Attention-deficit hyperactivity disorder pathophysiology

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ADHD appears to be highly heritable, although one-fifth of all cases are caused by trauma or exposure to toxins. Evidence suggests that ADHD is a heterogeneous disorder, meaning that several causes could create very similar symptomology.[1] Although there is evidence for dopamine abnormalities in ADHD, it is not clear whether abnormalities of the dopamine system are a molecular abnormality of ADHD or a secondary consequence of ADHD.



  • The exact pathogenesis of ADHD is not fully understood. It is believed that ADHD is caused by a complex interaction between genetic and environmental factors.[2] A meta-analysis of studies of functional and structural magnetic resonance imaging has identified several pathologies[3].


  • Common genetic variation accounts for around 75% of cases of ADHD.[4] Loci on chromosomes 7, 11, 12, 15, 16, and 17 are associated with ADHD, likely indicating that ADHD does not follow the traditional model of an hereditary disease.[2]

Dopamine Levels and Blood Circulation

  • It is likely not the dopamine transporter levels that indicate the presence of ADHD, but the brain's ability to produce dopamine itself. ADHD patients show lower levels of dopamine than healthy subjects across the board. Further, plasma homovanillic acid, an index of dopamine levels, is inversely related not only to childhood ADHD symptoms in adult psychiatric patients, but to "childhood learning problems" in healthy subjects as well.[10]

Glucose Metabolism

  • An early PET scan study found that global cerebral glucose metabolism was 8.1% lower in medication-naive adults who had been diagnosed as ADHD while children. The image on the left illustrates glucose metabolism in the brain of a "normal" adult while doing an assigned auditory attention task; the image on the right illustrates the areas of activity in the brain of an adult who had been diagnosed with ADHD as a child when given that same task. (These are not pictures of individual brains, which would contain substantial overlap, but rather images constructed to illustrate group-level differences.)
  • Additionally, the regions with the greatest deficit of activity in the ADHD patients (relative to the controls) included the premotor cortex and the superior prefrontal cortex.[11] ADHD symptoms are likely the result of impaired activity in specific regions of the brain, rather than a broad, global deficit.
PET scans of glucose metabolism in the brains of a normal adult (left) compared to an adult diagnosed with ADHD (right).[11] "This PET scan was taken from Zametkin's landmark 1990 study, which found lower glucose metabolism, in the brains of patients with ADHD who had never taken medication. Scans were taken while patients were engaging in tasks requiring focused attention. The greatest deficits were found in the premotor cortex and superior prefrontal cortex."

Associated Conditions


  1. Barkley, Russel A. "Attention-Deficit/Hyperactivity Disorder: Nature, Course, Outcomes, and Comorbidity". Retrieved 2006-06-26.
  2. 2.0 2.1 M. T. Acosta, M. Arcos-Burgos, M. Muenke (2004). "Attention deficit/hyperactivity disorder (ADHD): Complex phenotype, simple genotype?". Genetics in Medicine 6 (1): 1–15.
  3. Norman LJ, Carlisi C, Lukito S, Hart H, Mataix-Cols D, Radua J; et al. (2016). "Structural and Functional Brain Abnormalities in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder: A Comparative Meta-analysis". JAMA Psychiatry. 73 (8): 815–825. doi:10.1001/jamapsychiatry.2016.0700. PMID 27276220.
  4. 4.0 4.1 Cross-Disorder Group of the Psychiatric Genomics Consortium. "Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs." Nat Genet. (2013). 45(9):984-94. doi: 10.1038/ng.2711. Epub 2013 Aug 11.
  5. Briars, L., & Todd, T. (2016). A Review of Pharmacological Management of Attention-Deficit/Hyperactivity Disorder. The Journal of Pediatric Pharmacology and Therapeutics : JPPT, 21(3), 192–206.
  6. M. F. Wells, R. D. Wimmer, L. I. Schmitt, G. Feng, M. M. Halassa. (2016). "Thalamic reticular impairment underlies attention deficit in Ptchd1Y/− mice." Nature 532: 58-63.
  7. Lou HC, Andresen J, Steinberg B, McLaughlin T, Friberg L. "The striatum in a putative cerebral network activated by verbal awareness in normals and in ADHD children." Eur J Neurol. 1998 Jan;5(1):67–74. PMID 10210814
  8. Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras BK, Fischman AJ (1999). "Dopamine transporter density in patients with attention deficit hyperactivity disorder". Lancet. 354 (9196): 2132–-33. PMID 10609822.
  9. Dresel SH, Kung MP, Plössl K, Meegalla SK, Kung HF (1998). "Pharmacological effects of dopaminergic drugs on in vivo binding of [99mTc]TRODAT-1 to the central dopamine transporters in rats". European journal of nuclear medicine. 25 (1): 31–9. PMID 9396872.
  10. Coccaro EF, Hirsch SL, Stein MA (2007). "Plasma homovanillic acid correlates inversely with history of learning problems in healthy volunteer and personality disordered subjects". Psychiatry research. 149 (1–3): 297–302. doi:10.1016/j.psychres.2006.05.009. PMID 17113158.
  11. 11.0 11.1 Zametkin AJ, Nordahl TE, Gross M, et al. "Cerebral glucose metabolism in adults with hyperactivity of childhood onset." N Engl J Med. 1990 November 15;323(20):1361–6. PMID 2233902
  12. National Institute of Mental Health (NIH). (2016). "Attention Deficit Hyperactivity Disorder."

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