Cited by 220Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

ADHD and the Prefrontal Cortex

Open access
Arnsten, Amy F.T.·2009·The Journal of Pediatrics

Abstract

Attention deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention, impulsivity, and locomotor hyperactivity. Recent advances in neurobiology, imaging, and genetics have led to a greater understanding of the etiology and treatment of ADHD. Studies have found that ADHD is associated with weaker function and structure of prefrontal cortex (PFC) circuits, especially in the right hemisphere. The prefrontal association cortex plays a crucial role in regulating attention, behavior, and emotion, with the right hemisphere specialized for behavioral inhibition. The PFC is highly dependent on the correct neurochemical environment for proper function: noradrenergic stimulation of postsynaptic alpha-2A adrenoceptors and dopaminergic stimulation of D1 receptors is necessary for optimal prefrontal function. ADHD is associated with genetic changes that weaken catecholamine signaling and, in some patients, with slowed PFC maturation. Effective pharmacologic treatments for ADHD all enhance catecholamine signaling in the PFC and strengthen its regulation of attention and behavior. Recent animal studies show that therapeutic doses of stimulant medications preferentially increase norepinephrine and, to a lesser extent, dopamine, in the PFC. These doses reduce locomotor activity and improve PFC regulation of attention and behavior through enhanced catecholamine stimulation of alpha-2A and D1 receptors. These findings in animals are consistent with improved PFC function in normal human subjects and, more prominently, in patients with ADHD. Thus, a highly cohesive story is emerging regarding the etiology and treatment of ADHD.

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Crossref · 10.1016/j.jpeds.2009.01.018

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149 of 149 references verified0 citation errors · 0 not checkable

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  • Loss of catecholaminergic innervation underlies the most important ADHD symptoms.

    “Loss of catecholaminergic innervation underlies the most important ADHD symptoms [381].”

    From Development of prefrontal cortex (2022) · cites this paper as [381]

    In “Imaging Studies Show Changes in Catecholamine Transmission” (page not provided), the paper suggests that loss of catecholamines in the prefrontal cortex is most important for ADHD symptoms. It describes reduced release or signaling, not loss of catecholaminergic innervation, and presents the link as a suggestion rather than an established cause. (LLM, conf=0.86)

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  • Alteration of glutamate/GABA equilibrium has been related to a diminished capability to focus on demanding tasks and to result in DA dysregulation, causing inhibition of defective pyramidal neurons and a decrease shift in excitation towards tasks regulated in the PFC.

    “Alteration of glutamate/GABA equilibrium has been related to a diminished capability to focus on demanding tasks [98] and to result in DA dysregulation, causing inhibition of defective pyramidal neurons and a decrease shift in excitation towards tasks regulated in the PFC [99, 100].”

    From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [99]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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Research works printed but not linked: 11

  1. [1]Solanto MV Solanto MV Arnsten AFT Castellanos FX Attention-Deficit/Hyperactivity Disorder: Clinical features Stimulant Drugs and ADHD: Basic and Clinical Neuroscience 2001 New York Oxford University Press 3 30
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  7. [112]Comings DE Clinical and molecular genetics of ADHD and Tourette syndrome. Two related polygenic disorders Ann N Y Acad Sci 2001 931 50 83 11462757
  8. [122]van Dyck CH Quinlan DM Cretella L Staley JK Malison RT Baldwin RM Striatal dopamine transporter availability with [123I]β-CIT SPECT is unaltered in adult Attention Deficit Hyperactivity Disorder Am. J. Psychiatry 2002 159 309 312 11823278
  9. [149]Engberg G Eriksson E Effects of alpha-2-adrenoceptor agonists on locus coeruleus firing rate and brain noradrenaline turnover in EEDQ-treated rats Naunyn-Schmiedebergs Arch. Pharmacol 1991 343 472 477 1652697
  10. [150]Scahill L Chappell PB Kim YS Schultz RT Katsovich L Shepherd E Guanfacine in the treatment of children with tic disorders and ADHD: A placebo-controlled study Amer. J. Psychiatry 2001 158 1067 1074 11431228
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Authors
Arnsten, A. F. T.
Affiliations
Yale University (US)
Corresponding author
Arnsten, Amy F.T.
Venue
The Journal of Pediatrics
Publisher
Elsevier BV
Published
2009-05
Volume
154
Issue
5
Pages
I-S43
ISSN
0022-3476 (ISSN-L)
OpenAlex
W11706560
Cited by
220
References
5
Citations by year
2026: 30 · 2025: 31 · 2024: 23 · 2023: 23 · 2022: 12 · 2021: 13 · 2020: 11 · 2019: 10 · 2018: 3 · 2017: 7 · 2016: 5 · 2015: 10 · 2014: 9 · 2013: 11 · 2012: 10
FWCI
4.54
Type
journal article
Language
en
Open access
Locations
  • The Journal of Pediatrics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (R37AG006036)
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, prefrontal cortex, right hemisphere, behavioral inhibition, catecholamine signaling, dopamine D1 receptor, prefrontal cortex maturation, stimulant medication, norepinephrine, dopamine, ADHD etiology, ADHD treatment

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