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

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ADHD and the Prefrontal Cortex

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

DOI 10.1016/j.jpeds.2009.01.018PMC PMC2894421

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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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Authors: Arnsten, A. F. T.
Affiliations: Yale University (US)
Corresponding author: Arnsten, Amy F.T.
ORCID: 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)
DOI: 10.1016/j.jpeds.2009.01.018
PMC: PMC2894421
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: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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