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Attention Deficit Hyperactivity Disorder:
A Practical Guide

Pathophysiology Specific structural, functional, and neurotransmitter changes in the brain may be associated with ADHD Specific structural, functional, and neurotransmitter changes in the brain may be associated with ADHD

Structural

Structural imaging studies include volumetric measurements of gray or white matter of the whole brain (including or excluding the cerebellum) and its lobes, and fine-grained measurements (e.g., cortical thickness, density of gray matter) acquired from individual voxels in the brain or across the cortical surface.19

Cortical Thickness
Right Hemisphere           Left Hemisphere

Adapted from Jadidian A, Hurley RA, Taber KH. Neurobiology of adult ADHD: Emerging evidence for network dysfunctions. J Neuropsychiatry Clin Neurosci. 2015;27(3):173-178.

Adapted from Jadidian A, Hurley RA, Taber KH. Neurobiology of adult ADHD: Emerging evidence for network dysfunctions. J Neuropsychiatry Clin Neurosci. 2015;27(3):173-178.

Individuals with ADHD have structural differences in their brains compared with individuals without ADHD

Gray matter density is lower20,21

Localized volumetric gray matter abnormalities in the basal ganglia20

Reduced right globus pallidus and putamen volumes and decreased caudate volumes in manual tracing studies in children with ADHD20

Volume reduction in the anterior cingulate cortex of adults with ADHD20


Smaller volume overall and in specific structures19,20,23

Large MRI study showed volumes of various brain structure were slightly smaller in children, adolescents, and adults with ADHD (N=1,713) compared with controls (N=1,529)23

White matter abnormalities

Lobar white matter volume reduced ~4% in children and adolescents (N=152) with ADHD aged 5-18 years19,22

Abnormally high fractional anisotropy in frontal networks in adolescents (N=14) with ADHD19


Cortical differences

Delayed cortical maturation in children and adolescents (N=223) aged 7-13 years24

Reduced cortical thickness in adults.20,25


Functional changes

Regions of the brain that are associated with ADHD correspond to networks involving frontal regions, executive function, and attention.26

Functional neuroimaging studies have shown variation in activation/suppression of networks in ADHD

– Under-activation of frontostriatal and frontoparietal circuits, and other frontal brain regions20,27-29
– Under-activation of systems involved in executive function and attention34,44
– Over-activation (reduced suppression) of the default mode network during task performance30,31


Neurotransmitter changes

Neuromodulatory influences over catecholamines in the fronto-striato-cerebellar regions play important roles in high-level executive functions32

ADHD symptoms may be related to dysregulation of basal, tonic catecholaminergic levels30,33

– Too low: distractibility
– Too high: hyperactivity and anxiety

Dopamine18,30,34

Dopamine molecule

– Deficit in dopaminergic signaling30

Noradrenaline

Noradrenaline molecule

– Noradrenergic signaling34,35

Glutamate36,37

Glutamate molecule

– Levels of glutamate/glutamine are significantly
reduced in the caudate/putamen of adults with
ADHD compared to adults without ADHD.

Jump to:

Neuroimaging studies Structural changes Functional changes Neurotransmitter changes Hereditary and genetic factors

References

18. Shaw P. ADHD: 10 years later. Cerebrum. 2013. Sep-Oct;2013:11.
19. Vaidya CJ. Neurodevelopmental abnormalities in ADHD. Curr Top Behav Neurosci. 2012;9:49-66.
20. Jadidian A, Hurley RA, Taber KH. Neurobiology of adult ADHD: Emerging evidence for network dysfunctions. J Neuropsychiatry Clin Neurosci. 2015;27(3):173-178.
21. Ellison-Wright I, Ellison-Wright Z, Bullmore E. Structural brain change in Attention Deficit Hyperactivity Disorder identified by meta-analysis. BMC Psychiatry. 2008;8.
22. Castellanos FX, Lee PP, Sharp W, Jeffries NO, Greenstein DK, Clasen LS, et al. Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA. 2002;288(14):1740-1748.
23. Hoogman M, Bralten J, Hibar DP, Mennes M, Zwiers MP, Schweren LSJ, et al. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis. The Lancet Psychiatry. 2017;4(4):310-319.
24. Shaw P, Eckstrand K, Sharp W, Blumenthal J, Lerch JP, Greenstein D, et al. Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. PNAS. 2007;104(49):19649-19654.
25. Shaw P, Malek M, Watson B, et al. Development of cortical surface area and gyrification in attention-deficit/hyperactivity disorder. Biol Psychiatry. 2012; 72:191-197. 26. Purper-Ouakil D, Ramoz N, Lepagnol-Bestel AM, et al. Neurobiology of attention deficit/hyperactivity disorder. Pediatr Res. 2011;69:69R-76R.
27. Morein-Zamir S, Dodds C, van Hartevelt TJ, et al. Hypoactivation in right inferior frontal cortex is specifically associated with motor response inhibition in adult ADHD. Hum Brain Mapp. 2014;35:5141-5152.
28. Karch S, Voelker JM, Thalmeier T, et al. Deficits during voluntary selection in adult patients with ADHD: new insights from single-trial coupling of simultaneous EEG/fMRI. Front Psychiatry. 2014;5:41.
29. Cubillo A, Halari R, Smith A, Taylor E, Rubia K, Cubillo A, Halari R, Giampietro V, et al. A review of fronto-striatal and fronto-cortical brain abnormalities in children and adults with Attention Deficit Hyperactivity Disorder (ADHD) and new evidence for dysfunction in adults with ADHD during motivation and attention. Cortex. 2012;48(2):194-215.
30. Aboitiz F, Ossandón T, Zamorano F, Palma B, Carrasco X. Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional networks. Front Psychol. 2014;5:183.
31. Peterson BS, Potenza MN, Wang Z, et al. An FMRI study of the effects of psychostimulants on default-mode processing during Stroop task performance in youths with ADHD. Am J Psychiatry. 2009;166:1286-1294.
32. Del Campo N, Chamberlain SR, Sahakian BJ, Robbins TW. The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2011;69(12):e145-57.
33. Prince J. Catecholamine dysfunction in attention-deficit/hyperactivity disorder: an update. J Clin Psychopharmacol. 2008;28(3 Suppl 2):S39-S45.
34. Economidou D, Theobald DE, Robbins TW, et al. Norepinephrine and dopamine modulate impulsivity on the five-choice serial reaction time task through opponent actions in the shell and core sub-regions of the nucleus accumbens. Neuropsychopharmacology. 2012;37:2057-2066.
35. Liu YP, Lin YL, Chuang CH, et al. Alpha adrenergic modulation on effects of norepinephrine transporter inhibitor reboxetine in five-choice serial reaction time task. J Biomed Sci. 2009;16:72.
36. Maltezos S, Horder J, Coghlan S, et al. Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study. Transl Psychiatry. 2014;4:e373.
37 Perlov E, Philipsen A, Hesslinger B, et al. Reduced cingulate glutamate/ glutamine-to-creatine ratios in adult patients with attention deficit/ hyperactivity disorder — a magnet resonance spectroscopy study. J Psychiatr Res. 2007;41:934-941.
44. Krull KR. Attention deficit hyperactivity disorder in children and adolescents: Clinical features and diagnosis. UpToDate. September 2018. Available at https://www.uptodate.com/contents/attention-deficithyperactivity-disorder-in-children-and-adolescents-clinical-featuresand-diagnosis?sectionName=DIFFERENTIAL%20DIAGNOSIS&topicRef=6172&anchor=H341279665&source=see_link#H189248586.

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