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ADHD Insights: D2 Receptors and Executive Function

D2 Receptors Modify Dopamine Metabolism   Barkley's Executive Function

If you don’t know the science, you’ll be less likely to predict ADHD Medication outcome. D2 Receptor polymorphism may sound like a mouthful, but if you don’t know that those dopamine receptors change genetically, that they vary in their ability to receive dopamine signals, you’ll miss an important part of the evolving science regarding that much more effective new name for ADHD: Executive Function Disorder. 

See this earlier CorePsych Blog posting on D2 genetics and measurement for a brief introduction.

D2 Receptor Changes Modify Executive Function

The important point: executive function problems arise from a variety of issues, some genetics, even epigenetics, – associated with now-measurable biologic modifications of the dopamine pathway[s]. See these several quotes from this interesting paper on D2 Receptor Polymorphism1 [link to pdf], sent in from my colleague Ken Blum PhD. Let’s start with their Executive Function definition, then touch upon the conclusion to whet your appetite for these interesting considerations – that also significantly contribute to RDS – Reward Deficiency Syndrome.2

Defining Executive Functions
Executive functions are complex cognitive abilities requiring
the synchronization of several sub-processes to achieve a particular
goal [2]. They control and regulate other abilities and
behaviors and involve cognitive control processes that regulate
thought and action on representations stored in the prefrontal
cortex (PFC) [3]. Executive functions are localized in neural
networks and, when activated, enable access to the stored
actions. Indeed, executive functions can be viewed as computational
procedures or algorithms that are localized in neural
networks [4]. Theorists differ with regard to whether executive
functions are unified with respect to process, nor whether they
include specific cognitive abilities [5–9]. Consensus is lacking
with regard to which of many diverse cognitive functions are
considered relevant to executive functioning. At the very least,
the term encompasses a host of processes that act in harmony
and are responsible for the higher-level action of monitoring
and controlling behaviors necessary for maintaining focus and
achieving outcomes in possibly adverse circumstances. The
efficacy measure of any successful high mental skill is a function
of our intellectual integrity and mental capabilities. The
outcome of our behavior depends on the ability of our brain to
exert control over its processing of reflexive reactions to the
environment and directing those behaviors toward conscious as
well as non-conscious goals [10].

And Regarding Neurotransmitter Precursors – Same Paper

The availability of certain neurotransmitters can be influenced
by dietary supply of their amino acid precursor. For
example, tryptophan is the dietary precursor of serotonin
and tyrosine is that of DA and norepinephrine [135]. Many
of these neurotransmitters serve a dual role, functioning also
as growth factors that influence the intricate choreography
of growth of neural systems in the developing brain [136,
137]. Thus, one of the mechanisms whereby changes in the
availability of nutrient supply may result in disturbances of
specific brain and behavioral functions during development
is through their selective effect on some of these systems
and not others. This emerging understanding has important
implications for the design and interpretation of
studies on the cognitive effects of specific nutrients during
development [138].

D2 Receptor Polymorphism and ADHD Connected

Finally, being somewhat complex, abnormal increases in
D(2) receptor activity cause a more general impairment in
behavioral flexibility especially in patients with attention
deficit hyperactivity disorder [154]. These findings suggest
that deficits in these forms of executive functioning observed
in disorders linked to dysfunction of the DA system
may be attributable in part to aberrant increases or decreases
in mesoaccumbens DA activity [155–160]. The control of
DA release in PFC and other brain regions is regulated by
many neurotransmitters and second messenger genes and
constitute a genetic map that could provide important information
relating to a predisposition to poor judgment.

Conclusion

The differential modulation of fronto-executive function by
discrete neurochemical systems highlights a degree of specificity
for these “nonspecific” neuromodulatory pathways,
which hitherto have been underestimated. These systems
interact not only within the PFC at the level of single
pyramidal neurons but also at the level of functional modules
in order to optimize overall executive control. Preservation
of the neurological underpinnings of executive
functions requires integrity of entire neural systems as well
as specific genes and associated polymorphisms. Genetic
mapping may serve as a probable diagnostic tool and a
therapeutic target for eventual augmentation of executive
functioning capabilities.

These remarks identify important considerations at every level of Executive Function consideration,

cp

1  Neuropsychopharmacology and neurogenetic aspects of executive functioning: should reward gene polymorphisms constitute a diagnostic tool to identify individuals at risk for impaired judgment? Bowirrat A, Chen TJ, Oscar-Berman M, Madigan M, Chen AL, Bailey JA, Braverman ER, Kerner M, Giordano J, Morse S, Downs BW, Waite RL, Fornari F, Armaly Z, Blum K. Mol Neurobiol. 2012 Apr;45(2):298-313. Epub 2012 Feb 28. PMID: 22371275, PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/22371275 [168 References]

2 Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors. Blum K, Braverman ER, Holder JM, Lubar JF, Monastra VJ, Miller D, Lubar JO, Chen TJ, Comings DE. J Psychoactive Drugs. 2000 Nov;32 Suppl:i-iv, 1-112.  PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/11280926

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3 Comments
  1. Hello

    I recenetly got my biomarkers measured by a lab and my results were:

    Dopamine 240
    Norepinephrine 15
    Epinephrine 0.91

    How do I bring up my Norepinephrine and Epinephrine without increasing Dopamine?

    Thank for your time

    • Eric,
      Without knowing more I hesitate to tell you one thing when so many other issues could be present but unaccounted for. One item likely at play, copper. Copper does help convert dopamine to norepinephrine, but without knowing your entire picture, including IgG, TMA and OATS this devolves to the kind of speculation that proves so counterproductive. See the videos and information on these tests: http://corepsych.com/tests
      cp

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