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Inside the
ADHD brain

Explore the latest science on how 3 neurotransmitters may serve an important role in the symptoms of ADHD^1,2

While the roles of dopamine (DA) and norepinephrine (NE) in ADHD are well studied, recent evidence suggests that serotonin (5-HT) may be pivotal in both the diagnostic symptoms and associated symptoms of ADHD—such as emotional dysregulation and executive dysfunction—in addition to frequently co-occurring conditions like depression and anxiety.^1-3 The interplay between these neurotransmitters may be responsible for the heterogeneity of ADHD symptoms within patients.^4,5

Interactions among the 3 neurotransmitters are complex^1,6,7

Reciprocal projections among NE, DA, and 5-HT neurons exist throughout the brain. Attempts to enhance transmission of 1 monoamine system can lead to a decrease in function of others.⁸

Jump to watch a video on the role of neurotransmitters in ADHD

Diagram with the header 'Monoaminergic systems influence each others' signaling.' Disclaimer reads: 'This is a simplified representation of monoamine interactions. Actual effects vary by brain region and receptor subtypes.'

The roles of NE, DA, and 5-HT in the symptoms of ADHD often overlap^1,6,7

The overlapping symptoms in bold below illustrate the complex neurobiology of ADHD, involving multiple pathophysiological pathways in the brain.^1,6,7

The noradrenergic system is thought to play a role in:^1,2,7

Attention
Mood
Regulation in cognitive functions
Arousal
Signal-to-noise processing
Stress response

The dopaminergic system is thought to play a role in:¹

Attention
Mood
Reward processing
Cognitive processes
Regulation of movement
Learning and memory

The serotoninergic system is thought to play a role in:^1–3

Mood
Reward processing
Emotional regulation
Executive control
Impulse control

Associated symptoms and comorbidities

NE, DA, and 5-HT are likely to contribute to emotional dysregulation and executive dysfunction.^1-3The dysregulation of these neurotransmitters has been linked to depression and anxiety.¹

The interplay of NE, DA, and 5-HT is present across multiple brain regions implicated in ADHD

Connections within and between key brain networks thought to be involved in ADHD are modulated by monoaminergic inputs⁷
5-HT modulates DA activity in the prefrontal cortex and nucleus accumbens/striatum, impacting key regions involved in both diagnostic (impulsivity and inattention) and associated symptoms (mood, cognition, sleep) of ADHD^7,10-12
NE/DA play a complementary and critical role in prefrontal cortex function^7,10-12

These brain regions play many roles, including some that are thought to be related to ADHD⁷

Prefrontal cortex

Working memory
Planning
Selective attention

Parietal cortex

Attention
Cognitive flexibility

Anterior cingulate cortex

Mood
Cognitive aspects of executive control, attention, cognition

Amygdala

Emotion
Reward processing

Ventral striatum/basal ganglia

Reward processing
Motivation

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1.
Faraone SV, et al. Larsson H. Genetics of attention deficit hyperactivity disorder. Mol Psychiatry. 2019;24:562-575.
2.
da Silva BS, et al. An overview on neurobiology and therapeutics of attention‑deficit/hyperactivity disorder. Disc Mental Health. 2023;3(1):1-21.
3.
Shaw P, et al. Emotional dysregulation in attention-deficit/hyperactivity disorder. Am J Psychiatry. 2014;171(3):276-293.
4.
Sonuga-Barke EJS, et al. Annual research review: perspectives on progress in ADHD science—from characterisation to cause. J Child Psychol Psychiatry. 2023;64(4):506-532.
5.
Banerjee E, Nandagopal K. Does serotonin deﬁcit mediate susceptibility to ADHD? Neurochem Int. 2015;82:52-68.
6.
Hilger K, Fiebach CJ. ADHD symptoms are associated with the modular structure of intrinsic brain networks in a representative sample of healthy adults. Netw Neurosci. 2019;3(2):567-88.
7.
Faraone SV, et al. Attention-deficit/hyperactivity disorder. Nat Rev Dis Primers. 2024;10(11):1-21.
8.
Blier P. Rational site-directed pharmacotherapy for major depressive disorder. Int J Neuropsychopharmacol. 2014;17(7):997-1008.
9.
Guiard BP, et al. Functional interactions between dopamine, serotonin and norepinephrine neurons: an in-vivo electrophysiological study in rats with monoaminergic lesions. Int J Neuropsychopharmacol. 2008;11(5):625-639.
10.
Pourhamzeh M, et al. The roles of serotonin in neuropsychiatric disorders. Cell Mol Neurobiol. 2022;42(6):1671-92
11.
Madhyastha A, et al. Serotonergic and adrenergic neuroreceptor manipulation ameliorates core symptoms of ADHD through modulating dopaminergic receptors in spontaneously hypertensive rats. Int J Mol Sci. 2024;25(4):2300.
12.
Conio B, et al. Opposite effects of dopamine and serotonin on resting-state networks: review and implications for psychiatric disorder. Mol Psychiatry. 2020;25(1):82-93.