Dear readers of ADxS.org, please forgive the disruption.

ADxS.org needs about $36850 in 2023. In 2022 we received donations from third parties of about $ 13870. Unfortunately, 99.8% of our readers do not donate. If everyone who reads this request makes a small contribution, our fundraising campaign for 2023 would be over after a few days. This donation request is displayed 18,000 times a week, but only 40 people donate. If you find ADxS.org useful, please take a minute and support ADxS.org with your donation. Thank you!

Since 01.06.2021 ADxS.org is supported by the non-profit ADxS e.V..

$27450 of $36850 - as of 2023-11-30
74%
ADxS.org Logo
ADxS.org Logo
Search Sitemap Donations Last Changes Deutsche Version
Register

Existing Account? Login

Header Image
9. Disorders of the dopamine system in ADHD

Sitemap

The ADxS.org project
Abstract of ADxS.org
Symptoms
Consequences
Origin
Stress
Neurological aspects
Neurophysiological correlates of ADHD symptoms.
Aggression in ADHD - Neurophysiological correlates
Drive problems in ADHD - Neurophysiological correlates
Arousal and activation in ADHD - Neurophysiological correlates
Attention problems in ADHD - Neurophysiological correlates
Thinking blocks and decision problems in ADHD - Neurophysiological correlates
Emotional dysregulation - Neurophysiological correlates
Hyperactivity in ADHD - Neurophysiological correlates
Impulsivity in ADHD - Neurophysiological correlates
Learning problems in ADHD - Neurophysiological correlates
Motivation in ADHD - Neurophysiological correlates
Organizational and executive function problems in ADHD - Neurophysiological correlates
Sleep problems in ADHD - Neurophysiological correlates
Social phobia - Neurophysiological correlates
Diagnostics
Prevention
Treatment and therapy
This and That about ADHD
Tests and surveys
Forum

9. Disorders of the dopamine system in ADHD

Previous Page Next Page

ADHD, in our view, mediates its symptoms in a manner comparable to chronic stress through dopamine and norepinephrine (effect) deficiency, among other factors.

Further, in our view, early childhood chronic stress, as well as dopamine and norepinephrine deficiencies caused genetically, epigenetically, or otherwise, can impair brain development, leading to ADHD symptoms. For more on this, see ⇒ Brain development disorder and ADHD in the chapter Emergence.

9.1. Genetic abnormalities with dopaminergic background in ADHD

In ADHD, a striking number of polymorphisms (specific gene variants) are involved in genes that affect dopamine levels, e.g.:

  • DRD21
  • DRD31
  • DRD4
    • The 7-repeat allele of DRD4 causes the sensitivity of the D4 dopamine receptor (DRD4) to dopamine to be reduced. In subtype ADHD-I (without hyperactivity), the PFC is primarily affected.2 Against the background that hyperactivity neurophysiologically originates in the striatum and can be caused there by reduced as well as excessive dopamine levels, this would be plausible.
  • DRD5
  • DAT1
    • Dopamine transporters (DAT) bear the brunt of dopamine degradation in the striatum.
  • COMT
    • Dopamine degradation in the PFC occurs primarily by the enzyme COMT as well as NET, which reuptake more dopamine than norepinephrine in the PFC. The COMT Val/Val polymorphism causes a 4-fold faster dopamine degradation in the PFC. This could contribute to a dopamine deficit in the PFC, as suspected in ADHD. However, most genetic studies to date have found no correlation between variants of the COMT gene and ADHD.3 Surprisingly, one study found Val/Val improved sustained attention in children with ADHD. Val/Met or Met/Met variants, on the other hand, showed significantly worse sustained attention in children with ADHD than the norm.4 This could also be explained by the fact that ADHD would be associated with dopamine excess in the PFC, since increased dopamine depletion would then bring dopamine levels into the midrange associated with optimal cognitive ability. This is because dopamine excess and dopamine deficiency are equally impairing.5. However, this conflicts with the fact that amphetamine medications, which increase dopamine levels in the PFC, can improve sustained attention in ADHD. 0.25 mg/kg amphetamine improved physiological efficiency in healthy Val/Val gene carriers (= increased dopamine depletion) and worsened it in healthy Met/Met gene carriers (slowed dopamine depletion).6 However, it is possible that such affected individuals could also be AMP nonresponders.
    • Mb-COMT knockout mice (mice lacking membrane-bound COMT) show increased levels of dopamine in the striatum. This suggests that mb-COMT is also involved in dopamine degradation in the striatum.7

9.2. Alterations of the dopamine system in ADHD, chronic and acute stress

The literature suggests that ADHD is characterized by decreased levels of dopamine and norepinephrine in the PFC and striatum/nucleus accumbens,8 as is the case with chronic stress. In contrast, acute stress is characterized by increased dopamine levels in these brain regions.910 The symptoms of dopamine and norepinephrine deficiency (ADHD, chronic stress) and dopamine and norepinephrine excess (acute stress) are nevertheless partly identical and confusable. They occur when the optimal neurotransmitter level for information transmission in the brain is exceeded or undershot (inverted-U theory).8 Primarily affected are the dlPFC (working memory - executive functions), the striatum (motivation and motor inhibition) and the cerebellum (time processing).

However, there are also animal models with excessive dopamine levels that show ADHD symptoms. The DAT-KO mouse shows dramatically increased basal dopamine levels in the striatum, but phasic dopamine release in the striatum is reduced. The DAT-KO mouse (especially the heterozygous variant, in which the DAT are approximately halved) shows almost the full picture of ADHD symptoms. There are (rarely) also people without or with very strongly reduced DAT. However, these show other symptoms that are not typical for ADHD (e.g. early Parkinson’s dystonia) and are therefore rarely misdiagnosed with ADHD and rather with cerebral palsy. Many affected individuals die as teenagers.11 Excess extracellular dopamine leads to decreased production of dopamine (and thus decreased storage of dopamine in vesicles) and downregulation or desensitization of dopamine receptors through activation of presynaptic D2 autoreceptors, resulting in phasic dopamine deficiency and dopamine action deficiency.12

While acute and chronic stress in adulthood usually cause reversible neurotransmitter changes, repeated acute stress or chronic stress can trigger permanent damage, especially during periods of brain developmental surges. Particularly vulnerable ages are from conception to 3 years and during puberty. Thus, ADHD may be a consequence of severe chronic stress that causes dopamine deficiency, which in turn leads to brain developmental dysfunction. ⇒ Brain developmental disorder and ADHD Ultimately, the growing brain should not care whether the dopamine that is actually needed for development and is now lacking is reduced because of a genetic basis, an epigenetically inherited ancestral experience, or its own experience of stress.

The permanent changes in neurotransmitter levels (dopamine, norepinephrine, and others) seen in ADHD may be triggered by inherited gene variants (stress-independent), may be caused by acute environmental influences, or may be the result of environmental influences that trigger epigenetic changes that can then also be passed on (over a limited number of generations). (⇒ How ADHD develops: genes or genes + environment)
In the first years of life, the most important brain regions and neurotransmitter systems develop. A stress-induced disturbance during this development easily leads to permanent maladjustments of the neurotransmitter systems. Depending on the genetic disposition as well as the type and intensity of early childhood stress, the disruption of the maturation of the dopaminergic pathways can be made up for with a time delay.13

9.3. Learning problems due to changes in the dopamine system in ADHD, chronic and acute stress

An increase in phasic dopamine by acute stress increases long-term potentiation (LTP) via D1 receptor-dependent afferents from the hippocampus to the PFC,14 while chronic stress impairs LTP.15. Dopaminergically induced changes in phosphorylation of second messenger molecules such as CREB and DARPP-32 are required for induction of LTP.1617 Their effects last well beyond the period of dopamine receptor stimulation.18
Electrical stimulation in the PFC triggers LTP when tonic dopamine is present. If this is absent, as after several weeks of chronic stress, long-term depression (LTD) is triggered instead.1918

9.4. Different dopaminergic hypotheses on ADHD

There are different explanatory models of how the dopaminergic system is altered in ADHD.20 All of them can explain the behavioral changes in ADHD patients.
We suggest that the different models do not contradict each other, but that they may apply - alone or in combination - to different affected individuals.

Some studies suggest increased dopamine transporter density with rapid reuptake of synaptic dopamine, resulting in a deficiency of dopamine in the synaptic cleft.212223
The fact that, according to recent studies, dopaminergic synapses do not contain dopamine receptors but GABA receptors, and that the dopamine receptors are instead arranged spatially around the synapse, does not change the significance of the DAT, since they are also located outside the synapse.

Other studies suggest a dopamine deficit, along with low dopamine release associated with low transporter density in untreated cases.2425

Recent PET imaging studies suggest that transporter density is decreased in drug-naïve ADHD sufferers and increases with chronic stimulant treatment.2627

9.4.1. Alteration of dopamine degradation in ADHD

According to one view, ADHD sufferers have too many DAT in the striatum, which declines with age. A 50-year-old has only half as many dopamine transporters as a 10-year-old.28 This may partly explain why ADHD fades after adolescence in some sufferers and why symptoms change in adulthood.
DAT occur predominantly in the striatum, where they bear the brunt of dopamine degradation.
If there are too many too active DAT in the striatum, the dopamine released by the sending nerve cell into the synaptic cleft to the receiving nerve cell is already reabsorbed there by these overactive reuptake transporters (located on the sending side of the synapse) before it could be taken up by the receptors of the receiving nerve cell. Thus, a deficiency of dopamine occurs. Thus, the signal that should be delivered by the dopamine does not arrive cleanly at the receiving nerve cell.
ADHD medications, nicotine (smoking - though dysfunctional as a drug) and zinc block the DAT and thus reduce its overactivity.29 However, to successfully treat ADHD with zinc, amounts of zinc would have to be taken that are otherwise hazardous to health (zinc flu).

Studies of dopamine levels in ADHD in areas other than the striatum have been highly inconsistent and suffer from small subject numbers.30
One study (with small subject numbers) found slightly decreased dopamine metabolism in the left, medial, and right PFC in ADHD.31 Another study with a very small number of subjects found increased dopamine levels in ADHD in the right midbrain.32
Another study suggests that in an ADHD-HI animal model, the SHR, dopamine is decreased in the PFC while norepinephrine is increased.33

Other studies also suggest underactivation of the PFC and other brain areas outside the striatum. See ⇒ for more information The neurological explanation of drive and motivation problems, folded in there at the end of the article.

In chronic stress - depending on the origin and constellation - a tonic dopamine deficiency is given, just as in early and long-lasting stress a downregulation is also described with regard to the stress hormones CRH and cortisol and their receptors.34

Although downregulation of CRH and cortisol can be verified by the dexamethasone or combined dexamethasone/CRH test, we have encountered use of this test for ADHD in only a few reports.
⇒ Cortisol in ADHD

In ADHD and autism, beta-phenyletlyamine (a dopamine degrader but not a peptide) might be decreased in urine.35

9.4.2. Alteration of dopamine synthesis in ADHD?

The effect of dopamine deficiency in the PFC and striatum may result from reduced dopamine action by desensitized receptors in addition to reduced dopamine levels. This may result from increased degradation of dopamine (too much(e) or too active DAT, COMT, MAO-A, etc.) or from deficient dopamine synthesis.

Various studies on the question of whether dopamine synthesis is impaired in ADHD came to no clear conclusion.36
Two studies found evidence of increased synthesis of phenylalanine (a precursor to dopamine),3738 two studies found evidence of decreased phenylalanine production in ADHD3940 and one study found no differences between ADHD sufferers and non-affected individuals.41

9.4.3. Dopamine deficiency in the striatum due to overactivated PFC?

9.4.3.1. DAT elevation in the striatum?

Many findings are conflicting as to whether dopamine transporters are increased or decreased in ADHD:

  • Increased DAT for inattention in adolescents with ADHD and cerebral blood flow problems after preterm birth.42
    Increased DAT is associated with decreased extracellular and increased phasic dopamine levels, as we understand.
  • 6 of 8 studies found increased DAT binding in (mostly drug-naïve) children and adults with ADHD-HI. 3 studies found decreased DAT binding after methylphenidate treatment.43
  • The 3′-UTR but not the intron8 VNTR genotype of the DAT gene correlated with increased DAT binding in ADHD-HI affected as in unaffected individuals. S3′-UTR polymorphism of the DAT gene and ADHD-HI status had an additive effect on DAT binding.44
  • One study found evidence more suggestive of decreased DAT number or binding in ADHD.45
  • DAT and D2 and D3 receptors showed reduced binding in ADHD sufferers in24
    • DAT
      • Nucleus accumbens
      • Midbrain*
      • Left caudate nucleus
    • D(2)/D(3) receptors
      • Nucleus accumbens*
      • Midbrain*
      • Nucleus caudatus left*
      • Hypothalamus*
    • Regions marked with * showed a correlation with attention problems
  • Certain gene polymorphisms of the DAT gene appear to contribute to ADHD. Commonly mentioned are 9R and 10R. One study found higher working memory activity at 9R and 10R in different brain regions in ADHD.46
  • Methylation of the dopamine transporter gene in blood may also be an indicator of DAT density in the striatum and may one day serve as a tool for ADHD diagnosis.47
  • Lack of oxygen at birth increases the risk of ADHD.48 Hypoxy-ischemic conditions around birth (e.g. asphyxia) cause a deficient supply of oxygen to the brain. This can lead to cognitive impairment, and its occurrence after oxygen deprivation is influenced by dopamine transporter gene polymorphisms.49

Most studies do not differentiate by subtype. The evidence we have gathered on the different (phasic) cortisol stress responses of the subtypes would justify examining this question with subtype in mind.

9.4.3.2. High dopamine level in the mPFC decreases dopamine level in the striatum

Acute severe stress briefly increases dopamine levels in the PFC (dopamine stress response, phasic dopamine).
Chronic and early childhood stress can permanently increase or decrease dopamine levels in the PFC (basal dopamine levels, tonic dopamine), depending on the stressor and age at exposure. More ⇒ Neurophysiological correlates of stress.

The mPFC controls the interplay between subcortical regions that control pleasure-oriented actions. Increased excitability of the mPFC results in a decreased dopaminergic response of the striatum. This inhibits the drive of behavior to dopaminergic stimulation. Sustained overactivation of the mPFC results in stable suppression of natural reward-motivated behavior (encoded with phasic dopamine) and correlates in degree with anhedonic behavior. In summary, much dopamine in the (m)PFC decreases dopamine levels in the nucleus accumbens50 and in the striatum as a whole.51525354

This mechanism could be based on the fact that dopamine in the PFC decreases the activity of glutamatergic pyramidal cells and stimulates GABAergic cells, which also inhibits glutamate. This could lead to a strong inhibition of glutamatergic projection in BA 9 and BA 10, triggering a reduction of dopamine levels in the ventral and dorsal striatum.55

Conversely, blockade of dopamine receptors in the PFC results in disinhibited dopamine turnover in the striatum.54

According to other sources, anhedonia correlates with decreased dopamine levels in the mesocorticolimbic system and nucleus accumbens.56 The dysfunction of the dopaminergic system in anhedonia is thought to be directly remediable with ketamine medication.57

(Tonic) dopamine deficiency correlates with an increase in dopamine transporter numbers.58

9.4.4. Decreased tonic and increased phasic dopamine in the caudate nucleus in ADHD

An MRI study found evidence in adults with ADHD-C of decreased tonic dopamine levels at rest and increased phasic dopamine levels during a flanker task, both in the right caudate nucleus (part of the striatum).59

Another study also found evidence of increased phasic dopamine in the striatum and linked this to symptoms of high impulsivity and low inhibition.60

Another model assumes decreased tonic dopamine in the striatum as a cause of ADHD.61

  1. Diamond: Attention-deficit disorder (attention-deficit/hyperactivity disorder without hyperactivity): A neurobiologically and behaviorally distinct disorder from attention-deficit (with hyperactivity), Development and Psychopathology 17 (2005), 807–825, Seite 809 ↥ ↥

  2. Diamond: Attention-deficit disorder (attention-deficit/hyperactivity disorder without hyperactivity): A neurobiologically and behaviorally distinct disorder from attention-deficit (with hyperactivity), Development and Psychopathology 17 (2005), 807–825, Seite 810, 811 ↥

  3. Bonvicini, Faraone, Scassellati (2016): Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies. Mol Psychiatry. 2016 Jul;21(7):872-84. doi: 10.1038/mp.2016.74. Erratum in: Mol Psychiatry. 2016 Nov;21(11):1643. PMID: 27217152; PMCID: PMC5414093. ↥

  4. Bellgrove, Domschke, Hawi, Kirley, Mullins, Robertson, Gill ( The methionine allele of the COMT polymorphism impairs prefrontal cognition in children and adolescents with ADHD. Exp Brain Res. 2005 Jun;163(3):352-60. doi: 10.1007/s00221-004-2180-y. PMID: 15654584. ↥

  5. Stitzinger (2006): Der Einfluss genetischer Variationen im COMT Gen auf kognitive Phänotypen. Dissertation. S. 32 ↥

  6. Mattay, Goldberg, Fera, Hariri, Tessitore, Egan, Kolachana, Callicott, Weinberger (2003): Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6186-91. doi: 10.1073/pnas.0931309100. PMID: 12716966; PMCID: PMC156347. ↥

  7. Tammimaki, Aonurm-Helm, Zhang, Poutanen, Duran-Torres, Garcia-Horsman, Mannisto (2016): Generation of membrane-bound catechol-O-methyl transferase deficient mice with disctinct sex dependent behavioral phenotype. J Physiol Pharmacol. 2016 Dec;67(6):827-842. ↥

  8. Arnsten, Pliszka (2011): Catecholamine influences on prefrontal cortical function: relevance to treatment of attention deficit/hyperactivity disorder and related disorders. Pharmacol Biochem Behav. 2011 Aug;99(2):211-6. doi: 10.1016/j.pbb.2011.01.020. PMID: 21295057; PMCID: PMC3129015. REVIEW ↥ ↥

  9. Gresch, Sved, Zigmond, Finlay (1994); Stress-induced sensitization of dopamine and norepinephrine efflux in medial prefrontal cortex of the rat. J Neurochem. 1994 Aug;63(2):575-83. doi: 10.1046/j.1471-4159.1994.63020575.x. PMID: 8035182. ↥

  10. Morrow, Redmond, Roth, Elsworth (2000): The predator odor, TMT, displays a unique, stress-like pattern of dopaminergic and endocrinological activation in the rat. Brain Res. 2000 May 2;864(1):146-51. doi: 10.1016/s0006-8993(00)02174-0. PMID: 10793199. ↥

  11. OMIM: PARKINSONISM-DYSTONIA, INFANTILE, 1; PKDYS1 ↥

  12. Kurian, Gissen, Smith, Heales, Clayton (2011): The monoamine neurotransmitter disorders: an expanding range of neurological syndromes. Lancet Neurol. 2011 Aug;10(8):721-33. doi: 10.1016/S1474-4422(11)70141-7. PMID: 21777827. ↥

  13. Müller, Candrian, Kropotov (2011): ADHS – Neurodiagnostik in der Praxis, Seite 84 ↥

  14. Gurden, Takita, Jay (2000): Essential role of D1 but not D2 receptors in the NMDA receptor-dependent long-term potentiation at hippocampal-prefrontal cortex synapses in vivo. J Neurosci. 2000 Nov 15;20(22):RC106. doi: 10.1523/JNEUROSCI.20-22-j0003.2000. PMID: 11069975; PMCID: PMC6773154. ↥

  15. Goto, Grace (2006): Alterations in medial prefrontal cortical activity and plasticity in rats with disruption of cortical development. Biol Psychiatry. 2006 Dec 1;60(11):1259-67. doi: 10.1016/j.biopsych.2006.05.046. PMID: 16950218. ↥

  16. Greengard P, Allen PB, Nairn AC. Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade. Neuron. 1999 Jul;23(3):435-47. doi: 10.1016/s0896-6273(00)80798-9. PMID: 10433257. REVIEW ↥

  17. Hotte, Thuault, Dineley, Hemmings, Nairn, Jay (2007): Phosphorylation of CREB and DARPP-32 during late LTP at hippocampal to prefrontal cortex synapses in vivo. Synapse. 2007 Jan;61(1):24-8. doi: 10.1002/syn.20339. PMID: 17068779. ↥

  18. Goto, Otani, Grace (2007): The Yin and Yang of dopamine release: a new perspective. Neuropharmacology. 2007;53(5):583-587. doi:10.1016/j.neuropharm.2007.07.007 REVIEW ↥ ↥

  19. Matsuda, Marzo, Otani (2006): The presence of background dopamine signal converts long-term synaptic depression to potentiation in rat prefrontal cortex. J Neurosci. 2006 May 3;26(18):4803-10. doi: 10.1523/JNEUROSCI.5312-05.2006. PMID: 16672653; PMCID: PMC6674173. ↥

  20. Caye, Swanson, Coghill, Rohde (2019): Treatment strategies for ADHD: an evidence-based guide to select optimal treatment. Mol Psychiatry. 2019 Mar;24(3):390-408. doi: 10.1038/s41380-018-0116-3. PMID: 29955166. ↥

  21. Dougherty, Bonab, Spencer, Rauch, Madras, Fischman (1999): Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet. 1999 Dec 18-25;354(9196):2132-3. doi: 10.1016/S0140-6736(99)04030-1. PMID: 10609822. n = 6 ↥

  22. Krause, Dresel, Krause, Kung, Tatsch, Lochmüller (2002): Elevated striatal dopamine transporter in a drug naive patient with Tourette syndrome and attention deficit/ hyperactivity disorder: positive effect of methylphenidate. J Neurol. 2002 Aug;249(8):1116-8. doi: 10.1007/s00415-002-0746-9. PMID: 12420715., n = 1 ↥

  23. Spencer, Biederman, Madras, Dougherty, Bonab, Livni, Meltzer, Martin, Rauch, Fischman (2006): Further evidence of dopamine transporter dysregulation in ADHD: a controlled PET imaging study using altropane. Biol Psychiatry. 2007 Nov 1;62(9):1059-61. doi: 10.1016/j.biopsych.2006.12.008. PMID: 17511972; PMCID: PMC2715944. n = 47 ↥

  24. Volkow, Wang, Kollins, Wigal, Newcorn, Telang, Fowler, Zhu, Logan, Ma, Pradhan, Wong, Swanson (2009): Evaluating dopamine reward pathway in ADHD: clinical implications. JAMA. 2009 Sep 9;302(10):1084-91. doi: 10.1001/jama.2009.1308. Erratum in: JAMA. 2009 Oct 7;302(13):1420. PMID: 19738093; PMCID: PMC2958516. ↥ ↥

  25. Volkow, Wang, Newcorn, Telang, Solanto, Fowler, Logan, Ma Y, Schulz, Pradhan, Wong C, Swanson (2007): Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2007 Aug;64(8):932-40. doi: 10.1001/archpsyc.64.8.932. PMID: 17679638. ↥

  26. Fusar-Poli, Rubia, Rossi, Sartori, Balottin (2012): Striatal dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? A meta-analysis. Am J Psychiatry. 2012 Mar;169(3):264-72. doi: 10.1176/appi.ajp.2011.11060940. PMID: 22294258. METASTUDY, n = 342 ↥

  27. Volkow, Wang GJ, Tomasi, Kollins, Wigal, Newcorn, Telang, Fowler, Logan, Wong CT, Swanson (2012): Methylphenidate-elicited dopamine increases in ventral striatum are associated with long-term symptom improvement in adults with attention deficit hyperactivity disorder. J Neurosci. 2012 Jan 18;32(3):841-9. doi: 10.1523/JNEUROSCI.4461-11.2012. PMID: 22262882; PMCID: PMC3350870. ↥

  28. Krause, Krause (2014): ADHS im Erwachsenenalter, Schattauer ↥

  29. Steinhausen, Rothenberger, Döpfner (2010): Handbuch ADHS, Seite 78 ↥

  30. Solanto (2002): Dopamine dysfunction in AD/HD: integrating clinical and basic neuroscience research; Behavioural Brain Research 130 (2002) 65–71 ↥

  31. Ernst, Zametkin, Matochik, Jons, Cohen (1998): DOPA Decarboxylase Activity in Attention Deficit Hyperactivity Disorder Adults. A [Fluorine-18]Fluorodopa Positron Emission Tomographic Study; The Journal of Neuroscience, August 1, 1998, 18(15):5901–5907; n = 40 ↥

  32. Ernst, Zametkin, Matochik, Pascualvaca, Jons, Cohen (1999): High Midbrain [18F]DOPA Accumulation in Children With Attention Deficit Hyperactivity Disorder; Am J Psychiatry 1999; 156:1209–1215; n = 20 ↥

  33. Russell (2002): Hypodopaminergic and hypernoradrenergic activity in prefrontal cortex slices of an animal model for attention-deficit hyperactivity disorder — the spontaneously hypertensive rat; Behavioural Brain Research, Volume 130, Issues 1–2, 10 March 2002, Pages 191-196, Behavioural Brain Research; https://doi.org/10.1016/S0166-4328(01)00425-9 ↥

  34. ebenso: Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Chapter 12: Attention deficit hyperactivity disorder and its treatment, Seite 488 ↥

  35. Kusaga (2002): [Decreased beta-phenylethylamine in urine of children with attention deficit hyperactivity disorder and autistic disorder]. [Article in Japanese]; No To Hattatsu. 2002 May;34(3):243-8. ↥

  36. Bull-Larsen, Mohajeri (2019): The Potential Influence of the Bacterial Microbiome on the Development and Progression of ADHD. Nutrients. 2019 Nov 17;11(11). pii: E2805. doi: 10.3390/nu11112805. ↥

  37. Aarts, Ederveen, Naaijen, Zwiers, Boekhorst, Timmerman, Smeekens, Netea, Buitelaar, Franke, van Hijum, Arias Vasquez (2017): Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS One. 2017 Sep 1;12(9):e0183509. doi: 10.1371/journal.pone.0183509. eCollection 2017. ↥

  38. Antshel, Waisbren (2003): Developmental timing of exposure to elevated levels of phenylalanine is associated with ADHD symptom expression. J Abnorm Child Psychol. 2003 Dec;31(6):565-74. ↥

  39. Baker, Bornstein, Rouget, Ashton, van Muyden, Coutts (1991): Phenylethylaminergic mechanisms in attention-deficit disorder. Biol Psychiatry. 1991 Jan 1;29(1):15-22. ↥

  40. Bornstein, Baker, Carroll, King, Wong, Douglass (1990): Plasma amino acids in attention deficit disorder. Psychiatry Res. 1990 Sep;33(3):301-6. ↥

  41. Bergwerff, Luman, Blom, Oosterlaan (2016): No Tryptophan, Tyrosine and Phenylalanine Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder. PLoS One. 2016 Mar 3;11(3):e0151100. doi: 10.1371/journal.pone.0151100. eCollection 2016. ↥

  42. Lou, Rosa, Pryds, Karrebaek, Lunding, Cumming, Gjedde (2004): ADHD: increased dopamine receptor availability linked to attention deficit and low neonatal cerebral blood flow. Dev Med Child Neurol. 2004 Mar;46(3):179-83. doi: 10.1017/s0012162204000313. PMID: 14995087. n = 6 ↥

  43. Spencer, Biederman, Madras, Faraone, Dougherty, Bonab, Fischman (2005): In vivo neuroreceptor imaging in attention-deficit/hyperactivity disorder: a focus on the dopamine transporter. Biol Psychiatry. 2005 Jun 1;57(11):1293-300. doi: 10.1016/j.biopsych.2005.03.036. PMID: 15950001. REVIEW ↥

  44. Spencer, Biederman, Faraone, Madras, Bonab, Dougherty, Batchelder, Clarke, Fischman (2013): Functional genomics of attention-deficit/hyperactivity disorder (ADHD) risk alleles on dopamine transporter binding in ADHD and healthy control subjects. Biol Psychiatry. 2013 Jul 15;74(2):84-9. doi: 10.1016/j.biopsych.2012.11.010. PMID: 23273726; PMCID: PMC3700607. ↥

  45. Volkow, Wang, Newcorn, Fowler, Telang, Solanto, Logan, Wong, Ma, Swanson, Schulz, Pradhan (2007): Brain dopamine transporter levels in treatment and drug naïve adults with ADHD. Neuroimage. 2007 Feb 1;34(3):1182-90. doi: 10.1016/j.neuroimage.2006.10.014. PMID: 17126039. n = 45 ↥

  46. Pineau, Villemonteix, Slama, Kavec, Balériaux, Metens, Baijot, Mary, Ramoz, Gorwood, Peigneux, Massat (2019): Dopamine transporter genotype modulates brain activity during a working memory task in children with ADHD. Res Dev Disabil. 2019 Sep;92:103430. doi: 10.1016/j.ridd.2019.103430. ↥

  47. Wiers, Lohoff, Lee, Muench, Freeman, Zehra, Marenco, Lipska, Auluck, Feng, Sun, Goldman, Swanson, Wang, Volkow (2018): Methylation of the dopamine transporter gene in blood is associated with striatal dopamine transporter availability in ADHD: A preliminary study. Eur J Neurosci. 2018 Aug;48(3):1884-1895. doi: 10.1111/ejn.14067. ↥

  48. Banaschewski, Ursachen von ADHS, Neurologen und Psychiater im Netz ↥

  49. Miguel, Pereira, Barth, de Mendonça Filho, Pokhvisneva, Nguyen, Garg, Razzolini, Koh, Gallant, Sassi, Hall, O’Donnell, Meaney, Silveira (2019): Prefrontal Cortex Dopamine Transporter Gene Network Moderates the Effect of Perinatal Hypoxic-Ischemic Conditions on Cognitive Flexibility and Brain Gray Matter Density in Children. Biol Psychiatry. 2019 Apr 3. pii: S0006-3223(19)31154-0. doi: 10.1016/j.biopsych.2019.03.983. ↥

  50. Ironside, Kumar, Kang, Pizzagalli (2018): Brain mechanisms mediating effects of stress on reward sensitivity. Curr Opin Behav Sci. 2018 Aug;22:106-113. doi: 10.1016/j.cobeha.2018.01.016. PMID: 30349872; PMCID: PMC6195323. ↥

  51. Ferenczi, Zalocusky, Liston, Grosenick, Warden, Amatya, Katovich, Mehta, Patenaude, Ramakrishnan, Kalanithi, Etkin, Knutson, Glover, Deisseroth (2016): Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior. Science. 2016 Jan 1;351(6268):aac9698. doi: 10.1126/science.aac9698 ↥

  52. Heinz (2000): Das dopaminerge Verstärkungssystem, Seite 10 ↥

  53. Kolachana, Saunders, Weinberger (1995): Augmentation of prefrontal cortical monoaminergic activity inhibits dopamine release in the caudate nucleus: an in vivo neurochemical assessment in the rhesus monkey. Neuroscience. 1995 Dec;69(3):859-68. ↥

  54. Louilot, Le Moal, Simon (1989): Opposite influences of dopaminergic pathways to the prefrontal cortex or the septum on the dopaminergic transmission in the nucleus accumbens. An in vivo voltammetric study. Neuroscience. 1989;29(1):45-56. ↥ ↥

  55. Heinz (2000): Das dopaminerge Verstärkungssystem, Seite 107 ↥

  56. Rodrigues, Leão, Carvalho, Almeida, Sousa (2010): Potential programming of dopaminergic circuits by early life stress. Psychopharmacology (Berl). 2011 Mar;214(1):107-20. doi: 10.1007/s00213-010-2085-3. ↥

  57. Rincón-Cortés, Grace (2019): Antidepressant effects of ketamine on depression-related phenotypes and dopamine dysfunction in rodent models of stress. Behav Brain Res. 2020 Feb 3;379:112367. doi: 10.1016/j.bbr.2019.112367. PMID: 31739001; PMCID: PMC6948930. ↥

  58. Brake, Sullivan, Gratton (2000): Perinatal Distress Leads to Lateralized Medial Prefrontal Cortical Dopamine Hypofunction in Adult Rats; Journal of Neuroscience 15 July 2000, 20 (14) 5538-5543 ↥

  59. Badgaiyan, Sinha, Sajjad, Wack (2015): Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder. PLoS One. 2015 Sep 30;10(9):e0137326. doi: 10.1371/journal.pone.0137326. PMID: 26422146; PMCID: PMC4589406. n = 44 ↥

  60. Cherkasova, Faridi, Casey, O’Driscoll, Hechtman, Joober, Baker, Palmer, Dagher, Leyton, Benkelfat (2014): Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD. Neuropsychopharmacology. 2014 May;39(6):1498-507. doi: 10.1038/npp.2013.349. PMID: 24378745; PMCID: PMC3988554. n = 33 ↥

  61. Grace (2001): Psychostimulant actions on dopamine and limbic system function: relevance to the pathophysiology and treatment of ADHD In: Solanto, Arnsten, Castellanos (Herausgeber): Stimulant Drugs and ADHD: Basic and Clinical Neuroscience Oxford University Press: New York; 134–157; zitert nach Cherkasova, Faridi, Casey, O’Driscoll, Hechtman, Joober, Baker, Palmer, Dagher, Leyton, Benkelfat (2014): Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD. Neuropsychopharmacology. 2014 May;39(6):1498-507. doi: 10.1038/npp.2013.349. PMID: 24378745; PMCID: PMC3988554. ↥

Diese Seite wurde am 13.03.2023 zuletzt aktualisiert.
Previous Page Next Page