of school-age children. Clinical and community based epidemiological studies in Pakistan have shown a high prevalence of ADHD among school going children. A thorough review of literature shows that no studies of teachers' training programs regarding ADHD have been published in Pakistani research literature. The aim of the present study is the development and evaluation of an ADHD training program for teachers. A teachers' training program for ADHD was designed and a pilot run in 3 schools of Karachi, Pakistan. Teachers knowledge regarding signs and symptoms of ADHD was tested before and after the workshop and then again after 6 months using an ADHD knowledge questionnaire. Forty-nine teachers, all of them women, completed the questionnaires before and after the training program, and 35 of them filled it out at the 6-month interval. Mean scores of these tests were compared using a paired t test. The authors found the difference of mean score of 1.48 +/- 2.95, and this was statistically significant (p < .005). The authors conclude that the workshop improved the knowledge of the school teachers regarding ADHD symptomatology, and it remained significant even after 6 months of training.

ADHD and Depression Symptoms in Parent Couples Predict Response to Child ADHD and ODD Behavior.

PubMed

Wymbs, Brian T; Dawson, Anne E; Egan, Theresa E; Sacchetti, Gina M; Tams, Sean T; Wymbs, Frances A

2017-04-01

Parents of children with attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) often have elevated ADHD and depressive symptoms, both of which increase the risk of ineffective parenting and interparental discord. However, little is known about whether child ADHD/ODD behavior and parent ADHD or depressive symptoms uniquely or synergistically predict the quality of parenting and interparental communication during triadic (mother-father-child) interactions. Ninety parent couples, including 51 who have children diagnosed with ADHD, were randomly assigned to interact with a 9-12 year-old confederate child (84 % male) exhibiting either ADHD/ODD-like behavior or typical behavior. Parents reported their own ADHD and depressive symptoms, and parents and observers rated the quality of parenting and interparental communication during the interaction. Actor-partner interdependence modeling indicated that child ADHD/ODD behavior predicted less positive and more negative parenting and communication, independent of adult ADHD and depressive symptoms. Parent couples including two parents with elevated ADHD communicated more positively while managing children exhibiting ADHD/ODD behavior than couples managing children behaving typically or couples with only one parent with elevated ADHD symptoms. Couples including one parent with, and one parent without, elevated ADHD or depressive symptoms parented less positively and more negatively, and communicated more negatively, when managing children exhibiting ADHD/ODD behavior than when managing children behaving typically. Taken together, depending on the similarity of ADHD and depressive symptom levels in parent couples, adults managing children exhibiting ADHD/ODD behavior may parent or communicate positively or negatively. Findings highlight the need to consider the psychopathology of both parents when treating children with ADHD in two-parent homes.

The atypical antipsychotic quetiapine increases both noradrenaline and dopamine release in the rat prefrontal cortex.

PubMed

Pira, Luigi; Mongeau, Raymond; Pani, Luca

2004-11-03

Quetiapine is a novel atypical antipsychotic drug with multi-receptorial affinity. Using in vivo microdialysis, we investigated if quetiapine modulates extracellular noradrenaline and dopamine in brain areas generally believed to be involved in the pathophysiology of schizophrenia and in the action of antipsychotic drugs. Quetiapine (5, 10 and 20 mg/kg, i.p.) increased levels of noradrenaline in both the prefrontal cortex and the caudate nucleus, while it increased dopamine levels mainly in the prefrontal cortex. It is argued that the marked increase of dopaminergic transmission in the prefrontal cortex induced by quetiapine might be relevant to its therapeutical action.

No association between catechol-O-methyltransferase (COMT) genotype and attention deficit hyperactivity disorder (ADHD) in Japanese children.

PubMed

Yatsuga, Chiho; Toyohisa, Daiki; Fujisawa, Takashi X; Nishitani, Shota; Shinohara, Kazuyuki; Matsuura, Naomi; Ikeda, Shinobu; Muramatsu, Masaaki; Hamada, Akinobu; Tomoda, Akemi

2014-08-01

This study ascertained the association between attention deficit/hyperactivity disorder (ADHD) in Japanese children and a polymorphism of catechol-O-methyltransferase (COMT), a dopamine-control gene. The secondary aim of the study was the evaluation of a putative association between methylphenidate (MPH) effect/adverse effects and the COMT genotype. To ascertain the distribution of the Val158Met variant of COMT, 50 children meeting ADHD inclusion criteria were compared with 32 healthy children. Clinical improvement and the occurrence of adverse effects were measured before and 3 months after MPH administration in children with ADHD, and analyzed for genotype association. Wechsler Intelligence Scale for Children-Third Edition (WISC-III), age, MPH dose were included as co-variables. The occurrence of the COMT Val/Val genotype was significantly higher in children with ADHD (χ(2)(1)=7.13, p<0.01). However, there was no significant difference in the Val/Val genotype according to disorder, and WISC and ADHD rating scale scores, after correcting for the interaction between disorder and COMT genotype. Furthermore, no significant difference in MPH effect/adverse effects was observed in association with the COMT genotype in the ADHD group. These results showed a lack of association between the COMT Val/Val genotype and ADHD in Japan. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Response time variability under slow and fast-incentive conditions in children with ASD, ADHD and ASD+ADHD.

PubMed

Tye, Charlotte; Johnson, Katherine A; Kelly, Simon P; Asherson, Philip; Kuntsi, Jonna; Ashwood, Karen L; Azadi, Bahare; Bolton, Patrick; McLoughlin, Gráinne

2016-12-01

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) show significant behavioural and genetic overlap. Both ADHD and ASD are characterised by poor performance on a range of cognitive tasks. In particular, increased response time variability (RTV) is a promising indicator of risk for both ADHD and ASD. However, it is not clear whether different indices of RTV and changes to RTV according to task conditions are able to discriminate between the two disorders. Children with ASD (n = 19), ADHD (n = 18), ASD + ADHD (n = 29) and typically developing controls (TDC; n = 26) performed a four-choice RT task with slow-baseline and fast-incentive conditions. Performance was characterised by mean RT (MRT), standard deviation of RT (SD-RT), coefficient of variation (CV) and ex-Gaussian distribution measures of Mu, Sigma and Tau. In the slow-baseline condition, categorical diagnoses and trait measures converged to indicate that children with ADHD-only and ASD + ADHD demonstrated increased MRT, SD-RT, CV and Tau compared to TDC and ASD-only. Importantly, greater improvement in MRT, SD-RT and Tau was demonstrated in ADHD and ASD + ADHD from slow-baseline to fast-incentive conditions compared to TDC and ASD-only. Slower and more variable RTs are markers of ADHD compared to ASD and typically developing controls during slow and less rewarding conditions. Energetic factors and rewards improve task performance to a greater extent in children with ADHD compared to children with ASD. These findings suggest that RTV can be distinguished in ASD, ADHD and ASD + ADHD based on the indices of variability used and the conditions in which they are elicited. Further work identifying neural processes underlying increased RTV is warranted, in order to elucidate disorder-specific and disorder-convergent aetiological pathways. © 2016 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for

ADHD

MedlinePlus

... ADHD? Everyone has trouble at times with paying attention, listening, or waiting. But people with ADHD have ... is a medical condition that affects a person's attention and self-control. Because of ADHD, people have ...

Association between Urine Phthalate Levels and Poor Attentional Performance in Children with Attention-Deficit Hyperactivity Disorder with Evidence of Dopamine Gene-Phthalate Interaction

PubMed Central

Park, Subin; Kim, Bung-Nyun; Cho, Soo-Churl; Kim, Yeni; Kim, Jae-Won; Lee, Ju-Young; Hong, Soon-Beom; Shin, Min-Sup; Yoo, Hee Jeong; Im, Hosub; Cheong, Jae Hoon; Han, Doug Hyun

2014-01-01

Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child’s urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT) were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4), dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms. PMID:24978879

Association between urine phthalate levels and poor attentional performance in children with attention-deficit hyperactivity disorder with evidence of dopamine gene-phthalate interaction.

PubMed

Park, Subin; Kim, Bung-Nyun; Cho, Soo-Churl; Kim, Yeni; Kim, Jae-Won; Lee, Ju-Young; Hong, Soon-Beom; Shin, Min-Sup; Yoo, Hee Jeong; Im, Hosub; Cheong, Jae Hoon; Han, Doug Hyun

2014-06-27

Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child's urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT) were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4), dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms.

Interaction of DRD4 Methylation and Phthalate Metabolites Affects Continuous Performance Test Performance in ADHD.

PubMed

Kim, Johanna Inhyang; Kim, Jae-Won; Shin, Inkyung; Kim, Bung-Nyun

2018-05-01

We investigated the interaction effect between the methylation of dopamine receptor D4 (DRD4) and phthalate exposure in ADHD on continuous performance test (CPT) variables. Urine concentrations of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MBP) were tested. The methylation status was analyzed for CpG sites of DRD4. Multivariable linear regression models were applied to investigate the interaction effects of methylation and phthalate levels. There was a significant interaction effect of the methylation of CpG26 and CpG28 with the MEHHP level on omission errors in ADHD patients, but not in controls. The post hoc analysis revealed a significant correlation between the MEHHP concentration and omission errors in the methylated group, but not in the unmethylated group. The interaction between the methylation status of CpG sites of DRD4, particularly CpG26 and CpG28, and phthalate metabolite levels affects the attention level in ADHD patients.

The dual pathway model of AD/HD: an elaboration of neuro-developmental characteristics.

PubMed

Sonuga-Barke, Edmund J S

2003-11-01

The currently dominant neuro-cognitive model of Attention Deficit Hyperactivity Disorder (AD/HD) presents the condition as executive dysfunction (EDF) underpinned by disturbances in the fronto-dorsal striatal circuit and associated dopaminergic branches (e.g. meso-cortical). In contrast, motivationally-based accounts focus on altered reward processes and implicate fronto-ventral striatal reward circuits and those meso-limbic branches that terminate in the ventral striatum especially the nucleus accumbens. One such account, delay aversion (DEL), presents AD/HD as a motivational style-characterised by attempts to escape or avoid delay-arising from fundamental disturbances in these reward centres. While traditionally regarded as competing, EDF and DEL models have recently been presented as complimentary accounts of two psycho-patho-physiological subtypes of AD/HD with different developmental pathways, underpinned by different cortico-striatal circuits and modulated by different branches of the dopamine system. In the current paper we describe the development of this model in more detail. We elaborate on the neuro-circuitry possibly underpinning these two pathways and explore their developmental significance within a neuro-ecological framework.

Sound-Field Amplification to Increase Compliance to Directions in Students with ADHD

ERIC Educational Resources Information Center

Maag, John W.; Anderson, Jean M.

2007-01-01

This study determined the effects of sound-field amplification (SFA) on the speed with which students with attention deficit hyperactivity disorder (ADHD) followed teacher directions. A multiple baseline design was used with 3 elementary-aged students with ADHD to assess the effects of SFA across 4 types of directions: (a) task demand (e.g., get…

Increasing On-Task Performance for Students with ADHD

ERIC Educational Resources Information Center

Fowler, Mary

2010-01-01

Inattention and/or impulsivity and hyperactivity are the core symptoms of attention deficit hyperactivity disorder (ADHD). In the day-to-day grind of teaching, when problems emerge, the teachers' best intentions and sensitivities are tested. Fidgety, loud, disorganized, disruptive, hurried, careless, and off-task behavior coupled with messy,…

Institutional care and iron deficiency increase ADHD symptomology and lower IQ 2.5-5 years post-adoption.

PubMed

Doom, Jenalee R; Georgieff, Michael K; Gunnar, Megan R

2015-05-01

Increased ADHD symptomology and lower IQ have been reported in internationally adopted (IA) children compared to non-adopted peers (Hostinar, Stellern, Schaefer, Carlson & Gunnar, 2012; Kreppner, O'Connor & Rutter, 2001). However, it is unclear whether these outcomes are due to institutional deprivation specifically or to co-occurring micronutrient deficiencies that disrupt brain development (Fuglestad, Rao & Georgieff, 2008b). In this study, IA children were compared to children raised in their biological families to examine differences in ADHD symptomology and IQ 2.5-5 years post-adoption and to assess the contributions of iron deficiency (ID) and duration of deprivation to these cognitive outcomes. ADHD symptoms (parent- and experimenter-reported) and IQ were evaluated in 88 IA (M = 62.1 months, SD = 2.4) and 35 non-adopted children (M = 61.4 months, SD = 1.6). IA children were assessed 29-64 months post-adoption (M = 41.9 months, SD = 10.2). ID was assessed during the initial post-adoption medical visit in 69 children, and children were classified into four groups by iron status, ranging from normal to ID anemia (most severe). IA children had greater ADHD symptomology, p < .01, and lower IQ, p = .001, than non-adopted children. Within the IA group, children with more severe ID at adoption had greater ADHD symptomology, r(69) = 0.40, p = .001, and lower IQ, r(68) = -0.28, p < .05. Duration of institutional care was positively correlated with ADHD symptoms, r(86) = .28, p < .01, but not IQ, r(85) = -.08, p = .52. Longitudinal results indicate improvement in IQ from 12 months post-adoption to age 5 for children with greater ID severity at adoption and longer duration of institutional care but no improvement in ADHD symptoms. These results signify continuing effects of early deprivation and ID on ADHD symptoms and IQ years after adoption. A video abstract of this article can be viewed at http://www.youtube.com/watch?v=vUFDAS3DD1c. © 2014 John Wiley & Sons Ltd.

Genetic targeting of the amphetamine and methylphenidate-sensitive dopamine transporter: On the path to an animal model of attention-deficit hyperactivity disorder

PubMed Central

Mergy, Marc A.; Gowrishankar, Raajaram; Davis, Gwynne L.; Jessen, Tammy N.; Wright, Jane; Stanwood, Gregg D.; Hahn, Maureen K.; Blakely, Randy D.

2014-01-01

Alterations in dopamine (DA) signaling underlie the most widely held theories of molecular and circuit level perturbations that lead to risk for attention-deficit hyperactivity disorder (ADHD). The DA transporter (DAT), a presynaptic reuptake protein whose activity provides critical support for DA signaling by limiting DA action at pre- and postsynaptic receptors, has been consistently associated with ADHD through pharmacological, behavioral, brain imaging and genetic studies. Currently, the animal models of ADHD exhibit significant limitations, stemming in large part from their lack of construct validity. To remedy this situation, we have pursued the creation of a mouse model derived from a functional nonsynonymous variant in the DAT gene (SLC6A3) of ADHD probands. We trace our path from the identification of these variants to in vitro biochemical and physiological studies to the production of the DAT Val559 mouse model. We discuss our initial findings with these animals and their promise in the context of existing rodent models of ADHD. PMID:24332984

ADHD Perspectives: Medicalization and ADHD Connectivity

ERIC Educational Resources Information Center

Wright, Gloria Sunnie

2012-01-01

Today's "ADHDscape" is no longer confined to images of fidgety children falling off classroom chairs. Trans-generational images flood popular culture, from "ADHD creator" with entrepreneurial style, to "ADHD troublemaker". Indeed, ADHD's enigmatic characteristics seem to apply as much to crying babies as to forgetful grannies. With the recent…

Psychostimulants affect dopamine transmission through both dopamine transporter-dependent and independent mechanisms

PubMed Central

dela Peña, Ike; Gevorkiana, Ruzanna; Shi, Wei-Xing

2015-01-01

The precise mechanisms by which cocaine and amphetamine-like psychostimulants exert their reinforcing effects are not yet fully defined. It is widely believed, however, that these drugs produce their effects by enhancing dopamine neurotransmission in the brain, especially in limbic areas such as the nucleus accumbens, by inducing dopamine transporter-mediated reverse transport and/or blocking dopamine reuptake though the dopamine transporter. Here, we present the evidence that aside from dopamine transporter, non-dopamine transporter-mediated mechanisms also participate in psychostimulant-induced dopamine release and contribute to the behavioral effects of these drugs, such as locomotor activation and reward. Accordingly, psychostimulants could increase norepinephrine release in the prefrontal cortex, the latter then alters the firing pattern of dopamine neurons resulting in changes in action potential-dependent dopamine release. These alterations would further affect the temporal pattern of dopamine release in the nucleus accumbens, thereby modifying information processing in that area. Hence, a synaptic input to a nucleus accumbens neuron may be enhanced or inhibited by dopamine depending on its temporal relationship to dopamine release. Specific temporal patterns of dopamine release may also be required for certain forms of synaptic plasticity in the nucleus accumbens. Together, these effects induced by psychostimulants, mediated through a non-dopamine transporter-mediated mechanism involving norepinephrine and the prefrontal cortex, may also contribute importantly to the reinforcing properties of these drugs. PMID:26209364

ADHD Medications

MedlinePlus

... Staying Safe Videos for Educators Search English Español ADHD Medicines KidsHealth / For Teens / ADHD Medicines What's in ... en español Medicamentos para el TDAH What Is ADHD Medicine? After someone is diagnosed with ADHD , doctors ...

Novel in silico multivariate mapping of intrinsic and anticorrelated connectivity to neurocognitive functional maps supports the maturational hypothesis of ADHD.

PubMed

de Lacy, Nina; Kodish, Ian; Rachakonda, Srinivas; Calhoun, Vince D

2018-04-22

From childhood to adolescence, strengthened coupling in frontal, striatal and parieto-temporal regions associated with cognitive control, and increased anticorrelation between task-positive and task-negative circuits, subserve the reshaping of behavior. ADHD is a common condition peaking in adolescence and regressing in adulthood, with a wide variety of cognitive control deficits. Alternate hypotheses of ADHD emphasize lagging circuitry refinement versus categorical differences in network function. However, quantifying the individual circuit contributions to behavioral findings, and relative roles of maturational versus categorical effects, is challenging in vivo or in meta-analyses using task-based paradigms within the same pipeline, given the multiplicity of neurobehavioral functions implicated. To address this, we analyzed 46 positively-correlated and anticorrelated circuits in a multivariate model in resting-state data from 504 age- and gender-matched youth, and created a novel in silico method to map individual quantified effects to reverse inference maps of 8 neurocognitive functions consistently implicated in ADHD, as well as dopamine and hyperactivity. We identified only age- and gender-related effects in intrinsic connectivity, and found that maturational refinement of circuits in youth with ADHD occupied 3-10x more brain locations than in typical development, with the footprint, effect size and contribution of individual circuits varying substantially. Our analysis supports the maturational hypothesis of ADHD, suggesting lagging connectivity reorganization within specific subnetworks of fronto-parietal control, ventral attention, cingulo-opercular, temporo-limbic and cerebellar sub-networks contribute across neurocognitive findings present in this complex condition. We present the first analysis of anti-correlated connectivity in ADHD and suggest new directions for exploring residual and non-responsive symptoms. © 2018 Wiley Periodicals, Inc.

Increase in Teachers' Knowledge about ADHD after a Week-Long Training Program: A Pilot Study

ERIC Educational Resources Information Center

Syed, Ehsan Ullah; Hussein, Sajida Abdul

2010-01-01

Objectives: ADHD affects 3% to 5% of school-age children. Clinical and community based epidemiological studies in Pakistan have shown a high prevalence of ADHD among school going children. A thorough review of literature shows that no studies of teachers' training programs regarding ADHD have been published in Pakistani research literature. The…

Orbitofrontal Dopamine Depletion Upregulates Caudate Dopamine and Alters Behavior via Changes in Reinforcement Sensitivity

PubMed Central

Cardinal, R. N.; Rygula, R.; Hong, Y. T.; Fryer, T. D.; Sawiak, S. J.; Ferrari, V.; Cockcroft, G.; Aigbirhio, F. I.; Robbins, T. W.; Roberts, A. C.

2014-01-01

Schizophrenia is associated with upregulation of dopamine (DA) release in the caudate nucleus. The caudate has dense connections with the orbitofrontal cortex (OFC) via the frontostriatal loops, and both areas exhibit pathophysiological change in schizophrenia. Despite evidence that abnormalities in dopaminergic neurotransmission and prefrontal cortex function co-occur in schizophrenia, the influence of OFC DA on caudate DA and reinforcement processing is poorly understood. To test the hypothesis that OFC dopaminergic dysfunction disrupts caudate dopamine function, we selectively depleted dopamine from the OFC of marmoset monkeys and measured striatal extracellular dopamine levels (using microdialysis) and dopamine D2/D3 receptor binding (using positron emission tomography), while modeling reinforcement-related behavior in a discrimination learning paradigm. OFC dopamine depletion caused an increase in tonic dopamine levels in the caudate nucleus and a corresponding reduction in D2/D3 receptor binding. Computational modeling of behavior showed that the lesion increased response exploration, reducing the tendency to persist with a recently chosen response side. This effect is akin to increased response switching previously seen in schizophrenia and was correlated with striatal but not OFC D2/D3 receptor binding. These results demonstrate that OFC dopamine depletion is sufficient to induce striatal hyperdopaminergia and changes in reinforcement learning relevant to schizophrenia. PMID:24872570

Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine

NASA Astrophysics Data System (ADS)

Malvindi, Maria Ada; di Corato, Riccardo; Curcio, Annalisa; Melisi, Daniela; Rimoli, Maria Grazia; Tortiglione, Claudia; Tino, Angela; George, Chandramohan; Brunetti, Virgilio; Cingolani, Roberto; Pellegrino, Teresa; Ragusa, Andrea

2011-12-01

The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release.The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed

Stimulant ADHD medication and risk for substance abuse

PubMed Central

Chang, Zheng; Lichtenstein, Paul; Halldner, Linda; D’Onofrio, Brian; Serlachius, Eva; Fazel, Seena; Långström, Niklas; Larsson, Henrik

2013-01-01

Background There are persistent concerns of long-term effects of stimulant ADHD medication on the development of substance abuse. Methods Using Swedish national registers, we studied all individuals born 1960–1998 and diagnosed with ADHD (26,249 men and 12,504 women). We investigated the association between stimulant ADHD medication in 2006 and substance abuse during 2009. Substance abuse was indexed by substance-related death, crime, or hospital visits. Results ADHD medication was not associated with increased rate of substance abuse. Actually, the rate during 2009 was 31% lower among those prescribed ADHD medication in 2006, even after controlling for medication in 2009 and other covariates (hazard ratio: 0.69; 95% confidence interval: 0.57–0.84). Also the longer duration of medication, the lower the rate of substance abuse. Similar risk reductions were suggested among children and when investigating the association between stimulant ADHD medication and concomitant short-term abuse. Conclusions We found no indication of increased risks of substance abuse among individuals prescribed stimulant ADHD medication; if anything, the data suggested a long-term protective effect on substance abuse. Although stimulant ADHD medication does not seem to increase the risk for substance abuse, clinicians should remain alert to the potential problem of stimulant misuse and diversion in ADHD patients. PMID:25158998

Increased dopamine receptor expression and anti-depressant response following deep brain stimulation of the medial forebrain bundle.

PubMed

Dandekar, Manoj P; Luse, Dustin; Hoffmann, Carson; Cotton, Patrick; Peery, Travis; Ruiz, Christian; Hussey, Caroline; Giridharan, Vijayasree V; Soares, Jair C; Quevedo, Joao; Fenoy, Albert J

2017-08-01

Among several potential neuroanatomical targets pursued for deep brain stimulation (DBS) for treating those with treatment-resistant depression (TRD), the superolateral-branch of the medial forebrain bundle (MFB) is emerging as a privileged location. We investigated the antidepressant-like phenotypic and chemical changes associated with reward-processing dopaminergic systems in rat brains after MFB-DBS. Male Wistar rats were divided into three groups: sham-operated, DBS-Off, and DBS-On. For DBS, a concentric bipolar electrode was stereotactically implanted into the right MFB. Exploratory activity and depression-like behavior were evaluated using the open-field and forced-swimming test (FST), respectively. MFB-DBS effects on the dopaminergic system were evaluated using immunoblotting for tyrosine hydroxylase (TH), dopamine transporter (DAT), and dopamine receptors (D1-D5), and high-performance liquid chromatography for quantifying dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in brain homogenates of prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens (NAc). Animals receiving MFB-DBS showed a significant increase in swimming time without alterations in locomotor activity, relative to the DBS-Off (p<0.039) and sham-operated groups (p<0.014), indicating an antidepressant-like response. MFB-DBS led to a striking increase in protein levels of dopamine D2 receptors and DAT in the PFC and hippocampus, respectively. However, we did not observe appreciable differences in the expression of other dopamine receptors, TH, or in the concentrations of dopamine, DOPAC, and HVA in PFC, hippocampus, amygdala, and NAc. This study was not performed on an animal model of TRD. MFB-DBS rescues the depression-like phenotypes and selectively activates expression of dopamine receptors in brain regions distant from the target area of stimulation. Copyright © 2017. Published by Elsevier B.V.

3,4-Dihydroxyphenylethanol (Hydroxytyrosol) Mitigates the Increase in Spontaneous Oxidation of Dopamine during Monoamine Oxidase Inhibition in PC12 Cells

PubMed Central

Goldstein, David S.; Jinsmaa, Yunden; Sullivan, Patti; Holmes, Courtney; Kopin, Irwin J.; Sharabi, Yehonatan

2016-01-01

The catecholaldehyde hypothesis predicts that monoamine oxidase (MAO) inhibition should slow the progression of Parkinson’s disease, by decreasing production of the autotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). Inhibiting MAO, however, diverts the fate of cytoplasmic dopamine toward potentially harmful spontaneous oxidation products, indicated by increased 5-S-cysteinyl-dopamine (Cys-DA) levels. 3,4-Dihydroxyphenylethanol (hydroxytyrosol) is an abundant anti-oxidant phenol in constituents of the Mediterranean diet. Whether hydroxytyrosol alters enzymatic or spontaneous oxidation of dopamine has been unknown. Rat pheochromocytoma PC12 cells were incubated with hydroxytyrosol (10 μM, 180 minutes) alone or with the MAO-A inhibitor clorgyline (1 nM) or the MAO-B inhibitors rasagiline or selegiline (0.5 μM). Hydroxytyrosol decreased levels of DOPAL by 30% and Cys-DA by 49% (p<0.0001 each). Co-incubation with hydroxytyrosol prevented the increases in Cys-DA seen with all 3 MAO inhibitors. Hydroxytyrosol therefore inhibits both enzymatic and spontaneous oxidation of endogenous dopamine and mitigates the increase in spontaneous oxidation during MAO inhibition. PMID:27220335

Neuron membrane trafficking and protein kinases involved in autism and ADHD.

PubMed

Kitagishi, Yasuko; Minami, Akari; Nakanishi, Atsuko; Ogura, Yasunori; Matsuda, Satoru

2015-01-30

A brain-enriched multi-domain scaffolding protein, neurobeachin has been identified as a candidate gene for autism patients. Mutations in the synaptic adhesion protein cell adhesion molecule 1 (CADM1) are also associated with autism spectrum disorder, a neurodevelopmental disorder of uncertain molecular origin. Potential roles of neurobeachin and CADM1 have been suggested to a function of vesicle transport in endosomal trafficking. It seems that protein kinase B (AKT) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) have key roles in the neuron membrane trafficking involved in the pathogenesis of autism. Attention deficit hyperactivity disorder (ADHD) is documented to dopaminergic insufficiencies, which is attributed to synaptic dysfunction of dopamine transporter (DAT). AKT is also essential for the DAT cell-surface redistribution. In the present paper, we summarize and discuss the importance of several protein kinases that regulate the membrane trafficking involved in autism and ADHD, suggesting new targets for therapeutic intervention.

Increased vesicular monoamine transporter binding during early abstinence in human methamphetamine users: Is VMAT2 a stable dopamine neuron biomarker?

PubMed

Boileau, Isabelle; Rusjan, Pablo; Houle, Sylvain; Wilkins, Diana; Tong, Junchao; Selby, Peter; Guttman, Mark; Saint-Cyr, Jean A; Wilson, Alan A; Kish, Stephen J

2008-09-24

Animal data indicate that methamphetamine can damage striatal dopamine terminals. Efforts to document dopamine neuron damage in living brain of methamphetamine users have focused on the binding of [(11)C]dihydrotetrabenazine (DTBZ), a vesicular monoamine transporter (VMAT2) positron emission tomography (PET) radioligand, as a stable dopamine neuron biomarker. Previous PET data report a slight decrease in striatal [(11)C]DTBZ binding in human methamphetamine users after prolonged (mean, 3 years) abstinence, suggesting that the reduction would likely be substantial in early abstinence. We measured striatal VMAT2 binding in 16 recently withdrawn (mean, 19 d; range, 1-90 d) methamphetamine users and in 14 healthy matched-control subjects during a PET scan with (+)[(11)C]DTBZ. Unexpectedly, striatal (+)[(11)C]DTBZ binding was increased in methamphetamine users relative to controls (+22%, caudate; +12%, putamen; +11%, ventral striatum). Increased (+)[(11)C]DTBZ binding in caudate was most marked in methamphetamine users abstinent for 1-3 d (+41%), relative to the 7-21 d (+15%) and >21 d (+9%) groups. Above-normal VMAT2 binding in some drug users suggests that any toxic effect of methamphetamine on dopamine neurons might be masked by an increased (+)[(11)C]DTBZ binding and that VMAT2 radioligand binding might not be, as is generally assumed, a "stable" index of dopamine neuron integrity in vivo. One potential explanation for increased (+)[(11)C]DTBZ binding is that VMAT2 binding is sensitive to changes in vesicular dopamine storage levels, presumably low in drug users. If correct, (+)[(11)C]DTBZ might be a useful imaging probe to correlate changes in brain dopamine stores and behavior in users of methamphetamine.

Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques

PubMed Central

Siciliano, Cody A.; Calipari, Erin S.; Yorgason, Jordan T.; Lovinger, David M.; Mateo, Yolanda; Jimenez, Vanessa A.; Helms, Christa M.; Grant, Kathleen A.; Jones, Sara R.

2016-01-01

Rationale Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use, and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are unknown. Objective Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Methods Female rhesus macaques completed one year of daily (22 hr/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa-opioid receptor agonist) induced inhibition of dopamine release. Results Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa-opioid receptors, which both act as negative regulators of presynaptic dopamine release, were moderately and robustly enhanced in ethanol drinkers. Conclusions Greater uptake rates and sensitivity to D2-type autoreceptor and kappa-opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system, and suggest that the dopamine and dynorphin/kappa-opioid receptor systems may be efficacious pharmcotherapeutic targets in the treatment of alcohol use disorders. PMID:26892380

Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques.

PubMed

Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T; Lovinger, David M; Mateo, Yolanda; Jimenez, Vanessa A; Helms, Christa M; Grant, Kathleen A; Jones, Sara R

2016-04-01

Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are not fully understood. Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Female rhesus macaques completed 1 year of daily (22 h/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa opioid receptor agonist) induced inhibition of dopamine release. Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa opioid receptors, which both act as negative regulators of presynaptic dopamine release, was moderately and robustly enhanced in ethanol drinkers. Greater uptake rates and sensitivity to D2-type autoreceptor and kappa opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system and suggest that the dopamine and dynorphin/kappa opioid receptor systems may be efficacious pharmacotherapeutic targets in the treatment of alcohol use disorders.

Stimulant ADHD medication and risk for substance abuse.

PubMed

Chang, Zheng; Lichtenstein, Paul; Halldner, Linda; D'Onofrio, Brian; Serlachius, Eva; Fazel, Seena; Långström, Niklas; Larsson, Henrik

2014-08-01

There are persistent concerns of long-term effects of stimulant ADHD medication on the development of substance abuse. Using Swedish national registers, we studied all individuals born between 1960 and 1998 and diagnosed with ADHD (26,249 men and 12,504 women). We investigated the association between stimulant ADHD medication in 2006 and substance abuse during 2009. Substance abuse was indexed by substance-related death, crime, or hospital visits. ADHD medication was not associated with increased rate of substance abuse. Actually, the rate during 2009 was 31% lower among those prescribed ADHD medication in 2006, even after controlling for medication in 2009 and other covariates (hazard ratio: 0.69; 95% confidence interval: 0.57-0.84). Also, the longer the duration of medication, the lower the rate of substance abuse. Similar risk reductions were suggested among children and when investigating the association between stimulant ADHD medication and concomitant short-term abuse. We found no indication of increased risks of substance abuse among individuals prescribed stimulant ADHD medication; if anything, the data suggested a long-term protective effect on substance abuse. Although stimulant ADHD medication does not seem to increase the risk for substance abuse, clinicians should remain alert to the potential problem of stimulant misuse and diversion in ADHD patients. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volkow, Nora D.; Wang, Gene-Jack; Smith, Lisa

Metamphetamine’s widepread abuse and concerns that it may increase Parkinson’s disease led us to assess if the reported loss of dopamine transporters (DAT) in methamphetamine abusers (MA) reflected damage to dopamine neurons. Using PET with [ 11C]cocaine to measure DAT, and with [ 11C]raclopride to measure dopamine release (assessed as changes in specific binding of [ 11C]raclopride between placebo and methylphenidate), which was used as marker of dopamine neuronal function, we show that MA (n=16), tested during early detoxification, had lower DAT (20-30%) but overall normal DA release in striatum (except for a small decrease in left putamen), when comparedmore » to controls (n=15). In controls, DAT were positively correlated with DA release (higher DAT associated with larger DA increases), consistent with DAT serving as markers of DA terminals. In contrast, MA showed a trend for a negative correlation (p=0.07) (higher DAT associated with lower DA increases), consistent with reduced DA re-uptake following DAT downregulation. MA who remained abstinent nine-months later (n=9) showed significant increases in DAT (20%) but methylphenidate-induced dopamine increases did not change. In contrast, in controls, DAT did not change when retested 9 months later but methylphenidate-induced dopamine increases in ventral striatum were reduced (p=0.05). Baseline D2/D3 receptors in caudate were lower in MA than in controls and did not change with detoxification, nor did they change in the controls upon retest. The loss of DAT in the MA, which was not associated with a concomitant reduction in dopamine release as would have been expected if DAT loss reflected DA terminal degneration; as well as the recovery of DAT after protracted detoxification, which was not associated with increased dopamine release as would have been expected if DAT increases reflected terminal regeneration, indicate that the loss of DAT in these MA does not reflect degeneration of dopamine terminals.« less

Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release.

PubMed

Volkow, Nora D; Wang, Gene-Jack; Smith, Lisa; Fowler, Joanna S; Telang, Frank; Logan, Jean; Tomasi, Dardo

2015-11-01

Methamphetamine's widepread abuse and concerns that it might increase Parkinson's disease led us to assess if the reported loss of dopamine transporters (DAT) in methamphetamine abusers (MA) reflected damage to dopamine neurons. Using PET with [(11)C]cocaine to measure DAT, and with [(11)C]raclopride to measure dopamine release (assessed as changes in specific binding of [(11)C]raclopride between placebo and methylphenidate), which was used as a marker of dopamine neuronal function, we show that MA (n=16), tested during early detoxification, had lower DAT (20-30%) but overall normal DA release in striatum (except for a small decrease in left putamen), when compared to controls (n=15). In controls, DAT were positively correlated with DA release (higher DAT associated with larger DA increases), consistent with DAT serving as markers of DA terminals. In contrast, MA showed a trend for a negative correlation (p=0.07) (higher DAT associated with lower DA increases), consistent with reduced DA re-uptake following DAT downregulation. MA who remained abstinent nine-months later (n=9) showed significant increases in DAT (20%) but methylphenidate-induced dopamine increases did not change. In contrast, in controls, DAT did not change when retested 9 months later but methylphenidate-induced dopamine increases in ventral striatum were reduced (p=0.05). Baseline D2/D3 receptors in caudate were lower in MA than in controls and did not change with detoxification, nor did they change in the controls upon retest. The loss of DAT in the MA, which was not associated with a concomitant reduction in dopamine release as would have been expected if DAT loss reflected DA terminal degneration; as well as the recovery of DAT after protracted detoxification, which was not associated with increased dopamine release as would have been expected if DAT increases reflected terminal regeneration, indicate that the loss of DAT in these MA does not reflect degeneration of dopamine terminals

Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release

DOE PAGES

Volkow, Nora D.; Wang, Gene-Jack; Smith, Lisa; ...

2015-07-21

Metamphetamine’s widepread abuse and concerns that it may increase Parkinson’s disease led us to assess if the reported loss of dopamine transporters (DAT) in methamphetamine abusers (MA) reflected damage to dopamine neurons. Using PET with [ 11C]cocaine to measure DAT, and with [ 11C]raclopride to measure dopamine release (assessed as changes in specific binding of [ 11C]raclopride between placebo and methylphenidate), which was used as marker of dopamine neuronal function, we show that MA (n=16), tested during early detoxification, had lower DAT (20-30%) but overall normal DA release in striatum (except for a small decrease in left putamen), when comparedmore » to controls (n=15). In controls, DAT were positively correlated with DA release (higher DAT associated with larger DA increases), consistent with DAT serving as markers of DA terminals. In contrast, MA showed a trend for a negative correlation (p=0.07) (higher DAT associated with lower DA increases), consistent with reduced DA re-uptake following DAT downregulation. MA who remained abstinent nine-months later (n=9) showed significant increases in DAT (20%) but methylphenidate-induced dopamine increases did not change. In contrast, in controls, DAT did not change when retested 9 months later but methylphenidate-induced dopamine increases in ventral striatum were reduced (p=0.05). Baseline D2/D3 receptors in caudate were lower in MA than in controls and did not change with detoxification, nor did they change in the controls upon retest. The loss of DAT in the MA, which was not associated with a concomitant reduction in dopamine release as would have been expected if DAT loss reflected DA terminal degneration; as well as the recovery of DAT after protracted detoxification, which was not associated with increased dopamine release as would have been expected if DAT increases reflected terminal regeneration, indicate that the loss of DAT in these MA does not reflect degeneration of dopamine terminals.« less

Dopamine Increases CD14+CD16+ Monocyte Transmigration across the Blood Brain Barrier: Implications for Substance Abuse and HIV Neuropathogenesis.

PubMed

Calderon, Tina M; Williams, Dionna W; Lopez, Lillie; Eugenin, Eliseo A; Cheney, Laura; Gaskill, Peter J; Veenstra, Mike; Anastos, Kathryn; Morgello, Susan; Berman, Joan W

2017-06-01

In human immunodeficiency virus-1 (HIV) infected individuals, substance abuse may accelerate the development and/or increase the severity of HIV associated neurocognitive disorders (HAND). It is proposed that CD14 + CD16 + monocytes mediate HIV entry into the central nervous system (CNS) and that uninfected and infected CD14 + CD16 + monocyte transmigration across the blood brain barrier (BBB) contributes to the establishment and propagation of CNS HIV viral reservoirs and chronic neuroinflammation, important factors in the development of HAND. The effects of substance abuse on the frequency of CD14 + CD16 + monocytes in the peripheral circulation and on the entry of these cells into the CNS during HIV neuropathogenesis are not known. PBMC from HIV infected individuals were analyzed by flow cytometry and we demonstrate that the frequency of peripheral blood CD14 + CD16 + monocytes in HIV infected substance abusers is increased when compared to those without active substance use. Since drug use elevates extracellular dopamine concentrations in the CNS, we examined the effects of dopamine on CD14 + CD16 + monocyte transmigration across our in vitro model of the human BBB. The transmigration of this monocyte subpopulation is increased by dopamine and the dopamine receptor agonist, SKF 38393, implicating D1-like dopamine receptors in the increase in transmigration elicited by this neurotransmitter. Thus, elevated extracellular CNS dopamine may be a novel common mechanism by which active substance use increases uninfected and HIV infected CD14 + CD16 + monocyte transmigration across the BBB. The influx of these cells into the CNS may increase viral seeding and neuroinflammation, contributing to the development of HIV associated neurocognitive impairments.

ADHD in acute care psychiatric inpatients.

PubMed

Lines, Katherine L; Sadek, Joseph

2018-06-01

to patients without comorbid ADHD. Patients with ADHD also scored significantly higher in the individual domains of this rating scale, suggesting impairment in family, work and social functioning as well as decreased life-skills, poor self-concept and increased risk-taking behavior. In this sample, the prevalence of ADHD is significantly higher among acute care psychiatric inpatients than in the general population. Patients with concomitant ADHD suffer more functional impairment than those without. These findings merit further investigation into the value of routine screening and patient-specific treatment of ADHD in this patient population.

Impact of Attention-Deficit/Hyperactivity Disorder (ADHD) on prescription dug spending for children and adolescents: increasing relevance of health economic evidence

PubMed Central

Schlander, Michael

2007-01-01

Background During the last decade, pharmaceutical spending for patients with attention-deficit-hyperactivity disorder (ADHD) has been escalating internationally. Objectives First, to estimate future trends of ADHD-related drug expenditures from the perspectives of the statutory health insurance (SHI; Gesetzliche Krankenversicherung, GKV) in Germany and the National Health Service (NHS) in England, respectively, for children and adolescents age 6 to 18 years. Second, to evaluate the budgetary impact on individual prescribers (child and adolescent psychiatrists and pediatricians treating patients with ADHD) in Germany. Methods A model was developed to predict plausible scenarios of future pharmaceutical expenditures for treatment of ADHD. Model inputs were derived from demographic and epidemiological data, a literature review of past spending trends, and an analysis of new pharmaceutical products in development for ADHD. Only products in clinical development phase III or later were considered. Uncertainty was addressed by way of scenario analysis. For each jurisdiction, five scenarios used different assumptions of future diagnosis prevalence, treatment prevalence, rates of adoption and unit costs of novel drugs, and treatment intensity. Results Annual ADHD pharmacotherapy expenditures for children and adolescents will further increase and may exceed €310 m (D; E: ₤78 m) in 2012 (2002: ~€21.8 m; ~₤7.0 m). During this period, overall drug spending by individual physicians may increase 2.3- to 9.5-fold, resulting from the multiplicative effects of four variables: increased number of diagnosed cases, growing acceptance and intensity of pharmacotherapy, and higher unit costs of novel medications. Discussion Even for an extreme low case scenario, a more than six-fold increase of pharmaceutical spending for children and adolescents is predicted over the decade from 2002 to 2012, from the perspectives of both the NHS in England and the GKV in Germany. This budgetary

Cholinergic Interneurons Underlie Spontaneous Dopamine Release in Nucleus Accumbens

PubMed Central

2017-01-01

The release of dopamine from terminals in the NAc is regulated by a number of factors, including voltage-gated ion channels, D2-autoreceptors, and nAChRs. Cholinergic interneurons (CINs) drive dopamine release through activation of nAChRs on dopamine terminals. Using cyclic voltammetry in mouse brain slices, nAChR-dependent spontaneous dopamine transients and the mechanisms underlying the origin were examined in the NAc. Spontaneous events were infrequent (0.3 per minute), but the rate and amplitude were increased after blocking Kv channels with 4-aminopyridine. Although the firing frequency of CINs was increased by blocking glutamate reuptake with TBOA and the Sk blocker apamin, only 4-aminopyridine increased the frequency of dopamine transients. In contrast, inhibition of CIN firing with the μ/δ selective opioid [Met5]enkephalin (1 μm) decreased spontaneous dopamine transients. Cocaine increased the rate and amplitude of dopamine transients, suggesting that the activity of the dopamine transporter limits the detection of these events. In the presence of cocaine, the rate of spontaneous dopamine transients was further increased after blocking D2-autoreceptors. Blockade of muscarinic receptors had no effect on evoked dopamine release, suggesting that feedback inhibition of acetylcholine release was not involved. Thus, although spontaneous dopamine transients are reliant on nAChRs, the frequency was not strictly governed by the activity of CINs. The increase in frequency of spontaneous dopamine transients induced by cocaine was not due to an increase in cholinergic tone and is likely a product of an increase in detection resulting from decreased dopamine reuptake. SIGNIFICANCE STATEMENT The actions of dopamine in the NAc are thought to be responsible for endogenous reward and the reinforcing properties of drugs of abuse, such as psychostimulants. The present work examines the mechanisms underlying nAChR-induced spontaneous dopamine release. This study

Effect of atomoxetine on hyperactivity in an animal model of attention-deficit/hyperactivity disorder (ADHD).

PubMed

Moon, Su Jin; Kim, Chang Ju; Lee, Yeon Jung; Hong, Minha; Han, Juhee; Bahn, Geon Ho

2014-01-01

Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD). To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus. Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined. The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner. Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway.

Effect of Atomoxetine on Hyperactivity in an Animal Model of Attention-Deficit/Hyperactivity Disorder (ADHD)

PubMed Central

Moon, Su Jin; Kim, Chang Ju; Lee, Yeon Jung; Hong, Minha; Han, Juhee; Bahn, Geon Ho

2014-01-01

Background Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD). Purpose To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus. Methods Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined. Results The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner. Conclusion Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway. PMID:25271814

Coaching for ADHD

ERIC Educational Resources Information Center

Murphy, Kevin; Ratey, Nancy; Maynard, Sandy; Sussman, Susan; Wright, Sarah D.

2010-01-01

Despite limited scientific study on ADHD coaching as an intervention for adults with ADHD, the field of ADHD coaching has grown significantly and gained popularity in recent years. ADHD coaching is becoming a bona fide profession where one must advance through a rigorous training process, in order to be certified as a professional ADHD coach.…

Systemic blockade of dopamine D2-like receptors increases high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

PubMed

Yang, Chen; Ge, Shun-Nan; Zhang, Jia-Rui; Chen, Lei; Yan, Zhi-Qiang; Heng, Li-Jun; Zhao, Tian-Zhi; Li, Wei-Xin; Jia, Dong; Zhu, Jun-Ling; Gao, Guo-Dong

2013-01-01

High-voltage spindles (HVSs) have been reported to appear spontaneously and widely in the cortical-basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP) and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D₁-like receptors or D₂-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1) in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D₂-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D₂-like receptor antagonists. On the contrary, the selective dopamine D₁-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D₂-like receptors, but not D₁-like receptors, were involved in HVS regulation. This supports the important role of dopamine D₂-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.

Dopamine and serotonin transporter genotypes moderate sensitivity to maternal expressed emotion: the case of conduct and emotional problems in attention deficit/hyperactivity disorder.

PubMed

Sonuga-Barke, Edmund J S; Oades, Robert D; Psychogiou, Lamprini; Chen, Wai; Franke, Barbara; Buitelaar, Jan; Banaschewski, Tobias; Ebstein, Richard P; Gil, Michael; Anney, Richard; Miranda, Ana; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Steinhausen, Hans Christoph; Thompson, Margaret; Asherson, Philip; Faraone, Stephen V

2009-09-01

Mothers' positive emotions expressed about their children with attention deficit/hyperactivity disorder (ADHD) are associated with a reduced likelihood of comorbid conduct problems (CP). We examined whether this association with CP, and one with emotional problems (EMO), is moderated by variants within three genes, previously reported to be associated with ADHD and to moderate the impact of environmental risks on conduct and/or emotional problems; the dopamine transporter gene (SLC6A3/DAT1), the dopamine D4 receptor gene (DRD4) and the serotonin transporter gene (SLC6A4/5HTT). Seven hundred and twenty-eight males between the ages of 5 and 17 with a DSM-IV research diagnosis of combined type ADHD were included in these analyses. Parents and teachers rated children's conduct and emotional problems. Positive maternal expressed emotion (PMEE) was coded by independent observers on comments made during a clinical assessment with the mother based on current or recent medication-free periods. Sensitivity to the effects of PMEE on CP was moderated by variants of the DAT1 and 5HTT genes. Only children who did not carry the DAT1 10R/10R or the 5HTT l/l genotypes showed altered levels of CP when exposed to PMEE. The effect was most marked where the child with ADHD had both these genotypes. For EMO, sensitivity to PMEE was found only with those who carried the DAT1 9R/9R. There was no effect of DRD4 on CP or EMO. The gene-environment interactions observed suggested that genetic make-up can alter the degree of sensitivity an ADHD patients has to their family environment. Further research should focus on distinguishing general sensitivity genotypes from those conferring risk or protective qualities.

Increasing Dopamine Levels in the Brain Improves Feedback-Based Procedural Learning in Healthy Participants: An Artificial-Grammar-Learning Experiment

ERIC Educational Resources Information Center

de Vries, Meinou H.; Ulte, Catrin; Zwitserlood, Pienie; Szymanski, Barbara; Knecht, Stefan

2010-01-01

Recently, an increasing number of studies have suggested a role for the basal ganglia and related dopamine inputs in procedural learning, specifically when learning occurs through trial-by-trial feedback (Shohamy, Myers, Kalanithi, & Gluck. (2008). "Basal ganglia and dopamine contributions to probabilistic category learning." "Neuroscience and…

Optimal management of ADHD in older adults.

PubMed

Torgersen, Terje; Gjervan, Bjorn; Lensing, Michael B; Rasmussen, Kirsten

2016-01-01

The manifestation of attention-deficit/hyperactivity disorder (ADHD) among older adults has become an interesting topic of interest due to an increasing number of adults aged 50 years and older (≥50 years) seeking assessment for ADHD. Unfortunately, there is a lack of research on ADHD in older adults, and until recently only a few case reports existed. A systematic search was conducted in the databases Medline/PubMed and PsycINFO in order to identify studies regarding ADHD in adults ≥50 years. ADHD persists into older ages in many patients, but the prevalence of patients fulfilling the criteria for the diagnosis at age ≥50 years is still unknown. It is reason to believe that the prevalence is falling gradually with age, and that the ADHD symptom level is significantly lower in the age group 70-80 years than the group 50-60 years. There is a lack of controlled studies of ADHD medication in adults ≥50 years, but this review suggests that many patients aged ≥50 years experience beneficial effects of pharmacological treatment. The problem with side effects and somatic complications may rise to a level that makes pharmacotherapy for ADHD difficult after the age of 65 years. Physical assessment prior to initiation of ADHD medication in adults ≥50 years should include a thorough clinical examination, and medication should be titrated with low doses initially and with a slow increase. In motivated patients, different psychological therapies alone or in addition to pharmacotherapy should be considered. It is essential when treating older adult patients with ADHD to provide good support based on knowledge and understanding of how ADHD symptoms have affected health, quality of life, and function through the life span. Individualized therapy for each elderly patient should be recommended to balance risk-benefit ratio when pharmacotherapy is considered to be a possible treatment.

Peer influence as a potential magnifier of ADHD diagnosis.

PubMed

Aronson, Brian

2016-11-01

The prevalence of Attention Deficit and Hyperactivity Disorder (ADHD) is growing in America, but its cause is unclear. Scholars have identified many environmental factors that can cause or confound ADHD diagnosis, but epidemiological studies that try to control for confounding factors still find evidence that rates of ADHD diagnosis are increasing. As a preliminary explanation to ADHD's increasing prevalence, this article examines whether core ADHD diagnostic traits are subject to peer influence. If ADHD diagnosis can be confounded by peer influence, there are several mechanisms that could have caused increased rates of diagnosis. With data drawn from two schools across three waves in the National Longitudinal Survey of Adolescent Health (n = 2193), the author uses a stochastic actor oriented model to estimate the effect of peer influence on inattention, controlling for alternative network and behavioral causes. Results indicate that respondents have a strong likelihood to modify their self-reports of inattention, a core ADHD trait, to resemble that of their friends. Copyright © 2016 Elsevier Ltd. All rights reserved.

"I Use Weed for My ADHD": A Qualitative Analysis of Online Forum Discussions on Cannabis Use and ADHD.

PubMed

Mitchell, John T; Sweitzer, Maggie M; Tunno, Angela M; Kollins, Scott H; McClernon, F Joseph

2016-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for problematic cannabis use. However, clinical and anecdotal evidence suggest an increasingly popular perception that cannabis is therapeutic for ADHD, including via online resources. Given that the Internet is increasingly utilized as a source of healthcare information and may influence perceptions, we conducted a qualitative analysis of online forum discussions, also referred to as threads, on the effects of cannabis on ADHD to systematically characterize the content patients and caregivers may encounter about ADHD and cannabis. A total of 268 separate forum threads were identified. Twenty percent (20%) were randomly selected, which yielded 55 separate forum threads (mean number of individual posts per forum thread = 17.53) scored by three raters (Cohen's kappa = 0.74). A final sample of 401 posts in these forum threads received at least one endorsement on predetermined topics following qualitative coding procedures. Twenty-five (25%) percent of individual posts indicated that cannabis is therapeutic for ADHD, as opposed to 8% that it is harmful, 5% that it is both therapeutic and harmful, and 2% that it has no effect on ADHD. This pattern was generally consistent when the year of each post was considered. The greater endorsement of therapeutic versus harmful effects of cannabis did not generalize to mood, other (non-ADHD) psychiatric conditions, or overall domains of daily life. Additional themes emerged (e.g., cannabis being considered sanctioned by healthcare providers). Despite that there are no clinical recommendations or systematic research supporting the beneficial effects of cannabis use for ADHD, online discussions indicate that cannabis is considered therapeutic for ADHD-this is the first study to identify such a trend. This type of online information could shape ADHD patient and caregiver perceptions, and influence cannabis use and clinical care.

Maternal ADHD, parenting, and psychopathology among mothers of adolescents with ADHD

PubMed Central

Babinski, Dara E.; Pelham, William E.; Molina, Brooke S.G.; Gnagy, Elizabeth M.; Waschbusch, Daniel A.; Wymbs, Brian T.; Sibley, Margaret H.; Derefinko, Karen J.; Kuriyan, Aparajita B.

2012-01-01

Objective This study describes the parenting and psychopathology of mothers with ADHD of adolescents with ADHD (MCA), non-ADHD mothers of adolescents with ADHD (CA), and non-ADHD mothers of adolescents without ADHD (COMP). Method Two sets of pairwise comparisons: 1) COMP vs. CA and 2) CA vs. MCA were conducted. We hypothesized that CA would experience greater distress in parenting and psychopathology compared to COMP, and that MCA would experience even more impairment compared to CA. Results Few differences emerged in comparisons of CA and COMP, with the exception of CA reporting greater parent-adolescent conflict and internalizing problems. In contrast, differences consistently emerged in comparisons of MCA and CA showing more difficulty for MCA in parenting and psychopathology. Conclusion These findings underscore the need for treatments that address parental ADHD when adolescent ADHD is the intended target. PMID:23160485

Organisation of services for managing ADHD.

PubMed

Coghill, D R

2017-10-01

There is considerable variation in practice, both between and with different countries in the management of attention deficit hyperactivity disorder (ADHD). Whilst there is no one optimal model of service organisation there are general principles of care that can be introduced to reduce this variability. There are frequent debates and discussions about which professional group is best placed to manage ADHD at different points in the life cycle. Who delivers care is however less important than ensuring that training schemes provide adequate exposure, training and experience to both the core and non-core skills required to provide a comprehensive package of care. Most evidence-based guidelines recommend a multi-modal, multi-professional and multi-agency approach. Many also promote the use of both stepped care and shared care approaches for the management of ADHD. As most of those with ADHD continue to have ADHD-related problems into adulthood, it is important to consider how best to transition care into adulthood and think about who should deliver care to adults with ADHD. Young people with ADHD should generally be transferred to adult mental health services if they continue to have significant symptoms of ADHD or other coexisting conditions that require treatment. Unfortunately services for adults with ADHD remain relatively scarce across much of the world and some adult psychiatrists remain unsure of the diagnosis and uncertain about the appropriate use of ADHD medications in adults, but there is a strong case for increased services for adults. ADHD is on the one hand easy to treat; it is much more difficult to treat well. Although optimised care for ADHD requires routine measurement of outcomes, this often does not happen in routine clinical practice. Focusing on optimising symptoms and minimising adverse effects can significantly improve both short- and long-term outcomes.

A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in ADHD boys and siblings

PubMed Central

Sonuga-Barke, Edmund J. S.; Kumsta, Robert; Schlotz, Wolff; Lasky-Su, Jessica; Marco, Rafaela; Miranda, Ana; Mulas, Fernando; Oades, Robert D.; Banaschewski, Tobias; Mueller, Ueli; Andreou, Penny; Christiansen, Hanna; Gabriels, Isabel; Uebel, Henrik; Kuntsi, Jonna; Franke, Barbara; Buitelaar, Jan; Ebstein, Richard; Gill, Michael; Anney, Richard; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Steinhausen, Hans Christoph; Asherson, Philip; Faraone, Stephen V.

2011-01-01

Background Impulsive drive for immediate reward (IDIR) and delay aversion are dissociable elements of the preference for immediate over delayed rewards seen in Attention Deficit/Hyperactivity Disorder (ADHD). We hypothesized that IDIR would be associated with dopamine regulating genes and delay aversion with serotonin regulating genes. Methods IDIR and delay aversion were measured in 459 male children and adolescents (328 ADHD and 131 unaffected siblings) using a laboratory choice task. The sample was genotyped for the 5HTT (SLC6A4) promoter 5-HTTLPR polymorphism and a DAT1 (SLC6A3) 40-base pair VNTR located in the 3`-untranslated region of the gene. Results There was no effect of DAT1 on IDIR. As predicted 5-HTTLPR s-allele carriers were more delay averse. This effect was driven by the s/l genotype in the ADHD group. These results were not altered by taking account of the rs25531 A/G SNP and were independent of age, IQ and ODD symptoms. Conclusions The results support the genetic distinctiveness of IDIR and delay aversion in ADHD and implicate serotonin function in delay aversion. Possible explanations of the heterosis effect in the ADHD cases are presented. PMID:21497794

Estradiol increases the sensitivity of ventral tegmental area dopamine neurons to dopamine and ethanol.

PubMed

Vandegrift, Bertha J; You, Chang; Satta, Rosalba; Brodie, Mark S; Lasek, Amy W

2017-01-01

Gender differences in psychiatric disorders such as addiction may be modulated by the steroid hormone estrogen. For instance, 17β-estradiol (E2), the predominant form of circulating estrogen in pre-menopausal females, increases ethanol consumption, suggesting that E2 may affect the rewarding properties of ethanol and thus the development of alcohol use disorder in females. The ventral tegmental area (VTA) is critically involved in the rewarding and reinforcing effects of ethanol. In order to determine the role of E2 in VTA physiology, gonadally intact female mice were sacrificed during diestrus II (high E2) or estrus (low E2) for electrophysiology recordings. We measured the excitation by ethanol and inhibition by dopamine (DA) of VTA DA neurons and found that both excitation by ethanol and inhibition by dopamine were greater in diestrus II compared with estrus. Treatment of VTA slices from mice in diestrus II with an estrogen receptor antagonist (ICI 182,780) reduced ethanol-stimulated neuronal firing, but had no effect on ethanol-stimulated firing of neurons in slices from mice in estrus. Surprisingly, ICI 182,780 did not affect the inhibition by DA, indicating different mechanisms of action of estrogen receptors in altering ethanol and DA responses. We also examined the responses of VTA DA neurons to ethanol and DA in ovariectomized mice treated with E2 and found that E2 treatment enhanced the responses to ethanol and DA in a manner similar to what we observed in mice in diestrus II. Our data indicate that E2 modulates VTA neuron physiology, which may contribute to both the enhanced reinforcing and rewarding effects of alcohol and the development of other psychiatric disorders in females that involve alterations in DA neurotransmission.

Estradiol increases the sensitivity of ventral tegmental area dopamine neurons to dopamine and ethanol

PubMed Central

Vandegrift, Bertha J.; You, Chang; Satta, Rosalba; Brodie, Mark S.

2017-01-01

Gender differences in psychiatric disorders such as addiction may be modulated by the steroid hormone estrogen. For instance, 17β-estradiol (E2), the predominant form of circulating estrogen in pre-menopausal females, increases ethanol consumption, suggesting that E2 may affect the rewarding properties of ethanol and thus the development of alcohol use disorder in females. The ventral tegmental area (VTA) is critically involved in the rewarding and reinforcing effects of ethanol. In order to determine the role of E2 in VTA physiology, gonadally intact female mice were sacrificed during diestrus II (high E2) or estrus (low E2) for electrophysiology recordings. We measured the excitation by ethanol and inhibition by dopamine (DA) of VTA DA neurons and found that both excitation by ethanol and inhibition by dopamine were greater in diestrus II compared with estrus. Treatment of VTA slices from mice in diestrus II with an estrogen receptor antagonist (ICI 182,780) reduced ethanol-stimulated neuronal firing, but had no effect on ethanol-stimulated firing of neurons in slices from mice in estrus. Surprisingly, ICI 182,780 did not affect the inhibition by DA, indicating different mechanisms of action of estrogen receptors in altering ethanol and DA responses. We also examined the responses of VTA DA neurons to ethanol and DA in ovariectomized mice treated with E2 and found that E2 treatment enhanced the responses to ethanol and DA in a manner similar to what we observed in mice in diestrus II. Our data indicate that E2 modulates VTA neuron physiology, which may contribute to both the enhanced reinforcing and rewarding effects of alcohol and the development of other psychiatric disorders in females that involve alterations in DA neurotransmission. PMID:29107956

Shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) traits in children and clinical ADHD.

PubMed

Stergiakouli, Evie; Martin, Joanna; Hamshere, Marian L; Langley, Kate; Evans, David M; St Pourcain, Beate; Timpson, Nicholas J; Owen, Michael J; O'Donovan, Michael; Thapar, Anita; Davey Smith, George

2015-04-01

Twin studies and genome-wide complex trait analysis (GCTA) are not in agreement regarding heritability estimates for behavioral traits in children from the general population. This has sparked a debate on the possible difference in genetic architecture between behavioral traits and psychiatric disorders. In this study, we test whether polygenic risk scores associated with variation in attention-deficit/hyperactivity disorder (ADHD) trait levels in children from the general population predict ADHD diagnostic status and severity in an independent clinical sample. Single nucleotide polymorphisms (SNPs) with p < .5 from a genome-wide association study of ADHD traits in 4,546 children (mean age, 7 years 7 months) from the Avon Longitudinal Study of Parents and Children (ALSPAC; general population sample) were selected to calculate polygenic risk scores in 508 children with an ADHD diagnosis (independent clinical sample) and 5,081 control participants. Polygenic scores were tested for association with case-control status and severity of disorder in the clinical sample. Increased polygenic score for ADHD traits predicted ADHD case-control status (odds ratio = 1.17 [95% CI = 1.08-1.28], p = .0003), higher ADHD symptom severity (β = 0.29 [95% CI = 0.04-0.54], p = 0.02), and symptom domain severity in the clinical sample. This study highlights the relevance of additive genetic variance in ADHD, and provides evidence that shared genetic factors contribute to both behavioral traits in the general population and psychiatric disorders at least in the case of ADHD. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Cannabis use and adult ADHD symptoms.

PubMed

Fergusson, David M; Boden, Joseph M

2008-05-01

The present study examined the associations between cannabis use in adolescence and young adulthood and self-reported adult attention deficit/hyperactivity disorder (ADHD) symptoms in adulthood. A 25-year prospective longitudinal study of the health, development, and adjustment of a birth cohort of 1265 New Zealand children. Measures included assessments of adolescent and young adult cannabis use and ADHD symptoms at age 25, measures of childhood socioeconomic disadvantage, family adversity, childhood and early adolescent behavioural adjustment and cognitive ability, and adolescent and young adult other drug use. Cannabis use by age 25 was significantly (p<.0001) associated with increasing self-reported adult ADHD symptoms at age 25. Adjustment of the association for potentially confounding factors from childhood and early adolescence reduced the magnitude of the association, but it remained statistically significant (p<.0001). However, control for the mediating effects of other drug use in adolescence and early adulthood reduced the association between cannabis use and adult ADHD symptoms to statistical non-significance (p>.20). The current study suggested that the association between cannabis use and adult ADHD symptoms was mediated by other substance use that was associated with cannabis use. The results suggest that cannabis use leads to other drug use, which in turn leads to increased ADHD symptoms. However, it should be noted that the potential influence of such factors as genetic predispositions may still be unaccounted for.

Comparison of QEEG Findings between Adolescents with Attention Deficit Hyperactivity Disorder (ADHD) without Comorbidity and ADHD Comorbid with Internet Gaming Disorder.

PubMed

Park, Jeong Ha; Hong, Ji Sun; Han, Doug Hyun; Min, Kyoung Joon; Lee, Young Sik; Kee, Baik Seok; Kim, Sun Mi

2017-03-01

Internet gaming disorder (IGD) is often comorbid with attention deficit hyperactivity disorder (ADHD). In this study, we compared the neurobiological differences between ADHD comorbid with IGD (ADHD+IGD group) and ADHD without comorbidity (ADHD-only group) by analyzing quantitative electroencephalogram (QEEG) findings. We recruited 16 male ADHD+IGD, 15 male ADHD-only adolescent patients, and 15 male healthy controls (HC group). Participants were assessed using Young's Internet Addiction Scale and ADHD Rating Scale. Relative power and inter- and intra-hemispheric coherences of brain waves were measured using a digital electroencephalography (EEG) system. Compared to the ADHD-only group, the ADHD+IGD group showed lower relative delta power and greater relative beta power in temporal regions. The relative theta power in frontal regions were higher in ADHD-only group compared to HC group. Inter-hemispheric coherence values for the theta band between F3-F4 and C3-C4 electrodes were higher in ADHD-only group compared to HC group. Intra-hemispheric coherence values for the delta, theta, alpha, and beta bands between P4-O2 electrodes and intra-hemispheric coherence values for the theta band between Fz-Cz and T4-T6 electrodes were higher in ADHD+IGD group compared to ADHD-only group. Adolescents who show greater vulnerability to ADHD seem to continuously play Internet games to unconsciously enhance attentional ability. In turn, relative beta power in attention deficit in ADHD+IGD group may become similar to that in HC group. Repetitive activation of brain reward and working memory systems during continuous gaming may result in an increase in neuronal connectivity within the parieto-occipital and temporal regions for the ADHD+IGD group.

Cognitive and neural correlates of the 5-repeat allele of the dopamine D4 receptor gene in a population lacking the 7-repeat allele.

PubMed

Takeuchi, Hikaru; Tomita, Hiroaki; Taki, Yasuyuki; Kikuchi, Yoshie; Ono, Chiaki; Yu, Zhiqian; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

2015-04-15

The 5-repeat allele of a common length polymorphism in the gene that encodes the dopamine D4 receptor (DRD4) is robustly associated with the risk of attention deficit hyperactivity disorder (ADHD) and substantially exists in Asian populations, which have a lower ADHD prevalence. In this study, we investigated the effect of this allele on microstructural properties of the brain and on its functional activity during externally directed attention-demanding tasks and creative performance in the 765 Asian subjects. For this purpose, we employed diffusion tensor imaging, N-back functional magnetic resonance imaging paradigms, and a test to measure creativity by divergent thinking. The 5-repeat allele was significantly associated with increased originality in the creative performance, increased mean diffusivity (the measure of how the tissue includes water molecules instead of neural and vessel components) in the widespread gray and white matter areas of extensive areas, particularly those where DRD4 is expressed, and reduced task-induced deactivation in the areas that are deactivated during the tasks in the course of both the attention-demanding working memory task and simple sensorimotor task. The observed neural characteristics of 5-repeat allele carriers may lead to an increased risk of ADHD and behavioral deficits. Furthermore, the increased originality of creative thinking observed in the 5-repeat allele carriers may support the notion of the side of adaptivity of the widespread risk allele of psychiatric diseases. Copyright © 2015. Published by Elsevier Inc.

Estradiol, dopamine and motivation.

PubMed

Yoest, Katie E; Cummings, Jennifer A; Becker, Jill B

2014-01-01

The gonadal hormone estradiol modulates mesolimbic dopamine systems in the female rat. This modulatory effect is thought to be responsible for the observed effects of estradiol on motivated behaviors. Dopamine acting in the nucleus accumbens is thought to be important for the attribution of incentive motivational properties to cues that predict reward delivery, while dopamine in the striatum is associated with the expression of repetitive or stereotyped behaviors. Elevated concentrations of estradiol are associated with increased motivation for sex or cues associated with access to a mate, while simultaneously attenuating motivation for food. This shift in motivational salience is important for adaptive choice behavior in the natural environment. Additionally, estradiol's adaptive effects on motivation can be maladaptive when increasing motivation for non-natural reinforcers, such as drugs of abuse. Here we discuss the effect of estradiol on mesotelencephalic dopamine transmission and subsequent effects on motivated behaviors.

Methamphetamine Regulation of Firing Activity of Dopamine Neurons

PubMed Central

Lin, Min; Sambo, Danielle

2016-01-01

Methamphetamine (METH) is a substrate for the dopamine transporter that increases extracellular dopamine levels by competing with dopamine uptake and increasing reverse transport of dopamine via the transporter. METH has also been shown to alter the excitability of dopamine neurons. The mechanism of METH regulation of the intrinsic firing behaviors of dopamine neurons is less understood. Here we identified an unexpected and unique property of METH on the regulation of firing activity of mouse dopamine neurons. METH produced a transient augmentation of spontaneous spike activity of midbrain dopamine neurons that was followed by a progressive reduction of spontaneous spike activity. Inspection of action potential morphology revealed that METH increased the half-width and produced larger coefficients of variation of the interspike interval, suggesting that METH exposure affected the activity of voltage-dependent potassium channels in these neurons. Since METH has been shown to affect Ca2+ homeostasis, the unexpected findings that METH broadened the action potential and decreased the amplitude of afterhyperpolarization led us to ask whether METH alters the activity of Ca2+-activated potassium (BK) channels. First, we identified BK channels in dopamine neurons by their voltage dependence and their response to a BK channel blocker or opener. While METH suppressed the amplitude of BK channel-mediated unitary currents, the BK channel opener NS1619 attenuated the effects of METH on action potential broadening, afterhyperpolarization repression, and spontaneous spike activity reduction. Live-cell total internal reflection fluorescence microscopy, electrophysiology, and biochemical analysis suggest METH exposure decreased the activity of BK channels by decreasing BK-α subunit levels at the plasma membrane. SIGNIFICANCE STATEMENT Methamphetamine (METH) competes with dopamine uptake, increases dopamine efflux via the dopamine transporter, and affects the excitability of

Comparison of QEEG Findings between Adolescents with Attention Deficit Hyperactivity Disorder (ADHD) without Comorbidity and ADHD Comorbid with Internet Gaming Disorder

PubMed Central

2017-01-01

Internet gaming disorder (IGD) is often comorbid with attention deficit hyperactivity disorder (ADHD). In this study, we compared the neurobiological differences between ADHD comorbid with IGD (ADHD+IGD group) and ADHD without comorbidity (ADHD-only group) by analyzing quantitative electroencephalogram (QEEG) findings. We recruited 16 male ADHD+IGD, 15 male ADHD-only adolescent patients, and 15 male healthy controls (HC group). Participants were assessed using Young's Internet Addiction Scale and ADHD Rating Scale. Relative power and inter- and intra-hemispheric coherences of brain waves were measured using a digital electroencephalography (EEG) system. Compared to the ADHD-only group, the ADHD+IGD group showed lower relative delta power and greater relative beta power in temporal regions. The relative theta power in frontal regions were higher in ADHD-only group compared to HC group. Inter-hemispheric coherence values for the theta band between F3–F4 and C3–C4 electrodes were higher in ADHD-only group compared to HC group. Intra-hemispheric coherence values for the delta, theta, alpha, and beta bands between P4–O2 electrodes and intra-hemispheric coherence values for the theta band between Fz–Cz and T4–T6 electrodes were higher in ADHD+IGD group compared to ADHD-only group. Adolescents who show greater vulnerability to ADHD seem to continuously play Internet games to unconsciously enhance attentional ability. In turn, relative beta power in attention deficit in ADHD+IGD group may become similar to that in HC group. Repetitive activation of brain reward and working memory systems during continuous gaming may result in an increase in neuronal connectivity within the parieto-occipital and temporal regions for the ADHD+IGD group. PMID:28145657

Comparative Study of Children with ADHD Only, Autism Spectrum Disorder + ADHD, and Chronic Multiple Tic Disorder + ADHD

ERIC Educational Resources Information Center

Gadow, Kenneth D.; DeVincent, Carla J.; Schneider, Jayne

2009-01-01

Objective: Identification of differences among children with ADHD only, autism spectrum disorder (ASD)+ADHD, and chronic multiple tic disorder (CMTD)+ADHD may lead to better understanding of clinical phenotypes. Method: Children were evaluated using the parent- and teacher-completed questionnaires. Results: All three groups were highly similar in…

Lifespan persistence of ADHD: the life transition model and its application.

PubMed

Turgay, Atilla; Goodman, David W; Asherson, Philip; Lasser, Robert A; Babcock, Thomas F; Pucci, Michael L; Barkley, Russell

2012-02-01

The understanding that attention-deficit/hyperactivity disorder (ADHD) often persists throughout life has heightened interest of patients, families, advocates, and professionals in a longitudinal approach to management. Such an approach must recognize and address known patient- and systems-based challenges of long-term mental health treatment, shifting of clinical presentations of ADHD, and commonality of psychiatric comorbidity with ADHD. The ADHD Life Transition Model is a step toward developing criteria to optimize recognition and clinical management of ADHD (eg, response, remission) across an individual's lifespan and across diverse medical subspecialties. To support therapeutic efficiency and adaptability, our proposed model highlights periods when external resources for managing ADHD are reduced, cognitive and behavioral stressors are increased, and individuals may be reevaluating how they perceive, accept, and adhere to ADHD treatment. Such a model aims to support the clinical community by placing in context new findings, which suggest that the prevention of adult psychopathology in individuals with pediatric ADHD may be possible. The ADHD Life Transition Model seeks to improve care for individuals with ADHD by (1) underscoring that ADHD persists beyond childhood in at least two-thirds of patients, (2) raising awareness of the need to approach ADHD from a chronic illness standpoint, and (3) increasing mental health professionals' diligence in symptom recognition and management of ADHD across developmental phases from childhood through adulthood. © Copyright 2012 Physicians Postgraduate Press, Inc.

Resting-State Neurophysiological Activity Patterns in Young People with ASD, ADHD, and ASD + ADHD.

PubMed

Shephard, Elizabeth; Tye, Charlotte; Ashwood, Karen L; Azadi, Bahar; Asherson, Philip; Bolton, Patrick F; McLoughlin, Grainne

2018-01-01

Altered power of resting-state neurophysiological activity has been associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. We compared resting-state neurophysiological power in children with ASD, ADHD, co-occurring ASD + ADHD, and typically developing controls. Children with ASD (ASD/ASD + ADHD) showed reduced theta and alpha power compared to children without ASD (controls/ADHD). Children with ADHD (ADHD/ASD + ADHD) displayed decreased delta power compared to children without ADHD (ASD/controls). Children with ASD + ADHD largely presented as an additive co-occurrence with deficits of both disorders, although reduced theta compared to ADHD-only and reduced delta compared to controls suggested some unique markers. Identifying specific neurophysiological profiles in ASD and ADHD may assist in characterising more homogeneous subgroups to inform treatment approaches and aetiological investigations.

Social Skills Training and ADHD-What Works?

PubMed

Mikami, Amori Yee; Smit, Sophie; Khalis, Adri

2017-10-30

Many children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have difficulties in their social skills and peer relationships. Because social problems exacerbate later maladjustment in ADHD populations, it is important to address this serious impairment. Although social skills training (SST) is a common intervention approach, evidence to date suggests that SST has limited efficacy, at least when provided in traditional, clinic-based settings. The current review summarizes recent advances to traditional SST approaches that may potentially enhance their efficacy. We identify two promising directions in which SST may be modified to make it more efficacious for ADHD populations. The first direction involves providing increased reinforcement and reminders of appropriate social behavior at the point of performance to youth with ADHD (e.g., in vivo, in real life peer situations as opposed to in the clinic). We note the importance of ensuring that youth with ADHD are receptive to such reminders. The second direction involves encouraging peers to be more socially accepting and inclusive of youth with ADHD. This avenue has been understudied in the literature to date. SST for children and adolescents with ADHD may be enhanced by providing more in vivo reminders and feedback at the point of performance and by making efforts to alter peers' impressions about youth with ADHD.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Obesity: Update 2016.

PubMed

Cortese, Samuele; Tessari, Luca

2017-01-01

While psychiatric comorbidities of attention-deficit/hyperactivity disorder (ADHD) have been extensively explored, less attention has been paid to somatic conditions possibly associated with this disorder. However, mounting evidence in the last decade pointed to a possible significant association between ADHD and certain somatic conditions, including obesity. This papers provides an update of a previous systematic review on the relationship between obesity and ADHD (Cortese and Vincenzi, Curr Top Behav Neurosci 9:199-218, 2012), focusing on pertinent peer-reviewed empirical papers published since 2012. We conducted a systematic search in PubMed, Ovid, and Web of Knowledge databases (search dates: from January 1st, 2012, to July 16th, 2016). We retained a total of 41 studies, providing information on the prevalence of obesity in individuals with ADHD, focusing on the rates of ADHD in individuals with obesity, or reporting data useful to gain insight into possible mechanisms underlying the putative association between ADHD and obesity. Overall, over the past 4 years, an increasing number of studies have assessed the prevalence of obesity in individuals with ADHD or the rates of ADHD in patients with obesity. Although findings are mixed across individual studies, meta-analytic evidence shows a significant association between ADHD and obesity, regardless of possible confounding factors such as psychiatric comorbidities. An increasing number of studies have also addressed possible mechanisms underlying the link between ADHD and obesity, highlighting the role, among others, of abnormal eating patterns, sedentary lifestyle, and possible common genetic alterations. Importantly, recent longitudinal studies support a causal role of ADHD in contributing to weight gain. The next generation of studies in the field should explore if and to which extent the treatment of comorbid ADHD in individuals with obesity may lead to long-term weight loss, ultimately improving their

The Association Between ADHD and Antisocial Personality Disorder (ASPD): A Review.

PubMed

Storebø, Ole Jakob; Simonsen, Erik

2016-10-01

Children with ADHD have an increased risk of later developing personality disorders and criminal behavior. The object of the present review is to analyze the associations between ADHD and antisocial personality disorder (ASPD). A review of literature was done using EMBASE, PsycINFO, and Medline databases. Eighteen prospective studies (n = 5,501) showed that ADHD with and without comorbid conduct disorder (CD) is a strong predictor for the risk of later development of antisocial personality disorder (ASPD). Some of the 13 cross-sectional/retrospective studies (n = 2,451) suggested that ADHD and CD might be a separate subtype of ADHD, that especially impulsivity in ADHD is a predictor for later development of ASPD, or that callous-unemotional traits in the ADHD children are called for a risk factor for later ASPD. There is an increased risk for children with ADHD with or without comorbid CD to develop later onset of antisocial personality disorder. © The Author(s) 2013.

Home environment: association with hyperactivity/impulsivity in children with ADHD and their non-ADHD siblings

PubMed Central

Mulligan, Aisling; Anney, Richard; Butler, Louise; O’Regan, Myra; Richardson, Thomas; Tulewicz, Edyta Maria; Fitzgerald, Michael; Gill, Michael

2011-01-01

Objective We wished to ascertain if there is an association between symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) and home environment in children with ADHD and non-ADHD siblings, controlling for other environmental measures. Method 96 children with ADHD combined type (ADHD-CT) and their siblings participated in the study. Parent and teacher Conners’ rating scales were completed and home environment was assessed using the Middle Childhood and Early Adolescent Home Observation for Measurement of the Environment (HOME). ADHD symptoms were assessed for correlation with HOME in children with ADHD-CT and non-ADHD siblings and multiple regression analysis was used to control for gender, socio-economic status, exposure to nicotine, exposure to alcohol in utero, birth weight, gestational age, pregnancy and perinatal risk factors. The presence of oppositional disorders was assessed for association with HOME score in those with ADHD-CT. The multiple regression analysis was repeated controlling for environmental factors and for oppositional disorders in those with ADHD-CT. Oppositional symptoms were assessed for correlation with HOME score in non-ADHD siblings. Results Teacher-rated hyperactive/impulsive scores correlated with HOME (r = −.27, p <.01) in children with ADHD-CT. This association remained significant when other environmental factors and oppositional disorders were controlled for. Environmental factors and gender contributed to 30% of the variance of ADHD symptoms in ADHD-CT. Parent-rated hyperactive/impulsive scores also correlated with HOME (r = −.28, p < .05) for non-ADHD siblings. An association between HOME and diagnosis of oppositional defiant disorder or CD was found for children with ADHD-CT and between HOME and oppositional symptoms in non-ADHD siblings. Conclusions The home environment has a small but significant association with hyperactive/impulsive symptoms in children with ADHD-CT and non-ADHD siblings. This association remained

Intrahippocampal Infusions of Anisomycin Produce Amnesia: Contribution of Increased Release of Norepinephrine, Dopamine, and Acetylcholine

ERIC Educational Resources Information Center

Qi, Zhenghan; Gold, Paul E.

2009-01-01

Intra-amygdala injections of anisomycin produce large increases in the release of norepinephrine (NE), dopamine (DA), and serotonin in the amygdala. Pretreatment with intra-amygdala injections of the beta-adrenergic receptor antagonist propranolol attenuates anisomycin-induced amnesia without reversing the inhibition of protein synthesis, and…

Risky decision making in adults with ADHD.

PubMed

Matthies, S; Philipsen, A; Svaldi, J

2012-09-01

Risky decision making and disadvantageous choices constitute core characteristics of patients with attention-deficit/hyperactivity disorder (ADHD). Consequences include negative psychosocial and health-related outcomes. However, risky decision making and its interrelations with emotional states in ADHD are poorly understood. Therefore, the authors investigated risky decision making without and after boredom induction in adults with and without ADHD. In study 1, ADHD patients (n = 15) and age/education matched controls (CG; n = 16) were compared on the Game of Dice Task (GDT), an established task measuring decision making in unambiguous situations. In study 2, ADHD patients (n = 14) and CG (n = 13) underwent boredom induction prior to the GDT. In study 1, ADHD patients selected the disadvantageous alternatives significantly more often than CG. In study 2, no significant group differences were found due to an increase in risky decision making in CG following the boredom induction. Even if severity of depression did not affect our results, it may be necessary to compare GDT responses in ADHD patients with and without current depression. Risk as a motor of disadvantageous decision making needs to be taken into account in therapeutic contexts as a maintenance factor of dysfunctional behaviour. The findings of study 2 are in line with postulated alterations of emotional state adjustment in ADHD. The link between decisions making and emotional regulation in ADHD needs further attention in research. Copyright © 2012 Elsevier Ltd. All rights reserved.

Association of ADHD, Tics, and Anxiety with Dopamine Transporter ("DAT1") Genotype in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Gadow, Kenneth D.; Roohi, Jasmin; DeVincent, Carla J.; Hatchwell, Eli

2008-01-01

Background: Autism spectrum disorder (ASD) is associated with high rates of psychiatric disturbance to include attention-deficit/hyperactivity disorder (ADHD), tic disorder, and anxiety disorders. The aim of the present study was to examine the association between a variable number tandem repeat (VNTR) functional polymorphism located in the…

[Dopamine receptor signaling regulates human osteoclastogenesis].

PubMed

Hanami, Kentaro; Nakano, Kazuhisa; Tanaka, Yoshiya

2013-01-01

Although the central nervous system and the neurotransmitters are known to control not only the immune system but also the homeostasis of bone mass, their pathological relevance to bone disorders remains unclear. Osteoclasts in the synovium of rheumatoid arthritis (RA) play an important role in bone destruction. It is known that increased sympathetic nervous activity increases both differentiation and function of osteoclasts, which leads to bone loss. Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. We previously reported that dopamine plays an important role in IL-6-IL-17 axis and subsequent joint destruction in RA. The major source of dopamine in the synovial tissue of RA was dendritic cells (DCs) that stored and secreted dopamine. Dopamine released by DCs bounded to D1-like dopamine receptors on T cells and induced activation of cAMP and differentiation to Th17 cells via IL-6 production We here overview the interplay among the immune system, bone metabolism and neurologic system shedding light upon dopaminergic signals upon osteoclastogenesis.

Adolescent social defeat increases adult amphetamine conditioned place preference and alters D2 dopamine receptor expression

PubMed Central

Burke, Andrew R.; Watt, Michael J.; Forster, Gina L.

2011-01-01

Components of the brain’s dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. Rats exposed to repeated social defeat in adolescence (P35–P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70). In contrast, rats experiencing foot-shock during the same developmental period exhibited amphetamine CPP levels similar to non-stressed controls. Our previous experiments suggested adolescent defeat alters dopamine activity in the mesocorticolimbic system. Furthermore, dopamine receptors have been implicated in the expression of amphetamine CPP. Therefore, we hypothesized that alteration to dopamine receptor expression in the mesocorticolimbic system may be associated with to heightened amphetamine CPP of adult rats exposed to adolescence defeat. We measured D1 and D2 dopamine receptor protein content in the medial prefrontal cortex, nucleus accumbens (NAc) and dorsal striatum following either adolescent social defeat or foot-shock stress and then adult amphetamine CPP. In controls, amphetamine CPP training reduced D2 receptor protein content in the NAc core. However, this down-regulation of NAc core D2 receptors was blocked by exposure to social defeat but not foot-shock stress in adolescence. These results suggest social defeat stress in adolescence alters the manner in which later amphetamine exposure down-regulates D2 receptors. Furthermore, persistent alterations to adult D2 receptor expression and amphetamine responses may depend on the type of stress experienced in adolescence. PMID:21933700

Differential effects of anxiety and depressive symptoms on working memory components in children and adolescents with ADHD combined type and ADHD inattentive type.

PubMed

Ferrin, Maite; Vance, Alasdair

2014-12-01

Working memory (WM) deficits have been shown to be associated with core ADHD symptoms, worse academic achievement and peer-relationship problems. Internalizing symptoms, such as anxiety and depression, have also been associated with impaired WM performance. However, the association of anxiety and depression and WM performance remains unclear for children and adolescents with ADHD. Further, it is unknown how these comorbid conditions might affect WM performance in the two main ADHD subtypes. The association of anxiety and depression and the specific components of spatial (SWM) and verbal working memory (VWM) were examined in 303 children and adolescents with ADHD, combined type (ADHD-CT) and 77 ADHD, inattentive type (ADHD-IA) compared to 128 age- and gender-matched typically developing participants. The relationship between anxiety and depression and WM was assessed using multiple linear regression analyses and separate simple regression analyses. Higher levels of anxiety/depression were associated with (1) increased between-search errors in the typically developing participants alone, (2) a better strategy performance in the ADHD-CT group, and (3) a better spatial span performance in the ADHD-IA group. VWM was equally impaired in the ADHD-CT and ADHD-IA groups, independent of the levels of anxiety and depression. The results suggest that the effects of internalizing symptoms on WM differ in typically developing children and adolescents compared to those with ADHD. Further, high levels of anxiety and depression modified WM performance differently according to the specific ADHD subtypes. This might help explain contradictory findings observed in previous studies of mixed samples of participants with ADHD-CT and ADHD-IA.

Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis.

PubMed

Cortese, Samuele; Moreira-Maia, Carlos Renato; St Fleur, Diane; Morcillo-Peñalver, Carmen; Rohde, Luis Augusto; Faraone, Stephen V

2016-01-01

Impulsivity and inattention related to attention deficit hyperactivity disorder (ADHD) may increase food intake and, consequently, weight gain. However, findings on the association between obesity/overweight and ADHD are mixed. The authors conducted a meta-analysis to estimate this association. A broad range of databases was searched through Aug. 31, 2014. Unpublished studies were also obtained. Study quality was rated with the Newcastle-Ottawa Scale. Random-effects models were used. Forty-two studies that included a total of 728,136 individuals (48,161 ADHD subjects; 679,975 comparison subjects) were retained. A significant association between obesity and ADHD was found for both children (odds ratio=1.20, 95% CI=1.05-1.37) and adults (odds ratio=1.55, 95% CI=1.32-1.81). The pooled prevalence of obesity was increased by about 70% in adults with ADHD (28.2%, 95% CI=22.8-34.4) compared with those without ADHD (16.4%, 95% CI=13.4-19.9), and by about 40% in children with ADHD (10.3%, 95% CI=7.9-13.3) compared with those without ADHD (7.4%, 95% CI=5.4-10.1). The significant association between ADHD and obesity remained when limited to studies 1) reporting odds ratios adjusted for possible confounding factors; 2) diagnosing ADHD by direct interview; and 3) using directly measured height and weight. Gender, study setting, study country, and study quality did not moderate the association between obesity and ADHD. ADHD was also significantly associated with overweight. Individuals medicated for ADHD were not at higher risk of obesity. This study provides meta-analytic evidence for a significant association between ADHD and obesity/overweight. Further research should address possible underlying mechanisms and the long-term effects of ADHD treatments on weight in individuals with both ADHD and obesity.

Executive Functioning Heterogeneity in Pediatric ADHD.

PubMed

Kofler, Michael J; Irwin, Lauren N; Soto, Elia F; Groves, Nicole B; Harmon, Sherelle L; Sarver, Dustin E

2018-04-28

Neurocognitive heterogeneity is increasingly recognized as a valid phenomenon in ADHD, with most estimates suggesting that executive dysfunction is present in only about 33%-50% of these children. However, recent critiques question the veracity of these estimates because our understanding of executive functioning in ADHD is based, in large part, on data from single tasks developed to detect gross neurological impairment rather than the specific executive processes hypothesized to underlie the ADHD phenotype. The current study is the first to comprehensively assess heterogeneity in all three primary executive functions in ADHD using a criterion battery that includes multiple tests per construct (working memory, inhibitory control, set shifting). Children ages 8-13 (M = 10.37, SD = 1.39) with and without ADHD (N = 136; 64 girls; 62% Caucasian/Non-Hispanic) completed a counterbalanced series of executive function tests. Accounting for task unreliability, results indicated significantly improved sensitivity and specificity relative to prior estimates, with 89% of children with ADHD demonstrating objectively-defined impairment on at least one executive function (62% impaired working memory, 27% impaired inhibitory control, 38% impaired set shifting; 54% impaired on one executive function, 35% impaired on two or all three executive functions). Children with working memory deficits showed higher parent- and teacher-reported ADHD inattentive and hyperactive/impulsive symptoms (BF 10  = 5.23 × 10 4 ), and were slightly younger (BF 10  = 11.35) than children without working memory deficits. Children with vs. without set shifting or inhibitory control deficits did not differ on ADHD symptoms, age, gender, IQ, SES, or medication status. Taken together, these findings confirm that ADHD is characterized by neurocognitive heterogeneity, while suggesting that contemporary, cognitively-informed criteria may provide improved precision for identifying a

Thirty-day self-reported risky driving behaviors of ADHD and non-ADHD drivers.

PubMed

Rosenbloom, Tova; Wultz, Boaz

2011-01-01

The present study aims to compare differences in reported risky driving behaviors of drivers - males and females - having and not having Attention Deficit Hyperactivity Disorder (ADHD), by using a checklist of driving behaviors based on the Driving Behavior Questionnaire (DBQ). Unlike the studies which employ the DBQ by asking the subjects to fill the questionnaire once, in this present study, the participants were asked to report their behaviors on a daily basis for 30 consequent days. The checklist included two factors of risky driving behavior: Violation and Faults. Thirty-eight drivers - 10 males and 9 females with ADHD, and 9 males and 10 females without ADHD (N-ADHD) as control groups - participated in the study. The results showed that the mean of the unsafe behaviors of ADHD was higher, i.e., less safe driving, compared to that of N-ADHD. However, a statistically significant effect was found only between male ADHD and male N-ADHD for the Faults. In order to check the effect of the length of the study, the 30 days duration of the research was divided into three consecutive periods. The reported driving habits of the female ADHD showed safer behaviors than those of the males. Unlike the findings of N-ADHD of both genders, which showed a tendency towards safer driving reports in the three periods, both genders of the ADHD showed higher rates of Faults, i.e., a decrease in safety driving reports, in the three periods. The findings suggest that ADHD drivers differ from the N-ADHD drivers in making driving mistakes, i.e., Faults, due to their lack of sustained attention, but not in making Violations. However, some of the results in the present study were not very strong. Possible explanations for this as well as methodological considerations are discussed, and further research is suggested. Copyright © 2010 Elsevier Ltd. All rights reserved.

Increased dopamine transporter function as a mechanism for dopamine hypoactivity in the adult infralimbic medial prefrontal cortex following adolescent social stress.

PubMed

Novick, Andrew M; Forster, Gina L; Hassell, James E; Davies, Daniel R; Scholl, Jamie L; Renner, Kenneth J; Watt, Michael J

2015-10-01

Being bullied during adolescence is associated with later mental illnesses characterized by deficits in cognitive tasks mediated by prefrontal cortex (PFC) dopamine (DA). Social defeat of adolescent male rats, as a model of teenage bullying victimization, results in medial PFC (mPFC) dopamine (DA) hypofunction in adulthood that is associated with increased drug seeking and working memory deficits. Increased expression of the DA transporter (DAT) is also seen in the adult infralimbic mPFC following adolescent defeat. We propose the functional consequence of this increased DAT expression is enhanced DA clearance and subsequently decreased infralimbic mPFC DA availability. To test this, in vivo chronoamperometry was used to measure changes in accumulation of the DA signal following DAT blockade, with increased DAT-mediated clearance being reflected by lower DA signal accumulation. Previously defeated rats and controls were pre-treated with the norepinephrine transporter (NET) inhibitor desipramine (20 mg/kg, ip.) to isolate infralimbic mPFC DA clearance to DAT, then administered the selective DAT inhibitor GBR-12909 (20 or 40 mg/kg, sc.). Sole NET inhibition with desipramine produced no differences in DA signal accumulation between defeated rats and controls. However, rats exposed to adolescent social defeat demonstrated decreased DA signal accumulation compared to controls in response to both doses of GBR-12909, indicating greater DAT-mediated clearance of infralimbic mPFC DA. These results suggest that protracted increases in infralimbic mPFC DAT function represent a mechanism by which adolescent social defeat stress produces deficits in adult mPFC DA activity and corresponding behavioral and cognitive dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

[ADHD and addiction: a complicated liaison].

PubMed

Matthys, F; Tremmery, S; Autrique, M; Joostens, P; Möbius, D; Stes, S; Sabbe, B G C

2012-01-01

The presence of ADHD has been linked to a 100% increase in a person's chance of developing a substance use disorder. The prevalence of childhood and adult ADHD in substance-abusing populations has been estimated to be three times higher than in the general population. In addiction centres ADHD is often unrecognized and untreated. To describe the obstacles to the diagnosis and treatment of ADHD in addicts. Using a historical approach, we analysed the evolution of the diagnostic descriptions of the two disorders, giving attention to the influence of social change and scientific research. The two disorders have developed in remarkably similar ways; people have been and still are much inclined to make moral judgments about these disorders than about other psychic disorders. Neurobiological research has added a extra dimension to the debate on topics such as impulsivity, personal responsibility and free will. It is only recently that ADHD has been recognised as having a place in addiction treatment and, as a result, there is a growing need for explanatory models.

Distinct effects of ASD and ADHD symptoms on reward anticipation in participants with ADHD, their unaffected siblings and healthy controls: a cross-sectional study.

PubMed

van Dongen, Eelco V; von Rhein, Daniel; O'Dwyer, Laurence; Franke, Barbara; Hartman, Catharina A; Heslenfeld, Dirk J; Hoekstra, Pieter J; Oosterlaan, Jaap; Rommelse, Nanda; Buitelaar, Jan

2015-01-01

Autism spectrum disorder (ASD) traits are continuously distributed throughout the population, and ASD symptoms are also frequently observed in patients with attention-deficit/hyperactivity disorder (ADHD). Both ASD and ADHD have been linked to alterations in reward-related neural processing. However, whether both symptom domains interact and/or have distinct effects on reward processing in healthy and ADHD populations is currently unknown. We examined how variance in ASD and ADHD symptoms in individuals with ADHD and healthy participants was related to the behavioural and neural response to reward during a monetary incentive delay (MID) task. Participants (mean age: 17.7 years, range: 10-28 years) from the NeuroIMAGE study with a confirmed diagnosis of ADHD (n = 136), their unaffected siblings (n = 83), as well as healthy controls (n = 105) performed an MID task in a magnetic resonance imaging (MRI) scanner. ASD and ADHD symptom scores were used as predictors of the neural response to reward anticipation and reward receipt. Behavioural responses were modeled using linear mixed models; neural responses were analysed using FMRIB's Software Library (FSL) proprietary mixed effects analysis (FLAMEO). ASD and ADHD symptoms were associated with alterations in BOLD activity during reward anticipation, but not reward receipt. Specifically, ASD scores were related to increased insular activity during reward anticipation across the sample. No interaction was found between this effect and the presence of ADHD, suggesting that ASD symptoms had no differential effect in ADHD and healthy populations. ADHD symptom scores were associated with reduced dorsolateral prefrontal activity during reward anticipation. No interactions were found between the effects of ASD and ADHD symptoms on reward processing. Variance in ASD and ADHD symptoms separately influence neural processing during reward anticipation in both individuals with (an increased risk of) ADHD and healthy

Exploring deficient emotion regulation in adult ADHD: electrophysiological evidence.

PubMed

Shushakova, Anna; Ohrmann, Patricia; Pedersen, Anya

2018-06-01

Emotional dysregulation (ED) is being increasingly recognized as a core feature of attention-deficit/hyperactivity disorder (ADHD), but the pathophysiological underpinnings remain unclear. In this study, we provide meaningful electrophysiological evidence of ED in adult patients with ADHD (n = 39) compared to healthy controls (n = 40) by exploring the electrophysiological correlates of the emotion regulation strategies reappraisal, distraction, and expressive suppression. Event-related potentials (ERPs) were recorded during passive viewing of neutral and negative images, as well as during emotion regulation. The patients with ADHD exhibited increased frontal late positive potential (LPP) amplitudes during passive viewing of the aversive images and during emotion regulation. Compared with the healthy controls, a subgroup of medication-naïve patients with ADHD (n = 25) also exhibited larger centroparietal LPP amplitudes and provided more negative ratings of the aversive and neutral images. Both the frontal and centroparietal LPP amplitudes were associated with ADHD symptom severity. However, no significant deficit in LPP modulation during emotion regulation was found. These findings strongly support the clinical observation of increased emotional responsivity toward negative stimuli and difficulty during the implementation of emotion regulation strategies and thus encourage the implementation of emotion regulation modules in the treatment of adult patients with ADHD.

Measuring impairment when diagnosing adolescent ADHD: Differentiating problems due to ADHD versus other sources.

PubMed

Vazquez, Alejandro L; H Sibley, Margaret; Campez, Mileini

2018-06-01

The DSM-5 requires clinicians to link ADHD symptoms to clinically meaningful impairments in daily life functioning. Measuring impairment during ADHD assessments may be particularly challenging in adolescence, when ADHD is often not the sole source of a youth's difficulties. Existing impairment rating scales are criticized for not specifying ADHD as the source of impairment in their instructions, leading to potential problems with rating scale specificity. The current study utilized a within subjects design (N = 107) to compare parent report of impairment on two versions of a global impairment measure: one that specified ADHD as the source of impairment (Impairment Rating Scale-ADHD) and a standard version that did not (Impairment Rating Scale). On the standard family impairment item, parents endorsed greater impairment as compared to the IRS-ADHD. This finding was particularly pronounced when parents reported high levels of parenting stress. More severe ADHD symptoms were associated with greater concordance between the two versions. Findings indicate that adolescent family related impairments reported during ADHD assessments may be due to sources other than ADHD symptoms, such as developmental maladjustment. To prevent false positive diagnoses, symptom-specific wording may optimize impairment measures when assessing family functioning in diagnostic assessments for adolescents with ADHD. Copyright © 2018 Elsevier B.V. All rights reserved.

Multisensory integration and ADHD-like traits: Evidence for an abnormal temporal integration window in ADHD.

PubMed

Panagiotidi, Maria; Overton, Paul G; Stafford, Tom

2017-11-01

Abnormalities in multimodal processing have been found in many developmental disorders such as autism and dyslexia. However, surprisingly little empirical work has been conducted to test the integrity of multisensory integration in Attention Deficit Hyperactivity Disorder (ADHD). The main aim of the present study was to examine links between symptoms of ADHD (as measured using a self-report scale in a healthy adult population) and the temporal aspects of multisensory processing. More specifically, a Simultaneity Judgement (SJ) and a Temporal Order Judgement (TOJ) task were used in participants with low and high levels of ADHD-like traits to measure the temporal integration window and Just-Noticeable Difference (JND) (respectively) between the timing of an auditory beep and a visual pattern presented over a broad range of stimulus onset asynchronies. The Point of Subjective Similarity (PSS) was also measured in both cases. In the SJ task, participants with high levels of ADHD-like traits considered significantly fewer stimuli to be simultaneous than participants with high levels of ADHD-like traits, and the former were found to have significantly smaller temporal windows of integration (although no difference was found in the PSS in the SJ or TOJ tasks, or the JND in the latter). This is the first study to identify an abnormal temporal integration window in individuals with ADHD-like traits. Perceived temporal misalignment of two or more modalities can lead to distractibility (e.g., when the stimulus components from different modalities occur separated by too large of a temporal gap). Hence, an abnormality in the perception of simultaneity could lead to the increased distractibility seen in ADHD. Copyright © 2017 Elsevier B.V. All rights reserved.

Sodium benzoate-rich beverage consumption is associated with increased reporting of ADHD symptoms in college students: a pilot investigation.

PubMed

Beezhold, Bonnie L; Johnston, Carol S; Nochta, Kathleen A

2014-04-01

Sodium benzoate, a common additive in popular beverages, has recently been linked to ADHD. This research examined the relationship between sodium benzoate-rich beverage ingestion and symptoms related to ADHD in college students. College students (N = 475) completed an anonymous survey in class in fall 2010. The survey assessed recent intake of a noninclusive list of sodium benzoate-rich beverages and ADHD-related symptoms using a validated screener. Sodium benzoate-rich beverage intake was significantly associated with ADHD-related symptoms (p = .001), and significance was retained after controlling for covariates. Students scoring ≥4 on the screener (scores that may be consistent with ADHD; n = 67) reported higher intakes (34.9 ± 4.4 servings/month) than the remainder of the sample (16.7 ± 1.1 servings/month). These data suggest that a high intake of sodium benzoate-rich beverages may contribute to ADHD-related symptoms in college students and warrants further investigation.

Rethinking a Right Hemisphere Deficit in ADHD

ERIC Educational Resources Information Center

Hale, T. Sigi; Loo, Sandra K.; Zaidel, Eran; Hanada, Grant; Macion, James; Smalley, Susan L.

2009-01-01

Introduction: Early observations from lesion studies suggested right hemisphere (RH) dysfunction in ADHD. However, a strictly right-lateralized deficit has not been well supported. An alternatively view suggests increased R greater than L asymmetry of brain function and abnormal interhemispheric interaction. If true, RH pathology in ADHD should…

The Structure and Diagnosis of Adult ADHD: An Analysis of Expanded Symptom Criteria from the Adult ADHD Clinical Diagnostic Scale (ACDS)

PubMed Central

Kessler, Ronald C.; Green, Jennifer Greif; Adler, Lenard A.; Barkley, Russell A.; Chatterji, Somnath; Faraone, Stephen V.; Finkelman, Matthew; Greenhill, Laurence L.; Gruber, Michael J.; Jewell, Mark; Russo, Leo J.; Sampson, Nancy A.; Van Brunt, David L.

2011-01-01

comparison, are more specific and consistently important predictors of DSM-IV adult ADHD despite not being in DSM-IV, suggesting that the number of executive functioning symptoms should be increased in DSM-V/ICD-11. PMID:21041618

Higher Reported Levels of Depression, Stress, and Anxiety Are Associated with Increased Endorsement of ADHD Symptoms by Postsecondary Students

ERIC Educational Resources Information Center

Harrison, Allyson G.; Alexander, Sandra J.; Armstrong, Irene T.

2013-01-01

This study examined the extent to which postsecondary students endorse symptoms of Attention Deficit/Hyperactivity Disorder (ADHD) and whether experienced level of stress, depression, or anxiety are associated with higher reporting of ADHD symptoms. Students attending a combined health and counseling service completed the Conners Adult ADHD Rating…

Handwriting in children with ADHD.

PubMed

Langmaid, Rebecca A; Papadopoulos, Nicole; Johnson, Beth P; Phillips, James G; Rinehart, Nicole J

2014-08-01

Children with ADHD-combined type (ADHD-CT) display fine and gross motor problems, often expressed as handwriting difficulties. This study aimed to kinematically characterize the handwriting of children with ADHD using a cursive letter l's task. In all, 28 boys (7-12 years), 14 ADHD-CT and 14 typically developing (TD), without developmental coordination disorder (DCD) or comorbid autism, wrote a series of four cursive letter l's using a graphics tablet and stylus. Children with ADHD-CT had more inconsistent writing size than did TD controls. In addition, ADHD-CT symptom severity, specifically inattention, predicted poorer handwriting outcomes. In a sample of children with ADHD-CT who do not have DCD or autism, subtle handwriting differences were evident. It was concluded that handwriting might be impaired in children with ADHD in a manner dependent on symptom severity. This may reflect reports of underlying motor impairment in ADHD. © 2011 SAGE Publications.

Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD.

PubMed

McLaughlin, Thomas; Blum, Kenneth; Steinberg, Bruce; Modestino, Edward J; Fried, Lyle; Baron, David; Siwicki, David; Braverman, Eric R; Badgaiyan, Rajendra D

2018-03-01

Background Addictive-like behaviors (e.g., hoarding and shopping) may be the result of the cumulative effects of dopaminergic and other neurotransmitter genetic variants as well as elevated stress levels. We, therefore, propose that dopamine homeostasis may be the preferred goal in combating such challenging and unwanted behaviors, when simple dopaminergic activation through potent agonists may not provide any resolution. Case presentation C.J. is a 38-year-old, single, female, living with her mother. She has a history of substance use disorder as well as attention deficit hyperactivity disorder, inattentive type. She had been stable on buprenorphine/naloxone combination and amphetamine, dextroamphetamine mixed salts for many years when unexpectedly she lost her job for oversleeping and not calling into work. KB200z (a pro-dopamine compound) was added to her regimen for complaints of low drive and motivation. After taking this nutraceutical for 4 weeks, she noticed a marked improvement in her mental status and many behaviors. She noted that her shopping and hoarding addictions had appreciably decreased. Furthermore, her lifelong history of terrifying lucid dreams was eliminated. Finally, she felt more in control; her locus of control shifted from external to more internal. Discussion The hypothesis is that C.J.'s reported, behavioral, and psychological benefits resulted from the pro-dopamine-regulating effect of KB220Z across the brain reward system. Conclusions This effect, we surmise, could be the result of a new dopamine balance, across C.J.'s brain reward system. Dopamine homeostasis is an effect of KB220Z seen in both animal and human placebo-controlled fMRI experiments.

Increasing Endocannabinoid Levels in the Ventral Pallidum Restore Aberrant Dopamine Neuron Activity in the Subchronic PCP Rodent Model of Schizophrenia

PubMed Central

Chen, Li; Lodge, Daniel J

2015-01-01

Background: Schizophrenia is a debilitating disorder that affects 1% of the US population. While the exogenous administration of cannabinoids such as tetrahydrocannabinol is reported to exacerbate psychosis in schizophrenia patients, augmenting the levels of endogenous cannabinoids has gained attention as a possible alternative therapy to schizophrenia due to clinical and preclinical observations. Thus, patients with schizophrenia demonstrate an inverse relationship between psychotic symptoms and levels of the endocannabinoid anandamide. In addition, increasing endocannabinoid levels (by blockade of enzymatic degradation) has been reported to attenuate social withdrawal in a preclinical model of schizophrenia. Here we examine the effects of increasing endogenous cannabinoids on dopamine neuron activity in the sub-chronic phencyclidine (PCP) model. Aberrant dopamine system function is thought to underlie the positive symptoms of schizophrenia. Methods: Using in vivo extracellular recordings in chloral hydrate–anesthetized rats, we now demonstrate an increase in dopamine neuron population activity in PCP-treated rats. Results: Interestingly, endocannabinoid upregulation, induced by URB-597, was able to normalize this aberrant dopamine neuron activity. Furthermore, we provide evidence that the ventral pallidum is the site where URB-597 acts to restore ventral tegmental area activity. Conclusions: Taken together, we provide preclinical evidence that augmenting endogenous cannabinoids may be an effective therapy for schizophrenia, acting in part to restore ventral pallidal activity. PMID:25539511

Duration-dependence of the effect of treadmill exercise on hyperactivity in attention deficit hyperactivity disorder rats.

PubMed

Ji, Eun-Sang; Kim, Chang-Ju; Park, Jun Heon; Bahn, Geon Ho

2014-04-01

Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder, and its symptoms are hyperactivity and deficits in learning and memory. Physical exercise increases dopamine synthesis and neuronal activity in various brain regions. In the present study, we investigate the duration-dependence of the treadmill exercise on hyperactivity in relation with dopamine expression in ADHD. Spontaneously hypertensive rats were used for the ADHD rats and Wistar-Kyoto rats were used for the control rats. The rats in the exercise groups were forced to run on a treadmill for 10 min, 30 min, and 60 min once daily for 28 consecutive days. For this experiment, open field test and immunohistochemistry for tyrosine hydroxylase were conducted. The present results revealed that ADHD rats showed hyperactivity, and tyrosine hydroxylase expression in the striatum and substantia nigra were decreased in ADHD rats. Treadmill exercise alleviated hyperactivity and also increased TH expression in ADHD rats. Treadmill exercise for 30 min per day showed most potent suppressing effect on hyperactivity, and this dose of treadmill exercise also most potently inhibited tyrosine hydroxylase expression. The present study suggests that treadmill exercise for 30 min once a day is the most effective therapeutic intervention for ADHD patients.

Cognitive Load Differentially Impacts Response Control in Girls and Boys with ADHD

PubMed Central

Mostofsky, Stewart H.; Rosch, Keri S.

2015-01-01

Children with attention-deficit hyperactivity disorder (ADHD) consistently show impaired response control, including deficits in response inhibition and increased intrasubject variability (ISV) compared to typically-developing (TD) children. However, significantly less research has examined factors that may influence response control in individuals with ADHD, such as task or participant characteristics. The current study extends the literature by examining the impact of increasing cognitive demands on response control in a large sample of 81children with ADHD (40 girls) and 100 TD children (47 girls), ages 8–12 years. Participants completed a simple Go/No-Go (GNG) task with minimal cognitive demands, and a complex GNG task with increased cognitive load. Results showed that increasing cognitive load differentially impacted response control (commission error rate and tau, an ex-Gaussian measure of ISV) for girls, but not boys, with ADHD compared to same-sex TD children. Specifically, a sexually dimorphic pattern emerged such that boys with ADHD demonstrated higher commission error rate and tau on both the simple and complex GNG tasks as compared to TD boys, whereas girls with ADHD did not differ from TD girls on the simple GNG task, but showed higher commission error rate and tau on the complex GNG task. These findings suggest that task complexity influences response control in children with ADHD in a sexually dimorphic manner. The findings have substantive implications for the pathophysiology of ADHD in boys versus girls with ADHD. PMID:25624066

Olfactory discrimination deficits in mice lacking the dopamine transporter or the D2 dopamine receptor.

PubMed

Tillerson, Jennifer L; Caudle, W Michael; Parent, Jack M; Gong, C; Schallert, Timothy; Miller, Gary W

2006-09-15

Previous pharmacological studies have implicated dopamine as a modulator of olfactory bulb processing. Several disorders characterized by altered dopamine homeostasis in olfaction-related brain regions display olfactory deficits. To further characterize the role of dopamine in olfactory processing, we subjected dopamine transporter knockout mice (DAT -/-) and dopamine receptor 2 knockout mice (D2 -/-) to a battery of olfactory tests. In addition to behavioral characterization, several neurochemical markers of olfactory bulb integrity and function were examined. DAT -/- mice displayed an olfactory discrimination deficit, but did not differ detectably from DAT wildtype (DAT +/+) mice in odor habituation, olfactory sensitivity, or odor recognition memory. Neurochemically, DAT -/- mice have decreased D2 receptor staining in the periglomerular layer of the olfactory bulb and increased tyrosine hydroxylase immunoreactivity compared to DAT +/+ controls. D2 -/- mice exhibited the same olfactory deficit as the DAT -/- mice, further supporting the role of dopamine at the D2 synapse in olfactory discrimination processing. The findings presented in this paper reinforce the functional significance of dopamine and more specifically the D2 receptor in olfactory discrimination and may help explain the behavioral phenotype in the DAT and D2 knockout mice.

Prevalence of ADHD symptoms across clinical stages of major depressive disorder.

PubMed

Bron, Tannetje I; Bijlenga, Denise; Verduijn, Judith; Penninx, Brenda W J H; Beekman, Aartjan T F; Kooij, J J Sandra

2016-06-01

Depression and ADHD often co-occur in clinical samples. Depression severity may be linked to ADHD symptomatology. We therefore assessed ADHD symptoms across clinical stages of major depressive disorder (MDD). We used 4-year follow-up data of the Netherlands Study of Depression and Anxiety (September 2008 until April 2011), including healthy controls, groups with remitted and current MDD (N=2053; age range 21-69 years; 66.8% females). Probable ADHD was defined as having current ADHD symptoms on the Conners Adult ADHD Rating Scale and a positive score on childhood or early-adolescent ADHD indicators. We examined ADHD symptom rates across (i) those with and without lifetime MDD, (ii) clinical characteristics of MDD including severity, course and outcomes, (iii) clinical stages of MDD. (i) The prevalence of ADHD symptoms was 0.4% in healthy controls, 5.7% in remitted MDD and 22.1% in current MDD (OR=4.5; 95% CI 3.1-6.5). (ii) ADHD symptom rates and odds were significantly increased among those with more severe depression (29.4%; OR=6.8; 95% CI 2.9-16.1), chronic depression (21.8%; OR=3.8; 95% CI 2.5-5.7), earlier age of onset of depressive symptoms (9.9%; OR=1.5; 95% CI 1.0-2.3), and comorbid anxiety disorders (29.0%; OR=3.4; 95% CI 2.0-5.7). (iii) ADHD symptom rates increased across clinical stages of MDD, up to 22.5% in chronic MDD. We used self-reports on ADHD symptoms. Also, clinical staging models have not yet been validated for mental disorders. ADHD symptoms are very common among MDD patients, especially among those in recurrent and chronic stages of MDD. Considering ADHD may be an important step forward in improving the treatment of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Neonatal exposure to estradiol valerate increases dopamine content in nigrostriatal pathway during adulthood in the rat.

PubMed

Cruz, G; Riquelme, R; Espinosa, P; Jara, P; Dagnino-Subiabre, A; Renard, G M; Sotomayor-Zárate, R

2014-05-01

Research in programming has focused in the study of stimuli that affect sensitive periods of development such as prenatal and neonatal stage. We previously showed that exposure to estradiol valerate to female rats during the first 12 h of life increased catecholamine content in ventromedial-arcuatus hypothalamus of the adult rat. However, changes in others dopaminergic circuits have not been studied. The purpose of this work was to determine the neurotransmitters changes induced by neonatal estradiol valerate (0.1 mg/50 μl s. c. per rat) administration on nigrostriatal pathway of adult female rats. Sesame oil (50 μl s. c. per rat) was administered in a control parallel group. EV-1 adult rats presented effective markers of long-term estrogenization as decreased serum levels of progesterone and a reduction in the size of estrogen-sensitive organs. In the brain, neonatal estradiol valerate administration led to a significant increase in dopamine content in striatum, substantia nigra and ventral tegmental area. With respect to the contents of dopamine metabolites, only 3-methoxytyramine content increased in substantia nigra and ventral tegmental area. In addition, the content of noradrenaline increased only in striatum. Interestingly, estrogenized rats lacked locomotor activity induced by acute dose of amphetamine (1 mg/kg i. p.). Altogether, these results show that neonatal exposure to estradiol valerate permanently modified the content of monoamine neurotransmitters in nigrostriatal pathway and amphetamine-induced locomotor activity of adult female rats. This might imply that estrogenized rats could have changes in the expression of key proteins in dopaminergic regulation, as tyrosine hydroxylase and dopamine transporter. © Georg Thieme Verlag KG Stuttgart · New York.

Ventral striatal hyperconnectivity during rewarded interference control in adolescents with ADHD.

PubMed

Ma, Ili; van Holstein, Mieke; Mies, Gabry W; Mennes, Maarten; Buitelaar, Jan; Cools, Roshan; Cillessen, Antonius H N; Krebs, Ruth M; Scheres, Anouk

2016-09-01

Attention-deficit/hyperactivity disorder (ADHD) is characterized by cognitive deficits (e.g., interference control) and altered reward processing. Cognitive control is influenced by incentive motivation and according to current theoretical models, ADHD is associated with abnormal interactions between incentive motivation and cognitive control. However, the neural mechanisms by which reward modulates cognitive control in individuals with ADHD are unknown. We used event-related functional resonance imaging (fMRI) to study neural responses during a rewarded Stroop color-word task in adolescents (14-17 years) with ADHD (n = 25; 19 boys) and healthy controls (n = 33; 22 boys). Adolescents with ADHD showed increased reward signaling within the superior frontal gyrus and ventral striatum (VS) relative to controls. Importantly, functional connectivity analyses revealed a hyperconnectivity between VS and motor control regions in the ADHD group, as a function of reward-cognitive control integration. Connectivity was associated with performance improvement in controls but not in the ADHD group, suggesting inefficient connectivity. Adolescents with ADHD show increased neural sensitivity to rewards and its interactions with interference control in VS and motor regions, respectively. The findings support theoretical models of altered reward-cognitive control integration in individuals with ADHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Paradigm shift in consciousness research: the child's self-awareness and abnormalities in autism, ADHD and schizophrenia.

PubMed

Lou, Hans C

2012-02-01

Self-awareness is a pivotal component of any conscious experience and conscious self-regulation of behaviour. A paralimbic network is active, specific and causal in self-awareness. Its regions interact by gamma synchrony. Gamma synchrony develops throughout infancy, childhood and adolescence into adulthood and is regulated by dopamine and other neurotransmitters via GABA interneurons. Major derailments of this network and self-awareness occur in developmental disorders of conscious self-regulation like autism, attention deficit hyperactivity disorder (ADHD) and schizophrenia. Recent research on conscious experience is no longer limited to the study of neural 'correlations' but is increasingly lending itself to the study of causality. This paradigm shift opens new perspectives for understanding the neural mechanisms of the developing self and the causal effects of their disturbance in developmental disorders. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, E.H. Jr.; Stein, M.A.; Krasowski, M.D.

Attention-deficit hyperactivity disorder (ADHD) has been shown to be familial and heritable, in previous studies. As with most psychiatric disorders, examination of pedigrees has not revealed a consistent Mendelian mode of transmission. The response of ADHD patients to medications that inhibit the dopamine transporter, including methylphenidate, amphetamine, pemoline, and bupropion, led us to consider the dopamine transporter as a primary candidate gene for ADHD. To avoid effects of population stratification and to avoid the problem of classification of relatives with other psychiatric disorders as affected or unaffected, we used the haplotype-based haplotype relative risk (HHRR) method to test for associationmore » between a VNTR polymorphism at the dopamine transporter locus (DAT1) and DSM-III-R-diagnosed ADHD (N = 49) and undifferentiated attention-deficit disorder (UADD) (N = 8) in trios composed of father, mother, and affected offspring. HHRR analysis revealed significant association between ADHS/UADD and the 480-bp DAT1 allele (X{sup 2} 7.51, 1 df, P = .006). When cases of UADD were dropped from the analysis, similar results were found (X{sup 2} 7.29, 1 df, P = .007). If these findings are replicated, molecular analysis of the dopamine transporter gene may identify mutations that increase susceptibility to ADHD/UADD. Biochemical analysis of such mutations may lead to development of more effective therapeutic interventions. 36 refs., 4 tabs.« less

Can we prevent smoking in children with ADHD: a review of the literature.

PubMed

Modesto-Lowe, Vania; Danforth, Jeffrey S; Neering, Carla; Easton, Caroline

2010-04-01

Cigarette smokers pose public health challenges and are over-represented among individuals with attention deficit hyperactivity disorder (ADHD). This article reviews the link between ADHD and smoking across various developmental stages with an emphasis on factors that interact with ADHD (e.g., comorbidity with conduct disorder) to modify risk for nicotine dependence from childhood through adulthood. A literature review was conducted for 2000-2009 using key words ADHD, smoking, adolescents, adulthood. Childhood, adolescent and adult ADHD all increase risk for smoking. Childhood ADHD increases risk for early smoking during adolescence, particularly if untreated and in combination with conduct disorder (CD). Attention deficit hyperactivity disorder in adolescence increases the risk of daily smoking in adulthood. These findings underscore the importance of smoking prevention for children and adolescents with ADHD and other risk factors (e.g., CD). Pharmacotherapy for ADHD offers promise to lower the risk of smoking during adolescence. Preventing the development of conduct disorder (CD) or controlling the symptoms of CD is also possible and may reduce smoking and associated outcomes.

Enhanced dopamine D2 autoreceptor function in the adult prefrontal cortex contributes to dopamine hypoactivity following adolescent social stress.

PubMed

Weber, Matthew A; Graack, Eric T; Scholl, Jamie L; Renner, Kenneth J; Forster, Gina L; Watt, Michael J

2018-06-14

Adult psychiatric disorders characterized by cognitive deficits reliant on prefrontal cortex (PFC) dopamine are promoted by teenage bullying. Similarly, male Sprague-Dawley rats exposed to social defeat in mid-adolescence (P35-39) show impaired working memory in adulthood (P56-70), along with decreased medial PFC (mPFC) dopamine activity that results in part from increased dopamine transporter-mediated clearance. Here, we determined if dopamine synthesis and D2 autoreceptor-mediated inhibition of dopamine release in the adult mPFC are also enhanced by adolescent defeat to contribute to later dopamine hypofunction. Control and previously defeated rats did not differ in either DOPA accumulation following amino acid decarboxylase inhibition (NSD-1015 100 mg/kg ip.) or total/phosphorylated tyrosine hydroxylase protein expression, suggesting dopamine synthesis in the adult mPFC is not altered by adolescent defeat. However, exposure to adolescent defeat caused greater decreases in extracellular dopamine release (measured using in vivo chronoamperometry) in the adult mPFC upon local infusion of the D2 receptor agonist quinpirole (3 nM), implying greater D2 autoreceptor function. Equally enhanced D2 autoreceptor-mediated inhibition of dopamine release is seen in the adolescent (P40 or P49) mPFC, which declines in control rats by adulthood. However, this developmental decrease in autoreceptor function is absent following adolescent defeat, suggesting retention of an adolescent-like phenotype into adulthood. Current and previous findings indicate adolescent defeat decreases extracellular dopamine availability in the adult mPFC via both enhanced inhibition of dopamine release and increased dopamine clearance, which may be viable targets for improving treatment of cognitive deficits seen in neuropsychiatric disorders promoted by adolescent stress. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Institutional Care and Iron Deficiency Increase ADHD Symptomology and Lower IQ 2.5-5 Years Post-Adoption

ERIC Educational Resources Information Center

Doom, Jenalee R.; Georgieff, Michael K.; Gunnar, Megan R.

2015-01-01

Increased ADHD symptomology and lower IQ have been reported in internationally adopted (IA) children compared to non-adopted peers (Hostinar, Stellern, Schaefer, Carlson & Gunnar, 2012; Kreppner, O'Connor & Rutter, 2001). However, it is unclear whether these outcomes are due to institutional deprivation specifically or to co-occurring…

Are the performance overestimates given by boys with ADHD self-protective?

PubMed

Ohan, Jeneva L; Johnston, Charlotte

2002-06-01

Tested the self-protective hypothesis that boys with attention deficit hyperactivity disorder (ADHD) overestimate their performance to protect a positive self-image. We examined the impact of performance feedback on the social and academic performance self-perceptions of 45 boys with and 43 boys without ADHD ages 7 to 12. Consistent with the self-protective hypothesis, positive feedback led to increases in social performance estimates in boys without ADHD but to decreases in estimates given by boys with ADHD. This suggests that boys with ADHD can give more realistic self-appraisals when their self-image has been bolstered. In addition, social performance estimates in boys with ADHD were correlated with measures of self-esteem and positive presentation bias. In contrast, for academic performance estimates, boys in both groups increased their performance estimates after receiving positive versus average or no feedback, and estimates were not correlated with self-esteem or social desirability for boys with ADHD. We conclude that the self-protective hypothesis can account for social performance overestimations given by boys with ADHD but that other factors may better account for their academic performance overestimates.

Variability of attention processes in ADHD: observations from the classroom.

PubMed

Rapport, Mark D; Kofler, Michael J; Alderson, R Matt; Timko, Thomas M; Dupaul, George J

2009-05-01

Classroom- and laboratory-based efforts to study the attentional problems of children with ADHD are incongruent in elucidating attentional deficits; however, none have explored within- or between-minute variability in the classroom attentional processing in children with ADHD. High and low attention groups of ADHD children defined via cluster analysis, and 36 typically developing children, were observed while completing academic assignments in their general education classrooms. All children oscillated between attentive and inattentive states; however, children in both ADHD groups switched states more frequently and remained attentive for shorter durations relative to typically developing children. Overall differences in attention and optimal ability to maintain attention among the groups are consistent with laboratory studies of increased ADHD-related interindividual and intergroup variability but inconsistent with laboratory results of increased intra-individual variability and attention decrements over time.

Associations of sleep disturbance with ADHD: implications for treatment.

PubMed

Hvolby, Allan

2015-03-01

Attention-deficit/hyperactivity disorder (ADHD) is commonly associated with disordered or disturbed sleep. The relationships of ADHD with sleep problems, psychiatric comorbidities and medications are complex and multidirectional. Evidence from published studies comparing sleep in individuals with ADHD with typically developing controls is most concordant for associations of ADHD with: hypopnea/apnea and peripheral limb movements in sleep or nocturnal motricity in polysomnographic studies; increased sleep onset latency and shorter sleep time in actigraphic studies; and bedtime resistance, difficulty with morning awakenings, sleep onset difficulties, sleep-disordered breathing, night awakenings and daytime sleepiness in subjective studies. ADHD is also frequently coincident with sleep disorders (obstructive sleep apnea, peripheral limb movement disorder, restless legs syndrome and circadian-rhythm sleep disorders). Psychostimulant medications are associated with disrupted or disturbed sleep, but also 'paradoxically' calm some patients with ADHD for sleep by alleviating their symptoms. Long-acting formulations may have insufficient duration of action, leading to symptom rebound at bedtime. Current guidelines recommend assessment of sleep disturbance during evaluation of ADHD, and before initiation of pharmacotherapy, with healthy sleep practices the first-line option for addressing sleep problems. This review aims to provide a comprehensive overview of the relationships between ADHD and sleep, and presents a conceptual model of the modes of interaction: ADHD may cause sleep problems as an intrinsic feature of the disorder; sleep problems may cause or mimic ADHD; ADHD and sleep problems may interact, with reciprocal causation and possible involvement of comorbidity; and ADHD and sleep problems may share a common underlying neurological etiology.

Impact of attention-deficit/hyperactivity disorder (ADHD) treatment on smoking cessation intervention in ADHD smokers: a randomized, double-blind, placebo-controlled trial.

PubMed

Winhusen, Theresa M; Somoza, Eugene C; Brigham, Gregory S; Liu, David S; Green, Carla A; Covey, Lirio S; Croghan, Ivana T; Adler, Lenard A; Weiss, Roger D; Leimberger, Jeffrey D; Lewis, Daniel F; Dorer, Emily M

2010-12-01

High smoking rates in adults with attention-deficit/hyperactivity disorder (ADHD) and nicotine's amelioration of ADHD suggest that effective ADHD treatment might facilitate abstinence in smokers with ADHD. The present study evaluated if using osmotic-release oral system methylphenidate (OROS-MPH) to treat ADHD enhances response to smoking cessation treatment in smokers with ADHD. A randomized, double-blind, placebo-controlled, 11-week trial with a 1-month follow-up was conducted at 6 clinical sites between December 2005 and January 2008. Adults (aged 18-55 years) meeting DSM-IV criteria for ADHD and interested in quitting smoking were randomly assigned to OROS-MPH titrated to 72 mg/d (n = 127) or placebo (n = 128). All participants received brief weekly individual smoking cessation counseling for 11 weeks and 21 mg/d nicotine patches starting on the smoking quit day (day 27) through study week 11. Outcome measures included prolonged smoking abstinence and DSM-IV ADHD Rating Scale (ADHD-RS) score. Of 255 randomly assigned participants, 204 (80%) completed the trial. Prolonged abstinence rates, 43.3% and 42.2%, for the OROS-MPH and placebo groups, respectively, did not differ significantly (OR = 1.1; 95% CI, 0.63-1.79; P = .81). Relative to placebo, OROS-MPH evidenced a greater reduction in DSM-IV ADHD-RS score (P < .0001) and in cigarettes per day during the post-quit phase (P = .016). Relative to placebo, OROS-MPH increased blood pressure and heart rate to a statistically, but not clinically, significant degree (P < .05); medication discontinuation did not differ significantly between treatments. Treatment for ADHD did not improve smoking cessation success; OROS-MPH, relative to placebo, effectively treated ADHD and was safe and generally well tolerated in this healthy sample of adult ADHD smokers. clinical trials.gov Identifier: NCT00253747. © Copyright 2010 Physicians Postgraduate Press, Inc.

Comorbidity in ADHD: implications for research, practice, and DSM-V.

PubMed

Jensen, P S; Martin, D; Cantwell, D P

1997-08-01

Since the introduction of DSM-III/III-R, clinicians and investigators have shown increasing interest in the study of conditions comorbid with attention-deficit hyperactivity disorder (ADHD). Better understanding ADHD comorbidity patterns is needed to guide treatment, research and future classification approaches. The ADHD literature from the past 15 years was reviewed to (1) explore the most prevalent patterns of ADHD comorbidity; (2) examine the correlates and longitudinal predictors of comorbidity; and (3) determine the extent to which comorbid patterns convey unique information concerning ADHD etiology, treatment and outcomes. To identify potential new syndromes, the authors examined comorbid patterns based on eight validational criteria. The largest available body of literature concerned the comorbidity with ADHD and conduct disorder/aggression, with a substantially smaller amount of data concerning other comorbid conditions. In many areas the literature was sparse, and pertinent questions concerning comorbidity patterns remain unexplored. Nonetheless available data warrant the delineation of two new subclassifications of ADHD: (1) ADHD aggressive subtype, and (2) ADHD, anxious subtype. Additional studies of the frequency of comorbidity and associated factors are greatly needed to include studies of differential effects of treatment of children with various comorbid ADHD disorders, as well as of ADHD children who differ on etiological factors.

Life Span Studies of ADHD-Conceptual Challenges and Predictors of Persistence and Outcome.

PubMed

Caye, Arthur; Swanson, James; Thapar, Anita; Sibley, Margaret; Arseneault, Louise; Hechtman, Lily; Arnold, L Eugene; Niclasen, Janni; Moffitt, Terrie; Rohde, Luis Augusto

2016-12-01

There is a renewed interest in better conceptualizing trajectories of attention-deficit/hyperactivity disorder (ADHD) from childhood to adulthood, driven by an increased recognition of long-term impairment and potential persistence beyond childhood and adolescence. This review addresses the following major issues relevant to the course of ADHD in light of current evidence from longitudinal studies: (1) conceptual and methodological issues related to measurement of persistence of ADHD, (2) estimates of persistence rate from childhood to adulthood and its predictors, (3) long-term negative outcomes of childhood ADHD and their early predictors, and (4) the recently proposed new adult-onset ADHD. Estimates of persistence vary widely in the literature, and diagnostic criteria, sample characteristics, and information source are the most important factors explaining variability among studies. Evidence indicates that ADHD severity, comorbid conduct disorder and major depressive disorder, and treatment for ADHD are the main predictors of ADHD persistence from childhood to adulthood. Comorbid conduct disorder and ADHD severity in childhood are the most important predictors of adverse outcomes in adulthood among children with ADHD. Three recent population studies suggested the existence of a significant proportion of individuals who report onset of ADHD symptoms and impairments after childhood. Finally, we highlight areas for improvement to increase our understanding of ADHD across the life span.

Dopamine Gene Profiling to Predict Impulse Control and Effects of Dopamine Agonist Ropinirole.

PubMed

MacDonald, Hayley J; Stinear, Cathy M; Ren, April; Coxon, James P; Kao, Justin; Macdonald, Lorraine; Snow, Barry; Cramer, Steven C; Byblow, Winston D

2016-07-01

Dopamine agonists can impair inhibitory control and cause impulse control disorders for those with Parkinson disease (PD), although mechanistically this is not well understood. In this study, we hypothesized that the extent of such drug effects on impulse control is related to specific dopamine gene polymorphisms. This double-blind, placebo-controlled study aimed to examine the effect of single doses of 0.5 and 1.0 mg of the dopamine agonist ropinirole on impulse control in healthy adults of typical age for PD onset. Impulse control was measured by stop signal RT on a response inhibition task and by an index of impulsive decision-making on the Balloon Analogue Risk Task. A dopamine genetic risk score quantified basal dopamine neurotransmission from the influence of five genes: catechol-O-methyltransferase, dopamine transporter, and those encoding receptors D1, D2, and D3. With placebo, impulse control was better for the high versus low genetic risk score groups. Ropinirole modulated impulse control in a manner dependent on genetic risk score. For the lower score group, both doses improved response inhibition (decreased stop signal RT) whereas the lower dose reduced impulsiveness in decision-making. Conversely, the higher score group showed a trend for worsened response inhibition on the lower dose whereas both doses increased impulsiveness in decision-making. The implications of the present findings are that genotyping can be used to predict impulse control and whether it will improve or worsen with the administration of dopamine agonists.

Current issues around the pharmacotherapy of ADHD in children and adults.

PubMed

Meijer, Willemijn M; Faber, Adrianne; van den Ban, Els; Tobi, Hilde

2009-10-01

New drugs and new formulations enter the growing market for ADHD medication. The growing awareness of possible persistence of ADHD impairment beyond childhood and adolescence resulting in increased pharmacotherapy of ADHD in adults, is also a good reason for making an inventory of the what is generally known about pharmacotherapy in ADHD. To discuss current issues in the possible pharmacotherapy treatment of ADHD in children, adolescents and adults with respect to the position of pharmacotherapy in ADHD treatment guidelines, the pharmacoepidemiological trends, and current concerns about the drugs used. A search of the literature with an emphasis on the position of pharmacotherapy in ADHD treatment guidelines, the pharmacoepidemiological trends, and current concerns about the drugs used in pharmacotherapy. According to the guidelines, the treatment of ADHD in children consists of psychosocial interventions in combination with pharmacotherapy when needed. Stimulants are the first-choice drugs in the pharmacological treatment of ADHD in children despite a number of well known and frequently reported side effects like sleep disorders and loss of appetite. With regard to the treatment of adults, stimulant treatment was recommended as the first-choice pharmacotherapy in the single guideline available. Both in children and adults, there appears to be an additional though limited role for the nonadrenergic drug atomoxetine. The increase of ADHD medication use, in children, adolescents and in adults, can not only be interpreted as a sign of overdiagnosis of ADHD. Despite the frequent use of stimulants, there is still a lack of clarity on the effects of long-term use on growth and nutritional status of children. Cardiovascular effects of both stimulants and atomoxetine are rare but can be severe. The literature suggests that atomoxetine may be associated with suicidal ideation in children. Although pharmacotherapy is increasing common in the treatment of ADHD in both

IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

PubMed

Akirov, Amit; Greenman, Yona; Glaser, Benjamin; S'chigol, Irena; Mansiterski, Yossi; Eizenberg, Yoav; Shraga-Slutzky, Ilana; Shimon, Ilan

2018-05-04

Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

Motives underlying smoking in college students with ADHD.

PubMed

Murphy, Kerrie Glass; Flory, Kate

2017-05-01

The positive association between attention deficit hyperactivity disorder (ADHD) symptoms and smoking in youth has been well documented. Less research has examined why individuals with ADHD, particularly college students, are at increased risk for smoking. This longitudinal study examined whether smoking motives [cognitive enhancement, tolerance, negative reinforcement (smoking to reduce negative affect or stress), craving, social influences, and weight control] helped to explain the relation between ADHD symptoms (inattention and hyperactivity/impulsivity) and cigarette smoking among college students. Participants were 889 undergraduates (21% men) and their parents who completed online surveys at the beginning and end of the Fall semester regarding their smoking behaviors, ADHD symptoms, and smoking motives. Structural equation modeling was used to analyze data and answer research questions. Nineteen percent of students reported smoking, while 20% reported one or more inattentive symptoms, 35% reported one or more hyperactive/impulsive symptoms, and 3.3% met criteria for ADHD. All smoking motives significantly moderated the relation between inattentive symptoms and smoking, while most smoking motives (negative reinforcement, tolerance, craving, cognitive enhancement, and weight control) moderated the link between hyperactive/impulsive symptoms and smoking. Results remained significant after controlling for stimulant medication use and conduct disorder symptoms. Conclusions/Importance. Addressing negative reinforcement, craving, social influences, and tolerance in prevention and intervention efforts on college campuses may reduce smoking. Results also highlight the importance of assessing a range of ADHD symptoms in college students as ADHD symptoms, even at subthreshold levels, were associated with increased smoking rates among college students.

Increased risk of developing psychiatric disorders in children with attention deficit and hyperactivity disorder (ADHD) receiving sensory integration therapy: a population-based cohort study.

PubMed

Tzang, Ruu-Fen; Chang, Yue-Cune; Kao, Kai-Liang; Huang, Yu-Hsin; Huang, Hui-Chun; Wang, Yu-Chiao; Muo, Chih-Hsin; Wu, Shu-I; Sung, Fung-Chang; Stewart, Robert

2018-06-05

Parents of children with attention deficit hyperactivity disorder (ADHD) have been found to prefer sensory integration (SI) training rather than guideline-recommended ADHD treatment. This study investigated whether SI intervention for children with ADHD was associated with a reduced risk of subsequent mental disorders. From children < 8-years-old newly diagnosed with ADHD in a nationwide population-based dataset, we established a SI cohort and a non-SI cohort (N =  1945) matched by propensity score. Incidence and hazard ratios of subsequent psychiatric disorders were compared after a maximum follow-up of 9 years. The incidence of psychiatric disorders was 1.4-fold greater in the SI cohort, with an adjusted hazard ratio of 1.41 (95% confidence interval 1.20-1.67), comparing to the non-SI cohort. Risks were elevated for emotional disturbances, conduct disorders, and adjustment disorders independent of age, gender, or comorbidity. Among children with only psychosocial intervention, the incidence of psychiatric disorders was 3.5-fold greater in the SI cohort than in the non-SI cohort. To our knowledge, this is the first study to report an increased risk of developing psychiatric disorders for children with ADHD who received SI compared to those who did not. Potential adverse effects of SI for ADHD children should be carefully examined and discussed before practice.

DSM-5 changes enhance parent identification of symptoms in adolescents with ADHD.

PubMed

Sibley, Margaret H; Kuriyan, Aparajita B

2016-08-30

This study evaluates the impact of the DSM-5 ADHD symptom wording changes on symptom endorsement among adolescents with ADHD. Parents of adolescents with systematically diagnosed DSM-IV-TR ADHD (N=78) completed counterbalanced DSM-IV-TR and DSM-5 ADHD symptom checklists in a single sitting. General linear models were conducted to evaluate whether the new DSM-5 symptom descriptors influenced the total number of ADHD symptoms and overall ADHD symptom severity endorsed by parents, how demographic factors were associated with noted changes in symptom endorsement when moving to the DSM-5, and which DSM ADHD items displayed notable changes in endorsement rates under the new wording. On average, parents identified 1.15 additional symptoms of ADHD in adolescents when moving from the DSM-IV-TR to the DSM-5. Increased symptom identification was not specific to age, sex, ethnicity, race, or socioeconomic status. Over half of the sample experienced increased symptom endorsement when changing texts (59.0%). Under the new DSM-5 wording, four symptoms had statistically significant endorsement increases (range: 11.2-16.7%): difficulty sustaining attention, easily distracted, difficulty organizing tasks and activities, and does not seem to listen. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Video game addiction, ADHD symptomatology, and video game reinforcement.

PubMed

Mathews, Christine L; Morrell, Holly E R; Molle, Jon E

2018-06-06

Up to 23% of people who play video games report symptoms of addiction. Individuals with attention deficit hyperactivity disorder (ADHD) may be at increased risk for video game addiction, especially when playing games with more reinforcing properties. The current study tested whether level of video game reinforcement (type of game) places individuals with greater ADHD symptom severity at higher risk for developing video game addiction. Adult video game players (N = 2,801; Mean age = 22.43, SD = 4.70; 93.30% male; 82.80% Caucasian) completed an online survey. Hierarchical multiple linear regression analyses were used to test type of game, ADHD symptom severity, and the interaction between type of game and ADHD symptomatology as predictors of video game addiction severity, after controlling for age, gender, and weekly time spent playing video games. ADHD symptom severity was positively associated with increased addiction severity (b = .73 and .68, ps < 0.001). Type of game played or preferred the most was not associated with addiction severity, ps > .05. The relationship between ADHD symptom severity and addiction severity did not depend on the type of video game played or preferred most, ps > .05. Gamers who have greater ADHD symptom severity may be at greater risk for developing symptoms of video game addiction and its negative consequences, regardless of type of video game played or preferred most. Individuals who report ADHD symptomatology and also identify as gamers may benefit from psychoeducation about the potential risk for problematic play.

ADHD: Tips to Try

MedlinePlus

... Staying Safe Videos for Educators Search English Español ADHD: Tips to Try KidsHealth / For Teens / ADHD: Tips to Try Print en español TDAH: Consejos que puedes probar ADHD , short for attention deficit hyperactivity disorder , is a ...

Dopamine D2 receptors mediate the increase in reinstatement of the conditioned rewarding effects of cocaine induced by acute social defeat.

PubMed

Reguilón, Marina Daiana; Montagud-Romero, Sandra; Ferrer-Pérez, Carmen; Roger-Sánchez, Concepción; Aguilar, María Asunción; Miñarro, José; Rodríguez-Arias, Marta

2017-03-15

Social stress modifies the activity of brain areas involved in the rewarding effects of psychostimulants, inducing neuroadaptations in the dopaminergic mesolimbic system and modifying the sensitivity of dopamine receptors. In the present study we evaluated the effect of the dopamine D 1 - and D 2 -like receptor antagonists (SCH23390 and raclopride, respectively) on the short-time effects of acute social defeat (ASD). Male OF1 mice were socially defeated before each conditioning session of the conditioned place preference (CPP) induced by 1mg/kg or 25mg/kg of cocaine plus the corresponding dopamine antagonist. A final experiment was designed to evaluate the effect of the dopamine antagonists on the CPP induced by 3mg/kg of cocaine with or without a stress experience. Mice exposed to ASD showed an increase in reinstatement of the conditioned reinforcing effects of cocaine that was blocked by all of the dopamine receptor antagonists. Blockade of dopamine D 2 -like receptors with raclopride specifically prevented the effects of stress without affecting the rewarding properties of cocaine. However, SCH23390 inhibited cocaine-induced preference in the control groups and even induced aversion in defeated mice conditioned with the lower dose of cocaine. Moreover, the lowest dose of SCH23390 blocked the rewarding effects of 3mg/kg of cocaine-induced CPP. Our results confirm that the dopamine D 2 receptor is involved in the short-term effects of ASD on the rewarding effects of cocaine. The dopamine D 1 receptor is clearly involved in the rewarding effects of cocaine, but its role in the effects of ASD remains to be demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

Risk factors of autistic symptoms in children with ADHD.

PubMed

Kröger, Anne; Hänig, Susann; Seitz, Christiane; Palmason, Haukur; Meyer, Jobst; Freitag, Christine M

2011-12-01

Autistic symptoms are frequently observed in children with attention-deficit/hyperactivity disorder (ADHD), but their etiology remains unclear. The main aim of this study was to describe risk factors for increased autistic symptoms in children with ADHD without an autism or autism-spectrum diagnosis. Comorbid psychiatric disorders, developmental delay, current medication, prenatal biological and postnatal psychosocial risk factors as well as parental autistic traits were assessed in 205 children with ADHD. Linear regression models identified maternal autistic traits, current familial risk factors and hyperactive symptoms as predictors of autistic symptoms in children with ADHD. Findings are indicative of possible genetic as well as environmental risk factors mediating autistic symptoms in children with ADHD. An additional validity analysis by ROC, area under the curve (AUC), suggested a cut-off of 11 to differentiate between ADHD and high-functioning ASD by the Social Communication Questionnaire (SCQ).

Peripheral Administration of Ethanol Results in a Correlated Increase in Dopamine and Serotonin Within the Posterior Ventral Tegmental Area

PubMed Central

Deehan, Gerald A.; Knight, Christopher P.; Waeiss, R. Aaron; Engleman, Eric A.; Toalston, Jamie E.; McBride, William J.; Hauser, Sheketha R.; Rodd, Zachary A.

2016-01-01

Aims Two critical neurotransmitter systems regulating ethanol (EtOH) reward are serotonin (5-HT) and dopamine (DA). Within the posterior ventral tegmental area (pVTA), 5-HT receptors have been shown to regulate DA neuronal activity. Increased pVTA neuronal activity has been linked to drug reinforcement. The current experiment sought to determine the effect of EtOH on 5-HT and DA levels within the pVTA. Methods Wistar rats were implanted with cannula aimed at the pVTA. Neurochemical levels were determined using standard microdialysis procedures with concentric probes. Rats were randomly assigned to one of the five groups (n = 41; 7–9 per group) that were treated with 0–3.0 g/kg EtOH (intraperitoneally). Results Ethanol produced increased extracellular DA levels in the pVTA that resembled an inverted U-shape dose–response curve with peak levels (~200% of baseline) at the 2.25 g/kg dose. The increase in DA levels was observed for an extended period of time (~100 minutes). The effects of EtOH on extracellular 5-HT levels in the pVTA also resembled an inverted U-shape dose–response curve. However, increased 5-HT levels were only observed during the initial post-injection sample. The increases in extracellular DA and 5-HT levels were significantly correlated. Conclusion The data indicate intraperitoneal EtOH administration stimulated the release of both 5-HT and DA within the pVTA, the levels of which were significantly correlated. Overall, the current findings suggest that the ability of EtOH to stimulate DA activity within the mesolimbic system may be modulated by increases in 5-HT release within the pVTA. Short summary Two critical neurotransmitter systems regulating ethanol reward are serotonin and dopamine. The current experiment determined that intraperitoneal ethanol administration increased serotonin and dopamine levels within the pVTA (levels were significantly correlated). The current findings suggest the ability of EtOH to stimulate serotonin and

Reappraisal of abnormal EEG findings in children with ADHD: on the relationship between ADHD and epileptiform discharges.

PubMed

Kanazawa, Osamu

2014-12-01

Attention-deficit hyperactivity disorder is suggested to be closely related to epilepsy. A recent large-scale study revealed that ADHD in children is often accompanied by epilepsy. In Japan, methylphenidate (MPH) as a sustained-action tablet and atomoxetine (ATX) became commercially available as medications for children recently. Since then, the number of prescriptions of both medicines has increased rapidly. Methylphenidate, as a psychostimulant, has been a source of concern because of the perceived lowered threshold for convulsions in children. Based on this background, reappraisal of EEG findings in children with ADHD is important in order to detect indications of potential comorbid epilepsy and to investigate the developmental mechanisms of the neurophysiological manifestations in patients with ADHD. EEG findings in children newly diagnosed with ADHD and their relationship with clinical findings were investigated. The author evaluated 208 patients with ADHD newly diagnosed between 2008 and 2013. Of these, there were 145 patients for whom EEG findings were obtained along with a clinical follow-up for at least three months. Patients with IQ<70 were excluded in order to obtain a homogenous group of patients with ADHD. The male-to-female ratio was 130:15, and the age range was between 5 years, 9 months and 19 years, 9 months, with mean age of 11 years, 4 months. The results revealed that about half (48.3%) of the children with ADHD had abnormal EEG findings and that 22.1% of them had epileptiform discharges. Patients without comorbidity of autism spectrum disorder (ore homogenous group with ADHD) were especially likely to show abnormal EEG findings (51.0%) including epileptiform discharges (24.5%). Afebrile seizures, that is, epileptic seizures, occurred in a boy three days after commencement of administration with MPH as a sustained-action tablet. In four patients with a past history of epilepsy, neither relapse of EEG abnormality nor epileptic seizures were

Attention-Deficit/Hyperactivity Disorder (ADHD): Interaction between socioeconomic status and parental history of ADHD determines prevalence.

PubMed

Rowland, Andrew S; Skipper, Betty J; Rabiner, David L; Qeadan, Fares; Campbell, Richard A; Naftel, A Jack; Umbach, David M

2018-03-01

Many studies have reported a higher prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) among disadvantaged populations, but few have considered how parental history of ADHD might modify that relationship. We evaluated whether the prevalence of ADHD varies by socioeconomic status (SES) and parental history of ADHD in a population-sample of elementary school children age 6-14 years. We screened all children in grades 1-5 in 17 schools in one North Carolina (U.S.) county for ADHD using teacher rating scales and 1,160 parent interviews, including an ADHD structured interview (DISC). We combined parent and teacher ratings to determine DSM-IV ADHD status. Data analysis was restricted to 967 children with information about parental history of ADHD. SES was measured by family income and respondent education. We found an interaction between family income and parental history of ADHD diagnosis (p = .016). The SES gradient was stronger in families without a parental history and weaker among children with a parental history. Among children without a parental history of ADHD diagnosis, low income children had 6.2 times the odds of ADHD (95% CI 3.4-11.3) as high income children after adjusting for covariates. Among children with a parental history, all had over 10 times the odds of ADHD as high income children without a parental history but the SES gradient between high and low income children was less pronounced [odds ratio (OR) = 1.4, 95% CI 0.6-3.5]. Socioeconomic status and parental history of ADHD are each strong risk factors for ADHD that interact to determine prevalence. More research is needed to dissect the components of SES that contribute to risk of ADHD. Future ADHD research should evaluate whether the strength of other environmental risk factors vary by parental history. Early identification and interventions for children with low SES or parental histories of ADHD should be explored. © 2017 Association for Child and Adolescent Mental Health.

Health Behaviors, Physical Health, and Health Care Utilization in Children With ADHD.

PubMed

Park, Se Jin; Jang, Hyesue; Lee, Yeeun; Kim, Chul Eung; Park, Subin

2018-05-01

To compare health behaviors, physical health outcomes, and health care utilization between children with and without ADHD. In this cross-sectional study, we obtained data for children with and without ADHD from the Korean National Health and Nutrition Examination Survey. To investigate the association between ADHD and health outcomes, we estimated the adjusted prevalence ratios (APRs) in these groups. Among 10,838 children aged 7 to 18 years with and without ADHD, those with ADHD had significantly higher APRs for overall health problems, physical illness, and injuries than those without ADHD. Despite having health care needs, children with ADHD were less likely than those without ADHD to use health care services. However, there were no significant associations between most health behaviors and ADHD. Increased efforts are needed to provide quality health care services to address the medical conditions of children with ADHD and to enhance their health care utilization when needed.

Transcranial direct-current stimulation increases extracellular dopamine levels in the rat striatum

PubMed Central

Tanaka, Tomoko; Takano, Yuji; Tanaka, Satoshi; Hironaka, Naoyuki; Kobayashi, Kazuto; Hanakawa, Takashi; Watanabe, Katsumi; Honda, Manabu

2013-01-01

Background: Transcranial direct-current stimulation (tDCS) is a non-invasive procedure that achieves polarity-dependent modulation of neuronal membrane potentials. It has recently been used as a functional intervention technique for the treatment of psychiatric and neurological diseases; however, its neuronal mechanisms have not been fully investigated in vivo. Objective/Hypothesis: To investigate whether the application of cathodal or anodal tDCS affects extracellular dopamine and serotonin levels in the rat striatum. Methods: Stimulation and in vivo microdialysis were carried out under urethane anesthesia, and microdialysis probes were slowly inserted into the striatum. After the collection of baseline fractions in the rat striatum, cathodal or anodal tDCS was applied continuously for 10 min with a current intensity of 800 μA from an electrode placed on the skin of the scalp. Dialysis samples were collected every 10 min until at least 400 min after the onset of stimulation. Results: Following the application of cathodal, but not anodal, tDCS for 10 min, extracellular dopamine levels increased for more than 400 min in the striatum. There were no significant changes in extracellular serotonin levels. Conclusion: These findings suggest that tDCS has a direct and/or indirect effect on the dopaminergic system in the rat basal ganglia. PMID:23596399

State Variation in Increased ADHD Prevalence: Links to NCLB School Accountability and State Medication Laws.

PubMed

Fulton, Brent D; Scheffler, Richard M; Hinshaw, Stephen P

2015-10-01

The study's objective was to investigate whether attention-deficit hyperactivity disorder (ADHD) diagnoses from 2003 to 2011 were associated with either public school consequential accountability reforms initiated by the No Child Left Behind (NCLB) Act, particularly for low-income children, or with state psychotropic medication laws that prohibit public schools from recommending or requiring medication use. Logistic regression difference-in-differences models were estimated with repeated U.S. and state-representative cross-sections of responses to the 2003, 2007, and 2011 National Survey of Children's Health. Each wave included approximately 35,000 public school children between ages six and 13. From 2003 to 2007, the change in adjusted diagnostic prevalence was 2.8 percentage points higher for children ages six to 13 in households with incomes ≤185% of the federal poverty level residing in states first exposed to consequential accountability through NCLB (from 8.5% to 13.2%), compared with demographically similar children residing in other states (from 10.2% to 12.1%). From 2003 to 2011, the change in adjusted diagnostic prevalence was 2.2 percentage points lower for children ages six to 13 residing in states with a psychotropic medication law (from 8.1% to 7.8%), compared with children residing in other states (from 8.1% to 10.1%). NCLB-initiated consequential accountability reforms were associated with more ADHD diagnoses among low-income children, consistent with increased academic pressures from NCLB for this subgroup. In contrast, psychotropic medication laws were associated with fewer ADHD diagnoses, because they may indirectly reduce diagnoses via restrictions on recommending or requiring medication use. Future research should investigate whether children most affected by these policies are receiving appropriate diagnoses.

Risk of unintentional injuries in children and adolescents with ADHD and the impact of ADHD medications: A systematic review and meta-analysis.

PubMed

Ruiz-Goikoetxea, Maite; Cortese, Samuele; Aznarez-Sanado, Maite; Magallón, Sara; Alvarez Zallo, Noelia; Luis, Elkin O; de Castro-Manglano, Pilar; Soutullo, Cesar; Arrondo, Gonzalo

2018-01-01

A systematic review with meta-analyses was performed to: 1) quantify the association between ADHD and risk of unintentional physical injuries in children/adolescents ("risk analysis"); 2) assess the effect of ADHD medications on this risk ("medication analysis"). We searched 114 databases through June 2017. For the risk analysis, studies reporting sex-controlled odds ratios (ORs) or hazard ratios (HRs) estimating the association between ADHD and injuries were combined. Pooled ORs (28 studies, 4,055,620 individuals without and 350,938 with ADHD) and HRs (4 studies, 901,891 individuals without and 20,363 with ADHD) were 1.53 (95% CI=1.40,1.67) and 1.39 (95% CI=1.06,1.83), respectively. For the medication analysis, we meta-analysed studies that avoided the confounding-by-indication bias [four studies with a self-controlled methodology and another comparing risk over time and groups (a "difference in differences" methodology)]. The pooled effect size was 0.879 (95% CI=0.838,0.922) (13,254 individuals with ADHD). ADHD is significantly associated with an increased risk of unintentional injuries and ADHD medications have a protective effect, at least in the short term, as indicated by self-controlled studies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Attention-Deficit Hyperactivity Disorder (ADHD) in Epilepsy and Primary ADHD: Differences in Symptom Dimensions and Quality of Life.

PubMed

Ekinci, Ozalp; Okuyaz, Çetin; Erdoğan, Semra; Gunes, Serkan; Ekinci, Nuran; Kalınlı, Merve; Teke, Halenur; Direk, Meltem Çobanoğulları

2017-12-01

We aimed to (1) compare quality of life (QOL) among children with epilepsy, epilepsy and attention-deficit hyperactivity disorder (ADHD), and primary ADHD and (2) compare ADHD symptom dimensions and subtypes between children with epilepsy-ADHD and primary ADHD. A total of 140 children; 53 with epilepsy, 35 with epilepsy-ADHD, and 52 with primary ADHD were included. KINDL-R (quality of life measure), Turgay DSM-IV Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S), and Conners' Parent Rating Scale (CPRS) were completed. Neurology clinic charts were reviewed for epilepsy-related variables. Children with epilepsy-ADHD had the lowest (poorest) KINDL-R total scores. Epilepsy-ADHD group had more inattentiveness symptoms, whereas primary ADHD group had more hyperactivity/impulsivity symptoms. The frequencies of ADHD combined and inattentiveness subtypes were 60% and 40% in children with epilepsy-ADHD and 80.7% and 19.3% in children with primary ADHD, respectively ( P = .034). ADHD in epilepsy is associated with a significantly poor quality of life and predominantly inattentiveness symptoms.

A systematic review of global publication trends regarding long-term outcomes of ADHD.

PubMed

Hodgkins, Paul; Arnold, L Eugene; Shaw, Monica; Caci, Hervé; Kahle, Jennifer; Woods, Alisa G; Young, Susan

2011-01-01

There is increased global recognition of attention deficit hyperactivity disorder (ADHD) as a serious medical condition with long-term consequences. Although originally conceived of as a childhood disorder, ADHD is being increasingly recognized in adults. Individual geographic regions may have specific interests and objectives for the study of ADHD. A systematic review of long-term outcomes (LTOs) in ADHD was conducted to evaluate research on ADHD LTOs on a global scale. Studies that were at least 2 years in duration were examined. A total of 351 studies were identified in the final analysis. We identified nine outcomes of interest and classified studies by specific geographical regions, age groups studied and study design by region and over time. Published studies of LTOs in ADHD have increased in all geographical regions over the past three decades, with a peak number of 42 publications in 2008. This rise in publications on ADHD LTOs may reflect a rise in global interest and recognition of consequences and impairment associated with ADHD. Although many world regions have published on ADHD LTOs, the majority of studies have emerged from the US and Canada, followed by Europe. While investigators in the US and Canada were predominantly interested in drug addiction as a LTO, European researchers were more interested in antisocial behavior, and Eastern Asian investigators focused on both of these LTOs as well as self-esteem. Geographical differences in the focus of ADHD LTO studies may reflect regional variations in cultural values. Proportionally fewer prospective longitudinal studies and proportionally more retrospective and cross-sectional studies have been published in more recent decades. Finally, more studies focusing on ADHD in adolescents and adults have been conducted in recent years, and particularly adolescents in Eastern Asia. These changes in basic study design may reflect an increase in the recognition that ADHD is a lifetime chronic disorder. This

A Systematic Review of Global Publication Trends Regarding Long-Term Outcomes of ADHD

PubMed Central

Hodgkins, Paul; Arnold, L. Eugene; Shaw, Monica; Caci, Hervé; Kahle, Jennifer; Woods, Alisa G; Young, Susan

2012-01-01

There is increased global recognition of attention deficit hyperactivity disorder (ADHD) as a serious medical condition with long-term consequences. Although originally conceived of as a childhood disorder, ADHD is being increasingly recognized in adults. Individual geographic regions may have specific interests and objectives for the study of ADHD. A systematic review of long-term outcomes (LTOs) in ADHD was conducted to evaluate research on ADHD LTOs on a global scale. Studies that were at least 2 years in duration were examined. A total of 351 studies were identified in the final analysis. We identified nine outcomes of interest and classified studies by specific geographical regions, age groups studied and study design by region and over time. Published studies of LTOs in ADHD have increased in all geographical regions over the past three decades, with a peak number of 42 publications in 2008. This rise in publications on ADHD LTOs may reflect a rise in global interest and recognition of consequences and impairment associated with ADHD. Although many world regions have published on ADHD LTOs, the majority of studies have emerged from the US and Canada, followed by Europe. While investigators in the US and Canada were predominantly interested in drug addiction as a LTO, European researchers were more interested in antisocial behavior, and Eastern Asian investigators focused on both of these LTOs as well as self-esteem. Geographical differences in the focus of ADHD LTO studies may reflect regional variations in cultural values. Proportionally fewer prospective longitudinal studies and proportionally more retrospective and cross-sectional studies have been published in more recent decades. Finally, more studies focusing on ADHD in adolescents and adults have been conducted in recent years, and particularly adolescents in Eastern Asia. These changes in basic study design may reflect an increase in the recognition that ADHD is a lifetime chronic disorder. This

Personality profiles in adults with attention deficit hyperactivity disorder (ADHD).

PubMed

Perroud, Nader; Hasler, Roland; Golay, Nicolas; Zimmermann, Julien; Prada, Paco; Nicastro, Rosetta; Aubry, Jean-Michel; Ardu, Stefano; Herrmann, François R; Giannakopoulos, Panteleimon; Baud, Patrick

2016-06-14

Previous studies suggested that the presence of ADHD in children and young adolescents may affect the development of personality. Whether or not the persistence of ADHD in adult life is associated with distinct personality patterns is still matter for debate. To address this issue, we compared the profiles of the Temperament and Character Inventory (TCI) that assesses personality dimensions in 119 adults ADHD and 403 controls. ANCOVA were used to examine group differences (controls vs. ADHD and ADHD inattentive type vs. ADHD combined + hyperactive/impulsive types) in Temperaments and Characters. Partial correlation coefficients were used to assess correlation between TCI and expression and severity of symptoms of ADHD. High novelty seeking (NS), harm avoidance (HA) and self-transcendence (ST) scores as well as low self-directedness (SD) and cooperativeness (C) scores were associated with ADHD diagnosis. Low SD was the strongest personality trait associated with adult ADHD. Cases with the ADHD inattentive type showed higher HA and lower SD scores compared to the combined and hyperactive/impulsive types. High HA scores correlated with inattention symptoms whereas high NS and ST scores were related to hyperactive symptoms. Finally low SD and high NS were associated with increased ADHD severity. Distinct temperaments were associated with inattentive versus hyperactive/impulsive symptoms supporting the heterogeneous nature of the disorder.

Poly(dopamine) coating to biodegradable polymers for bone tissue engineering.

PubMed

Tsai, Wei-Bor; Chen, Wen-Tung; Chien, Hsiu-Wen; Kuo, Wei-Hsuan; Wang, Meng-Jiy

2014-02-01

In this study, a technique based on poly(dopamine) deposition to promote cell adhesion was investigated for the application in bone tissue engineering. The adhesion and proliferation of rat osteoblasts were evaluated on poly(dopamine)-coated biodegradable polymer films, such as polycaprolactone, poly(l-lactide) and poly(lactic-co-glycolic acid), which are commonly used biodegradable polymers in tissue engineering. Cell adhesion was significantly increased to a plateau by merely 15 s of dopamine incubation, 2.2-4.0-folds of increase compared to the corresponding untreated substrates. Cell proliferation was also greatly enhanced by poly(dopamine) deposition, indicated by shortened cell doubling time. Mineralization was also increased on the poly(dopamine)-deposited surfaces. The potential of poly(dopamine) deposition in bone tissue engineering is demonstrated in this study.

Intraindividual variability in inhibitory function in adults with ADHD--an ex-Gaussian approach.

PubMed

Gmehlin, Dennis; Fuermaier, Anselm B M; Walther, Stephan; Debelak, Rudolf; Rentrop, Mirjam; Westermann, Celina; Sharma, Anuradha; Tucha, Lara; Koerts, Janneke; Tucha, Oliver; Weisbrod, Matthias; Aschenbrenner, Steffen

2014-01-01

Attention deficit disorder (ADHD) is commonly associated with inhibitory dysfunction contributing to typical behavioral symptoms like impulsivity or hyperactivity. However, some studies analyzing intraindividual variability (IIV) of reaction times in children with ADHD (cADHD) question a predominance of inhibitory deficits. IIV is a measure of the stability of information processing and provides evidence that longer reaction times (RT) in inhibitory tasks in cADHD are due to only a few prolonged responses which may indicate deficits in sustained attention rather than inhibitory dysfunction. We wanted to find out, whether a slowing in inhibitory functioning in adults with ADHD (aADHD) is due to isolated slow responses. Computing classical RT measures (mean RT, SD), ex-Gaussian parameters of IIV (which allow a better separation of reaction time (mu), variability (sigma) and abnormally slow responses (tau) than classical measures) as well as errors of omission and commission, we examined response inhibition in a well-established GoNogo task in a sample of aADHD subjects without medication and healthy controls matched for age, gender and education. We did not find higher numbers of commission errors in aADHD, while the number of omissions was significantly increased compared with controls. In contrast to increased mean RT, the distributional parameter mu did not document a significant slowing in aADHD. However, subjects with aADHD were characterized by increased IIV throughout the entire RT distribution as indicated by the parameters sigma and tau as well as the SD of reaction time. Moreover, we found a significant correlation between tau and the number of omission errors. Our findings question a primacy of inhibitory deficits in aADHD and provide evidence for attentional dysfunction. The present findings may have theoretical implications for etiological models of ADHD as well as more practical implications for neuropsychological testing in aADHD.

PRESYNAPTIC DOPAMINE MODULATION BY STIMULANT SELF ADMINISTRATION

PubMed Central

España, Rodrigo A.; Jones, Sara R.

2013-01-01

The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine. PMID:23277050

Prepuberal intranasal dopamine treatment in an animal model of ADHD ameliorates deficient spatial attention, working memory, amino acid transmitters and synaptic markers in prefrontal cortex, ventral and dorsal striatum.

PubMed

Ruocco, L A; Treno, C; Gironi Carnevale, U A; Arra, C; Mattern, C; Huston, J P; de Souza Silva, M A; Nikolaus, S; Scorziello, A; Nieddu, M; Boatto, G; Illiano, P; Pagano, C; Tino, A; Sadile, A G

2014-09-01

Intranasal application of dopamine (IN-DA) has been shown to increase motor activity and to release DA in the ventral (VS) and dorsal striatum (DS) of rats. The aim of the present study was to assess the effects of IN-DA treatment on parameters of DA and excitatory amino acid (EAA) function in prepuberal rats of the Naples high-excitability (NHE) line, an animal model for attention-deficit hyperactivity disorder (ADHD) and normal random bred (NRB) controls. NHE and NRB rats were daily administered IN-DA (0.075, 0.15, 0.30 mg/kg) or vehicle for 15 days from postnatal days 28-42 and subsequently tested in the Làt maze and in the Eight-arm radial Olton maze. Soluble and membrane-trapped L-glutamate (L-Glu) and L-aspartate (L-Asp) levels as well as NMDAR1 subunit protein levels were determined after sacrifice in IN-DA- and vehicle-treated NHE and NRB rats in prefrontal cortex (PFc), DS and VS. Moreover, DA transporter (DAT) protein and tyrosine hydroxylase (TH) levels were assessed in PFc, DS, VS and mesencephalon (MES) and in ventral tegmental area (VTA) and substantia nigra, respectively. In NHE rats, IN-DA (0.30 mg/kg) decreased horizontal activity and increased nonselective attention relative to vehicle, whereas the lower dose (0.15 mg/kg) increased selective spatial attention. In NHE rats, basal levels of soluble EAAs were reduced in PFc and DS relative to NRB controls, while membrane-trapped EAAs were elevated in VS. Moreover, basal NMDAR1 subunit protein levels were increased in PFc, DS and VS relative to NRB controls. In addition, DAT protein levels were elevated in PFc and VS relative to NRB controls. IN-DA led to a number of changes of EAA, NMDAR1 subunit protein, TH and DAT protein levels in PFc, DS, VS, MES and VTA, in both NHE and NRB rats with significant differences between lines. Our findings indicate that the NHE rat model of ADHD may be characterized by (1) prefrontal and striatal DAT hyperfunction, indicative of DA hyperactivty, and (2

Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration

PubMed Central

Mor, Danielle E.; Tsika, Elpida; Mazzulli, Joseph R.; Gould, Neal S.; Kim, Hanna; Daniels, Malcolm J.; Doshi, Shachee; Gupta, Preetika; Grossman, Jennifer L.; Tan, Victor X.; Kalb, Robert G.; Caldwell, Kim A.; Caldwell, Guy A.; Wolfe, John H.; Ischiropoulos, Harry

2018-01-01

Parkinson’s disease is defined by the loss of dopaminergic neurons in the substantia nigra and formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated dopamine levels in addition to α-synuclein expression. Nigra-targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine without damaging neurons in non-transgenic mice. In contrast, raising dopamine in mice expressing human A53T mutant α-synuclein induced progressive nigrostriatal degeneration and reduced locomotion. Dopamine elevation in A53T mice increased levels of potentially toxic α-synuclein oligomers, resulting in conformationally and functionally modified species. Moreover, in genetically tractable C. elegans models expression of α-synuclein mutated at the site of interaction with dopamine prevented dopamine-induced toxicity. The data suggest a unique mechanism linking two cardinal features of Parkinson’s disease, dopaminergic cell death and α-synuclein aggregation. PMID:28920936

Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration.

PubMed

Mor, Danielle E; Tsika, Elpida; Mazzulli, Joseph R; Gould, Neal S; Kim, Hanna; Daniels, Malcolm J; Doshi, Shachee; Gupta, Preetika; Grossman, Jennifer L; Tan, Victor X; Kalb, Robert G; Caldwell, Kim A; Caldwell, Guy A; Wolfe, John H; Ischiropoulos, Harry

2017-11-01

Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated both dopamine levels and α-synuclein expression. Nigrally targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine levels without damaging neurons in non-transgenic mice. In contrast, raising dopamine levels in mice expressing human A53T mutant α-synuclein induced progressive nigrostriatal degeneration and reduced locomotion. Dopamine elevation in A53T mice increased levels of potentially toxic α-synuclein oligomers, resulting in conformationally and functionally modified species. Moreover, in genetically tractable Caenorhabditis elegans models, expression of α-synuclein mutated at the site of interaction with dopamine prevented dopamine-induced toxicity. These data suggest that a unique mechanism links two cardinal features of PD: dopaminergic cell death and α-synuclein aggregation.

Low Dopamine D2 Receptor Increases Vulnerability to Obesity Via Reduced Physical Activity, Not Increased Appetitive Motivation.

PubMed

Beeler, Jeff A; Faust, Rudolf P; Turkson, Susie; Ye, Honggang; Zhuang, Xiaoxi

2016-06-01

The dopamine D2 receptor (D2R) has received much attention in obesity studies. Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons. It is often suggested that reduced D2R generates a reward deficiency and altered appetitive motivation that induces compulsive eating and contributes to obesity. Although dopamine is known to regulate physical activity, it is often neglected in these studies, leaving open the question of whether reduced D2R contributes to obesity through alterations in energy expenditure and activity. We generated a D2R knockdown (KD) mouse line and assessed both energy expenditure and appetitive motivation under conditions of diet-induced obesity. The KD mice did not gain more weight or show increased appetitive motivation compared with wild-type mice in a standard environment; however, in an enriched environment with voluntary exercise opportunities, KD mice exhibited dramatically lower activity and became more obese than wild-type mice, obtaining no protective benefit from exercise opportunities. These data suggest the primary contribution of altered D2R signaling to obesity lies in altered energy expenditure rather than the induction of compulsive overeating. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Atypical Default Network Connectivity in Youth with ADHD

PubMed Central

Fair, Damien A.; Posner, Jonathan; Nagel, Bonnie J.; Bathula, Deepti; Dias, Taciana G. Costa; Mills, Kathryn L.; Blythe, Michael S.; Giwa, Aishat; Schmitt, Colleen F.; Nigg, Joel T.

2010-01-01

Background Attention deficit/hyperactivity disorder (ADHD) is a major public health concern. It has been suggested that the brain’s default network may provide a crucial avenue for understanding the neurobiology of ADHD. Evaluations of the default network have increased over recent years with the applied technique of resting-state functional connectivity MRI (rs-fcMRI). These investigations have established that spontaneous activity in this network is highly correlated at rest in young adult populations. This coherence seems to be reduced in adults with ADHD. This is an intriguing finding, as coherence in spontaneous activity within the default network strengthens with age. Thus, the pathophysiology of ADHD might include delayed or disrupted maturation of the default network. If so, it is important to determine whether an altered developmental picture can be detected using rs-fcMRI in children with ADHD. Methods The present study utilized the typical developmental context provided previously by Fair et al (1) to examine coherence of brain activity within the default network using rs-fcMRI in children with (n=23) and without ADHD (n=23). Results We found that functional connections previously shown as developmentally dynamic in the default network were atypical in children with ADHD - consistent with perturbation or failure of the maturational processes. Conclusions These findings are consistent with the hypothesis that atypical consolidation of this network over development plays a role in ADHD. PMID:20728873

In vitro and in vivo evaluation of poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate)/dopamine-coated electrodes for dopamine delivery.

PubMed

Sui, L; Song, X J; Ren, J; Cai, W J; Ju, L H; Wang, Y; Wang, L Y; Chen, M

2014-06-01

Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly(styrene sulfonate) (PSS) has a variety of chemical and biomedical applications. The application of PEDOT/PSS polymers in drug delivery has attracted attention. However, whether conducting polymers of PEDOT/PSS could be used for dopamine delivery has not clear. In the present study, the PEDOT/PSS coatings incorporated with dopamine were fabricated on 0.5 mm diameter platinum electrodes, electrochemical properties, and dopamine delivery capacities of these electrodes were evaluated in vitro and in vivo through implanting these electrodes into brain striatum area. The findings demonstrated that the PEDOT/PSS/dopamine coatings on platinum electrodes could reduce electrodes impedances, increase charge storage capacities, and release significant levels of dopamine upon electrical stimulation of these electrodes. These results indicated that polymers of PEDOT/PSS/dopamine could be used for dopamine delivery, implicating potential application of PEDOT/PSS/dopamine-coated implantable electrodes in the treatment of some diseases associated with dopamine deficits, such as, electrodes for the treatment of Parkinson's disease during deep brain stimulation. Copyright © 2013 Wiley Periodicals, Inc.

Affect Recognition in Adults with ADHD

ERIC Educational Resources Information Center

Miller, Meghan; Hanford, Russell B.; Fassbender, Catherine; Duke, Marshall; Schweitzer, Julie B.

2011-01-01

Objective: This study compared affect recognition abilities between adults with and without ADHD. Method: The sample consisted of 51 participants (34 men, 17 women) divided into 3 groups: ADHD-combined type (ADHD-C; n = 17), ADHD-predominantly inattentive type (ADHD-I; n = 16), and controls (n = 18). The mean age was 34 years. Affect recognition…

Neuropsychological Functioning In College Students with and without ADHD

PubMed Central

Weyandt, Lisa L.; Oster, Danielle R.; Gudmundsdottir, Bergljot Gyda; DuPaul, George J.; Anastopoulos, Arthur D.

2016-01-01

Increasing numbers of students with attention-deficit/hyperactivity disorder (ADHD) are attending college; however, little empirical information is available concerning the functional impairment experienced by these students. Although preliminary studies suggest that college students with ADHD are more likely to experience a variety of psychosocial and academic difficulties compared to their peers without the disorder, findings regarding neuropsychological functioning have been inconsistent with some studies reporting that college students with ADHD perform more poorly on various cognitive and neuropsychological tasks whereas others report no differences compared to non-ADHD peers. The purpose of the present study was to: a) examine the performance of 436 first-year college students with and without ADHD (51.6% female) on measures of executive function (EF) and intelligence; and b) investigate the association of self-reported use of stimulant medication with neuropsychological performance in students with ADHD. Participant data from their first year of involvement in the Trajectories Related to ADHD in College (TRAC) project, a longitudinal study following the 4-year outcomes of college students with and without ADHD, were analyzed. Participants with ADHD performed more poorly on task-based and self-report executive function measures relative to the comparison group. In contrast, no significant group differences in intellectual performance were found. Within the ADHD group, receipt of stimulant medication was associated with improved performance on some neuropsychological tasks, but not for intellectual functioning. Additional analyses also revealed significant group differences in EF based on clinical diagnostic status. Implications of these findings and suggestions for future research are advanced. PMID:27831696

ADHD Coaching with College Students: Exploring the Processes Involved in Motivation and Goal Completion

ERIC Educational Resources Information Center

Prevatt, Frances; Smith, Shannon M.; Diers, Sarah; Marshall, Diana; Coleman, Jennifer; Valler, Emilee; Miller, Nathan

2017-01-01

College students with attention-deficit/hyperactivity disorder (ADHD) often experience increased academic difficulties, which can negatively impact graduation rates, employment, self-esteem, and mental health. ADHD coaching assists students with ADHD to reduce such difficulties. The present study evaluated the processes involved in ADHD coaching…

Stimulants and growth in children with attention-deficit/hyperactivity disorder.

PubMed

Negrao, Bianca Lee; Viljoen, Margaretha

2011-07-01

Initial suggestions that suppression of growth may be an intrinsic characteristic of attention-deficit/hyperactivity disorder (ADHD) have now largely been disproven. Although controversy persists regarding the possible negative effect of adrenergic stimulants on growth in children with ADHD, the consensus that appears to be reached in the scientific literature is that stimulant usage may cause a manageable attenuation of growth in these children. Since it is known that stimulants increase the amount of dopamine and noradrenaline in the synapse, this writing suggests that these increases in dopamine and noradrenaline are responsible for the growth attenuation in these children. It appears that increased amounts of dopamine and noradrenaline have the ability to inhibit the secretion of growth hormone and growth-related hormones such as prolactin, thyroid hormones, sex hormones and insulin. Therefore, it would be reasonable to suggest that the increases in dopamine and noradrenaline caused by stimulant usage can disrupt the homeostasis of both growth hormone and growth-related hormones, generating the potential for the suppression of growth. Copyright © 2011 Elsevier Ltd. All rights reserved.

The impact of ADHD on the health and well-being of ADHD children and their siblings.

PubMed

Peasgood, Tessa; Bhardwaj, Anupam; Biggs, Katie; Brazier, John E; Coghill, David; Cooper, Cindy L; Daley, David; De Silva, Cyril; Harpin, Val; Hodgkins, Paul; Nadkarni, Amulya; Setyawan, Juliana; Sonuga-Barke, Edmund J S

2016-11-01

Childhood attention-deficit/hyperactivity disorder (ADHD) has been associated with reduced health and well-being of patients and their families. The authors undertook a large UK survey-based observational study of the burden associated with childhood ADHD. The impact of ADHD on both the patient (N = 476) and their siblings (N = 337) on health-related quality of life (HRQoL) and happiness was quantified using multiple standard measures [e.g. child health utility-9D (CHU-9D), EuroQol-5D-Youth]. In the analysis, careful statistical adjustments were made to ensure a like-for-like comparison of ADHD families with two different control groups. We controlled for carers' ADHD symptoms, their employment and relationship status and siblings' ADHD symptoms. ADHD was associated with a significant deficit in the patient's HRQoL (with a CHU-9D score of around 6 % lower). Children with ADHD also have less sleep and were less happy with their family and their lives overall. No consistent decrement to the HRQoL of the siblings was identified across the models, except that related to their own conduct problems. The siblings do, however, report lower happiness with life overall and with their family, even when controlling for the siblings own ADHD symptoms. We also find evidence of elevated bullying between siblings in families with a child with ADHD. Overall, the current results suggest that the reduction in quality of life caused by ADHD is experienced both by the child with ADHD and their siblings.

Women and Girls (With ADHD)

MedlinePlus

... ADHD Hospital and University ADHD Centers Insurance and Public Benefits The Insurance System Paying for Medications Private Health Insurance Public Health Insurance Disability Benefits Frequently Asked Questions about ADHD Myths and Misunderstandings ...

Time reproduction in children with ADHD and their nonaffected siblings.

PubMed

Rommelse, Nanda N J; Oosterlaan, Jaap; Buitelaar, Jan; Faraone, Stephen V; Sergeant, Joseph A

2007-05-01

Time reproduction is deficient in children with attention-deficit/hyperactivity disorder (ADHD). Whether this deficit is familial and could therefore serve as a candidate endophenotype has not been previously investigated. It is unknown whether timing deficits are also measurable in adolescent children with ADHD and nonaffected siblings. These issues were investigated in 226 children with ADHD, 188 nonaffected siblings, and 162 normal controls ages 5 to 19. Children participated in a visual and auditory time reproduction task. They reproduced interval lengths of 4, 8, 12, 16, and 20 seconds. Children with ADHD and their nonaffected siblings were less precise than controls, particularly when task difficulty was systematically increased. Time reproduction skills were familial. Time reproduction deficits were more pronounced in younger children with ADHD than in older children. Children with ADHD could be clearly dissociated from control children until the age of 9. After this age, group differences were somewhat attenuated, but were still present. Differences between nonaffected siblings and controls were constant across the age range studied. Deficits were unaffected by modality. Time reproduction may serve as a candidate endophenotype for ADHD, predominantly in younger children with (a genetic risk for) ADHD.

A new synthetic drug 5-(2-aminopropyl)indole (5-IT) induces rewarding effects and increases dopamine D1 receptor and dopamine transporter mRNA levels.

PubMed

Botanas, Chrislean Jun; Yoon, Seong Shoon; de la Peña, June Bryan; Dela Peña, Irene Joy; Kim, Mikyung; Custodio, Raly James; Woo, Taeseon; Seo, Joung-Wook; Jang, Choon-Gon; Yang, Ji Seul; Yoon, Yoon Mi; Lee, Yong Sup; Kim, Hee Jin; Cheong, Jae Hoon

2018-04-02

In recent years, there has been a marked increase in the use of recreational synthetic psychoactive substances, which is a cause of concern among healthcare providers and legal authorities. In particular, there have been reports on the misuse of 5-(2-aminopropyl)indole (5-API; 5-IT), a new synthetic drug, and of fatal and non-fatal intoxication. Despite these reports, little is known about its psychopharmacological effects and abuse potential. Here, we investigated the abuse potential of 5-IT by evaluating its rewarding and reinforcing effects through conditioned place preference (CPP) (1, 10, and 30 mg/kg, i.p.) in mice and self-administration test (0.1, 0.3, 1, and 3 mg/kg/inf., i.v.) in rats. We also examined whether 5-IT (1, 3, and 10 mg/kg, i.p.) induces locomotor sensitization in mice following a 7-day treatment and drug challenge. Then, we explored the effects of 5-IT (10 mg/kg, i.p.) on dopamine-related genes in the striatum, prefrontal cortex (PFC), and substantia nigra pars compacta (SNc)/ventral tegmental (VTA) of mice by quantitative real-time polymerase chain reaction. 5-IT produced CPP in mice but was not reliably self-administered by rats. 5-IT also induced locomotor sensitization following repeated administration and drug challenge. Moreover, 5-IT increased mRNA levels of dopamine D1 receptor in the striatum and PFC and dopamine transporter in the SNc/VTA of mice. These results indicate that 5-IT has psychostimulant and rewarding properties, which may be attributed to its ability to affect the dopaminergic system in the brain. These findings suggest that 5-IT poses a substantial risk for abuse and addiction in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

What Is ADHD?

MedlinePlus

... español TDAH What Is ADHD? ADHD stands for attention deficit hyperactivity disorder. It is a medical condition. ... in brain development and brain activity that affect attention, the ability to sit still, and self-control. ...

Different roles of retinal dopamine in albino Guinea pig myopia.

PubMed

Mao, Junfeng; Liu, Shuangzhen

2017-02-03

To investigate whether the different role of ocular dopamine was involved in the myopic development between spontaneous myopia (SM) and form deprivation myopia (FDM) in albino guinea pigs. 55 myopic animals were randomly divided into SM, Levodapa (L-DOPA), L-DOPA+carbidopa and vehicle. 70 non-myopic animals were randomly divided into normal control, FDM, L-DOPA+FDM, L-DOPA+carbidopa+FDM and vehicle. Once per day, for 14days, L-DOPA (10mg/kg) was injected intraperitoneally, and carbidopa (1μg) was injected at the same time into the peribulbar space of the right eye. Refractive parameters and dopamine content in neural retina and RPE/choroid complex were measured. In SM animals, high myopia was formed at 5 week of ages. L-DOPA treatment could reduce its myopic degree, and inhibit the increase of axial length and vitreous chamber depth with the increase of retinal dopamine in both eyes. Administration of carbidopa could prevent the increase of retinal dopamine induced by L-DOPA, but no influenced on its refractive state in the injected eyes. In non-SM animals, intraperitoneal L-DOPA could inhibit FDM, accompanied by the increase of retinal dopamine. Carbidopa treatment diminished the inhibition of FDM and prevented the increase in retinal dopamine by L-Dopa. Retinal dopamine was highly correlated with ocular refraction in FDM, but not in SM. There was no significant difference in dopamine content of RPE/choroid complex among all groups. The role of retinal dopamine was different between SM and FDM in albino guinea pigs. Although systemic L-DOPA could inhibit the development of SM and FDM, retinal dopamine was only involved in the L-DOPA inhibition on FDM, but not on SM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Emotion Regulation Mediates the Relationship between ADHD and Depressive Symptoms in Youth

ERIC Educational Resources Information Center

Seymour, Karen E.; Chronis-Tuscano, Andrea; Halldorsdottir, Thorhildur; Stupica, Brandi; Owens, Kristian; Sacks, Talia

2012-01-01

A significant literature suggests that youth diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD) are at increased risk for later depression relative to youth without ADHD. Youth with co-occurring ADHD and depression experience more serious impairments and worse developmental outcomes than those with either disorder alone, including…

Childhood ADHD Symptoms: Association with Parental Social Networks and Mental Health Service Use during Adolescence.

PubMed

Bussing, Regina; Meyer, Johanna; Zima, Bonnie T; Mason, Dana M; Gary, Faye A; Garvan, Cynthia Wilson

2015-09-22

This study examines the associations of childhood attention-deficit/hyperactivity disorder (ADHD) risk status with subsequent parental social network characteristics and caregiver strain in adolescence; and examines predictors of adolescent mental health service use. Baseline ADHD screening identified children at high risk (n = 207) and low risk (n = 167) for ADHD. At eight-year follow-up, parents reported their social network characteristics, caregiver strain, adolescents' psychopathology and mental health service utilization, whereas adolescents self-reported their emotional status and ADHD stigma perceptions. Analyses were conducted using ANOVAs and nested logistic regression modeling. Parents of youth with childhood ADHD reported support networks consisting of fewer spouses but more healthcare professionals, and lower levels of support than control parents. Caregiver strain increased with adolescent age and psychopathology. Increased parental network support, youth ADHD symptoms, and caregiver strain, but lower youth stigma perceptions were independently associated with increased service use. Raising children with ADHD appears to significantly impact parental social network experiences. Reduced spousal support and overall lower network support levels may contribute to high caregiver strain commonly reported among parents of ADHD youth. Parental social network experiences influence adolescent ADHD service use. With advances in social networking technology, further research is needed to elucidate ways to enhance caregiver support during ADHD care.

Predominantly Inattentive Type of ADHD is Associated With Social Anxiety Disorder.

PubMed

Koyuncu, Ahmet; Ertekin, Erhan; Yüksel, Çağrı; Aslantaş Ertekin, Banu; Çelebi, Fahri; Binbay, Zerrin; Tükel, Raşit

2015-10-01

The aim of this study was to determine the frequency of childhood ADHD comorbidity in patients with social anxiety disorder (SAD), and the influence of this comorbidity on various demographic and clinical variables in SAD. A total of 130 patients with SAD were assessed with K-SADS-PL's (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version) behavioral disorders module to determine the childhood diagnosis of ADHD. Patients with or without a comorbid childhood ADHD were compared in terms of clinical characteristics and rating scores. The mean age at onset of SAD was lower, and lifetime major depressive disorder and bipolar disorder (BD) comorbidity were higher in the SAD-ADHD group than in the SAD-without ADHD group. We have found high ADHD comorbidity in patients with SAD. Presence of comorbid ADHD was associated with increased severity, functional impairment, and BD comorbidity. © 2014 SAGE Publications.

The Mediterranean Diet and ADHD in Children and Adolescents.

PubMed

Ríos-Hernández, Alejandra; Alda, José A; Farran-Codina, Andreu; Ferreira-García, Estrella; Izquierdo-Pulido, Maria

2017-02-01

Although attention-deficit/hyperactivity disorder (ADHD) has been related to nutrient deficiencies and "unhealthy" diets, to date there are no studies that examined the relationship between the Mediterranean diet and ADHD. We hypothesized that a low adherence to a Mediterranean diet would be positively associated with an increase in ADHD diagnosis. A total of 120 children and adolescents (60 with newly diagnosed ADHD and 60 controls) were studied in a sex- and age-matched case-control study. ADHD diagnosis was made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Energy, dietary intake, adherence to a Mediterranean diet, and familial background were measured. Logistic regression was used to determine associations between the adherence to a Mediterranean diet and ADHD. Lower adherence to a Mediterranean diet was associated with ADHD diagnosis (odds ratio: 7.07; 95% confidence interval: 2.65-18.84; relative risk: 2.80; 95% confidence interval: 1.54-5.25). Both remained significant after adjusting for potential confounders. Lower frequency of consuming fruit, vegetables, pasta, and rice and higher frequency of skipping breakfast and eating at fast-food restaurants were associated with ADHD diagnosis (P < .05). High consumption of sugar, candy, cola beverages, and noncola soft drinks (P < .01) and low consumption of fatty fish (P < .05) were also associated with a higher prevalence of ADHD diagnosis. Although these cross-sectional associations do not establish causality, they raise the question of whether low adherence to a Mediterranean diet might play a role in ADHD development. Our data support the notion that not only "specific nutrients" but also the "whole diet" should be considered in ADHD. Copyright © 2017 by the American Academy of Pediatrics.

Enhanced Striatal Dopamine Release During Food Stimulation in Binge Eating Disorder

PubMed Central

Wang, Gene-Jack; Geliebter, Allan; Volkow, Nora D.; Telang, Frank W.; Logan, Jean; Jayne, Millard C.; Galanti, Kochavi; Selig, Peter A.; Han, Hao; Zhu, Wei; Wong, Christopher T.; Fowler, Joanna S.

2011-01-01

Subjects with binge eating disorder (BED) regularly consume large amounts of food in short time periods. The neurobiology of BED is poorly understood. Brain dopamine, which regulates motivation for food intake, is likely to be involved. We assessed the involvement of brain dopamine in the motivation for food consumption in binge eaters. Positron emission tomography (PET) scans with [11C]raclopride were done in 10 obese BED and 8 obese subjects without BED. Changes in extracellular dopamine in the striatum in response to food stimulation in food-deprived subjects were evaluated after placebo and after oral methylphenidate (MPH), a drug that blocks the dopamine reuptake transporter and thus amplifies dopamine signals. Neither the neutral stimuli (with or without MPH) nor the food stimuli when given with placebo increased extracellular dopamine. The food stimuli when given with MPH significantly increased dopamine in the caudate and putamen in the binge eaters but not in the nonbinge eaters. Dopamine increases in the caudate were significantly correlated with the binge eating scores but not with BMI. These results identify dopamine neurotransmission in the caudate as being of relevance to the neurobiology of BED. The lack of correlation between BMI and dopamine changes suggests that dopamine release per se does not predict BMI within a group of obese individuals but that it predicts binge eating. PMID:21350434

Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward.

PubMed

Pandit, Rahul; Omrani, Azar; Luijendijk, Mieneke C M; de Vrind, Véronne A J; Van Rozen, Andrea J; Ophuis, Ralph J A Oude; Garner, Keith; Kallo, Imre; Ghanem, Alexander; Liposits, Zsolt; Conzelmann, Karl-Klaus; Vanderschuren, Louk J M J; la Fleur, Susanne E; Adan, Roger A H

2016-08-01

The central melanocortin (MC) system mediates its effects on food intake via MC3 (MC3R) and MC4 receptors (MC4R). Although the role of MC4R in meal size determination, satiation, food preference, and motivation is well established, the involvement of MC3R in the modulation of food intake has been less explored. Here, we investigated the role of MC3R on the incentive motivation for food, which is a crucial component of feeding behavior. Dopaminergic neurons within the ventral tegmental area (VTA) have a crucial role in the motivation for food. We here report that MC3Rs are expressed on VTA dopaminergic neurons and that pro-opiomelanocortinergic (POMC) neurons in the arcuate nucleus of the hypothalamus (Arc) innervate these VTA dopaminergic neurons. Our findings show that intracerebroventricular or intra-VTA infusion of the selective MC3R agonist γMSH increases responding for sucrose under a progressive ratio schedule of reinforcement, but not free sucrose consumption in rats. Furthermore, ex vivo electrophysiological recordings show increased VTA dopaminergic neuronal activity upon γMSH application. Consistent with a dopamine-mediated effect of γMSH, the increased motivation for sucrose after intra-VTA infusion of γMSH was blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. Taken together, we demonstrate an Arc POMC projection onto VTA dopaminergic neurons that modulates motivation for palatable food via activation of MC3R signaling.

Maternal ADHD symptoms, personality, and parenting stress: Differences between mothers of children with ADHD and mothers of comparison children

PubMed Central

Algorta, Guillermo Perez; Kragh, Carolyn A.; Arnold, L. Eugene; Molina, Brooke S. G.; Hinshaw, Stephen P.; Swanson, James M.; Hetchman, Lily; Copley, LaRae M.; Lowe, Matthew; Jensen, Peter S.

2017-01-01

Mothers raising a child with ADHD can experience high parenting stress. Mothers’ personality traits and own ADHD symptoms could also affect parenting stress. 430 biological mothers from the Multimodal Treatment Study of Children with ADHD (MTA mothers) and 237 of a local normative comparison group (LNCG mothers) were evaluated at baseline. Interactions were tested between mothers’ group and maternal personality/ADHD symptoms related to parenting stress. Compared to LNCG, MTA mothers had higher parenting stress, self-reported ADHD, neuroticism, and lower conscientiousness and agreeableness. When personality and ADHD were evaluated together, ADHD symptoms interacted with mothers’ group: high maternal ADHD was positively associated with parenting stress for LNCG but not MTA mothers. Personality traits or ADHD characteristics do not appear operative for the high parenting stress of mothers of a child with ADHD. However, high maternal ADHD or low conscientiousness are associated with stress levels similar to raising a child with ADHD. PMID:25525155

Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder.

PubMed

Berk, M; Dodd, S; Kauer-Sant'anna, M; Malhi, G S; Bourin, M; Kapczinski, F; Norman, T

2007-01-01

Rational therapeutic development in bipolar is hampered by a lack of pathophysiological model. However, there is a wealth of converging data on the role of dopamine in bipolar disorder. This paper therefore examines the possibility of a dopamine hypothesis for bipolar disorder. A literature search was conducted using standard search engines Embase, PyschLIT, PubMed and MEDLINE. In addition, papers and book chapters known to the authors were retrieved and examined for further relevant articles. Collectively, in excess of 100 articles were reviewed from which approximately 75% were relevant to the focus of this paper. Pharmacological models suggest a role of increased dopaminergic drive in mania and the converse in depression. In Parkinson's disease, administration of high-dose dopamine precursors can produce a 'maniform' picture, which switches into a depressive analogue on withdrawal. It is possible that in bipolar disorder there is a cyclical process, where increased dopaminergic transmission in mania leads to a secondary down regulation of dopaminergic receptor sensitivity over time. This may lead to a period of decreased dopaminergic transmission, corresponding with the depressive phase, and the repetition of the cycle. This model, if verified, may have implications for rational drug development.

Intraindividual Variability in Inhibitory Function in Adults with ADHD – An Ex-Gaussian Approach

PubMed Central

Gmehlin, Dennis; Fuermaier, Anselm B. M.; Walther, Stephan; Debelak, Rudolf; Rentrop, Mirjam; Westermann, Celina; Sharma, Anuradha; Tucha, Lara; Koerts, Janneke; Tucha, Oliver; Weisbrod, Matthias; Aschenbrenner, Steffen

2014-01-01

Objective Attention deficit disorder (ADHD) is commonly associated with inhibitory dysfunction contributing to typical behavioral symptoms like impulsivity or hyperactivity. However, some studies analyzing intraindividual variability (IIV) of reaction times in children with ADHD (cADHD) question a predominance of inhibitory deficits. IIV is a measure of the stability of information processing and provides evidence that longer reaction times (RT) in inhibitory tasks in cADHD are due to only a few prolonged responses which may indicate deficits in sustained attention rather than inhibitory dysfunction. We wanted to find out, whether a slowing in inhibitory functioning in adults with ADHD (aADHD) is due to isolated slow responses. Methods Computing classical RT measures (mean RT, SD), ex-Gaussian parameters of IIV (which allow a better separation of reaction time (mu), variability (sigma) and abnormally slow responses (tau) than classical measures) as well as errors of omission and commission, we examined response inhibition in a well-established GoNogo task in a sample of aADHD subjects without medication and healthy controls matched for age, gender and education. Results We did not find higher numbers of commission errors in aADHD, while the number of omissions was significantly increased compared with controls. In contrast to increased mean RT, the distributional parameter mu did not document a significant slowing in aADHD. However, subjects with aADHD were characterized by increased IIV throughout the entire RT distribution as indicated by the parameters sigma and tau as well as the SD of reaction time. Moreover, we found a significant correlation between tau and the number of omission errors. Conclusions Our findings question a primacy of inhibitory deficits in aADHD and provide evidence for attentional dysfunction. The present findings may have theoretical implications for etiological models of ADHD as well as more practical implications for neuropsychological

How 'core' are motor timing difficulties in ADHD? A latent class comparison of pure and comorbid ADHD classes.

PubMed

van der Meer, Jolanda M J; Hartman, Catharina A; Thissen, Andrieke J A M; Oerlemans, Anoek M; Luman, Marjolein; Buitelaar, Jan K; Rommelse, Nanda N J

2016-04-01

Children with attention-deficit/hyperactivity disorder (ADHD) have motor timing difficulties. This study examined whether affected motor timing accuracy and variability are specific for ADHD, or that comorbidity with autism spectrum disorders (ASD) contributes to these motor timing difficulties. An 80-trial motor timing task measuring accuracy (μ), variability (σ) and infrequent long response times (τ) in estimating a 1-s interval was administered to 283 children and adolescents (8-17 years) from both a clinic and population based sample. They were divided into four latent classes based on the SCQ and L data. These classes were: without behavioral problems 'Normal-class' (n = 154), with only ADHD symptoms 'ADHD-class' (n = 49), and two classes with both ASD and ADHD symptoms; ADHD(+ASD)-class (n = 39) and ASD(+ADHD)-class (n = 41). The pure ADHD-class did not deviate from the Normal class on any of the motor timing measures (mean RTs 916 and 925 ms, respectively). The comorbid ADHD(+ASD) and ASD(+ADHD) classes were significantly less accurate (more time underestimations) compared to the Normal class (mean RTs 847 and 870 ms, respectively). Variability in motor timing was reduced in the younger children in the ADHD(+ASD) class, which may reflect a tendency to rush the tedious task. Only patients with more severe behavioral symptoms show motor timing deficiencies. This cannot merely be explained by high ADHD severity with ASD playing no role, as ADHD symptom severity in the pure ADHD-class and the ASD(+ADHD) class was highly similar, with the former class showing no motor timing deficits.

Childhood and persistent ADHD symptoms associated with educational failure and long-term occupational disability in adult ADHD.

PubMed

Fredriksen, Mats; Dahl, Alv A; Martinsen, Egil W; Klungsoyr, Ole; Faraone, Stephen V; Peleikis, Dawn E

2014-06-01

Few studies have examined the impact of childhood attention deficit hyperactivity disorder (ADHD) symptoms on adult ADHD functional outcomes. To address this issue dimensionally, ADHD symptoms in childhood and adulthood and their relation to educational deficits and work disability are studied in a clinical sample of adult patients with previously untreated ADHD. About 250 adults diagnosed systematically with ADHD according to DSM-IV were prospectively recruited. Primary outcomes were high school dropout and being out of the work last year. Childhood ADHD symptoms, sex differences, comorbidities of other mental disorders, and adult ADHD symptoms were examined by historical data, clinician interviews, and questionnaires. High levels of ADHD symptom severity in childhood were related to dropping out of high school [odds ratio (OR) = 3.0], as were higher numbers of hyperactive-impulsive symptoms in childhood. Significantly, more women than men were long-term work disabled (OR = 2.0). After adjusting for age and gender, persisting high levels of ADHD inattention symptoms in adulthood (OR = 2.5), number of comorbid disorders, and particularly anxiety disorders were significantly related to long-term work disability. Childhood hyperactive-impulsive symptoms and overall severity of childhood ADHD symptoms were associated with high school dropout rates; however, persisting ADHD inattention symptoms and comorbid mental disorders in adulthood were more correlated to occupational impairment. These findings underline proposals for studies on early recognition and interventions for ADHD and psychiatric comorbidity. They further suggest that inattentive symptoms be a focus of adult ADHD treatment and that workplace interventions be considered to prevent long-term work disability.

Dopamine and anorexia nervosa.

PubMed

Södersten, P; Bergh, C; Leon, M; Zandian, M

2016-01-01

We have suggested that reduced food intake increases the risk for anorexia nervosa by engaging mesolimbic dopamine neurons, thereby initially rewarding dieting. Recent fMRI studies have confirmed that dopamine neurons are activated in anorexia nervosa, but it is not clear whether this response is due to the disorder or to its resulting nutritional deficit. When the body senses the shortage of nutrients, it rapidly shifts behavior toward foraging for food as a normal physiological response and the mesolimbic dopamine neurons may be involved in that process. On the other hand, the altered dopamine status of anorexics has been suggested to result from a brain abnormality that underlies their complex emotional disorder. We suggest that the outcomes of the treatments that emerge from that perspective remain poor because they target the mental symptoms that are actually the consequences of the food deprivation that accompanies anorexia. On the other hand, a method that normalizes the disordered eating behavior of anorexics results in much better physiological, behavioral, and emotional outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mediators and Moderators of the Relation Between Parental ADHD Symptomatology and the Early Development of Child ADHD and ODD Symptoms

PubMed Central

Breaux, Rosanna P.; Brown, Hallie R.; Harvey, Elizabeth A.

2016-01-01

The present study examined mediators and moderators of the relation between parental ADHD symptomatology and the development of child attention deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms across the preschool years. Participants included 258 (138 boys) 3-year-old children (M = 44.13 months, SD = 3.39) with and without behavior problems and their parents who took part in a 3-year longitudinal study. Maternal ADHD symptoms predicted later ADHD symptoms in children, controlling for early child symptomatology. Both family history of ADHD and paternal comorbid psychopathology predicted later child ADHD and ODD symptoms, but they did not account for the association between maternal and child ADHD symptoms. Although paternal ADHD symptoms were associated with age 3 child ADHD symptoms, they did not significantly predict later child ADHD symptoms controlling for early symptomatology. Family adversity moderated the relation between maternal ADHD and child ADHD symptoms, such that the relation between maternal and child ADHD symptoms was stronger for families with less adversity. Maternal overreactive parenting mediated the relation between maternal ADHD symptoms and later child ADHD and ODD symptoms. Our findings suggest that targeting paternal comorbid psychopathology and maternal parenting holds promise for attenuating the effects of parental ADHD on children’s ADHD. PMID:27752934

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

PubMed Central

Hatcher, Jaime M.; Richardson, Jason R.; Guillot, Thomas S.; McCormack, Alison L.; Di Monte, Donato A.; Jones, Dean P.; Pennell, Kurt D.; Miller, Gary W.

2007-01-01

Numerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing Parkinson’s disease (PD). Here, we provide evidence that the insecticide dieldrin causes specific oxidative damage in the nigrostriatal dopamine (DA) system. We report that exposure of mice to low levels of dieldrin for 30 days resulted in alterations in dopamine-handling as evidenced by a decrease in dopamine metabolites, DOPAC (31.7% decrease) and HVA (29.2% decrease) and significantly increased cysteinyl-catechol levels in the striatum. Furthermore, dieldrin resulted in a 53% decrease in total glutathione, an increase in the redox potential of glutathione, and a 90% increase in protein carbonyls. α-Synuclein protein expression was also significantly increased in the striatum (25% increase). Finally, dieldrin caused a significant decrease in striatal expression of the dopamine transporter as measured by 3H-WIN 35,428 binding and 3H-dopamine uptake. These alterations occurred in the absence of dopamine neuron loss in the substantia nigra pars compacta. These effects represent the ability of low doses of dieldrin to increase the vulnerability of nigrostriatal dopamine neurons by inducing oxidative stress and suggest that pesticide exposure may act as a promoter of PD. PMID:17291500

Asperger Syndrome: a frequent comorbidity in first diagnosed adult ADHD patients?

PubMed

Roy, Mandy; Ohlmeier, Martin D; Osterhagen, Lasse; Prox-Vagedes, Vanessa; Dillo, Wolfgang

2013-06-01

Because adult ADHD is often accompanied by psychiatric comorbidities, the diagnostic process should include a thorough investigation for comorbid disorders. Asperger-Syndrome is rarely reported in adult ADHD and commonly little attention is paid to this possible comorbidity. We investigated 53 adult ADHD-patients which visited our out patient clinic for first ADHD-diagnosis (17 females, 36 males; range of age: 18-56 years) for the frequency of a comorbid Asperger-Syndrome. Diagnosis of this autism-spectrum disorder was confirmed by applying the appropriate DSM-IV-criteria. Additionally we tested the power of the two screening-instruments "Autism-spectrum quotient" (AQ) and "Empathy quotient" (EQ) by Baron-Cohen for screening Asperger-Syndrome in adult ADHD. Eight ADHD-patients were diagnosed with a comorbid Asperger-Syndrome (15.1%). The difference in AQ- and EQ-scores between pure ADHD-patients and comorbid patients was analysed, showing significantly higher scores in AQ and significant lower scores in EQ in comorbid patients. Results show that the frequency of Asperger-Syndrome seems to be substantially increased in adult ADHD (versus the prevalence of 0.06% in the general population), indicating that investigators of adult ADHD should also be attentive to autism-spectrum disorders. Especially the AQ seems to be a potential screening instrument for Asperger-Syndrome in adult ADHD-patients.

Brief Report: Adaptive Functioning in Children with ASD, ADHD and ASD + ADHD

ERIC Educational Resources Information Center

Ashwood, Karen L.; Tye, Charlotte; Azadi, Bahare; Cartwright, Sally; Asherson, Philip; Bolton, Patrick

2015-01-01

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often co-occur. Children with ASD and ADHD demonstrate deficits in adaptive functioning, yet pure and comorbid groups have not been directly compared. Vineland Adaptive Behaviour Scales (VABS-II) data were examined in boys with ASD (n = 17), ADHD (n = 31) and…

Impaired visuomotor adaptation in adults with ADHD.

PubMed

Kurdziel, Laura B F; Dempsey, Katherine; Zahara, Mackenzie; Valera, Eve; Spencer, Rebecca M C

2015-04-01

Attention-deficit hyperactivity disorder (ADHD) is a prevalent psychiatric disorder in children that often continues into adulthood. It has been suggested that motor impairments in ADHD are associated with underlying cerebellar pathology. If such is the case, individuals with ADHD should be impaired on motor tasks requiring healthy cerebellar function. To test this, we compared performance of individuals with ADHD and ADHD-like symptoms with non-ADHD controls on a visuomotor adaptation task known to be impaired following cerebellar lesions. Participants adapted reaching movements to a visual representation that was rotated by 30°. Individuals with ADHD and those with ADHD-like symptoms took longer to correct the angle of movement once the rotation was applied relative to controls. However, post-adaptation residual effect did not differ for individuals with ADHD and ADHD-like symptoms compared to the control group. These results are consistent with the hypothesis that mild cerebellar deficits are evident in the motor performance of adults with ADHD.

Exploring Behavioral Sleep Problems in Children With ADHD and Comorbid Autism Spectrum Disorder.

PubMed

Thomas, Simone; Lycett, Kate; Papadopoulos, Nicole; Sciberras, Emma; Rinehart, Nicole

2015-12-04

This study (a) compared behavioral sleep problems in children with comorbid ADHD and autism spectrum disorder (ASD) with those with ADHD and (b) examined child/family factors associated with sleep problems. Cross-sectional study comparison of 392 children with a confirmed ADHD diagnosis (ADHD+ASD, n=93, ADHD, n=299) recruited from 21 peadiatric practises in Victoria, Australia. Data were collected from parents. Key measures included the Child Sleep Habits Questionnaire (CSHQ). Children with ADHD + ASD experienced similar levels and types of behavioral sleep problems compared with those with ADHD. In both groups, the presence of co-occurring internalizing and externalizing comorbidities was associated with sleep problems. Sleep problems were also associated with parent age in the ADHD + ASD group and poorer parent mental health in the ADHD group. Findings suggest comorbid ASD is not associated with increased behavioral sleep problems in children with ADHD and that co-occurring internalizing and externalizing comorbidities may flag children in these groups with sleep problems. © The Author(s) 2015.

Central Processing Energetic Factors Mediate Impaired Motor Control in ADHD Combined Subtype but Not in ADHD Inattentive Subtype

ERIC Educational Resources Information Center

Egeland, Jens; Ueland, Torill; Johansen, Susanne

2012-01-01

Participants with attention-deficit/hyperactivity disorder (ADHD) are often impaired in visuomotor tasks. However, little is known about the contribution of modal impairment in motor function relative to central processing deficits or whether different processes underlie the impairment in ADHD combined (ADHD-C) versus ADHD inattentive (ADHD-I)…

Dopamine reward prediction error coding.

PubMed

Schultz, Wolfram

2016-03-01

Reward prediction errors consist of the differences between received and predicted rewards. They are crucial for basic forms of learning about rewards and make us strive for more rewards-an evolutionary beneficial trait. Most dopamine neurons in the midbrain of humans, monkeys, and rodents signal a reward prediction error; they are activated by more reward than predicted (positive prediction error), remain at baseline activity for fully predicted rewards, and show depressed activity with less reward than predicted (negative prediction error). The dopamine signal increases nonlinearly with reward value and codes formal economic utility. Drugs of addiction generate, hijack, and amplify the dopamine reward signal and induce exaggerated, uncontrolled dopamine effects on neuronal plasticity. The striatum, amygdala, and frontal cortex also show reward prediction error coding, but only in subpopulations of neurons. Thus, the important concept of reward prediction errors is implemented in neuronal hardware.

Dopamine reward prediction error coding

PubMed Central

Schultz, Wolfram

2016-01-01

Reward prediction errors consist of the differences between received and predicted rewards. They are crucial for basic forms of learning about rewards and make us strive for more rewards—an evolutionary beneficial trait. Most dopamine neurons in the midbrain of humans, monkeys, and rodents signal a reward prediction error; they are activated by more reward than predicted (positive prediction error), remain at baseline activity for fully predicted rewards, and show depressed activity with less reward than predicted (negative prediction error). The dopamine signal increases nonlinearly with reward value and codes formal economic utility. Drugs of addiction generate, hijack, and amplify the dopamine reward signal and induce exaggerated, uncontrolled dopamine effects on neuronal plasticity. The striatum, amygdala, and frontal cortex also show reward prediction error coding, but only in subpopulations of neurons. Thus, the important concept of reward prediction errors is implemented in neuronal hardware. PMID:27069377

Resting-State Neurophysiological Activity Patterns in Young People with ASD, ADHD, and ASD + ADHD

ERIC Educational Resources Information Center

Shephard, Elizabeth; Tye, Charlotte; Ashwood, Karen L.; Azadi, Bahar; Asherson, Philip; Bolton, Patrick F.; McLoughlin, Grainne

2018-01-01

Altered power of resting-state neurophysiological activity has been associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. We compared resting-state neurophysiological power in children with ASD, ADHD, co-occurring ASD + ADHD, and typically developing controls. Children with ASD…

The Role of Parental ADHD in Sustaining the Effects of a Family-School Intervention for ADHD

PubMed Central

Dawson, Anne E.; Wymbs, Brian T.; Marshall, Stephen A.; Mautone, Jennifer A.; Power, Thomas J.

2014-01-01

Objective This study investigated the extent to which parental Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms impact child and parent outcomes following a multimodal family-school intervention, the Family School Success (FSS) program, when compared to an active-control condition (CARE). Method Participants were 139 children with ADHD (67% male; 91% non-Hispanic; 77% Caucasian; grades 2–6) and their primary caretaker (91% female; aged 26–59) who participated in a randomized clinical trial evaluating the efficacy of FSS. Associations were examined between parent-reported ADHD symptoms at baseline and intervention outcomes reported by parents and teachers after treatment and at a 3-month follow-up, including child homework and classroom impairments, child ADHD and oppositional defiant disorder symptoms, parenting behaviors, and parent-teacher relationship quality. Results Across both treatment conditions, parental ADHD was not associated with parent or child outcomes at post-assessment. However, differences emerged between the two treatment groups at follow-up for parents with ADHD, particularly when an empirically-supported symptom cutoff was used to identify parents at-risk for having ADHD. In FSS, but not in CARE, parental ADHD was associated with declines in treatment gains in the quality of the parent-teacher relationship and the child’s homework performance. Conclusions Parents at-risk for ADHD had difficulty maintaining treatment effects for themselves and their child in the FSS intervention, but not in CARE. The supportive and educational components central to the CARE intervention may be helpful in promoting the sustainability of psychosocial interventions for children with ADHD who have parents with elevated ADHD symptoms. PMID:25496523

Sibling Relationships among Children with ADHD

ERIC Educational Resources Information Center

Mikami, Amori Yee; Pfiffner, Linda J.

2008-01-01

Objective: This study investigated the quality of sibling relationships among children with ADHD relative to those without ADHD. Additional analyses examined whether externalizing and internalizing problems comorbid with ADHD affected sibling relationships. Method: Participants were 77 children with ADHD and 14 nonproblem control children. Sibling…

Age dependent electroencephalographic changes in attention-deficit/hyperactivity disorder (ADHD).

PubMed

Poil, S-S; Bollmann, S; Ghisleni, C; O'Gorman, R L; Klaver, P; Ball, J; Eich-Höchli, D; Brandeis, D; Michels, L

2014-08-01

Objective biomarkers for attention-deficit/hyperactivity disorder (ADHD) could improve diagnostics or treatment monitoring of this psychiatric disorder. The resting electroencephalogram (EEG) provides non-invasive spectral markers of brain function and development. Their accuracy as ADHD markers is increasingly questioned but may improve with pattern classification. This study provides an integrated analysis of ADHD and developmental effects in children and adults using regression analysis and support vector machine classification of spectral resting (eyes-closed) EEG biomarkers in order to clarify their diagnostic value. ADHD effects on EEG strongly depend on age and frequency. We observed typical non-linear developmental decreases in delta and theta power for both ADHD and control groups. However, for ADHD adults we found a slowing in alpha frequency combined with a higher power in alpha-1 (8-10Hz) and beta (13-30Hz). Support vector machine classification of ADHD adults versus controls yielded a notable cross validated sensitivity of 67% and specificity of 83% using power and central frequency from all frequency bands. ADHD children were not classified convincingly with these markers. Resting state electrophysiology is altered in ADHD, and these electrophysiological impairments persist into adulthood. Spectral biomarkers may have both diagnostic and prognostic value. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

ADHD and Adolescent Athletes

PubMed Central

Nazeer, Ahsan; Mansour, Miriam; Gross, Kathleen A.

2014-01-01

Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that affects the child and adolescent population. It is characterized by impairment in attention/concentration, hyperactivity, and impulsivity, all of which can impact performance of athletes. ADHD treatment within the athletic population is a unique challenge. The research in this field has been relatively limited. The National Collegiate Athletic Association and International Olympic Committee both regulate the use of psychostimulants for treatment of ADHD due to their performance-enhancing effects. In this article, authors have discussed the screening methods, pharmacological treatment, side effects, and behavioral approaches for the treatment of ADHD in adolescent athletes. PMID:24987666

Psychosis proneness and ADHD in young relatives of schizophrenia patients.

PubMed

Keshavan, Matcheri S; Sujata, Mandayam; Mehra, Akhil; Montrose, Debra M; Sweeney, John A

2003-01-01

Symptoms resembling the attentional deficit hyperactivity disorder (ADHD) are frequently observed in young relatives at risk for schizophrenia (HR). We examined the frequency of the ADHD syndrome and its relationship to psychosis related psychopathology and neurobehavioral abnormalities in young HR subjects (n=29) and healthy comparison subjects (HC; n=30). Thirty-one percent of HR subjects (n=9) had ADHD as a lifetime Axis-I diagnosis (HR-A). Compared to healthy comparison subjects, the HR-A group had impaired neurological function. The HR-A group but not the HR subjects without ADHD had higher scores on the Chapman's magical ideation and perceptual aberration scales. Thus, ADHD-like features are more prevalent in the HR population than the one described in the general population and are associated with more frequent psychosis-like clinical features. Longitudinal studies can clarify whether an "ADHD subgroup" within HR subjects predict an increased risk for future emergence of schizophrenia.

Preservice School Personnel's Knowledge of Stimulant Medication and ADHD

ERIC Educational Resources Information Center

Pindiprolu, Sekhar S.

2014-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most commonly diagnosed disorders among children today. Stimulants are commonly prescribed to children with ADHD to improve attention span and decrease distractibility, hyperactivity, and impulsivity. Given the increased use of stimulant medication, school personnel need to be aware of…

[Attention deficit-hyperactivity disorder (ADHD) and comorbid mental disorders : ADHD-specific self-rating scales in differential diagnostics].

PubMed

Paucke, M; Stark, T; Exner, C; Kallweit, C; Hegerl, U; Strauß, M

2018-06-18

It is still unclear how well the established attention deficit-hyperactive disorder (ADHD)-specific rating scales can differentiate between ADHD symptoms and symptoms of other mental disorders. A total of 274 patients with suspected adult ADHD were extensively examined clinically and guideline-conform in an ADHD outpatient clinic. In 190 patients the diagnosis of ADHD could be made with certainty. The patients were also subsequently assessed according to the DSM IV criteria by self-rating scales on current (ADHS-SB, ASRS, CAARS) and retrospective (WURS-K) complaints. A binary logistic regression analysis was performed in order to extract from the questionnaires, which could best distinguish the diagnosis of ADHD from other mental disorders. The results showed that two self-rating scales (WURS-K and ADHS-SB) were sufficient to correctly diagnose ADHD in 83% of the patients examined with a sensitivity of 94% and specificity of 56%. The ADHD-specific self-rating scales are additionally useful for the diagnostic differentiation between ADHD-specific and other psychiatric symptoms in the clinical practice and can improve the safety of the diagnosis.

The dopamine theory of addiction: 40 years of highs and lows.

PubMed

Nutt, David J; Lingford-Hughes, Anne; Erritzoe, David; Stokes, Paul R A

2015-05-01

For several decades, addiction has come to be viewed as a disorder of the dopamine neurotransmitter system; however, this view has not led to new treatments. In this Opinion article, we review the origins of the dopamine theory of addiction and discuss the ability of addictive drugs to elicit the release of dopamine in the human striatum. There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels. Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions.

[Clinical and neurophysiological data of neurofeedback therapy in children with ADHD].

PubMed

Kubik, Alicja; Kubik, Paweł; Stanios, Martyna; Kraj, Bogusława

2016-01-01

ADHD occurs in 3% of school-age children (and in 70% of them in adulthood) and represents an important medical and social problem. It is characterized by attention deficits, hyperactivity and impulsiveness. Neurofeedback therapy (EEG biofeedback, NF) is carried out based on the analysis of EEG. To investigate the effect of NF therapy on clinical status and parameters of the EEG in ADHD. In the years 2007-2014, 287 children (191 boys), aged 6-17 years were included into the study. Some children with ADHD had other coexisting disorders like: tics, dyslexia, emotional or behavior disorders. Visual analysis of EEG was made and 7 selected parameters of bioelectrical activity were assessed. EEG tracing before and after NF therapy were compared. NF therapy lasted from 9 months to 3 years (mean 1.5 years). 60-240 NF training sessions were performed with the use of NF device, video-games and 16-channel Elmiko devices. Statistical analysis of the results was made. Children with ADHD additionally presented low self-esteem, anxiety and sleep disorders. The baseline theta/beta ratio in children with ADHD and ADHD with cooccurring dyslexia was >4.0 and in children with ADHD and coexisting tics 3.0-3.8, with coexisting behavioral disorders 3.7-4.0 and emotional disorders 3.3-3.7. After therapy, this ratio decreased significantly in all groups, but most significantly in ADHD and ADHD with dyslexia group. In the group with dyslexia theta and alpha activity in the left fronto-temporo-parietal region (the speech centers) has been increased. In children with ADHD and behavior disorders right-sided paroxysmal changes in the form of slow and sharp waves in the temporo-centro-parietal regions were found. In emotionally disturbed children increased fast beta activity in the right hemisphere (anxiety, fear) was observed. Initially NF therapy reduced hyperactivity and impulsivity of children, subsequently improvement of attention was observed and eventually reduction of emotional and

ADHD and academic performance: why does ADHD impact on academic performance and what can be done to support ADHD children in the classroom?

PubMed

Daley, D; Birchwood, J

2010-07-01

This paper reviews the relationship between attention deficit hyperactivity disorder (ADHD) and academic performance. First, the relationship at different developmental stages is examined, focusing on pre-schoolers, children, adolescents and adults. Second, the review examines the factors underpinning the relationship between ADHD and academic underperformance: the literature suggests that it is the symptoms of ADHD and underlying cognitive deficits not co-morbid conduct problems that are at the root of academic impairment. The review concludes with an overview of the literature examining strategies that are directed towards remediating the academic impairment of individuals with ADHD.

Comorbid anxiety and depression in school-aged children with attention deficit hyperactivity disorder (ADHD) and selfreported symptoms of ADHD, anxiety, and depression among parents of school-aged children with and without ADHD

PubMed Central

XIA, Weiping; SHEN, Lixiao; ZHANG, Jinsong

2015-01-01

Background Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in children that can extend into adulthood and that is often associated with a variety of comorbid psychiatric disorders. Aim Assess the comorbidity of ADHD with anxiety disorders and depressive disorders in school-aged children, and the relationship of the severity of ADHD, anxiety, and depressive symptoms in children who have ADHD with the severity of the corresponding symptoms in their parents. Methods A two-stage screening process identified children 7-10 years of age with and without ADHD treated at the Xin Hua Hospital in Shanghai. ADHD and other DSM-IV diagnoses were determined by a senior clinician using the Schedule for Affective Disorder and Schizophrenia for School-Aged Children (K-SADS-PL). One parent for each enrolled child completed three self-report scales: the ADHD Adult Self Report Scale (ASRS), the State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI). In total 135 children with ADHD and 65 control group children without ADHD were enrolled; parents for 94 of the children with ADHD and 63 of the children without ADHD completed the parental assessment scales. Results Among the 135 children with ADHD, 27% had a comorbid anxiety disorder, 18% had a comorbid depressive disorder, and another 15% had both comorbid anxiety and depressive disorders. Parents of children with ADHD self-reported more severe ADHD inattention symptoms than parents of children without ADHD and were more likely to meet criteria for adult ADHD. Mothers (but not fathers) of children with ADHD had significantly more severe trait anxiety and depressive symptoms than mothers of children without ADHD. Among children with ADHD, the severity of ADHD symptoms was not significantly correlated with the severity of ADHD symptoms in parents, but depressive symptoms and anxiety symptoms in the children were significantly correlated with the corresponding symptoms in the parents

Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.

PubMed

Goutier, W; Lowry, J P; McCreary, A C; O'Connor, J J

2016-05-01

Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

Antisocial Alcoholism in Parents of Adolescents and Young Adults with Childhood ADHD

PubMed Central

Molina, Brooke S.G.; Gnagy, Elizabeth M.; Joseph, Heather M.; Pelham, William E.

2017-01-01

Objective Test the hypothesis that alcoholism, including antisocial alcoholism, is more prevalent among mothers and fathers of children with versus without ADHD. Method Mothers (312 ADHD group, 235 non-ADHD group) and fathers (291 ADHD group, 227 non-ADHD group) in the Pittsburgh ADHD Longitudinal Study were interviewed along with their adolescent and young adult offspring. Results Maternal and paternal alcoholism, with and without comorbid antisociality, was more prevalent in the ADHD group. Paternal alcoholism without antisociality was only marginally higher for probands after controlling for paternal ADHD. Offspring conduct disorder comorbidity was associated with parental antisociality but not parental antisocial alcoholism. Conclusions Our findings that 44% of proband fathers and 25% of proband mothers experienced alcohol problems with or without antisociality, are further evidence of increased alcoholism prevalence in families affected by ADHD. Maternal alcoholism and antisociality are prominent contributors to this family-level vulnerability. These findings indicate the need to assess long-term offspring outcomes as a function of parental alcohol and externalizing comorbidities, and perhaps other indicators of parental alcoholism phenotype, as familial vulnerability unfolds across development. PMID:27895188

ADHD subtypes and comorbid anxiety, depression, and oppositional-defiant disorder: differences in sleep problems.

PubMed

Mayes, Susan Dickerson; Calhoun, Susan L; Bixler, Edward O; Vgontzas, Alexandros N; Mahr, Fauzia; Hillwig-Garcia, Jolene; Elamir, Belal; Edhere-Ekezie, Linda; Parvin, Matthew

2009-04-01

Sleep problems were analyzed in children with ADHD (Attention-deficit hyperactivity disorder). Scales were completed by parents of 135 control children and 681 children with ADHD combined type (ADHD-C) or inattentive type (ADHD-I) with or without comorbid oppositional defiant disorder (ODD), anxiety, or depression. Children with ADHD-I alone had the fewest sleep problems and did not differ from controls. Children with ADHD-C had more sleep problems than controls and children with ADHD-I. Comorbid anxiety/depression increased sleep problems, whereas ODD did not. Daytime sleepiness was greatest in ADHD-I and was associated with sleeping more (not less) than normal. Medicated children had greater difficulty falling asleep than unmedicated children. Differences in sleep problems were found as a function of ADHD subtype, comorbidity, and medication.

Demographic Characteristics and Psychiatric Comorbidity of Children and Adolescents Diagnosed with ADHD in Specialized Healthcare.

PubMed

Joelsson, Petteri; Chudal, Roshan; Gyllenberg, David; Kesti, Anna-Kaisa; Hinkka-Yli-Salomäki, Susanna; Virtanen, Juha-Pekka; Huttunen, Jukka; Ristkari, Terja; Parkkola, Kai; Gissler, Mika; Sourander, Andre

2016-08-01

Recent studies have shown an increasing incidence of attention-deficit/hyperactivity disorder (ADHD) among children diagnosed in specialized services. This study aims to describe children with ADHD in Finnish specialized healthcare by reporting the demographic characteristics, time trends in diagnosis, psychiatric comorbidity, and the validity of register-based diagnoses. All the singletons born in Finland between 1991 and 2005 and diagnosed with ADHD by 2011 were identified and their psychiatric comorbidity data was obtained from the Finnish Hospital Discharge Register (FHDR). Parents of 69 patients were interviewed via telephone for a diagnostic validation. A total of 10,409 children were identified with ADHD, with a male: female ratio of 5.3:1 and a psychiatric comorbidity rate of 76.7 %. Of the validation sample 88 % met the diagnostic criteria of ADHD for DSM-IV. There is an increasing trend of ADHD diagnosis among both males and females. Psychiatric comorbidity is common and includes a wide range of disorders among children with ADHD. There was an increase of ADHD diagnoses especially among boys. More attention is needed to detect ADHD among girls in health services. Diagnoses in the FHDR show diagnostic validity and their sociodemographic patterns are in line with previous studies.

Manipulation of dopamine metabolism contributes to attenuating innate high locomotor activity in ICR mice.

PubMed

Yamaguchi, Takeshi; Nagasawa, Mao; Ikeda, Hiromi; Kodaira, Momoko; Minaminaka, Kimie; Chowdhury, Vishwajit S; Yasuo, Shinobu; Furuse, Mitsuhiro

2017-06-15

Attention-deficit hyperactivity disorder (ADHD) is defined as attention deficiency, restlessness and distraction. The main characteristics of ADHD are hyperactivity, impulsiveness and carelessness. There is a possibility that these abnormal behaviors, in particular hyperactivity, are derived from abnormal dopamine (DA) neurotransmission. To elucidate the mechanism of high locomotor activity, the relationship between innate activity levels and brain monoamines and amino acids was investigated in this study. Differences in locomotor activity between ICR, C57BL/6J and CBA/N mice were determined using the open field test. Among the three strains, ICR mice showed the greatest amount of locomotor activity. The level of striatal and cerebellar DA was lower in ICR mice than in C57BL/6J mice, while the level of L-tyrosine (L-Tyr), a DA precursor, was higher in ICR mice. These results suggest that the metabolic conversion of L-Tyr to DA is lower in ICR mice than it is in C57BL/6J mice. Next, the effects of intraperitoneal injection of (6R)-5, 6, 7, 8-tetrahydro-l-biopterin dihydrochloride (BH 4 ) (a co-enzyme for tyrosine hydroxylase) and L-3,4-dihydroxyphenylalanine (L-DOPA) on DA metabolism and behavior in ICR mice were investigated. The DA level in the brain was increased by BH 4 administration, but the increased DA did not influence behavior. However, L-DOPA administration drastically lowered locomotor activity and increased DA concentration in several parts of the brain. The reduced locomotor activity may have been a consequence of the overproduction of DA. In conclusion, the high level of locomotor activity in ICR mice may be explained by a strain-specific DA metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

Injury among stimulant-treated youth with ADHD.

PubMed

Marcus, Steven C; Wan, George J; Zhang, Huabin F; Olfson, Mark

2008-07-01

To assess risk factors for injury among children and adolescents treated with stimulants for ADHD. An analysis was performed of pharmacy and service claims data from 2000-2003 California Medicaid (Medi-Cal) focusing on children and adolescents ages 6 to 17 years who initiated stimulant therapy for ADHD. Bivariate and multivariate analyses were performed to examine associations of demographic and clinical characteristics with injury. In a Cox proportional hazard model that controlled for background patient characteristics, patients ages 13 to 17 years, male gender, prescription of anxiolytic/hypnotic medications, and diagnosis of a mood disorder were each independently associated with increased risk of injury, whereas African American ancestry and other minority racial/ethnic ancestry were associated with lower risk. Youth with high stimulant medication possession ratios (MPR) had a nonsignificantly lower risk of injury as compared to those with a low stimulant MPR. These findings reveal several patient characteristics that may be associated with increased risk of injury among children and adolescents treated for ADHD.

Pediatric ADHD Medication Exposures Reported to US Poison Control Centers.

PubMed

King, Samantha A; Casavant, Marcel J; Spiller, Henry A; Hodges, Nichole L; Chounthirath, Thitphalak; Smith, Gary A

2018-06-01

: media-1vid110.1542/5754332180001PEDS-VA_2017-3872 Video Abstract OBJECTIVES: To describe the characteristics and trends of exposures to attention-deficit/hyperactivity disorder (ADHD) medications among individuals 0 to 19 years old reported to US poison control centers. National Poison Data System data from 2000 through 2014 were retrospectively analyzed to examine pediatric ADHD medication exposures. From 2000 through 2014, there were 156 365 exposures reported to US poison control centers related to ADHD medications. The overall rate of reported exposures increased 71.2% from 2000 to 2011, followed by a 6.2% decrease from 2011 to 2014. Three-fourths (76.0%) of exposures involved children ≤12 years old. Methylphenidate and amphetamine medications accounted for 46.2% and 44.5% of exposures, respectively. The most common reason for exposure was therapeutic error (41.6%). Intentional medication exposures (including suspected suicide and medication abuse and/or misuse) were reported most often among adolescents (13-19 years old), accounting for 50.2% of exposures in this age group. Overall, the majority of exposed individuals (60.4%) did not receive health care facility treatment; however, 6.2% were admitted to a hospital for medical treatment, and there were 3 deaths. The increasing number and rate of reported ADHD medication exposures during the study period is consistent with increasing trends in ADHD diagnosis and medication prescribing. Exposures associated with suspected suicide or medication abuse and/or misuse among adolescents are of particular concern. Unintentional and intentional pediatric exposures to ADHD medications are an increasing problem in the United States, affecting children of all ages. Copyright © 2018 by the American Academy of Pediatrics.

Under diagnosis of adult ADHD: cultural influences and societal burden.

PubMed

Asherson, Philip; Akehurst, Ron; Kooij, J J Sandra; Huss, Michael; Beusterien, Kathleen; Sasané, Rahul; Gholizadeh, Shadi; Hodgkins, Paul

2012-07-01

To explore the literature focusing on cultural influences in the diagnosis of adult ADHD and respective societal burden. A review of the literature over the past 10 years was performed using OVID. Although numerous articles focused on diagnosis and burden of adult ADHD, few focused on cultural factors influencing diagnosis. Like other mental health disorders, cultural and social perspectives contribute to our understanding of adult ADHD and may play a significant role in the diagnosis and varying acceptance of the condition. Moreover, adults with ADHD may underestimate the impact of ADHD symptoms, and in many cases have learned to compensate for ADHD related impairments by choosing lifestyles that help compensate for symptoms. Some adults with ADHD may appear to function well, however they may expend excessive amounts of energy to overcome impairments; and they may be distressed by ongoing symptoms such as restlessness, mood instability and low self-esteem. Research shows that ADHD can be detrimental to many areas of life including work, daily activities, social and family relationships and psychological and physical well-being. Patient-reported impairments in productivity due to poor time management, procrastination, and distractibility can translate into significant indirect costs and decreased quality of life. ADHD in adults is also associated with increased accidents, medical resource utilization, antisocial behaviour and drug alcohol abuse. The substantial societal burden of adult ADHD highlights the importance of providing a better understanding of the factors that contribute to accurate diagnosis and of improving the low recognition of the disorder in many world regions.

Insulin resistance impairs nigrostriatal dopamine function.

PubMed

Morris, J K; Bomhoff, G L; Gorres, B K; Davis, V A; Kim, J; Lee, P-P; Brooks, W M; Gerhardt, G A; Geiger, P C; Stanford, J A

2011-09-01

Clinical studies have indicated a link between Parkinson's disease (PD) and Type 2 Diabetes. Although preclinical studies have examined the effect of high-fat feeding on dopamine function in brain reward pathways, the effect of diet on neurotransmission in the nigrostriatal pathway, which is affected in PD and parkinsonism, is less clear. We hypothesized that a high-fat diet, which models early-stage Type 2 Diabetes, would disrupt nigrostriatal dopamine function in young adult Fischer 344 rats. Rats were fed a high fat diet (60% calories from fat) or a normal chow diet for 12 weeks. High fat-fed animals were insulin resistant compared to chow-fed controls. Potassium-evoked dopamine release and dopamine clearance were measured in the striatum using in vivo electrochemistry. Dopamine release was attenuated and dopamine clearance was diminished in the high-fat diet group compared to chow-fed rats. Magnetic resonance imaging indicated increased iron deposition in the substantia nigra of the high fat group. This finding was supported by alterations in the expression of several proteins involved in iron metabolism in the substantia nigra in this group compared to chow-fed animals. The diet-induced systemic and basal ganglia-specific changes may play a role in the observed impairment of nigrostriatal dopamine function. Copyright © 2011 Elsevier Inc. All rights reserved.

Confronting ADHD in the Music Classroom

ERIC Educational Resources Information Center

Moore, Patience

2009-01-01

Tell-tale signs of Attention Deficit Hyperactive Disorder (ADHD) ADHD and its relative ADD (Attention Deficit Disorder) include an inability to maintain attention, impulsive behaviors, and/or motor restlessness. There are three subcategories of ADHD; for the purpose of this article, the blanket term ADHD applies to all three. A crucial first step…

Relationship Between Sleep Problems and Quality of Life in Children With ADHD.

PubMed

Yürümez, Esra; Kılıç, Birim Günay

2016-01-01

The purpose of this study is to assess the sleep behaviors, sleep problems and frequency, and relationship with psychiatric comorbidities in ADHD Combined type and to evaluate the effect of sleep problems on quality of life. Forty-six boys, aged 7 to 13 years, with ADHD-combined type and 31 healthy boys were included. ADHD children were never treated for sleep or psychiatric disorders. Intelligence quotient (IQ) test scores were minimum 80, body mass index were normal and did not have medical disorders. Parents completed Children's Sleep Habits Questionnaire, Conners' Parent Rating Scale and The Pediatric Quality of Life Inventory (PedsQL) and participants were asked about sleep behaviors and were administered PedsQL and Schedule for Affective Disorders and Schizophrenia. The frequency of sleep problems in ADHD is 84.8%, higher than the control group (p = .002). Evaluating PedsQL scores, the quality of life is worse in physical, psychosocial health, and total life quality (p < .05). ADHD group with sleep problems have more night wakings than control group with sleep problems (p = .02). The comorbidity do not increase sleep problems. The frequency of parasomnias is increased in group with learning disorders (p = .05). The results of this study, which controls for a number of possible confounders found in previous examinations of ADHD and sleep, support the results of a number of other studies that have found an increased overall prevalence of parent-reported sleep disturbances in children with ADHD compared with healthy control participants. As the ADHD group have more night wakings than the control group through the night, it is thought that night wakings that cause a partitioned sleep may be important signs seen in ADHD. That could be suggested by two hypotheses. First one is that, daytime sleepiness is more common in ADHD and those children present excessive hyperactivity during the day to stay awake and the second one is the improvement of ADHD signs when the

Coaching for College Students with ADHD.

PubMed

Prevatt, Frances

2016-12-01

Evidence suggests that ADHD can impair academic achievement in college students and throughout the life span. College students with ADHD are an at-risk population who might benefit from interventions. An offshoot of CBT-oriented therapy that has grown significantly and gained popularity in recent years is ADHD coaching. ADHD coaching is a psychosocial intervention that helps individuals develop skills, strategies, and behaviors to cope with the core impairments associated with ADHD. Most coaching programs are primarily based on a CBT approach and target planning, time management, goal setting, organization, and problem solving. This paper describes ADHD coaching for college students and discusses how coaching is different from standard CBT treatment. This is followed by a review of empirical studies of the effectiveness of ADHD coaching for college students. Finally, some specific considerations and procedures used in coaching are described.

Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in Wistar and Spontaneously Hypertensive Rats.

PubMed

Gauthier, Jamie M; Tassin, David H; Dwoskin, Linda P; Kantak, Kathleen M

2014-07-15

Attention Deficit Hyperactivity Disorder (ADHD) is associated with dysfunctional prefrontal and striatal circuitry and dysregulated dopamine neurotransmission. Spontaneously Hypertensive Rats (SHR), a heuristically useful animal model of ADHD, were evaluated against normotensive Wistar (WIS) controls to determine whether dopamine D1 receptor blockade of either prelimbic prefrontal cortex (plPFC) or lateral dorsal striatum (lDST) altered learning functions of both interconnected sites. A strategy set shifting task measured plPFC function (behavioral flexibility/executive function) and a reward devaluation task measured lDST function (habitual responding). Prior to tests, rats received bilateral infusions of SCH 23390 (1.0 μg/side) or vehicle into plPFC or lDST. Following vehicle, SHR exhibited longer lever press reaction times, more trial omissions, and fewer completed trials during the set shift test compared to WIS, indicating slower decision-making and attentional/motivational impairment in SHR. After reward devaluation, vehicle-treated SHR responded less than WIS, indicating relatively less habitual responding in SHR. After SCH 23390 infusions into plPFC, WIS expressed the same behavioral phenotype as vehicle-treated SHR during set shift and reward devaluation tests. In SHR, SCH 23390 infusions into plPFC exacerbated behavioral deficits in the set shift test and maintained the lower rate of responding in the reward devaluation test. SCH 23390 infusions into lDST did not modify set shifting in either strain, but produced lower rates of responding than vehicle infusions after reward devaluation in WIS. This research provides pharmacological evidence for unidirectional interactions between prefrontal and striatal brain regions, which has implications for the neurological basis of ADHD and its treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Long-term consequences of childhood ADHD on criminal activities.

PubMed

Fletcher, Jason; Wolfe, Barbara

2009-09-01

Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent mental health problems facing children. Little is known of the long-term consequences of ADHD on young adult outcomes. We examine the associations between childhood ADHD symptoms and criminal activities as a young adult. We use a nationally representative study of US adolescents and logistic regression analysis to examine our research question. We also control for common family factors using sibling random and fixed effects and test the robustness of our results in several ways. The empirical estimates show that children who experience ADHD symptoms face a substantially increased likelihood of engaging in many types of criminal activities. An included calculation of the social costs associated with criminal activities by individuals with childhood ADHD finds the costs to be substantial. Our study provides the first evidence using a nationally representative dataset of the long term consequences on criminal activities of childhood ADHD. Our results are quite robust to a number of specification checks. Limitations of our study include that our measures of ADHD are retrospective, we have no information on treatment for ADHD, and it remains possible that our results are confounded by unmeasured variables. Our results suggest that children showing ADHD symptoms should be viewed as a group at high risk of poor outcomes as young adults. As such, a good case can be made for targeting intervention programs on this group of children and conducting evaluations to learn if such interventions are effective in reducing the probability that these children commit a crime. Development of such intervention programs and evaluating them for efficiency could be dollars well spent in terms of crime and drug abuse averted.

Inhibition, Reinforcement Sensitivity and Temporal Information Processing in ADHD and ADHD+ODD: Evidence of a Separate Entity?

ERIC Educational Resources Information Center

Luman, Marjolein; van Noesel, Steffen J. P.; Papanikolau, Alky; Van Oostenbruggen-Scheffer, Janneke; Veugelers, Diane; Sergeant, Joseph A.; Oosterlaan, Jaap

2009-01-01

This study compared children with ADHD-only, ADHD+ODD and normal controls (age 8-12) on three key neurocognitive functions: response inhibition, reinforcement sensitivity, and temporal information processing. The goal was twofold: (a) to investigate neurocognitive impairments in children with ADHD-only and children with ADHD+ODD, and (b) to test…

Interaction of recalled parental ADHD symptoms and rearing behavior with current attachment and emotional dysfunction in adult offspring with ADHD.

PubMed

Edel, Marc-Andreas; Juckel, Georg; Brüne, Martin

2010-06-30

Research into attachment and emotion regulation has shown that children with ADHD are at risk of developing attachment disorders and emotion regulation disturbances, which in part may be due to the rearing style of their parents. No such data exists for adults with persistent ADHD. We hypothesized that current attachment style and emotion processing of adult patients with ADHD may be influenced by the presence of parental ADHD symptoms when the now adult patients were children, assuming that ADHD symptoms of parents have an impact on their parenting style. We examined recalled parental ADHD symptoms and rearing style as well as current attachment and emotion regulation abilities in a sample of 73 adults with ADHD using several self-rating instruments. Recalled prevalence of ADHD symptoms in the mother, and less so in the father, of adult patients with ADHD was significantly associated with partly adverse parental rearing styles, current attachment problems in romantic partnerships and emotion regulation disturbances compared with adult ADHD patients without possibly affected parent. ADHD symptoms in parents of children with ADHD may present a risk factor for attachment problems and poor emotion regulation when ADHD children are grown.

Standardised assessment of functioning in ADHD: consensus on the ICF Core Sets for ADHD.

PubMed

Bölte, Sven; Mahdi, Soheil; Coghill, David; Gau, Susan Shur-Fen; Granlund, Mats; Holtmann, Martin; Karande, Sunil; Levy, Florence; Rohde, Luis A; Segerer, Wolfgang; de Vries, Petrus J; Selb, Melissa

2018-02-12

Attention-deficit/hyperactivity disorder (ADHD) is associated with significant impairments in social, educational, and occupational functioning, as well as specific strengths. Currently, there is no internationally accepted standard to assess the functioning of individuals with ADHD. WHO's International Classification of Functioning, Disability and Health-child and youth version (ICF) can serve as a conceptual basis for such a standard. The objective of this study is to develop a comprehensive, a common brief, and three age-appropriate brief ICF Core Sets for ADHD. Using a standardised methodology, four international preparatory studies generated 132 second-level ICF candidate categories that served as the basis for developing ADHD Core Sets. Using these categories and following an iterative consensus process, 20 ADHD experts from nine professional disciplines and representing all six WHO regions selected the most relevant categories to constitute the ADHD Core Sets. The consensus process resulted in 72 second-level ICF categories forming the comprehensive ICF Core Set-these represented 8 body functions, 35 activities and participation, and 29 environmental categories. A Common Brief Core Set that included 38 categories was also defined. Age-specific brief Core Sets included a 47 category preschool version for 0-5 years old, a 55 category school-age version for 6-16 years old, and a 52 category version for older adolescents and adults 17 years old and above. The ICF Core Sets for ADHD mark a milestone toward an internationally standardised functional assessment of ADHD across the lifespan, and across educational, administrative, clinical, and research settings.

College Students' Attitudes toward Their ADHD Peers

ERIC Educational Resources Information Center

Chew, Brandi L.; Jensen, Scott A.; Rosen, Lee A.

2009-01-01

Objective: The attitudes of college students with and without ADHD toward peers with ADHD were examined. Method: A total of 196 college students (30 diagnosed with ADHD) anonymously completed four attitude measures. General analyses of attitudes toward peers with ADHD as well as comparisons between those with and without ADHD are made. Results:…

Adolescent prescription ADHD medication abuse is rising along with prescriptions for these medications.

PubMed

Setlik, Jennifer; Bond, G Randall; Ho, Mona

2009-09-01

We sought to better understand the trend for prescription attention-deficit/hyperactivity disorder (ADHD) medication abuse by teenagers. We queried the American Association of Poison Control Center's National Poison Data System for the years of 1998-2005 for all cases involving people aged 13 to 19 years, for which the reason was intentional abuse or intentional misuse and the substance was a prescription medication used for ADHD treatment. For trend comparison, we sought data on the total number of exposures. In addition, we used teen and preteen ADHD medication sales data from IMS Health's National Disease and Therapeutic Index database to compare poison center call trends with likely availability. Calls related to teenaged victims of prescription ADHD medication abuse rose 76%, which is faster than calls for victims of substance abuse generally and teen substance abuse. The annual rate of total and teen exposures was unchanged. Over the 8 years, estimated prescriptions for teenagers and preteenagers increased 133% for amphetamine products, 52% for methylphenidate products, and 80% for both together. Reports of exposure to methylphenidate fell from 78% to 30%, whereas methylphenidate as a percentage of ADHD prescriptions decreased from 66% to 56%. Substance-related abuse calls per million adolescent prescriptions rose 140%. The sharp increase, out of proportion to other poison center calls, suggests a rising problem with teen ADHD stimulant medication abuse. Case severity increased over time. Sales data of ADHD medications suggest that the use and call-volume increase reflects availability, but the increase disproportionately involves amphetamines.

Increased sensorimotor gating in recreational and dependent cocaine users is modulated by craving and attention-deficit/hyperactivity disorder symptoms.

PubMed

Preller, Katrin H; Ingold, Nina; Hulka, Lea M; Vonmoos, Matthias; Jenni, Daniela; Baumgartner, Markus R; Vollenweider, Franz X; Quednow, Boris B

2013-02-01

Cocaine dependence has been associated with blunted dopamine and norepinephrine signaling, but it is unknown if recreational cocaine use is also associated with alterations of catecholamine systems. Prepulse inhibition (PPI) of the acoustic startle response-a measure of sensorimotor gating-is highly sensitive for manipulations of the catecholamine system. Therefore, we investigated whether relatively pure recreational users (RCU) and dependent cocaine users (DCU) display alterations of PPI, startle reactivity, and habituation. Moreover, the influences of methylenedioxymethamphetamine and cannabis co-use, craving, and attention-deficit/hyperactivity disorder (ADHD) symptoms on startle measures were examined. In 64 RCU, 29 DCU, and 66 stimulant-naïve control subjects, PPI of acoustic startle response, startle reactivity, habituation, ADHD symptoms, and cocaine craving were assessed. Drug use of all participants was controlled by hair and urine toxicologies. Both RCU and DCU showed increased PPI in comparison with control participants (Cohen's d=.38 and d=.67, respectively), while RCU and DCU did not differ in PPI measures (d=.12). No significant group differences were found in startle reactivity or habituation measures. In cocaine users, PPI was positively correlated with cumulative cocaine dose used, craving for cocaine, and ADHD symptoms. Users with a diagnosis of ADHD and strong craving symptoms displayed the highest PPI levels compared with control subjects (d=.78). The augmented PPI in RCU and DCU suggests that recreational use of cocaine is associated with altered catecholamine signaling, in particular if ADHD or craving symptoms are present. Finally, ADHD might be a critical risk factor for cocaine-induced changes of the catecholamine system. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Dopamine disruption increases negotiation for cooperative interactions in a fish

PubMed Central

Messias, João P. M.; Paula, José R.; Grutter, Alexandra S.; Bshary, Redouan; Soares, Marta C.

2016-01-01

Humans and other animals use previous experiences to make behavioural decisions, balancing the probabilities of receiving rewards or punishments with alternative actions. The dopaminergic system plays a key role in this assessment: for instance, a decrease in dopamine transmission, which is signalled by the failure of an expected reward, may elicit a distinct behavioural response. Here, we tested the effect of exogenously administered dopaminergic compounds on a cooperative vertebrate’s decision-making process, in a natural setting. We show, in the Indo-Pacific bluestreak cleaner wrasse Labroides dimidiatus, that blocking dopamine receptors in the wild induces cleaners to initiate more interactions with and to provide greater amounts of physical contact to their client fish partners. This costly form of tactile stimulation using their fins is typically used to prolong interactions and to reconcile with clients after cheating. Interestingly, client jolt rate, a correlate of cheating by cleaners, remained unaffected. Thus, in low effective dopaminergic transmission conditions cleaners may renegotiate the occurrence and duration of the interaction with a costly offer. Our results provide first evidence for a prominent role of the dopaminergic system in decision-making in the context of cooperation in fish. PMID:26853241

Game-based combined cognitive and neurofeedback training using Focus Pocus reduces symptom severity in children with diagnosed AD/HD and subclinical AD/HD.

PubMed

Johnstone, Stuart J; Roodenrys, Steven J; Johnson, Kirsten; Bonfield, Rebecca; Bennett, Susan J

2017-06-01

Previous studies report reductions in symptom severity after combined working memory (WM) and inhibitory control (IC) training in children with AD/HD. Based on theoretical accounts of the role of arousal/attention modulation problems in AD/HD, the current study examined the efficacy of combined WM, IC, and neurofeedback training in children with AD/HD and subclinical AD/HD. Using a randomized waitlist control design, 85 children were randomly allocated to a training or waitlist condition and completed pre- and post-training assessments of overt behavior, trained and untrained cognitive task performance, and resting and task-related EEG activity. The training group completed twenty-five sessions of training using Focus Pocus software at home over a 7 to 8-week period. Trainees improved at the trained tasks, while enjoyment and engagement declined across sessions. After training, AD/HD symptom severity was reduced in the AD/HD and subclinical groups according to parents, and in the former group only according to blinded teachers and significant-others. There were minor improvements in two of six near-transfer tasks, and evidence of far-transfer of training effects in four of five far-transfer tasks. Frontal region changes indicated normalization of atypical EEG features with reduced delta and increased alpha activity. It is concluded that technology developments provide an interesting a vehicle for delivering interventions and that, while further research is needed, combined WM, IC, and neurofeedback training can reduce AD/HD symptom severity in children with AD/HD and may also be beneficial to children with subclinical AD/HD. Copyright © 2017 Elsevier B.V. All rights reserved.

[Atomoxetine for treatment of children and adolescents with ADHD].

PubMed

Resen, Katarina; Pagsberg, Anne Katrine; Jörgens, Gesche

2014-03-03

Atomoxetine reduces ADHD symptoms in children and adolescents significantly and is indicated for ADHD with co-morbid anxiety, depression and tics or with an increased risk of abuse. Number needed to treat is 3.4-5. Common adverse effects are stomach pain, decreased appetite and somnolence. Serious adverse effects include increased vascular tone, decreased growth rate and increased suicidal behaviour. In most cases adverse effects are mild to moderate and transient. Since atomoxetine was launched in 2006, 117 cases of toxic exposures have been reported in Denmark.

[Legal aspects of hyperkinetic disorders/ADHD].

PubMed

Hässler, F; Reis, O; Buchmann, J; Bohne-Suraj, S

2008-07-01

With a prevalence of 2-6%, hyperkinetic disorders (F 90, ICD-10) and disturbances of activity and attention (F 90.0, ADHD, ICD-10) are among the psychiatric disorders most commonly diagnosed in children, adolescents, and adults. Children and adolescents diagnosed with ADHD suffer from hyperactivity and deficits in attention and impulse control. Adults usually have problems focusing on one goal, maintaining their attention, modulating emotions effectively, structuring their tasks, and controlling impulses and in executive functions. Legal implications derive from core symptoms and from treatment with stimulants governed by legislation on narcotics. This paper discusses juridical aspects of ADHD in connection with the administration of medication at school, trips abroad within and outside the Schengen area, driving, competitive sports, military service, the increased risk of delinquency, the individual capacity to incur criminal responsibility, developmental criteria for the ability to act responsibly, and modalities for withdrawal treatment or treatment during detention.

Prenatal exposure to methylphenidate affects the dopamine system and the reactivity to natural reward in adulthood in rats.

PubMed

Lepelletier, François-Xavier; Tauber, Clovis; Nicolas, Céline; Solinas, Marcello; Castelnau, Pierre; Belzung, Catherine; Emond, Patrick; Cortese, Samuele; Faraone, Stephen V; Chalon, Sylvie; Galineau, Laurent

2014-10-31

Methylphenidate (MPH) is a commonly-used medication for the treatment of children with Attention-Deficit/Hyperactivity Disorders (ADHD). However, its prescription to adults with ADHD and narcolepsy raises the question of how the brain is impacted by MPH exposure during pregnancy. The goal of this study was to elucidate the long-term neurobiological consequences of prenatal exposure to MPH using a rat model. We focused on the effects of such treatment on the adult dopamine (DA) system and on the reactivity of animals to natural rewards. This study shows that adult male rats prenatally exposed to MPH display elevated expression of presynaptic DA markers in the DA cell bodies and the striatum. Our results also suggest that MPH-treated animals could exhibit increased tonic DA activity in the mesolimbic pathway, altered signal-to-noise ratio after a pharmacological stimulation, and decreased reactivity to the locomotor effects of cocaine. Finally, we demonstrated that MPH rats display a decreased preference and motivation for sucrose. This is the first preclinical study reporting long-lasting neurobiological alterations of DA networks as well as alterations in motivational behaviors for natural rewards after a prenatal exposure to MPH. These results raise concerns about the possible neurobiological consequences of MPH treatment during pregnancy. © The Author 2015. Published by Oxford University Press on behalf of CINP.

5-(2-Aminopropyl)benzofuran and phenazepam demonstrate the possibility of dependence by increasing dopamine levels in the brain.

PubMed

Cha, Hye Jin; Lee, Kwang-Wook; Eom, Jang-Hyeon; Kim, Young-Hoon; Shin, Jisoon; Yun, Jaesuk; Han, Kyoungmoon; Kim, Hyung Soo

2016-10-01

Although 5-(2-aminopropyl)benzofuran (5-APB) and 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (phenazepam) are being used as recreational drugs, research on their dependence liability or mechanisms of action is lacking. The present study aimed to evaluate the behavioral effects and dependence liability of these drugs using conditioned place preference and self-administration paradigms in rodents. Additionally, biochemical techniques were used to assess the substance-induced alterations in synaptosome-released dopamine. While both of the tested substances elicited increases in conditioned place preference and dopamine, neither of them facilitated self-administration, suggesting that 5-APB and phenazepam have rewarding effects, rather than reinforcing effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Interactions between Early Parenting and a Polymorphism of the Child’s Dopamine Transporter Gene in Predicting Future Child Conduct Disorder Symptoms

PubMed Central

Lahey, Benjamin B.; Rathouz, Paul J.; Lee, Steve S.; Chronis-Tuscano, Andrea; Pelham, William E.; Waldman, Irwin D.; Cook, Edwin H.

2010-01-01

Mounting evidence suggests that genetic risks for mental disorders often interact with the social environment, but most studies still ignore environmental moderation of genetic influences. We tested interactions between maternal parenting and the variable number tandem repeat (VNTR) polymorphism in the 3′ untranslated region (UTR) of the dopamine transporter gene in the child to increase understanding of gene-environment interactions involving early parenting. Participants were part of a 9-year longitudinal study of 4–6-year-old children who met criteria for attention-deficit/hyperactivity disorder (ADHD) and demographically matched controls. Maternal parenting was observed during standard mother-child interactions in wave 1. The child’s conduct disorder (CD) symptoms 5–8 years later were measured using separate structured diagnostic interviews of the mother and youth. Controlling for ADHD symptoms and child disruptive behavior during the mother-child interaction, there was a significant inverse relation between levels of both positive and negative parenting at 4–6 years and the number of later CD symptoms, but primarily among children with two copies of the 9-repeat allele of the VNTR. The significant interaction with negative parenting was replicated in parent and youth reports of CD symptoms separately. PMID:21171728

ILLICIT DOPAMINE TRANSIENTS: RECONCILING ACTIONS OF ABUSED DRUGS

PubMed Central

Covey, Dan P.; Roitman, Mitchell F.; Garris, Paul A.

2014-01-01

Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural reward and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. PMID:24656971

Efficacy of osmotic-release oral system (OROS) methylphenidate for mothers with attention-deficit/hyperactivity disorder (ADHD): preliminary report of effects on ADHD symptoms and parenting.

PubMed

Chronis-Tuscano, Andrea; Seymour, Karen E; Stein, Mark A; Jones, Heather A; Jiles, Cynthia D; Rooney, Mary E; Conlon, Charles J; Efron, Lisa A; Wagner, Stephanie A; Pian, Jessica; Robb, Adelaide S

2008-12-01

A preliminary study to examine the efficacy of osmotic-release oral system (OROS) methylphenidate for attention-deficit/hyperactivity disorder (ADHD) symptoms and parenting behaviors in mothers with ADHD who had children with ADHD. Participants included 23 mother-child dyads in which both were diagnosed with DSM-IV ADHD. Mothers underwent a 5-week, double-blind titration (placebo, 36 mg/day, 54 mg/day, 72 mg/day, 90 mg/day) to an optimal dose of OROS methylphenidate, followed by random assignment to 2 weeks of placebo or their maximally effective dose. Primary outcome measures included maternal ADHD symptoms (Conners' Adult ADHD Rating Scale) and parenting (Alabama Parenting Questionnaire). Secondary outcomes included side effects ratings. Data were collected from December 2004 until August 2006. During Phase 1, mothers reported significant decreases in inattention (p < .001) and hyperactivity/impulsivity (p < .01) with increases in OROS methylphenidate dose. As dose increased, significant reductions in inconsistent discipline (p < .01) and corporal punishment use (p < .005) were also demonstrated. During Phase 2, small effects on inattention (d = 0.46) and hyperactivity/impulsivity (d = 0.38) were found for those randomly assigned to medication versus placebo. In addition, medium to large medication effects were found on maternal involvement (d = 0.52), poor monitoring/supervision (d = 0.70), and inconsistent discipline (d = 0.71), with small effects on corporal punishment (d = 0.42). During both phases, few adverse effects were noted. OROS methylphenidate was well tolerated and was associated with significant improvement in maternal ADHD symptoms and parenting. Variable effects on parenting suggest that behavioral interventions may be necessary to address impairments in parenting among adults with ADHD. clinicaltrials.gov Identifier: NCT00318981. Copyright 2008 Physicians Postgraduate Press, Inc.

Teachers' Knowledge of ADHD, Treatments for ADHD, and Treatment Acceptability: An Initial Investigation. Research Brief

ERIC Educational Resources Information Center

Vereb, Rebecca L.; DiPerna, James C.

2004-01-01

The purpose of this study was to begin to explore the relationship among teachers' knowledge of Attention Deficit Hyperactivity Disorder (ADHD), knowledge of common treatments for ADHD, and acceptability of different approaches to treatment for ADHD (medication and behavior management). Relationships also were explored between these variables and…

Auditory and Visual Attention Performance in Children With ADHD: The Attentional Deficiency of ADHD Is Modality Specific.

PubMed

Lin, Hung-Yu; Hsieh, Hsieh-Chun; Lee, Posen; Hong, Fu-Yuan; Chang, Wen-Dien; Liu, Kuo-Cheng

2017-08-01

This study explored auditory and visual attention in children with ADHD. In a randomized, two-period crossover design, 50 children with ADHD and 50 age- and sex-matched typically developing peers were measured with the Test of Various Attention (TOVA). The deficiency of visual attention is more serious than that of auditory attention in children with ADHD. On the auditory modality, only the deficit of attentional inconsistency is sufficient to explain most cases of ADHD; however, most of the children with ADHD suffered from deficits of sustained attention, response inhibition, and attentional inconsistency on the visual modality. Our results also showed that the deficit of attentional inconsistency is the most important indicator in diagnosing and intervening in ADHD when both auditory and visual modalities are considered. The findings provide strong evidence that the deficits of auditory attention are different from those of visual attention in children with ADHD.

Suicidal Behavior in Juvenile Delinquents: The Role of ADHD and Other Comorbid Psychiatric Disorders.

PubMed

Ruchkin, Vladislav; Koposov, Roman A; Koyanagi, Ai; Stickley, Andrew

2017-10-01

This study evaluated the role of psychiatric morbidity in relation to a history of suicidal behavior, with a particular focus on attention-deficit/hyperactivity disorder (ADHD). Suicidality and psychiatric diagnoses were assessed in 370 incarcerated male juvenile delinquents from Northern Russia using the semi-structured K-SADS-PL psychiatric interview. A lifetime history of suicidal ideation only (24.7 %) and suicidal ideation with suicide attempts (15.7 %) was common. Binary logistic regression analysis was used to assess the role of ADHD and other psychiatric disorders in suicidal ideation and suicide attempts. A history of suicidal ideation and of suicide attempts were associated with higher rates of psychiatric morbidity and with the number of comorbid psychiatric disorders. An ADHD diagnosis was associated with an increased risk for both suicidal ideation and for suicide attempts. The comorbidity of ADHD with drug dependence further increased the risk for suicidal ideation, while ADHD and alcohol dependence comorbidity increased the risk for suicide attempts. Our findings highlight the importance of adequately detecting and treating psychiatric disorders in vulnerable youths, especially when they are comorbid with ADHD.

Friendship Characteristics of Children With ADHD.

PubMed

Marton, Imola; Wiener, Judith; Rogers, Maria; Moore, Chris

2015-10-01

This study explored the friendship characteristics of 8 to 12 year old children with and without Attention-Deficit/Hyperactivity Disorder (ADHD). Friendship characteristics included number of nominated and corroborated friends, duration of friendships, amount of contact with friends, and the proportion of friends with learning and behavioral problems. The sample comprised 92 children, 50 with a diagnosis of ADHD and 42 comparison children. While children with ADHD did not differ from comparison children in the number of friends they nominated, parents and teachers of children with ADHD were less likely to corroborate that these friendships existed. The friendships of children with ADHD were also shorter in duration. While children with ADHD were indistinguishable from comparison children with regards to the amount of telephone contact with friends, they spent less time with friends outside of school than comparison children. Children with ADHD had a higher proportion of friends with learning and behavior problems. While children with ADHD differ from comparison children in the above friendship characteristics, it is promising that they still fall within the average range for the number of corroborated friendships and they demonstrate adequate stability in their friendships. © 2012 SAGE Publications.

Atypical Dopamine Uptake Inhibitors that Provide Clues About Cocaine's Mechanism at the Dopamine Transporter

NASA Astrophysics Data System (ADS)

Hauck Newman, Amy; Katz, Jonathan L.

The dopamine transporter (DAT) has been a primary target for cocaine abuse/addiction medication discovery. However predicted addiction liability and limited clinical evaluation has provided a formidable challenge for development of these agents for human use. The unique and atypical pharmacological profile of the benztropine (BZT) class of dopamine uptake inhibitors, in preclinical models of cocaine effects and abuse, has encouraged further development of these agents. Moreover, in vivo studies have challenged the original DAT hypothesis and demonstrated that DAT occupancy and subsequent increases in dopamine produced by BZT analogues are significantly delayed and long lasting, as compared to cocaine. These important and distinctive elements are critical to the lack of abuse liability among BZT analogues, and improve their potential for development as treatments for cocaine abuse and possibly other neuropsychiatric disorders.

Consequences of peripheral chemoreflex inhibition with low-dose dopamine in humans

PubMed Central

Niewinski, Piotr; Tubek, Stanislaw; Banasiak, Waldemar; Paton, Julian F R; Ponikowski, Piotr

2014-01-01

Low-dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double-blind, placebo-controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low-dose dopamine (2 μg kg–1 min–1) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function. PMID:24396060

Dopamine depletion increases the power and coherence of high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

PubMed

Ge, Shunnan; Yang, Chen; Li, Min; Li, Jiang; Chang, Xiaozan; Fu, Jian; Chen, Lei; Chang, Chongwang; Wang, Xuelian; Zhu, Junling; Gao, Guodong

2012-07-17

Studies on patients with Parkinson's disease and in animal models have observed enhanced synchronization of oscillations in several frequency bands within and between the cortical-basal ganglia (BG) structures. Recent research has also shown that synchronization of high-voltage spindles (HVSs) in the cortex, striatum and substantia nigra pars reticulate is increased by dopamine depletion. However, more evidence is needed to determine whether HVS activity in the whole cortex-BG network represents homologous alteration following dopamine depletion. As the globus pallidus (GP) is in a central position to propagate and synchronize oscillations in the cortical-BG circuits, we employed local-field potentials and electrocorticogram to simultaneously record oscillations in the GP and primary (M1) and secondary (M2) motor cortices on freely moving 6-hydroxydopamine (6-OHDA) lesioned and control rats. Results showed that HVS episodes recorded from GP, and M2 and M1 cortex areas were more numerous and longer in 6-OHDA lesioned rats compared to controls. Relative power associated with HVS activity in the GP, and M2 and M1 cortices of 6-OHDA lesioned rats was significantly greater than that for control rats. Coherence values for HVS activity between the GP, and M2 and M1 cortex areas were significantly increased by dopamine depletion. Time lag between the M1 cortex HVS and GP HVS was significantly shorter for dopamine depleted than normal rats. Findings indicate a crucial rule for dopamine in the regulation of HVS activity in the whole cortical-BG circuit, and suggest a close relationship between abnormally synchronized HVS oscillations in the cortex-BG network and Parkinson's disease. Copyright © 2012 Elsevier B.V. All rights reserved.

Stimulant medications for attention-deficit/hyperactivity disorder (ADHD) improve memory of emotional stimuli in ADHD-diagnosed college students.

PubMed

Maul, J; Advokat, C

2013-04-01

Stimulant medications do not improve the academic achievement of ADHD diagnosed undergraduates. One reason may be that stimulant-induced sympathetic arousal might impair memory. To test this hypothesis, we conducted a study between September 2011 and March 2012, to compare medicated (n=12) and non-medicated (n=11) ADHD diagnosed undergraduates, with non-ADHD students (n=12). All participants were presented with an audiovisual narrative that included an emotional segment, and answered questions about the story one week later. All groups remembered the emotional segment significantly better than the neutral segments. Non-medicated ADHD students recalled less of both segments than the medicated ADHD or non-ADHD groups, which did not differ from each other. Stimulants improved memory in ADHD students, and did not impair the relative retention of emotional, as opposed to neutral information. Stimulant-induced arousal cannot explain the academic deficit of ADHD undergraduates. Copyright © 2013 Elsevier Inc. All rights reserved.

Methylphenidate Ameliorates Depressive Comorbidity in ADHD Children without any Modification on Differences in Serum Melatonin Concentration between ADHD Subtypes

PubMed Central

Cubero-Millán, Isabel; Molina-Carballo, Antonio; Machado-Casas, Irene; Fernández-López, Luisa; Martínez-Serrano, Sylvia; Tortosa-Pinto, Pilar; Ruiz-López, Aida; Luna-del-Castillo, Juan-de-Dios; Uberos, José; Muñoz-Hoyos, Antonio

2014-01-01

The vast majority of Attention-deficit/hyperactivity disorder (ADHD) patients have other associated pathologies, with depressive symptoms as one of the most prevalent. Among the mediators that may participate in ADHD, melatonin is thought to regulate circadian rhythms, neurological function and stress response. To determine (1) the serum baseline daily variations and nocturnal excretion of melatonin in ADHD subtypes and (2) the effect of chronic administration of methylphenidate, as well as the effects on symptomatology, 136 children with ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR criteria) were divided into subgroups using the “Children’s Depression Inventory” (CDI). Blood samples were drawn at 20:00 and 09:00 h, and urine was collected between 21:00 and 09:00 h, at inclusion and after 4.61 ± 2.29 months of treatment. Melatonin and its urine metabolite were measured by radioimmunoassay RIA. Factorial analysis was performed using STATA 12.0. Melatonin was higher predominantly in hyperactive-impulsive/conduct disordered children (PHI/CD) of the ADHD subtype, without the influence of comorbid depressive symptoms. Methylphenidate ameliorated this comorbidity without induction of any changes in the serum melatonin profile, but treatment with it was associated with a decrease in 6-s-melatonin excretion in both ADHD subtypes. Conclusions: In untreated children, partial homeostatic restoration of disrupted neuroendocrine equilibrium most likely led to an increased serum melatonin in PHI/CD children. A differential cerebral melatonin metabolization after methylphenidate may underlie some of the clinical benefit. PMID:25257531

Modulation of motor behavior by dopamine and the D1-like dopamine receptor AmDOP2 in the honey bee

PubMed Central

Mustard, Julie A.; Pham, Priscilla M.; Smith, Brian H.

2009-01-01

Determining the specific molecular pathways through which dopamine affects behavior has been complicated by the presence of multiple dopamine receptor subtypes that couple to different second messenger pathways. The observation of freely moving adult bees in an arena was used to investigate the role of dopamine signaling in regulating the behavior of the honey bee. Dopamine or the dopamine receptor antagonist flupenthixol was injected into the hemolymph of worker honey bees. Significant differences between treated and control bees were seen for all behaviors (walking, stopped, upside down, grooming, flying and fanning), and behavioral shifts were dependent on drug dosage and time after injection. To examine the role of dopamine signaling through a specific dopamine receptor in the brain, RNA interference was used to reduce expression levels of a D1-like receptor, AmDOP2. Injection of Amdop2 dsRNA into the mushroom bodies reduced the levels of Amdop2 mRNA and produced significant changes in the amount of time honey bees spent performing specific behaviors with reductions in time spent walking offset by increases in grooming or time spent stopped. Taken together these results establish that dopamine plays an important role in regulating motor behavior of the honey bee. PMID:19945462

Modulation of motor behavior by dopamine and the D1-like dopamine receptor AmDOP2 in the honey bee.

PubMed

Mustard, Julie A; Pham, Priscilla M; Smith, Brian H

2010-04-01

Determining the specific molecular pathways through which dopamine affects behavior has been complicated by the presence of multiple dopamine receptor subtypes that couple to different second messenger pathways. The observation of freely moving adult bees in an arena was used to investigate the role of dopamine signaling in regulating the behavior of the honey bee. Dopamine or the dopamine receptor antagonist flupenthixol was injected into the hemolymph of worker honey bees. Significant differences between treated and control bees were seen for all behaviors (walking, stopped, upside down, grooming, flying and fanning), and behavioral shifts were dependent on drug dosage and time after injection. To examine the role of dopamine signaling through a specific dopamine receptor in the brain, RNA interference was used to reduce expression levels of a D1-like receptor, AmDOP2. Injection of Amdop2 dsRNA into the mushroom bodies reduced the levels of Amdop2 mRNA and produced significant changes in the amount of time honey bees spent performing specific behaviors with reductions in time spent walking offset by increases in grooming or time spent stopped. Taken together these results establish that dopamine plays an important role in regulating motor behavior of the honey bee. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

[Emotional regulation and motivation in children with ADHD].

PubMed

Høvik, Marie Farstad; Plessen, Kerstin J

2010-12-02

Impaired cognitive control functions have long been regarded as the main problem in the development of Attention-Deficit/Hyperactivity Disorder (ADHD). A more recent model emphasizes the importance of emotional and motivational problems. We have reviewed the evidence for this model, which may have important implications for clinical practice. The article is based on literature identified through a non-systematic search in PubMed. Although limited research was carried out in this topic earlier, studies are currently emerging. Persons with ADHD react differently than controls on tasks that include rewards and on tasks that stress their capacity to regulate emotions. Abnormal signals during examination with electroencephalography (EEG) and anatomical and functional magnetic resonance imaging (fMRI) reflect problems with emotional regulation in patients with ADHD. Neurobiological research supports a model that includes emotional and motivational problems in the development of ADHD. Increased knowledge about emotional and motivational problems may improve treatment of these patients through development of more individually adapted therapy.

Negative Consequences of Poor Driving Outcomes Reported by Adolescents With and Without ADHD.

PubMed

Narad, Megan E; Garner, Annie A; Antonini, Tanya N; Kingery, Kathleen M; Tamm, Leanne; Calhoun, Heather R; Epstein, Jeffery N

2015-03-16

Although adolescents with ADHD report less driving experience, a greater proportion of adolescents with ADHD report receiving at least one ticket; however, no study has examined the severity of infractions committed by adolescent drivers with ADHD. A total of 61 adolescents (28 ADHD, 33 controls) aged 16 to 17 with a valid driver's license completed a self-report Driving History Questionnaire (DHQ), which asked about months of driving experience, negative driving outcomes, and severity of consequences. A greater proportion of adolescents with ADHD reported receiving fines, points on their driver's license, and remedial driving class. Furthermore, adolescents with ADHD reported attending a greater number of hours in remedial driving class, and a greater expense associated with fines. Importantly, ADHD-related negative driving outcomes manifest early in driving careers. Furthermore, increased negative consequences of poor and/or risky driving among adolescents with ADHD were evident despite having fewer months of independent driving. © 2015 SAGE Publications.

Executive functions as endophenotypes in ADHD: evidence from the Cambridge Neuropsychological Test Battery (CANTAB).

PubMed

Gau, Susan Shur-Fen; Shang, Chi-Yung

2010-07-01

Little is known about executive functions among unaffected siblings of children with attention deficit/hyperactivity disorder (ADHD), and there is lack of such information from non-Western countries. We examined verbal and nonverbal executive functions in adolescents with ADHD, unaffected siblings and controls to test whether executive functions could be potential endophenotypes for ADHD. We assessed 279 adolescents (age range: 11-17 years) with a childhood diagnosis of DSM-IV ADHD, 136 biological siblings (108 unaffected, 79.4%), and 173 unaffected controls by using psychiatric interviews, the Wechsler Intelligence Scale for Children - 3rd edition (WISC-III), including digit spans, and the tasks involving executive functions of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-dimensional/Extra-dimensional Shifts (IED), Spatial Span (SSP), Spatial Working Memory (SWM), and Stockings of Cambridge (SOC). Compared with the controls, adolescents with ADHD and unaffected siblings had a significantly shorter backward digit span, more extra-dimensional shift errors in the IED, shorter spatial span length in the SSP, more total errors and poorer strategy use in the SWM, and fewer problems solved in the minimum number of moves and shorter initial thinking time in the SOC. The magnitudes of the differences in the SWM and SOC increased with increased task difficulties. In general, neither persistent ADHD nor comorbidity was associated with increased deficits in executive functions among adolescents with ADHD. The lack of much difference in executive dysfunctions between unaffected siblings and ADHD adolescents suggests that executive dysfunctions may be useful cognitive endophenotypes for ADHD genetic studies.

Tamoxifen protects male mice nigrostriatal dopamine against methamphetamine-induced toxicity.

PubMed

Bourque, Mélanie; Liu, Bin; Dluzen, Dean E; Di Paolo, Thérèse

2007-11-01

The selective estrogen receptor modulator tamoxifen and estradiol were shown to protect nigrostriatal dopamine concentration loss by methamphetamine in female mice whereas male mice were protected only by tamoxifen. The present study examined the protective properties of tamoxifen in male mice on several nigrostriatal dopaminergic markers and body temperature. Intact male mice were administered 12.5 or 50 microg tamoxifen 24 h before methamphetamine treatment. Basal body temperatures of male mice remained unchanged by the tamoxifen treatment. Methamphetamine reduced striatal dopamine and its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations, striatal and substantia nigra dopamine and vesicular monoamine transporter specific binding as well substantia nigra dopamine and vesicular monoamine transporter mRNA levels and increased striatal preproenkephalin mRNA levels. These methamphetamine effects were not altered by 12.5 microg tamoxifen except for increased striatal dopamine metabolites and turnover. Tamoxifen at 50 microg reduced the methamphetamine effect on striatal dopamine concentration, dopamine transporter specific binding and prevented the increase in preproenkephalin mRNA levels; in the substantia nigra tamoxifen prevented the decrease of dopamine transporter mRNA levels. The present results show a tamoxifen dose-dependent prevention of loss of various dopaminergic markers against methamphetamine-induced toxicity in male mice. Since this is the only known hormonal protection of male mice against methamphetamine toxicity, these findings provide important new information on specific parameters of nigrostriatal dopaminergic function preserved by tamoxifen.

Factors associated with caregiver burden among pharmacotherapy-treated children/adolescents with ADHD in the Caregiver Perspective on Pediatric ADHD survey in Europe.

PubMed

Fridman, Moshe; Banaschewski, Tobias; Sikirica, Vanja; Quintero, Javier; Erder, M Haim; Chen, Kristina S

2017-01-01

Burden on caregivers of children/adolescents with attention-deficit/hyperactivity disorder (ADHD) is multidimensional, but incompletely understood. To analyze caregiver burden across the concepts of work, social/family life, and parental worry/stress, in relation to selected contributing factors. The online Caregiver Perspective on Pediatric ADHD survey was fielded in ten European countries. Analysis included children/adolescents (6-17 years) who were receiving/had received ADHD pharmacotherapy in the previous 6 months. Caregivers recorded their child's/adolescent's symptoms "on"/"off" medication (ie, when the caregiver reported that the child/adolescent forgot/chose not to take medication, before the onset of medication effect, or medication worn off). Effects of ADHD severity, comorbidities, and medication adherence on each burden outcome were assessed (multiple regression models). In total, 2,326 caregivers were included (children/adolescents' mean age: 11.5 years, 80% male). Caregivers reported missed/altered work, avoiding social activity, increased parental worry/stress, and strain on family life, despite using ADHD pharmacotherapy. Child/adolescent comorbidities and ADHD severity were significantly related to all burden concepts measured; the strongest comorbidity associations were with altered work (odds ratios [ORs] =1.68 [95% confidence interval {CI} 1.33, 2.12], 1.87 [1.37, 2.54], 3.47 [2.51, 4.78] for 1, 2, 3+ comorbidities, respectively) and planning the day around the child/adolescent (OR =1.42 [95% CI 1.17, 1.72], 1.73 [1.33, 2.15], 2.65 [1.99, 3.53]); the strongest severity associations were: quitting a job (OR =1.41 [95% CI 1.26, 1.59]) and planning a day around the child/adolescent (OR =1.26 [95% CI 1.20, 1.32]). Increased medication adherence was most associated with reducing the caregiver burden for altered work (OR =0.57 [95% CI 0.45, 0.72]), worrying about how they are being perceived as a parent (OR =0.68 [0.56, 0.83]), and avoiding social

Low dopamine function in attention deficit/hyperactivity disorder: should genotyping signify early diagnosis in children?

PubMed

Gold, Mark S; Blum, Kenneth; Oscar-Berman, Marlene; Braverman, Eric R

2014-01-01

Attention deficit/hyperactivity disorder (ADHD) is present in 8% to 12% of children, and 4% of adults worldwide. Children with ADHD can have learning impairments, poor selfesteem, social dysfunction, and an increased risk of substance abuse, including cigarette smoking. Overall, the rate of treatment with medication for patients with ADHD has been increasing since 2008, with ≥ 2 million children now being treated with stimulants. The rise of adolescent prescription ADHD medication abuse has occurred along with a concomitant increase of stimulant medication availability. Of adults presenting with a substance use disorder (SUD), 20% to 30% have concurrent ADHD, and 20% to 40% of adults with ADHD have a history of SUD. Following a brief review of the etiology of ADHD, its diagnosis and treatment, we focus on the benefits of early and appropriate testing for a predisposition to ADHD. We suggest that by genotyping patients for a number of known, associated dopaminergic polymorphisms, especially at an early age, misdiagnoses and/or over-diagnosis can be reduced. Ethical and legal issues of early genotyping are considered. As many as 30% of individuals with ADHD are estimated to either have secondary side-effects or are not responsive to stimulant medication. We also consider the benefits of non-stimulant medication and alternative treatment modalities, which include diet, herbal medications, iron supplementation, and neurofeedback. With the goals of improving treatment of patients with ADHD and SUD prevention, we encourage further work in both genetic diagnosis and novel treatment approaches.

ADHD latent class clusters: DSM-IV subtypes and comorbidity

PubMed Central

Elia, Josephine; Arcos-Burgos, Mauricio; Bolton, Kelly L.; Ambrosini, Paul J.; Berrettini, Wade; Muenke, Maximilian

2014-01-01

ADHD (Attention Deficit Hyperactivity Disorder) has a complex, heterogeneous phenotype only partially captured by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. In this report, latent class analyses (LCA) are used to identify ADHD phenotypes using K-SADS-IVR (Schedule for Affective Disorders & Schizophrenia for School Age Children-IV-Revised) symptoms and symptom severity data from a clinical sample of 500 ADHD subjects, ages 6–18, participating in an ADHD genetic study. Results show that LCA identified six separate ADHD clusters, some corresponding to specific DSM-IV subtypes while others included several subtypes. DSM-IV comorbid anxiety and mood disorders were generally similar across all clusters, and subjects without comorbidity did not aggregate within any one cluster. Age and gender composition also varied. These results support findings from population-based LCA studies. The six clusters provide additional homogenous groups that can be used to define ADHD phenotypes in genetic association studies. The limited age ranges aggregating in the different clusters may prove to be a particular advantage in genetic studies where candidate gene expression may vary during developmental phases. DSM-IV comorbid mood and anxiety disorders also do not appear to increase cluster heterogeneity; however, longitudinal studies that cover period of risk are needed to support this finding. PMID:19900717

The Romantic Relationships of Adolescents With ADHD.

PubMed

Rokeach, Alan; Wiener, Judith

2018-01-01

This study compared the romantic relationships of adolescents with and without ADHD with regard to romantic involvement, relationship content, and relationship quality. A community sample of 58 participants (30 ADHD, 28 Comparison), ages 13 to 18, completed questionnaires assessing various features of romantic relationships. Adolescents with ADHD reported having more romantic partners than their typically developing (TD) peers. Females with ADHD were found to have shorter romantic relationships than TD adolescents while males with ADHD reported their age of first intercourse to be nearly 2 years sooner than TD peers. Irrespective of gender, adolescents with ADHD had nearly double the number of lifetime sexual partners. However, the romantic relationships of adolescents with and without ADHD did not differ on levels of aggression or relationship quality. Given the outcomes associated with poor-quality romantic relationships, comprehensive assessments of adolescents with ADHD should include queries into their romantic relationships.

Trans-synaptic (GABA-dopamine) modulation of cocaine induced dopamine release: A potential therapeutic strategy for cocaine abuse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dewey, S.L.; Straughter-Moore, R.; Chen, R.

We recently developed a new experimental strategy for measuring interactions between functionally-linked neurotransmitter systems in the primate and human brain with PET. As part of this research, we demonstrated that increases in endogenous GABA concentrations significantly reduced striatal dopamine concentrations in the primate brain. We report here the application of the neurotransmitter interaction paradigm with PET and with microdialysis to the investigation of a novel therapeutic strategy for treating cocaine abuse based on the ability of GABA to inhibit cocaine induced increases in striatal dopamine. Using gamma-vinyl GABA (GVG, a suicide inhibitor of GABA transaminase), we performed a series ofmore » PET studies where animals received a baseline PET scan with labeled raclopride injection, animals received cocaine (2.0 mg/kg). Normally, a cocaine challenge significantly reduces the striatal binding of {sup 11}C-raclopride. However, in animals pretreated with GVG, {sup 11}C-raclopride binding was less affected by a cocaine challenge compared to control studies. Furthermore, microdialysis studies in freely moving rats demonstrate that GVG (300 mg/kg) significantly inhibited cocaine-induced increases in extracellular dopamine release. GVG also attenuated cocaine-induced increases in locomotor activity. However, at a dose of 100 mg/kg, GVG had no effect. Similar findings were obtained with alcohol. Alcohol pretreatment dose dependantly (1-4 g/kg) inhibited cocaine-induced increases in extracellular dopamine concentrations in freely moving rats. Taken together, these studies suggest that therapeutic strategies targeted at increasing central GABA concentrations may be beneficial for the treatment of cocaine abuse.« less

Adult Attention-Deficit / Hyperactivity Disorder (ADHD)

MedlinePlus

Adult attention-deficit/hyperactivity disorder (ADHD) Overview Adult attention-deficit/hyperactivity disorder (ADHD) is a mental health disorder that ... combination of persistent problems, such as difficulty paying attention, hyperactivity and impulsive behavior. Adult ADHD can lead ...

Illicit dopamine transients: reconciling actions of abused drugs.

PubMed

Covey, Dan P; Roitman, Mitchell F; Garris, Paul A

2014-04-01

Phasic increases in brain dopamine are required for cue-directed reward seeking. Although compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyperactivating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyperactivation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural rewards and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dopamine in motivational control: rewarding, aversive, and alerting

PubMed Central

Bromberg-Martin, Ethan S.; Matsumoto, Masayuki; Hikosaka, Okihide

2010-01-01

SUMMARY Midbrain dopamine neurons are well known for their strong responses to rewards and their critical role in positive motivation. It has become increasingly clear, however, that dopamine neurons also transmit signals related to salient but non-rewarding experiences such as aversive and alerting events. Here we review recent advances in understanding the reward and non-reward functions of dopamine. Based on this data, we propose that dopamine neurons come in multiple types that are connected with distinct brain networks and have distinct roles in motivational control. Some dopamine neurons encode motivational value, supporting brain networks for seeking, evaluation, and value learning. Others encode motivational salience, supporting brain networks for orienting, cognition, and general motivation. Both types of dopamine neurons are augmented by an alerting signal involved in rapid detection of potentially important sensory cues. We hypothesize that these dopaminergic pathways for value, salience, and alerting cooperate to support adaptive behavior. PMID:21144997

Cardiac Reactivity and Stimulant Use in Adolescents with Autism Spectrum Disorders with Comorbid ADHD Versus ADHD

ERIC Educational Resources Information Center

Bink, M.; Popma, A.; Bongers, I. L.; van Boxtel, G. J. M.; Denissen, A.; van Nieuwenhuizen, Ch.

2015-01-01

A large number of youngsters with autism spectrum disorders (ASD) display comorbid attention deficit/hyperactivity disorder (ADHD) symptoms. However, previous studies are not conclusive whether psychophysiological correlates, like cardiac reactivity, are different for ASD with comorbid ADHD (ASD+) compared to ADHD. Therefore, the current study…

Cross-cultural reliability and validity of ADHD assessed by the ADHD Rating Scale in a pan-European study.

PubMed

Döpfner, Manfred; Steinhausen, Hans-Christoph; Coghill, David; Dalsgaard, Søren; Poole, Lynne; Ralston, Stephen J; Rothenberger, Aribert

2006-12-01

To provide psychometric information on the Attention-Deficit/Hyperactivity Disorder (ADHD) Rating Scale-IV (ADHD-RS-IV) in a large population of children with ADHD. Patients aged 6-18 years (n=1,478 in baseline analysis) were rated by 244 physicians on the ADHD-RS-IV based on a semi-structured interview with the patient's parent. Physicians additionally rated functional impairment (CGAS) and health status (CGI-S), and parents rated their child's behavioural and emotional problems (SDQ) and quality of life (CHIP-CE). Inattention and hyperactivity-impulsivity as dimensions of ADHD were replicated. 3-factor solutions reflecting the ICD-10 definition, with hyperactivity, impulsivity and inattention as separate dimensions were extracted in some national sub-samples and in separate analyses for boys and younger children.Good internal consistencies, strong country effects and small effects of age were found. Based on ADHD-RS-IV, 88.5% of patients met the criteria for any ADHD diagnosis. Correlations between ADHD-RS-IV and measures of functional impairment were low but statistically significant. The correlations with SDQ and CHIP-CE scales confirm the convergent and divergent validity of ADHD-RS-IV. Impressive evidence for the cross-cultural factorial validity, internal consistency as well as convergent and divergent validity of ADHD-RS-IV was found. ADHD can be assessed reliably and validly in routine care across Europe. The ICD-10 3-factor model seems to be less robust than the DSM-IV 2-factor model, but may be a good description for special populations (boys, younger children).

Saikosaponin A Alleviates Symptoms of Attention Deficit Hyperactivity Disorder through Downregulation of DAT and Enhancing BDNF Expression in Spontaneous Hypertensive Rats.

PubMed

Jichao, Sun; Xinmin, Han; Xianguo, Ren; Dongqi, Yin; Rongyi, Zhou; Shuang, Lei; Yue, You; Yuchen, Song; Jingnan, Ying

2017-01-01

The disturbed dopamine availability and brain-derived neurotrophic factor (BDNF) expression are due in part to be associated with attention deficit hyperactivity disorder (ADHD). In this study, we investigated the therapeutical effect of saikosaponin a (SSa) isolated from Bupleurum Chinese DC, against spontaneously hypertensive rat (SHR) model of ADHD. Methylphenidate and SSa were orally administered for 3 weeks. Activity was assessed by open-field test and Morris water maze test. Dopamine (DA) and BDNF were determined in specific brain regions. The mRNA or protein expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicles monoamine transporter (VMAT) was also studied. Both MPH and SSa reduced hyperactivity and improved the spatial learning memory deficit in SHRs. An increased DA concentration in the prefrontal cortex (PFC) and striatum was also observed after treating with the SSa. The increased DA concentration may partially be attributed to the decreased mRNA and protein expression of DAT in PFC while SSa exhibited no significant effects on the mRNA expression of TH and VMAT in PFC of SHRs. In addition, BDNF expression in SHRs was also increased after treating with SSa or MPH. The obtained result suggested that SSa may be a potential drug for treating ADHD.

Pyrethroid pesticide-induced alterations in dopamine transporter function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elwan, Mohamed A.; Department of Environmental and Occupational Health, School of Medicine, Emory University, Atlanta, GA 30322; Richardson, Jason R.

Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal dopaminergic pathway. Several epidemiological studies have demonstrated an association between pesticide exposure and the incidence of PD. Studies from our laboratory and others have demonstrated that certain pesticides increase levels of the dopamine transporter (DAT), an integral component of dopaminergic neurotransmission and a gateway for dopaminergic neurotoxins. Here, we report that repeated exposure (3 injections over 2 weeks) of mice to two commonly used pyrethroid pesticides, deltamethrin (3 mg/kg) and permethrin (0.8 mg/kg), increases DAT-mediated dopamine uptake by 31 and 28%, respectively. Using cells stably expressing DAT, we determinedmore » that exposure (10 min) to deltamethrin and permethrin (1 nM-100 {mu}M) had no effect on DAT-mediated dopamine uptake. Extending exposures to both pesticides for 30 min (10 {mu}M) or 24 h (1, 5, and 10 {mu}M) resulted in significant decrease in dopamine uptake. This reduction was not the result of competitive inhibition, loss of DAT protein, or cytotoxicity. However, there was an increase in DNA fragmentation, an index of apoptosis, in cells exhibiting reduced uptake at 30 min and 24 h. These data suggest that up-regulation of DAT by in vivo pyrethroid exposure is an indirect effect and that longer-term exposure of cells results in apoptosis. Since DAT can greatly affect the vulnerability of dopamine neurons to neurotoxicants, up-regulation of DAT by deltamethrin and permethrin may increase the susceptibility of dopamine neurons to toxic insult, which may provide insight into the association between pesticide exposure and PD.« less

Substance use disorder and ADHD: is ADHD a particularly "specific" risk factor?

PubMed

Kousha, Maryam; Shahrivar, Zahra; Alaghband-Rad, Javad

2012-05-01

To assess the pattern of substance use disorder (SUD) in adolescents with and without history of attention - deficit / hyperactivity disorder (ADHD) using an Iranian sample in the context of a cultural background and drug availability is differing from Western countries. In this case- control study, the participants were interviewed by a child psychiatrist and the measures included: kiddie Schedule for Affective Disorder and Schizophrenia for school age children (K-SADS), Opium Treatment Index (OTI) and Global Assessment Functioning (GAF). Data were analyzed with chi square test and T test and fisher exact test by EPI.6 soft ware. Adolescents with ADHD were younger at the time of starting cigarette smoking, substance use, abuse and dependency (p = 0.0001), a shorter period between their first-time substance use and substance dependence or abuse (p = 0.0001), more severe substance use (for cannabis, heroine, cigarette and drugs such as benzodiazepines p < 0.05) and more functional impairment (p = 0.0007). Average number of co morbid disorders were higher in ADHD group. (p = 0.03) Although the pattern and type of substance use may be different in Iranian culture, our findings about the relationship between ADHD and SUD are similar to other western and non western countries. The presence of ADHD may over-ride cultural barriers and lower availability of drugs to the development of SUD in Iranian adolescents. Early diagnosis and treatment of ADHD may propose with better prognosis of SUD and subsequent decrease in the prevalence of SUD and the costs of SUD-related pathology in this population.

Effect of beta-phenylethylamine on extracellular concentrations of dopamine in the nucleus accumbens and prefrontal cortex.

PubMed

Murata, Mikio; Katagiri, Nobuyuki; Ishida, Kota; Abe, Kenji; Ishikawa, Masago; Utsunomiya, Iku; Hoshi, Keiko; Miyamoto, Ken-ichi; Taguchi, Kyoji

2009-05-07

It is known that psychostimulants stimulate dopamine transmission in the nucleus accumbens. In the present study, we examined the effects of systemically administered beta-phenylethylamine (beta-PEA), a psychomotor-stimulating trace amine, on dopamine concentrations in the nucleus accumbens and prefrontal cortex in freely moving rats, using an in vivo microdialysis technique. Intraperitoneal administration of beta-PEA (12.5 and 25 mg/kg) significantly increased extracellular dopamine levels in the nucleus accumbens shell. The observed increase in the dopamine concentration in nucleus accumbens shell dialysate after intraperitoneal administration of 25 mg/kg beta-PEA was inhibited by pre-treatment with a dopamine uptake inhibitor, GBR12909 (10 mg/kg, i.p.). In contrast, beta-PEA (25 mg/kg, i.p.) did not affect dopamine release in the nucleus accumbens core. Although a high dose of beta-PEA (50 mg/kg) significantly increased dopamine levels in the nucleus accumbens core, the dopamine increasing effect of beta-PEA was more potent in the nucleus accumbens shell. Systemic administration of 12.5 and 25 mg/kg beta-PEA also increased extracellular dopamine levels in the prefrontal cortex of rats. However, systemic 25 mg/kg beta-PEA-induced increases in extracellular dopamine levels were not blocked by GBR12909 within the prefrontal cortex. These results suggest that beta-PEA has a greater effect in the shell than in the core and low-dose beta-PEA stimulates dopamine release in the nucleus accumbens shell through uptake by a dopamine transporter. Similarly, beta-PEA increased extracellular dopamine levels in the prefrontal cortex. Thus, beta-PEA may increase extracellular dopamine concentrations in the mesocorticolimbic pathway.

ADHD knowledge, misconceptions, and treatment acceptability.

PubMed

Sciutto, Mark J

2015-02-01

Despite the availability of several effective treatments, many children with ADHD do not receive adequate services. A variety of factors may influence help-seeking behavior among families of children with ADHD. This study explores two factors that may influence help-seeking decisions: knowledge and misconceptions of ADHD and treatment acceptability. A total of 196 participants completed measures of ADHD knowledge and use of information sources prior to rating the acceptability of two interventions: stimulant medication and sugar elimination diets. Higher levels of ADHD misconceptions were associated with lower acceptance of medication and higher acceptance of dietary interventions. However, analysis of individual misconceptions suggests that specific misconceptions are differentially related to perceptions of individual treatments. It may be important for clinicians to assess and deliberately target specific misconceptions as part of treatment for ADHD. © 2013 SAGE Publications.

Mindfulness Training for Parents and Their Children with ADHD Increases the Children's Compliance

ERIC Educational Resources Information Center

Singh, Nirbhay N.; Singh, Ashvind N.; Lancioni, Giulio E.; Singh, Judy; Winton, Alan S. W.; Adkins, Angela D.

2010-01-01

Children with ADHD are often non-compliant with parental instructions. Various methods have been used to reduce problem behaviors in these children, with medication and manipulation of behavioral contingencies being the most prevalent. An objection often raised by parents is that these management strategies require them to impose external control…

Depression and Anxiety among Transitioning Adolescents and College Students with ADHD, Dyslexia, or Comorbid ADHD/Dyslexia

ERIC Educational Resources Information Center

Nelson, Jason M.; Gregg, Noel

2012-01-01

Objective: To investigate depressive and anxious symptomatology among transitioning adolescents and college students with ADHD, dyslexia, or comorbid ADHD/dyslexia. Method: Transitioning adolescents and college students with these disorders along with a non-ADHD/dyslexia college sample completed self-report measures of depression and anxiety.…

Evaluation of sleep organization in patients with attention deficit hyperactivity disorder (ADHD) and ADHD as a comorbidity of epilepsy.

PubMed

Kalil Neto, Felipe; Nunes, Magda L

2017-05-01

Epilepsy or attention deficit hyperactivity disorder (ADHD) can influence sleep organization in different ways. The aim of this study was to evaluate sleep organization in children and adolescents with ADHD and epilepsy, and to analyze the influence of methylphenidate. This was an observational, cross-sectional study of children and adolescents with epilepsy, who were seizure free for at least three months, and were also diagnosed with ADHD. They were selected from the epilepsy and child neurology outpatient clinic of a university hospital in Brazil. After sample size calculation, patients were consecutively included into four different groups, with 21 patients each: epilepsy + ADHD using methylphenidate, epilepsy + ADHD not using methylphenidate, only ADHD, and a healthy control group. All participants were evaluated with the Sleep Disturbance Scale for Children (SDSC) and monitored with actigraphy for five nights/days. Actigraphic analysis showed a higher number of night awakenings in the epilepsy + ADHD groups; they were most prominent in the group without methylphenidate (p = 0.001). Parental reports demonstrated a higher risk for sleep disturbances in the epilepsy + ADHD without methylphenidate and the ADHD groups (p < 0.001). Primary ADHD as a comorbidity of epilepsy impairs sleep organization in children, and the use of short-acting methylphenidate seems to improve it. Both objective (actigraphic) and subjective (SDSC) measures showed significant sleep alterations between primary ADHD and ADHD as a comorbidity of epilepsy; this was most prominent in the group without methylphenidate. Copyright © 2016 Elsevier B.V. All rights reserved.

Stronger Dopamine D1 Receptor-Mediated Neurotransmission in Dyskinesia.

PubMed

Farré, Daniel; Muñoz, Ana; Moreno, Estefanía; Reyes-Resina, Irene; Canet-Pons, Júlia; Dopeso-Reyes, Iria G; Rico, Alberto J; Lluís, Carme; Mallol, Josefa; Navarro, Gemma; Canela, Enric I; Cortés, Antonio; Labandeira-García, José L; Casadó, Vicent; Lanciego, José L; Franco, Rafael

2015-12-01

Radioligand binding assays to rat striatal dopamine D1 receptors showed that brain lateralization of the dopaminergic system were not due to changes in expression but in agonist affinity. D1 receptor-mediated striatal imbalance resulted from a significantly higher agonist affinity in the left striatum. D1 receptors heteromerize with dopamine D3 receptors, which are considered therapeutic targets for dyskinesia in parkinsonian patients. Expression of both D3 and D1-D3 receptor heteromers were increased in samples from 6-hydroxy-dopamine-hemilesioned rats rendered dyskinetic by treatment with 3, 4-dihydroxyphenyl-L-alanine (L-DOPA). Similar findings were obtained using striatal samples from primates. Radioligand binding studies in the presence of a D3 agonist led in dyskinetic, but not in lesioned or L-DOPA-treated rats, to a higher dopamine sensitivity. Upon D3-receptor activation, the affinity of agonists for binding to the right striatal D1 receptor increased. Excess dopamine coming from L-DOPA medication likely activates D3 receptors thus making right and left striatal D1 receptors equally responsive to dopamine. These results show that dyskinesia occurs concurrently with a right/left striatal balance in D1 receptor-mediated neurotransmission.

Obesity in men with childhood ADHD: a 33-year controlled, prospective, follow-up study.

PubMed

Cortese, Samuele; Ramos Olazagasti, Maria A; Klein, Rachel G; Castellanos, F Xavier; Proal, Erika; Mannuzza, Salvatore

2013-06-01

To compare BMI and obesity rates in fully grown men with and without childhood attention-deficit/hyperactivity disorder (ADHD). We predicted higher BMI and obesity rates in: (1) men with, versus men without, childhood ADHD; (2) men with persistent, versus men with remitted, ADHD; and (3) men with persistent or remitted ADHD versus those without childhood ADHD. Men with childhood ADHD were from a cohort of 207 white boys (referred at a mean age of 8.3 years), interviewed blindly at mean ages 18 (FU18), 25 (FU25), and 41 years (FU41). At FU18, 178 boys without ADHD were recruited. At FU41, 111 men with childhood ADHD and 111 men without childhood ADHD self-reported their weight and height. Men with childhood ADHD had significantly higher BMI (30.1 ± 6.3 vs 27.6 ± 3.9; P = .001) and obesity rates (41.4% vs 21.6%; P = .001) than men without childhood ADHD. Group differences remained significant after adjustment for socioeconomic status and lifetime mental disorders. Men with persistent (n = 24) and remitted (n = 87) ADHD did not differ significantly in BMI or obesity rates. Even after adjustment, men with remitted (but not persistent) ADHD had significantly higher BMI (B: 2.86 [95% CI: 1.22 to 4.50]) and obesity rates (odds ratio: 2.99 [95% CI: 1.55 to 5.77]) than those without childhood ADHD. Children with ADHD are at increased risk of obesity as adults. Findings of elevated BMI and obesity rates in men with remitted ADHD require replication.

Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids

PubMed Central

Covey, Dan P.; Bunner, Kendra D.; Schuweiler, Douglas R.; Cheer, Joseph F.; Garris, Paul A.

2018-01-01

The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

PubMed

Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

2016-06-01

The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

Clinical and Functional Outcome of Childhood ADHD 33 Years Later

PubMed Central

Klein, Rachel G.; Mannuzza, Salvatore; Ramos Olazagasti, María A.; Roizen Belsky, Erica; Hutchison, Jesse A.; Lashua-Shriftman, Erin; Castellanos, F. Xavier

2012-01-01

. Conclusions The multiple disadvantages predicted by childhood ADHD well into adulthood began in adolescence, without increased onsets of new disorders after age 20. Findings highlight the importance of extended monitoring and treatment of children with ADHD. PMID:23070149

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volkow, N.D.; Wang, G.; Volkow, N.D.

Attention-deficit/hyperactivity disorder (ADHD) - characterized by symptoms of inattention and hyperactivity-impulsivity - is the most prevalent childhood psychiatric disorder that frequently persists into adulthood, and there is increasing evidence of reward-motivation deficits in this disorder. To evaluate biological bases that might underlie a reward/motivation deficit by imaging key components of the brain dopamine reward pathway (mesoaccumbens). We used positron emission tomography to measure dopamine synaptic markers (transporters and D{sub 2}/D{sub 3} receptors) in 53 nonmedicated adults with ADHD and 44 healthy controls between 2001-2009 at Brookhaven National Laboratory. We measured specific binding of positron emission tomographic radioligands for dopamine transportersmore » (DAT) using [{sup 11}C]cocaine and for D{sub 2}/D{sub 3} receptors using [{sup 11}C]raclopride, quantified as binding potential (distribution volume ratio -1). For both ligands, statistical parametric mapping showed that specific binding was lower in ADHD than in controls (threshold for significance set at P < .005) in regions of the dopamine reward pathway in the left side of the brain. Region-of-interest analyses corroborated these findings. The mean (95% confidence interval [CI] of mean difference) for DAT in the nucleus accumbens for controls was 0.71 vs 0.63 for those with ADHD (95% CI, 0.03-0.13, P = .004) and in the midbrain for controls was 0.16 vs 0.09 for those with ADHD (95% CI, 0.03-0.12; P {le} .001); for D{sub 2}/D{sub 3} receptors, the mean accumbens for controls was 2.85 vs 2.68 for those with ADHD (95% CI, 0.06-0.30, P = .004); and in the midbrain, it was for controls 0.28 vs 0.18 for those with ADHD (95% CI, 0.02-0.17, P = .01). The analysis also corroborated differences in the left caudate: the mean DAT for controls was 0.66 vs 0.53 for those with ADHD (95% CI, 0.04-0.22; P = .003) and the mean D{sub 2}/D{sub 3} for controls was 2.80 vs 2.47 for those with ADHD

Attention Deficit/Hyperactivity Disorder and Urinary Nonylphenol Levels: A Case-Control Study in Taiwanese Children

PubMed Central

Yu, Ching-Jung; Du, Jung-Chieh; Chiou, Hsien-Chih; Yang, Shang-Han; Liao, Kai-Wei; Yang, Winnie; Chung, Ming-Yi; Chien, Ling-Chu; Hwang, Betau; Chen, Mei-Lien

2016-01-01

Objective Nonylphenol (NP) belongs to the family of endocrine disruptors, and it is widely used in industrial applications and is ubiquitous in daily foods. Animal studies have suggested that NP exposure might promote motor hyperactivity, likely by causing deficits in dopaminergic neurons. However, research assessing NP exposure and epidemiology studies on human populations are limited. The aim of this study was to explore the association between child NP exposure and ADHD while considering particular covariants, such as lead levels and dopamine-related gene variations. Methods A case-control study was conducted on patients with clinically diagnosed ADHD; the Swanson, Nolan and Pelham, Fourth Revision (SNAP-IV) questionnaire was used to identify normal controls aged 4–15 years. Participants were examined for urinary NP concentrations, blood lead levels, and select single-nucleotide polymorphisms of two dopamine-related genes (D4 dopamine receptor, DRD4, and dopamine transporter, DAT1). Socio-demographic variables, maternal lifestyle factors during pregnancy and family medical history were obtained using a questionnaire. Results A total of 97 children with doctor-diagnosed ADHD and 110 normal controls were enrolled. The blood lead levels in both groups were similar (1.57±0.73 vs. 1.73±0.77 μg/dL, p = 0.15). No significant difference in urinary NP concentration was found between the children with ADHD and the control subjects (4.52±3.22 μg/g cr. vs. 4.64±2.95 μg/g cr., p = 0.43). ADHD was significantly more prevalent among males in this study (male to female ratio: 5:1 for the ADHD group and 1.3:1 for the control group, p<0.01). The analysis was repeated after excluding the females, but this had no effect on the association between NP and ADHD. The regression model, including or excluding females, indicated no increased odds of having ADHD in the context of NP exposure after adjusting for covariants. Conclusion This study indicated that NP exposure might not

Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children?

PubMed Central

Gold, Mark S.; Blum, Kenneth; Oscar-Berman, Marlene; Braverman, Eric R.

2014-01-01

Attention deficit/hyperactivity disorder (ADHD) is present in 8% to 12% of children, and 4% of adults worldwide. Children with ADHD can have learning impairments, poor self-esteem, social dysfunction, and an increased risk of substance abuse, including cigarette smoking. Overall, the rate of treatment with medication for patients with ADHD has been increasing since 2008, with > 2 million children now being treated with stimulants. The rise of adolescent prescription ADHD medication abuse has occurred along with a concomitant increase of stimulant medication availability. Of adults presenting with a substance use disorder (SUD), 20% to 30% have concurrent ADHD, and 20% to 40% of adults with ADHD have a history of SUD. Following a brief review of the etiology of ADHD, its diagnosis and treatment, we focus on the benefits of early and appropriate testing for a predisposition to ADHD. We suggest that by genotyping patients for a number of known, associated dopaminergic polymorphisms, especially at an early age, misdiagnoses and/or over-diagnosis can be reduced. Ethical and legal issues of early genotyping are considered. As many as 30% of individuals with ADHD are estimated to either have secondary side-effects or are not responsive to stimulant medication. We also consider the benefits of non-stimulant medication and alternative treatment modalities, which include diet, herbal medications, iron supplementation, and neurofeedback. With the goals of improving treatment of patients with ADHD and SUD prevention, we encourage further work in both genetic diagnosis and novel treatment approaches. PMID:24393762

Neuropsychological Performance Patterns of Adult ADHD Subtypes.

PubMed

LeRoy, Amy; Jacova, Claudia; Young, Caedy

2018-05-01

Neuropsychological performance patterns associated with adult ADHD subtypes are unknown. The aim of the current systematic review was to identify and synthesize available literature regarding neuropsychological performance associated with adult ADHD subtypes. Searches were completed using the databases PsycINFO and PubMed for studies published before March 2017 addressing adult ADHD subtypes and neuropsychological performance. Data characterizing the neuropsychological tests utilized in each study were obtained and sorted into eight domains. To summarize the results of all comparisons (ADHD subtype compared with control, or to each other), we counted the proportion of tests within each domain with significant group differences. We deemed four domains informative in differentiating ADHD subtypes from controls. Of these, memory was the only domain that held promise in distinguishing ADHD-Inattentive and ADHD-Combined. Limitations of the available literature are highlighted and recommendations for future research are provided.

Dopamine, T cells and multiple sclerosis (MS).

PubMed

Levite, Mia; Marino, Franca; Cosentino, Marco

2017-05-01

Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others. Interestingly, dopamine activates resting effector T cells (Teffs), but suppresses regulatory T cells (Tregs), and both effects lead eventually to Teff activation. Dopamine-induced effects on T cells are dynamic, context-sensitive and determined by the: T cell activation state, T cell type, DR type, and dopamine concentration. Dopamine itself, and also few dopaminergic molecules/ drugs that are in clinical use for cardiac, neurological and other non-immune indications, have direct effects on human T cells (summarized in this review). These dopaminergic drugs include: dopamine = intropin, L-DOPA, bromocriptine, pramipexole, pergolide, haloperidol, pimozide, and amantadine. Other dopaminergic drugs were not yet tested for their direct effects on T cells. Extensive evidence in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) show dopaminergic dysregulations in T cells in these diseases: D1-like DRs are decreased in Teffs of MS patients, and dopamine does not affect these cells. In contrast, D1-like DRs are increased in Tregs of MS patients, possibly causing functional Treg impairment in MS. Treatment of MS patients with interferon β (IFN-β) increases D1-like DRs and decreases D2-like DRs in Teffs, decreases D1-like DRs in Tregs, and most important: restores responsiveness of patient's Teffs to dopamine. DR agonists and antagonists confer some benefits in

New Repeat Polymorphism in the AKT1 Gene Predicts Striatal Dopamine D2/D3 Receptor Availability and Stimulant-Induced Dopamine Release in the Healthy Human Brain.

PubMed

Shumay, Elena; Wiers, Corinde E; Shokri-Kojori, Ehsan; Kim, Sung Won; Hodgkinson, Colin A; Sun, Hui; Tomasi, Dardo; Wong, Christopher T; Weinberger, Daniel R; Wang, Gene-Jack; Fowler, Joanna S; Volkow, Nora D

2017-05-10

The role of the protein kinase Akt1 in dopamine neurotransmission is well recognized and has been implicated in schizophrenia and psychosis. However, the extent to which variants in the AKT1 gene influence dopamine neurotransmission is not well understood. Here we investigated the effect of a newly characterized variant number tandem repeat (VNTR) polymorphism in AKT1 [major alleles: L- (eight repeats) and H- (nine repeats)] on striatal dopamine D2/D3 receptor (DRD2) availability and on dopamine release in healthy volunteers. We used PET and [ 11 C]raclopride to assess baseline DRD2 availability in 91 participants. In 54 of these participants, we also measured intravenous methylphenidate-induced dopamine release to measure dopamine release. Dopamine release was quantified as the difference in specific binding of [ 11 C]raclopride (nondisplaceable binding potential) between baseline values and values following methylphenidate injection. There was an effect of AKT1 genotype on DRD2 availability at baseline for the caudate ( F (2,90) = 8.2, p = 0.001) and putamen ( F (2,90) = 6.6, p = 0.002), but not the ventral striatum ( p = 0.3). For the caudate and putamen, LL showed higher DRD2 availability than HH; HL were in between. There was also a significant effect of AKT1 genotype on dopamine increases in the ventral striatum ( F (2,53) = 5.3, p = 0.009), with increases being stronger in HH > HL > LL. However, no dopamine increases were observed in the caudate ( p = 0.1) or putamen ( p = 0.8) following methylphenidate injection. Our results provide evidence that the AKT1 gene modulates both striatal DRD2 availability and dopamine release in the human brain, which could account for its association with schizophrenia and psychosis. The clinical relevance of the newly characterized AKT1 VNTR merits investigation. SIGNIFICANCE STATEMENT The AKT1 gene has been implicated in schizophrenia and psychosis. This association is likely to reflect modulation of dopamine signaling by

Co-Occurrence of ODD and CD in Preschool Children With Symptoms of ADHD.

PubMed

Bendiksen, Bothild; Svensson, Elisabeth; Aase, Heidi; Reichborn-Kjennerud, Ted; Friis, Svein; Myhre, Anne M; Zeiner, Pål

2017-07-01

Patterns of co-occurrence between ADHD, Oppositional Defiant Disorder (ODD), and Conduct Disorder (CD) were examined in a sample of non-referred preschool children. ADHD subtypes and sex differences were also explored. Children aged 3.5 years ( n = 1,048) with high scores on ADHD characteristics were recruited from the Norwegian Mother and Child Cohort Study and clinically assessed, including a semi-structured psychiatric interview. In children with ADHD, concurrent ODD was present more often than CD (31% vs. 10%), but having ADHD gave higher increase in the odds of CD than of ODD (ODD: odds ratio [OR] = 6.7, 95% confidence interval [CI] = [4.2, 10.8]; CD: OR = 17.6, 95% CI = [5.9, 52.9]). We found a greater proportion of children having the combined ADHD subtype as well as more severe inattentiveness among children with co-occurring CD compared with ODD. Sex differences were minor. There are important differences in co-occurring patterns of ODD and CD in preschool children with ADHD.

Family characteristics of anxious ADHD children: preliminary results.