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ADHD Insights: D2 Receptors and Executive Function

Posted Oct 26 2012 12:00am
  • Modify Dopamine Metabolism    ADHD Insights: D2 Receptors and 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: 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 Polymorphism 1 [link to pdf], sent in from my colleague 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 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 () [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 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.


    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,


    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:

    Dr Charles Parker: Author, Neuroscience Consultant, Child, Adolescent and Adult Psychiatrist. His book “New ADHD Medication Rules” – Preorder Discount at These Bookstores is the *only resource available to the public* that describes more precise medical diagnosis and measurable treatment strategies for ADHD. Visit CoreBrain Books for reading recommendations. His CoreBrain Training platform provides a coaching system from high school students to medical professionals for transitions to these new realities of mind-practice. Join Parker on the radio weekly at ADHD Meds | Straight Talk for ADHD Med details that work. Then follow @drcharlesparker on Twitter for more fresh details.

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