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Evaluating Dopamine Reward Pathway in ADHD: Clinical Implications
Open accessAbstract
We used positron emission tomography to measure dopamine synaptic markers (transporters and D2/D3 receptors) in 53 nonmedicated adults with ADHD and 44 healthy controls. For both ligands, statistical parametric mapping showed that specific binding was lower in ADHD than in controls in regions of the dopamine reward pathway in the left side of the brain. The mean for DAT in the nucleus accumbens for controls was 0.71 vs 0.63 for those with ADHD and in the midbrain for controls was 0.16 vs 0.09 for those with ADHD. For D2/D3 receptors, the mean in the caudate for controls was 2.80 vs 2.67 for those with ADHD; and in the accumbens for controls was 2.85 vs 2.68 for those with ADHD.
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“for D2/D3 receptors, the mean accumbens for controls was 2.85 vs 2.68 for those with ADHD (95% CI, 0.06–0.30, P=.004)”
§ Evaluating Dopamine Reward Pathway in ADHD > Abstract > Results
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In the paper
“differences in D2/D3 in the hypothalamic region, with controls having a mean of 0.12 vs 0.05 for those with ADHD (95% CI, 0.02–0.12; P=.004)”
§ Evaluating Dopamine Reward Pathway in ADHD > Abstract > Results
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In the paper
“but the reductions in left hypothalamic region were not significantly different (Table 2).”
§ Evaluating Dopamine Reward Pathway in ADHD > RESULTS > Dopamine Transporters
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In the paper
“and in the midbrain for controls was 0.16 vs 0.09 for those with ADHD (95% CI, 0.03–0.12; P ≤ .001)”
§ Evaluating Dopamine Reward Pathway in ADHD > Abstract > Results
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In the paper
“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)”
§ Evaluating Dopamine Reward Pathway in ADHD > Abstract > Results
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In the paper
“The correlations with reflectivity or impulsivity and the PET dopamine measures were not significant”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT > Limitations
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In the paper
“However, despite this limitation, significant differences in the latter regions between controls and participants with ADHD was shown.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT > Limitations
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
- Also stated in: § Dopamine D2/D3 Receptors · plain
“Statistical parametric mapping analysis of the [11C]raclopride distribution volume ratio images revealed 1 cluster with lower D2/D3 availability in ADHD participants than controls in the left hemisphere.”
- Also stated in: § Dopamine Transporters · plain
“Statistical parametric mapping analysis of the [11C]cocaine distribution volume ratio images revealed a cluster in the same location as manifested in the [11C]raclopride images.”
§ Evaluating Dopamine Reward Pathway in ADHD > Abstract > Results
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Dopamine D2/D3 Receptors · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean (95% CI for mean difference) of the K1 measures for [11C]cocaine did not differ in the left caudate with 0.49 among the controls vs 0.48 among those with ADHD (95% CI, −0.05 to 0.03) or in left accumbens region with a respective difference of 0.49 vs 0.51 among those with ADHD (95% CI, −0.02 to 0.07).”
§ Evaluating Dopamine Reward Pathway in ADHD > RESULTS > Dopamine Transporters
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast the K1 measures for [11C]raclopride (transport of radioligand from plasma to tissue) did not differ either in left caudate with the both groups having a mean 0.11 (95% confidence interval [CI], −0.01 to 0.006 mean difference) or in left accumbens region with the controls having a mean of 0.12 vs a mean of 0.11 for those with ADHD (95% CI, −0.01 to 0.005).”
§ Evaluating Dopamine Reward Pathway in ADHD > RESULTS > Dopamine D2/D3 Receptors
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- The quote only partly states this claim. 1
- Probably not a substantial claim. 18
- It may state two separate claims as one. 12
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no regions that were higher in ADHD participants than in controls.”
§ Evaluating Dopamine Reward Pathway in ADHD > RESULTS > Dopamine D2/D3 Receptors
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and with DAT in the midbrain (r=0.37; 95% CI, 0.16–0.53; P ≤ .001).”
§ Evaluating Dopamine Reward Pathway in ADHD > Abstract > Results
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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In the paper
“Lower than normal D2/D3 receptors and DAT availability in ADHD in the caudate was also demonstrated.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT
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In the paper
“Genetic and environmental etiologies that implicate the neurotransmitter dopamine have been proposed for ADHD.3”
§ Evaluating Dopamine Reward Pathway in ADHD > Abstract > Conclusion
What the sources say
- Not matchedcites [3]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“The psychometric properties of the SWAN rating scale are superior to those of truncated symptom-severity ratings scales.22”
§ Evaluating Dopamine Reward Pathway in ADHD > METHODS > Clinical Scales
What the sources say
- Not matchedcites [22]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Thus, this finding is preliminary and in need of replication.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT > Limitations
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In the paper
“which could reflect that the scores were low and thus the sensitivity to observe such a correlation was lacking.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT > Limitations
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The preliminary finding reported herein of lower than normal dopamine D2/D3 receptor availability in the hypothalamic region of ADHD participants is intriguing because if replicated, it could hypothetically provide a neurobiological basis for the high co-morbidity of ADHD with signs and symptoms suggestive of hypothalamic pathology45 such as sleep disturbances,46 overweight or obesity,47 and abnor”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“the laterality effects should be interpreted as preliminary and in need of replication.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT > Limitations
Strength:hedged· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This study was not initially designed to evaluate hypothalamic dopamine involvement in ADHD.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT > Limitations
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None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Evidence from brain imaging studies have shown that brain dopamine neurotransmission is disrupted in ADHD5–9 and that these deficits may underlie core symptoms of inattention8 and impulsivity.9”
§ Evaluating Dopamine Reward Pathway in ADHD > Abstract > Conclusion
What the sources say
- Not matchedcites [5]
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- Not matchedcites [6]
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- Not matchedcites [8]
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- Not matchedcites [9]
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Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Morphological MRI images were not obtained and thus whether volumetric differences in striatum in those with ADHD that could account for these findings could not be ascertained since volumetric differences in striatum have been reported in ADHD.36–40”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT > Limitations
What the sources say
- Not matchedcites [36]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [37]
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- Not matchedcites [38]
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- Not matchedcites [39]
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- Not matchedcites [40]
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Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In our study, the D2/D3 receptor measures in accumbens were correlated with the dimension of attention, which would implicate the dopamine reward pathway in the symptoms of inattention in ADHD.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“This pathway plays a key role in reinforcement-motivation and in learning stimuli-reward associations,51 and its involvement in ADHD supports the use of interventions to enhance the saliency of school and work tasks to improve performance.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT
What the sources say
- Not matchedcites [51]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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- Not matched
In the paper
“This rating system has been widely used in clinical and research settings and has well-established factor structure, reliability, and validity (Table 1).24”
§ Evaluating Dopamine Reward Pathway in ADHD > METHODS > Clinical Scales
What the sources say
- Not matchedcites [24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“The reward deficits in ADHD are characterized by a failure to delay gratification, impaired response to partial schedules of reinforcement, and preference for small immediate rewards over larger delayed rewards.31”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT
What the sources say
- Not matchedcites [31]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“Finally, because a low number of dopamine D2/D3 receptors in the nucleus accumbens have been associated with a greater risk for drug abuse,33 future work should determine if the lower than normal D2/D3 receptor availability in the accumbens region in ADHD underlies the higher vulnerability for substance abuse in this population.34”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT
What the sources say
- Not matchedcites [33]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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- Not matched
In the paper
“Both motivational interventions and contingency management have been shown to improve performance in ADHD patients.52”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT
What the sources say
- Not matchedcites [52]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Another study limitation was that measures of reward sensitivity were not performed. Thus, we can only infer that the decreases in the dopamine markers in the accumbens region could underlie the reward deficits that have been reported in patients with ADHD.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT > Limitations
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In the paper
“Multiple hypothalamic nuclei express dopamine D2 receptors,49 but the limited spatial resolution of a PET scan does not allow for localizing where the differences between the groups occurred.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT
What the sources say
- Not matchedcites [49]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“low statistical power may have contributed to the lack of significant ADHD-normal differences in the right brain regions.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT > Limitations
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Definitions for significant difference for the outcome measures1 were that statistical parametric mapping comparisons for the DAT and the D2/D3 images had to be significant at P<.005 (cluster corrected > 100 voxels) and the regional findings had to be corroborated by independently drawn region of interests2; comparisons for these corroborative measures had to be significant at P<.053; correlations”
§ Evaluating Dopamine Reward Pathway in ADHD > METHODS > Image Analysis and Statistics
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None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“The mesoaccumbens dopamine pathway, which projects from the ventral tegmental area (VTA) in the midbrain to the nucleus accumbens is critically involved in reward and motivation14 and has been hypothesized to underlie the reward and motivational deficits observed in ADHD.11,15”
§ Evaluating Dopamine Reward Pathway in ADHD > Abstract > Conclusion
What the sources say
- Not matchedcites [14]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [11]
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- Not matchedcites [15]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Not matched
In the paper
“Alternatively it could reflect the involvement of frontal regions in impulsivity,57 which could not be measured with current PET radioligands; D2/D3 receptors and DAT levels in frontal regions are very low.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT > Limitations
What the sources say
- Not matchedcites [57]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Rests on an assumption: D2/D3 receptors and DAT levels in frontal regions are very low.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“There is also increased awareness that patients with ADHD may have reward and motivation deficits.10–12”
§ Evaluating Dopamine Reward Pathway in ADHD > Abstract > Conclusion
What the sources say
- Not matchedcites [10]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [11]
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- Not matchedcites [12]
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Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“but the limited spatial resolution of a PET scan does not allow for localizing where the differences between the groups occurred.”
§ Evaluating Dopamine Reward Pathway in ADHD > COMMENT
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
No prior study has directly measured synaptic dopamine markers in the accumbens region of individuals with ADHD.
“However, to our knowledge no study has directly measured synaptic dopamine markers in the accumbens region of individuals with ADHD.”
The paper relies on this without support.
D2/D3 receptors and DAT levels in frontal regions are very low.
“D2/D3 receptors and DAT levels in frontal regions are very low.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“using positron emission tomography (PET) we showed lower than normal availability of DA D2/D3 receptors (measured with [ 11 C]raclopride) and of DA transporters (measured with [ 11 C]cocaine) in the midbrain and in NAcc in drug naïve ADHD participants compared to non-ADHD control subjects 10 .”
From Motivation Deficit in ADHD is Associated with Dysfunction of the Dopamine Reward Pathway (2011) · cites this paper as [10]
In the citing paper
“As a number of researchers have described [106,149], substance-use disorders are typically accompanied by decreased reward motivation for typical and non-pathological rewards, a phenomenon that has been variously termed ‘motivational toxicity’ [150] and ‘reward-deficiency syndrome’ [151].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [149]
In the citing paper
“The immediate and marked response of ADHD symptoms to stimulant medications such as amphetamines and methylphenidate, which increase levels of synaptic dopamine, suggests that the main underlying pathophysiological process may involve deficits or imbalances in catecholaminergic, dopaminergic, and nicotinergic functioning [109-111].”
From European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD (2010) · cites this paper as [111]
In the citing paper
“It readily applies to ADHD because children with ADHD are at elevated risk of addiction, and both addiction and ADHD have been strongly associated with dysfunction in ascending dopaminergic systems that relate to reward response (Volkow et al., 2009, Volkow et al., 2011a, Volkow et al., 2011b).”
From Characterizing heterogeneity in children with and without ADHD based on reward system connectivity (2015) · cites this paper as Volkow et al., 2009
In the citing paper
“It readily applies to ADHD because children with ADHD are at elevated risk of addiction, and both addiction and ADHD have been strongly associated with dysfunction in ascending dopaminergic systems that relate to reward response (Volkow et al., 2009, Volkow et al., 2011a, Volkow et al., 2011b).”
From Characterizing heterogeneity in children with and without ADHD based on reward system connectivity (2015) · cites this paper as Volkow et al., 2009
In the citing paper
“Stimulant treatment, such as methylphenidate, is known to act directly on brain regions associated with disrupted dopamine reward pathways in ADHD [62,63] and may be responsible for the global effects seen with stimulant treatment in ADHD.”
From Will Working Memory Training Generalize to Improve Off-Task Behavior in Children with Attention-Deficit/Hyperactivity Disorder? (2012) · cites this paper as [63]
In the citing paper
“A subsequent study of ADHD subjects showed the same finding of reduced D2 receptor binding in the ventral striatum and caudate (Volkow et al., 2009), which correlated inversely with attention.”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Volkow et al., 2009
In the citing paper
“Based on these results, this group hypothesized that decreased dopamine transmission plays a role in the motivation and reward deficits seen in ADHD, which are characterized by poor response inhibition and preference for small immediate rewards over larger delayed rewards (Volkow et al., 2009).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Volkow et al., 2009
In the citing paper
“A number of studies have shown that ADHD is associated with a motivational deficit due to a dopamine dysfunction in the basal ganglia [71–73].”
From The brain anatomy of attention-deficit/hyperactivity disorder in young adults—a magnetic resonance imaging study (2017) · cites this paper as [71]
In the citing paper
“Recent studies have further indicated deficits in the dopamine reward circuitry,3–5 as predicted by developmental neurobiological models of the disorder.6–8”
From Striatal sensitivity during reward processing in attention-deficit/hyperactivity disorder (2012) · cites this paper as [5]
In the citing paper
“Neurochemical studies have demonstrated alterations in dopaminergic signaling in the striatum and the midbrain in ADHD, and linked such alterations with inattention symptoms and motivation problems in children and adults with ADHD.5,27–29”
From Striatal sensitivity during reward processing in attention-deficit/hyperactivity disorder (2012) · cites this paper as [5]
In the citing paper
“A recent set of case–control PET studies in adult medication-naïve patients found that ADHD is associated with reduced dopamine transporter and dopamine D2/D3 receptor availability in selected brain regions of the left hemisphere, including the nucleus accumbens, caudate and midbrain (Volkow et al., 2007a, b, 2009).”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Volkow et al., 2007a, b, 2009
In the citing paper
“This question is particularly relevant because findings for both juvenile and adult ADHD have implicated functional and structural midbrain abnormalities in the pathophysiology of the disorder (Ernst et al., 1999; Jucaite et al., 2005; Volkow et al., 2009; Romanos et al., 2010), also consistent with experimental animal models of ADHD (Leo et al., 2003).”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Volkow et al., 2009
In the citing paper
“This result is consistent with previous evidence implicating the left caudate in inattentiveness, not only in patients with ADHD, but also in healthy subjects (Schrimsher et al., 2002; Volkow et al., 2007a, b, 2009) and is also congruent with reports that lesions in the left caudate produce attentional deficits (Benke et al., 2003).”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Volkow et al., 2007a, b, 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Reported correlation sign conflicts with the stated interpretation
MajorThe results call the association with attention negative, but the reported coefficient is positive (r=0.35), as are the other reported attention correlations. Because the paper says higher SWAN scores indicate more symptoms, the reported sign reverses the stated interpretation that lower dopamine measures accompany greater inattention.
“The dimension of attention (from the SWAN) was negatively correlated with D2/D3 receptor availability in the left accumbens region (r=0.35; 95% CI, 0.15–0.52; P=.001)”
“Because the SWAN scale rates symptoms with a positive scale (from 1 to 3) and the opposite of symptoms with a negative scales (from −1 to −3) the negative correlation indicates that the lower the dopamine measures, the greater the symptoms of inattention.”
Citations
Cites
Attention Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment
Barkley, R. A., & Poillion, M. J. (1994) · Behavioral Disorders · doi:10.1177/019874299401900205 · Cited by 4,635
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“With PET imaging, lower D2/D3 receptor and DAT availability in those with ADHD than in the control group was documented in 2 key brain regions for reward and motivation (accumbens and midbrain).(29) It also corroborates disruption of synaptic dopamine markers in caudate in adults with ADHD and provides preliminary evi…”
Logan, J., Fowler, J. S., Volkow, N. D., Wolf, A. P., Dewey, S. L., Schlyer, D. J., MacGregor, R. R., HITZEMANN, R. J., Bendriem, B., Gatley, S. J., et al. (1990) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1990.127 · Cited by 1,481 · cited 4×
“Forthisstudy,[(11)C]cocainewaschosenas theDATradioligand becauseitsspecificbindingisselectivefor DAT(itsbindingisinhibitedbydrugsthat blocktheDATbutnotbydrugstheblock the norepinephrine or the serotonin transporters)(25); itprovideswithreproduciblemeasureswhenparticipantsaretested onseparateoccasions(19)anditskinetics…”
InfluentialSelf-citationAttention Deficit Hyperactivity Disorder. A Handbook for Diagnosis and Treatment
Silver, L. B. (1991) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199107000-00040 · Cited by 1,395 · cited 1×
“This could provide an explanation of why the attentional deficits in individuals with ADHD are most evident in tasks that are considered boring, repetitive, and uninteresting (ie, tasks or assignments that are not intrinsically rewarding).(32) Finally, because a low number of dopamine D2/D3 receptors in the nucleus ac…”
Brown, A., Brummel‐Smith, K. V., Burgess, L., D’Agostino, R. B., Goldschmidt, J. W., Halter, J. B., Hazzard, W. R., Jahnigen, D. W., Phelps, C. E., Raskind, M. A., et al. (1988) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1988.tb02362.x · Cited by 1,331
Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement
Dalley, J. W., Fryer, T. D., Brichard, L., Robinson, E. S. J., Theobald, D. E. H., Lääne, K., Peña, Y., Murphy, E. R., Shah, Y., Probst, K., et al. (2007) · Science · doi:10.1126/science.1137073 · Cited by 1,188
Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder
Castellanos, F. X. (1996) · Archives of General Psychiatry · doi:10.1001/archpsyc.1996.01830070053009 · Cited by 1,183
Sonuga-Barke, E. J. S. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.09.008 · Cited by 962
Winstanley, C. A., Eagle, D. M., & Robbins, T. W. (2006) · Clinical Psychology Review · doi:10.1016/j.cpr.2006.01.001 · Cited by 893
Wise, R. A. (2002) · Neuron · doi:10.1016/s0896-6273(02)00965-0 · Cited by 881
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Abnormal striatal BOLD responses to reward anticipation and reward delivery in ADHD
Furukawa, E., Bado, P., Tripp, G., Mattos, P., Wickens, J. R., Bramati, I. E., Alsop, B., Ferreira, F. M., Lima, D., Tovar-Moll, F., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089129 · Cited by 90
“A reduction in dopamine synaptic markers including DAT1 has also been shown in the dopamine reward pathway [8].”
BackgroundNeural responses to monetary incentives among self-injuring adolescent girls
Sauder, C. L., Derbidge, C. M., & Beauchaine, T. P. (2016) · Development and Psychopathology · doi:10.1017/s0954579415000449 · Cited by 89
“Consistent with this theory, neuroimaging studies demonstrate reduced reward responding in mesolimbic and/or mesocortical structures across impulse control disorders including ADHD, CD, substance use disorders, and gambling addiction Note: MNI, Standard Montreal Neurological Institute stereotaxic coordinates (x, y, z)…”
BackgroundInfluentialIs ADHD a valid diagnosis in adults? Yes
Asherson, P. J., Adamou, M., Bolea-Alamanac, B. M., Müller, U., Dunn-Morua, S., Pitts, M. E., Thome, J., & Young, S. (2010) · BMJ · doi:10.1136/bmj.c549 · Cited by 92
Carmona, S., Hoekzema, E., Ramos‐Quiroga, J. A., Richarte, V., Canals, C., Bosch, R., Rovira, M., Carlos Soliva, J., Bulbena, A., Tobeña, A., et al. (2012) · Human Brain Mapping · doi:10.1002/hbm.21368 · Cited by 89
“For instance, a recent PET study assessing dopaminergic function in medication-naı̈ve adults with ADHD observed a reduced availability of the dopamine transporter as well as of D2 and D3-like receptors in the VStr in the patient with the disorder [Volkow et al., 2009].”
BackgroundCircadian Synchrony: Sleep, Nutrition, and Physical Activity
Healy, K. L., Morris, A. R., & Liu, A. C. (2021) · Frontiers in Network Physiology · doi:10.3389/fnetp.2021.732243 · Cited by 98
“ADHD is thought to be caused by a reduction in dopaminergic signaling (Volkow et al., 2009).”
Gold, M. S., Blum, K., Oscar‐Berman, M., & Braverman, E. R. (2014) · Postgraduate Medicine · doi:10.3810/pgm.2014.01.2735 · Cited by 93
Boekhoudt, L., Omrani, A., Luijendijk, M. C. M., Wolterink‐Donselaar, I. G., Wijbrans, E. C., Plasse, G., & Adan, R. A. H. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2016.09.003 · Cited by 87
Prevalence of hormone-related mood disorder symptoms in women with ADHD
Dorani, F., Bijlenga, D., Beekman, A. T. F., van Someren, E. J. W., & Kooij, J. J. S. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.12.005 · Cited by 86
Risky decision making in adults with ADHD
Matthies, S., Philipsen, A., & Svaldi, J. (2012) · Journal of Behavior Therapy and Experimental Psychiatry · doi:10.1016/j.jbtep.2012.02.002 · Cited by 85
Transgenic mouse models for ADHD
Leo, D., & Gainetdinov, R. R. (2013) · Cell and Tissue Research · doi:10.1007/s00441-013-1639-1 · Cited by 86
“…phenotype and the responses to psychostimulants in various strains of DAT-deficient mice generally support the clinical observations of decreased (Volkow et al. 2009b, 2007), rather than increased (Madras et al. 2005) DAT expression found in some ADHD patients, although these alterations might…”
BackgroundResultAttenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder
Badgaiyan, R. D., Sinha, S., Sajjad, M., & Wack, D. S. (2015) · PLOS ONE · doi:10.1371/journal.pone.0137326 · Cited by 84
“Findings suggesting reduced dopaminergic activity include small volume of the caudate [4–7], reduced regional blood flow in the striatum [8], increased uptake of (18)F-DOPA [9], attenuation of methylphenidate induced dopamine release in the caudate [10], correlation of methylphenidate induced dopamine release with cli…”
BackgroundADHD related behaviors are associated with brain activation in the reward system
Stark, R., Bauer, E., Merz, C. J., Zimmermann, M., Reuter, M., Plichta, M. M., Kirsch, P., Lesch, K. P., Fallgatter, A. J., Vaitl, D., et al. (2011) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2010.12.012 · Cited by 82
“…model (Williams & Dayan, 2005), the integrative ycholo t B w ( 2 & a t n c a t d t a d b h t s s t t r r m d r p i t h i ( A d ( l S t p r d a A h t F s a e e m t ( g e w T t i I b R. Stark et al. / Neurops heory (Nigg & Casey, 2005), and the dual pathway model (Sonugaarke, 2002, 2003, 2005).”
BackgroundXie, Y., Gao, X., Song, Y., Zhu, X., Chen, M., Yang, L., & Ren, Y. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.706625 · Cited by 86
Attention-Deficit/Hyperactivity Disorder: Is it time to Reappraise the Role of Sugar Consumption?
Johnson, R. J., Gold, M. S., Johnson, D. R., Ishimoto, T., Lanaspa, M. A., Zahniser, N. R., & Avena, N. M. (2011) · Postgraduate Medicine · doi:10.3810/pgm.2011.09.2458 · Cited by 90
Adisetiyo, V., Jensen, J. H., Tabesh, A., Deardorff, R. L., Fieremans, E., Martino, A. D., Gray, K. M., Castellanos, F. X., & Helpern, J. A. (2014) · Radiology · doi:10.1148/radiol.14140047 · Cited by 80
“In humans, evidence linking atypical brain iron levels with changes in the dopaminergic system has been observed in restless leg syndrome (36), a sensorimotor ADHD symptoms by predominantly increasing striatal dopamine (1,4,32) and that our results parallel previous molecular imaging findings of reduced striatal dopam…”
ResultBehavioral endophenotypes of drug addiction: Etiological insights from neuroimaging studies
Jupp, B., & Dalley, J. W. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.041 · Cited by 78
Psychophysiological Methods and Developmental Psychopathology
Zisner, A. R., & Beauchaine, T. P. (2016) · Wiley eBooks · doi:10.1002/9781119125556.devpsy222 · Cited by 84
A chaotic model of sustaining attention problem in attention deficit disorder
Baghdadi, G., Jafari, S., Sprott, J. C., Towhidkhah, F., & Golpayegani, M. R. (2014) · Communications in Nonlinear Science and Numerical Simulation · doi:10.1016/j.cnsns.2014.05.015 · Cited by 76
“ADD is also believed to be associated with decreased dopamine activity [33].”
BackgroundGonon, F., Konsman, J. P., Cohen, D., & Boraud, T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044275 · Cited by 85
“only one study [56] was echoed by three newspaper articles (Fig.”
BackgroundCha, J., Fekete, T., Siciliano, F., Biezonski, D., Greenhill, L., Pliszka, S. R., Blader, J. C., Krain Roy, A., Leibenluft, E., & Posner, J. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.18 · Cited by 75
Nusslock, R., Young, C. B., & Damme, K. S. F. (2014) · Behaviour Research and Therapy · doi:10.1016/j.brat.2014.08.011 · Cited by 83
“…useful biological marker for differentiating bipolar disorder from other psychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder (ADHD), both of which have also been associated with blunted frontostriatal neural activation (Grimm et al., 2014; Volkow et al., 2009).”
BackgroundPoor replication validity of biomedical association studies reported by newspapers
Dumas-Mallet, E., Smith, A., Boraud, T., & Gonon, F. (2017) · PLOS ONE · doi:10.1371/journal.pone.0172650 · Cited by 76
“In contrast, according to a subsequent study published in 2009 by JAMA (IF = 30), the dopamine transporter level was significantly decreased (-19%) in the left striatum of ADHD patients, but not in the right [27].”
ResultNatriuretic Hormones in Brain Function
Hodes, A., & Lichtstein, D. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00201 · Cited by 76
Psychostimulants Act Within the Prefrontal Cortex to Improve Cognitive Function
Spencer, R. C., Klein, R. M., & Berridge, C. W. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.12.002 · Cited by 74
Mahmoud, M. M., El-Mazary, A.-A. M., Maher, R., & Saber, M. M. (2011) · The Italian Journal of Pediatrics/Italian journal of pediatrics · doi:10.1186/1824-7288-37-60 · Cited by 75
“There were many etiological theories on the dysfunction of some brain areas that are implicated in inhibition of responses and functions of the brain [4-6].”
BackgroundWorking Memory Capacity Predicts Effects of Methylphenidate on Reversal Learning
van der Schaaf, M. E., Fallon, S. J., ter Huurne, N., Buitelaar, J. K., & Cools, R. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.100 · Cited by 73
Mergy, M. A., Gowrishankar, R., Gresch, P. J., Gantz, S. C., Williams, J. T., Davis, G. L., Wheeler, C. A., Stanwood, G. D., Hahn, M. K., & Blakely, R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417294111 · Cited by 71
“PET imaging studies of unmedicated ADHD subjects have provided evidence of reduced DAT protein levels (100), findings that predict elevated basal extracellular DA levels either because of competition of elevated DA with in vivo antagonist binding to DAT or because of reduced DA clearance.”
BackgroundThe dopamine transporter role in psychiatric phenotypes
Salatino‐Oliveira, A., Rohde, L. A., & Hutz, M. H. (2017) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32578 · Cited by 73
Bellis, M. D. D., Wang, L., Bergman, S. R., Yaxley, R. H., Hooper, S. R., & Huettel, S. A. (2013) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2013.05.020 · Cited by 76
Chou, W., Liu, T., Yang, P., Yen, C., & Hu, H. (2014) · Psychiatry Research · doi:10.1016/j.psychres.2014.11.003 · Cited by 81
“People with ADHD tend to seek enhanced stimulation of the reward pathway (Volkow et al., 2009).”
Association between ADHD and vision problems. A systematic review and meta-analysis
Bellato, A., Perna, J., Ganapathy, P. S., Solmi, M., Zampieri, A., Cortese, S., & Faraone, S. V. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01699-0 · Cited by 82
Methylphenidate Effects on Neural Activity During Response Inhibition in Healthy Humans
Costa, A. C. L., Riedel, M. J., Pogarell, O. M., Menzel-Zelnitschek, F., Schwarz, M., Reiser, M. F., Möller, H., Rubia, K., Meindl, T., & Ettinger, U. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhs107 · Cited by 70
Shen, C., Luo, Q., Chamberlain, S. R., Morgan, S. E., Romero-García, R., Du, J., Zhao, X., Touchette, É., Montplaisir, J. Y., Vitaro, F., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.03.010 · Cited by 76
Dougnon, G., & Matsui, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147550 · Cited by 76
“However, contradictory results exist to refute that hypothesis, confirming again the variability and inconsistency of results to explain ADHD molecular physiopathology [49].”
ResultKoirala, S., Grimsrud, G. J., Mooney, M. A., Larsen, B., Feczko, E., Elison, J. T., Nelson, S. M., Nigg, J. T., Tervo‐Clemmens, B., & Fair, D. A. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-024-00869-z · Cited by 78
“Such dysregulation in reward responses has been associated with alterations in synaptic dopamine processing in the ascending dopaminergic system 43,44 .”
Implications of Circadian Rhythm in Dopamine and Mood Regulation
Kim, J., Jang, S.-W., Choe, H. K., Chung, S., Son, G. H., & Kim, K. (2017) · Molecules and Cells · doi:10.14348/molcells.2017.0065 · Cited by 70
“Abnormalities in this circuit induce addiction, affective disorders, schizophrenia, and attention-deficit hyperactive disorder (Grace, 2016; Hyman and Malenka, 2001; Volkow et al., 2009).”
BackgroundTreatment for Substance Use Disorder with Co-Occurring Mental Illness
Iqbal, M. N., Levin, C. J., & Levin, F. R. (2019) · Focus · doi:10.1176/appi.focus.20180042 · Cited by 66
Ming, X., Chen, N., Ray, C., Brewer, G., Kornitzer, J., & Steer, R. A. (2018) · Child Neurology Open · doi:10.1177/2329048x18786799 · Cited by 64
Acute effects of modafinil on brain resting state networks in young healthy subjects
Esposito, R., Cilli, F., Pieramico, V., Ferretti, A., Macchia, A., Tommasi, M., Saggino, A., Ciavardelli, D., Manna, A., Navarra, R., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069224 · Cited by 66
Linking ADHD, Impulsivity, and Drug Abuse: A Neuropsychological Perspective
Urcelay, G. P., & Dalley, J. W. (2011) · Current topics in behavioral neurosciences · doi:10.1007/7854_2011_119 · Cited by 67
“Thus, a recent positron emission tomography (PET) imaging study in 53 nonmedicated adults with ADHD found that dopamine D2/3 receptors and dopamine transporter (DAT) availability are reduced in the left midbrain and NAcb (Volkow et al. 2009).”
BackgroundMoreno, M., Economidou, D., Mar, A. C., López-Granero, C., Caprioli, D., Theobald, D. E. H., Fernando, A. B. P., Newman, A. H., Robbins, T. W., & Dalley, J. W. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3010-3 · Cited by 63
“Preclinical and clinical studies demonstrate that high impulsivity and its related psychopathological disorders involve a dysregulation of the brain dopamine (DA) systems (Dalley et al. 2011; Fineberg et al. 2010; Volkow et al. 2009).”
BackgroundTraining Cognition in ADHD: Current Findings, Borrowed Concepts, and Future Directions
Rutledge, K. J., van den Bos, W., McClure, S. M., & Schweitzer, J. B. (2012) · Neurotherapeutics · doi:10.1007/s13311-012-0134-9 · Cited by 75
“We propose that ADHD symptoms are consistent with more narrowly defined deficits arising from: 1) deficits in cognitive control [34] related to improper function of the dorsolateral prefrontal cortex (DLPFC) and/or 2) an overdependence on immediate rewards indicative of mesolimbic dopamine dysfunction [35–38].”
BackgroundPharmacogenetic activation of midbrain dopaminergic neurons induces hyperactivity
Wang, S., Tan, Y., Zhang, J.-E., & Luo, M. (2013) · Neuroscience Bulletin · doi:10.1007/s12264-013-1327-x · Cited by 63
Park, B., Kebets, V., Larivière, S., Hettwer, M. D., Paquola, C., van Rooij, D., Buitelaar, J. K., Franke, B., Hoogman, M., Schmaal, L., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03963-z · Cited by 65
Miller, E. M., Pomerleau, F., Huettl, P. F., Russell, V. A., Gerhardt, G. A., & Glaser, P. E. A. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.08.020 · Cited by 62
“Finally, the NAc may play a role in the inattention observed in individuals with ADHD (Volkow et al. 2009; Volkow et al. 2011) and the differences in DA uptake between the SHR/NCrl and WKY/NCrl models of ADHD and the control strains provide preliminary neurochemical evidence for the inattentive behavior observed in th…”
BackgroundResultSmith, E., Koerting, J., Latter, S. M., Knowles, M. M., McCann, D., Thompson, M. J. J., & Sonuga-Barke, E. J. S. (2014) · Child Care Health and Development · doi:10.1111/cch.12146 · Cited by 71
Patel, B. R., Imran, S., Ye, W., Weng, H., Noroozifar, M., & Kerman, K. (2020) · Electrochimica Acta · doi:10.1016/j.electacta.2020.137094 · Cited by 61
Momentary reward induce changes in excitability of primary motor cortex
Thabit, M. N., Nakatsuka, M., Koganemaru, S., Fawi, G., Fukuyama, H., & Mima, T. (2011) · Clinical Neurophysiology · doi:10.1016/j.clinph.2011.02.021 · Cited by 59
“Also, in patients with attention deficit hyperactivity disorder (ADHD), in which there is dysfunction in the dopamine reward pathway (Volkow et al., 2009), SICI was also reduced (Moll et al.”
BackgroundVanicek, T., Spies, M., Rami-Mark, C., Savli, M., Höflich, A., Kranz, G. S., Hahn, A., Kutzelnigg, A., Traub-Weidinger, T., Mitterhauser, M., et al. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1226 · Cited by 61
Self-citationSainio, S., Palomäki, T., Rhode, S., Kauppila, M., Pitkänen, O., Selkälä, T., Tóth, G., Moram, M. A., Kordás, K., Koskinen, J., et al. (2015) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2015.01.059 · Cited by 60
Caprioli, D., Jupp, B., Hong, Y. T., Sawiak, S. J., Ferrari, V., Wharton, L., Williamson, D. J., McNabb, C. B., Berry, D. W., Aigbirhio, F. I., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3890-14.2015 · Cited by 59
Mowinckel, A. M., Alnæs, D., Pedersen, M. L., Ziegler, S., Fredriksen, M., Kaufmann, T., Sonuga-Barke, E. J. S., Endestad, T., Westlye, L. T., & Biele, G. (2017) · NeuroImage Clinical · doi:10.1016/j.nicl.2017.03.008 · Cited by 71
“…(DA) dense fronto-striatal and mesolimbic brain networks in ADHD due to the inhibition of synaptic reuptake of DA in these networks (Arnsten, 2006; Volkow et al., 2009, 2005) – effects that are reflected in improved functioning in executive functions and reward processing in ADHD (Barkley et al.,…”
Impulsivity and Vulnerability to Psychopathology
Neuhaus, E., & Beauchaine, T. P. (2017) · Wiley eBooks · doi:10.1002/9781394258932.ch6 · Cited by 65
Subcortical Local Functional Hyperconnectivity in Cannabis Dependence
Manza, P., Tomasi, D. G., & Volkow, N. D. (2017) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2017.11.004 · Cited by 58
Self-citationLong-term Effects of Multimodal Treatment on Adult Attention-Deficit/Hyperactivity Disorder Symptoms
Lam, A. P., Matthies, S., Graf, E., Colla, M., Jacob, C., Sobanski, E., Alm, B., Rösler, M., Retz, W., Retz‐Junginger, P., et al. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.4980 · Cited by 60
Reward Processing in Novelty Seekers: A Transdiagnostic Psychiatric Imaging Biomarker
Qi, S., Schumann, G., Bustillo, J., Turner, J. A., Jiang, R., Zhi, D., Fu, Z., Mayer, A. R., Vergara, V. M., Silva, R. F., et al. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.01.011 · Cited by 55
“Conversely, ADHD and MDD are associated with decreased dopamine activity (49,50).”
BackgroundCaprioli, D., Hong, Y. T., Sawiak, S. J., Ferrari, V., Williamson, D. J., Jupp, B., Adrian Carpenter, T., Aigbirhio, F. I., Everitt, B. J., Robbins, T. W., et al. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.44 · Cited by 58
Janssen, T. W. P., Bink, M., Geladé, K., van Mourik, R., Maras, A., & Oosterlaan, J. (2016) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2015.0144 · Cited by 58
The Mesolimbic Dopamine Pathway and Romantic Love
Xu, X., Weng, X., & Aron, A. P. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-397025-1.00057-9 · Cited by 57
Miller, D. K., Bowirrat, A., Manka, M., Miller, M., Stokes, S., Manka, D., Allen, C., Gant, C. E., Downs, B. W., Smolen, A., et al. (2010) · Postgraduate Medicine · doi:10.3810/pgm.2010.11.2236 · Cited by 57
“A low number of D 2 Rs suggests a hypodopaminergic function in addictive disorders and attention-deficit/ hyperactivity disorder (ADHD).(49,50) When there is a paucity of DA receptors, the person will be more prone to seek any substance or behavior that stimulates the dopaminergic system (a sort of “dopamine fi x”).”
BackgroundMusser, E. D., & Raiker, J. S. (2019) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2018.12.016 · Cited by 66
“Important to an integrated DP and RDoC approach, this model was initially developed in the context of addiction and substance abuse research; however, it fits well with models of ADHD, and has clear relevance, given that: 1) children with ADHD are at an increased risk of addiction in adolescence and adulthood and 2) A…”
BackgroundMethodLai, K. Y. C., Leung, P. W. L., Luk, E., Wong, A. S. Y., Law, L. S., & Ho, K. K. Y. (2011) · Journal of Attention Disorders · doi:10.1177/1087054711430711 · Cited by 55
“In neuroimaging and neurocognitive studies too, the SWAN scale can provide a continuum of ratings that facilitate the study of correlations between behaviors and brain functioning (Lui & Tannock, 2007; Volkow et al., 2009).”
BackgroundHu, D., Wang, Y., Chen, W., Zhang, Y., Li, H., Xiong, L., Zhu, H., Chen, H., Peng, S., Wan, Z., et al. (2017) · Environmental Pollution · doi:10.1016/j.envpol.2017.05.089 · Cited by 56
Garcia, A., & Kirkpatrick, K. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.10.017 · Cited by 58
“ADHD is characterized by deficits in the mesolimbic dopamine system [11] [65] [67] [68] [69] [70] [71] [72] [73], which is associated with reward anticipation and incentive motivation [74] [75] [76] [77] [78].”
BackgroundHabituation of reinforcer effectiveness
Lloyd, D. R., Medina, D. J., Hawk, L. W., Fosco, W. D., & Richards, J. B. (2014) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2013.00107 · Cited by 55
“This is particularly important for understanding the role of reinforcement mechanisms in the leading psychosocial (behavior therapy) and pharmacological (psychostimulant) ADHD treatments (Volkow et al., 2005, 2009; Tripp and Wickens, 2012).”
BackgroundSahakian, B. J., & Morein‐Zamir, S. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00004-8 · Cited by 55
White noise as a possible therapeutic option for children with ADHD
Pickens, T. A., Khan, S. P., & Berlau, D. J. (2018) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2018.11.012 · Cited by 58
Brain hyperserotonemia causes autism-relevant social deficits in mice
Tanaka, M., Sato, A., Kasai, S., Hagino, Y., Kotajima‐Murakami, H., Kashii, H., Takamatsu, Y., Nishito, Y., Inagaki, M., Mizuguchi, M., et al. (2018) · Molecular Autism · doi:10.1186/s13229-018-0243-3 · Cited by 63
The developmental psychopathology of motivation in adolescence
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Chronic Exercise for Core Symptoms and Executive Functions in ADHD: A Meta-analysis
Huang, H., Jin, Z., He, C., Guo, S., Zhang, Y., & Quan, M. (2022) · PEDIATRICS · doi:10.1542/peds.2022-057745 · Cited by 60
Daigre, C., Roncero, C., Grau‐López, L., Martínez‐Luna, N., Prat, G., Valero, S., Tejedor, R., Ramos‐Quiroga, J. A., & Casas, M. (2013) · The American Journal on Addictions · doi:10.1111/j.1521-0391.2013.12047.x · Cited by 52
Jeon, S. G., Yoo, A., Chun, D. W., Hong, S. B., Chung, H., Kim, J.-I., & Moon, M. (2020) · Aging and Disease · doi:10.14336/ad.2019.0718 · Cited by 57
“In addition, decreased dopamine synaptic markers have been reported in the dopamine reward pathway in ADHD patients [240].”
BackgroundDürsteler, K. M., Berger, E.-M., Strasser, H., Caflisch, C., Mutschler, J., Herdener, M., & Vogel, M. (2015) · Substance Abuse and Rehabilitation · doi:10.2147/sar.s50807 · Cited by 50
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Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD
Cherkasova, M. V., Faridi, N., Casey, K. F., O'Driscoll, G. A., Hechtman, L., Joober, R., Baker, G. B., Palmer, J., Dagher, A., Leyton, M., et al. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2013.349 · Cited by 49
“For example, both increases and decreases have been reported for D2/D3 receptor availability and for dopamine transporter (DAT) binding in ADHD patients vs controls (Lou et al, 2004; Spencer et al, 2005; Spencer et al, 2013; Volkow et al, 2007a; Volkow et al, 2009).”
BackgroundStevenson, M. P., & McNaughton, N. (2013) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.10.003 · Cited by 51
Swanson, J. M., Wigal, T. L., & Volkow, N. D. (2011) · Psychological Bulletin · doi:10.1037/a0024898 · Cited by 51
Self-citationCaviola, L., & Faber, N. S. (2015) · Frontiers in Psychology · doi:10.3389/fpsyg.2015.01852 · Cited by 48
“It is assumed that dopamine and norepinephrine are involved in its mechanisms (Ballon and Feifel, 2006; Volkow et al., 2009).”
BackgroundMartinsen, S., Flodin, P., Berrebi, J., Löfgren, M., Bilevičiūtė-Ljungar, I., Ingvar, M., Fransson, P., & Kosek, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0108637 · Cited by 51
“ADHD patients have been reported to experience not only difficulties with attention, but also problems with motor skills and they often report pain [46].”
BackgroundInfluentialWiers, C. E., Lohoff, F. W., Lee, J., Muench, C., Freeman, C. R., Zehra, A., Marenco, S., Lipska, B. K., Auluck, P. K., Feng, N., et al. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14067 · Cited by 51
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“PET studies in adult medication-naive ADHD patients found reduced D2/3 receptor availability in the NAcb and caudate (Volkow et al., 2009).”
BackgroundHuang-Pollock, C., Ratcliff, R., McKoon, G., Roule, A. L., Warner, T., Feldman, J., & Wise, S. (2020) · Neuropsychology · doi:10.1037/neu0000636 · Cited by 38
“Altered motivation and reward responsiveness have long featured in etiologic theories of ADHD (Volkow et al., 2009), suggesting that nonnormative evaluation of the task or task alternatives may contribute to ADHD-related sensitivity to the cost of engagement.”
BackgroundPanagiotidi, M., & Overton, P. (2018) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2018.08.004 · Cited by 45
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“Furthermore, dysfunction of NE and DA neurotransmission have been proposed to underlie the pathophysiology in ADHD (34,35,70).”
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Clock genes, ADHD and aggression
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“, 2013) or reduced DAT density compared to control subjects (Volkow et al., 2009).”
Animal models to guide clinical drug development in ADHD: lost in translation?
Wickens, J. R., Hyland, B. I., & Tripp, G. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01412.x · Cited by 45
“…stimulant medication on dopamine release and reuptake mechanisms at the synaptic level (Swanson et al., 2007); a reduction in dopamine synaptic markers associated with symptoms of inattention in ADHD (Volkow et al., 2009) and evidence from functional imaging of hypoactivity of the dopamine system.”
BackgroundEvaluating Dopamine Reward Pathway in ADHD: Clinical Implications
Stockman, J. (2011) · Yearbook of Pediatrics · doi:10.1016/s0084-3954(09)79647-2 · Cited by 107
Impulsive Behavior and Nicotinic Acetylcholine Receptors
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Time Estimation Abilities of College Students With ADHD
Prevatt, F., Proctor, B., Baker, L., Garrett, L., & Yelland, S. (2011) · Journal of Attention Disorders · doi:10.1177/1087054710370673 · Cited by 43
“Recent research has shown that adults with ADHD have impairment in the dopamine-reward pathway (Volkow et al., 2009).”
BackgroundAtypical perception of affective prosody in Autism Spectrum Disorder
Gebauer, L., Skewes, J., Hørlyck, L. D., & Vuust, P. (2014) · NeuroImage Clinical · doi:10.1016/j.nicl.2014.08.025 · Cited by 50
“Tables indicate coordinates for peak-voxels significant at both peak and cluster-levels.”
Performance analysis of univariate and multivariate EEG measurements in the diagnosis of ADHD
González, J. J., Méndez, L. D., Mañas, S., Duque, M. R., Pereda, E., & Vera, L. D. (2013) · Clinical Neurophysiology · doi:10.1016/j.clinph.2012.12.006 · Cited by 45
Bergman, O., Westberg, L., Lichtenstein, P., Eriksson, E., & Larsson, H. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711000502 · Cited by 43
“A lowered BDNF activity may consequently result in a dysfunction of the midbrain dopaminergic system, which has been suggested to be an important aspect of ADHD pathogenesis (Ernst et al. 1999; Jucaite et al. 2005; Leo et al. 2003; Volkow et al. 2009).”
BackgroundKiblawi, Z. N., Smith, L. M., LaGasse, L. L., Derauf, C., Newman, E., Shah, R., Arria, A. M., Huestis, M. A., DellaGrotta, S. A., Dansereau, L. M., et al. (2012) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e318277a1c5 · Cited by 44
“The child’s performance is scored based on 11 measures, which include (1) Omission, the number of pictures that the child incorrectly did not respond to; (2) Commission, the number of times the child incorrectly responded to the picture of the ball; (3) Hit reaction time, the overall response time recorded in millisec…”
BackgroundReward modulation of cognitive function in adult attention-deficit/hyperactivity disorder
Aarts, E., van Holstein, M., Hoogman, M., Onnink, A. M. H., Kan, C. C., Franke, B., Buitelaar, J. K., & Cools, R. (2014) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000116 · Cited by 45
“More specifically, disturbances in the executive mesocortical dopamine circuit, encompassing the dorsal striatum, dorsomedial thalamus and dorsolateral prefrontal cortex, underlie cognitive deficits in ADHD, whereas motivational deficits are grounded in disturbances in the mesolimbic reward circuit, including the vent…”
BackgroundInfluentialRhodes, J. D., Pelham, W. E., Gnagy, E. M., Shiffman, S. M., Derefinko, K. J., & Molina, B. S. G. (2016) · Psychology of Addictive Behaviors · doi:10.1037/adb0000188 · Cited by 45
Ventral striatal hyperconnectivity during rewarded interference control in adolescents with ADHD
Ma, I., van Holstein, M., Mies, G. W., Mennes, M., Buitelaar, J. K., Cools, R., Cillessen, A. H. N., Krebs, R. M., & Scheres, A. (2016) · Cortex · doi:10.1016/j.cortex.2016.05.021 · Cited by 42
Metadata
- Authors
- Volkow, N. D., Wang, G.-J., Kollins, S. H., Wigal, T. L., Newcorn, J. H., Telang, F., Fowler, J. S., Zhu, W., Logan, J., Ma, Y., Pradhan, K., Wong, C., & Swanson, J. M.
- Affiliations
- National Institute on Drug Abuse (US)
- Corresponding author
- Volkow, Nora D.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2009-09-09
- Volume
- 302
- Issue
- 10
- Pages
- 1084
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC2958516
- OpenAlex
- W2071411087
- Semantic Scholar
- 73303180da9a733fdf01dc78501b5769db289660
- Cited by
- 728
- References
- 69
- Citations by year
- 2026: 67 · 2025: 46 · 2024: 36 · 2023: 27 · 2022: 35 · 2021: 37 · 2020: 37 · 2019: 29 · 2018: 29 · 2017: 40 · 2016: 29 · 2015: 39 · 2014: 62 · 2013: 52 · 2012: 61
- FWCI
- 33.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (ZIAAA000550)
- National Institute of Mental Health (R01MH066961)
- National Institute on Drug Abuse (K24DA023464)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- attention deficit hyperactivity disorder, dopamine reward pathway, dopamine transporter, D2/D3 receptors, nucleus accumbens, caudate nucleus, adult ADHD, neuroimaging biomarkers, cocaine binding, left hemisphere lateralization, inattention, hyperactivity/impulsivity
- MeSH terms
- Adult, Attention Deficit Disorder with Hyperactivity, Brain, Brain Mapping, Carbon Radioisotopes, Cocaine, Dopamine, Female, Humans, Male, Mesencephalon, Synaptic Transmission, Reward, Dopamine Agents, Receptors, Dopamine D2, Raclopride, Positron-Emission Tomography, Dopamine Plasma Membrane Transport Proteins
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