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6. Resilience, increased sensitivity, genetic disposition and maternal care

6. Resilience, increased sensitivity, genetic disposition and maternal care

Not everyone is susceptible to ADHD.
ADHD can develop as a result of cortisolergic stress if the stress state is not ended in time. The probability of this happening is just as high in people with increased sensitivity1 as in those with a genetic disposition due to hereditary / family predisposition.

The neurological pathway is similar to that of post-traumatic stress disorder. In post-traumatic stress disorder, “severely stressful events alter subcortical centers of stress regulation and thus also impair the regulation of subsequent stressors”.2

6.1. High parental care causes resilience

A particularly caring maternal behavior including intense licking and intensive care of the offspring leads to a “neophilic” animal in rats, which explores new environments and reacts less emotionally, as well as to a lower cortisol stress response in the HPA axis in novel situations.
Poor maternal care, on the other hand, leads to a “neophobic” phenotype with increased emotional and HPA reactivity and less exploration of a novel situation.3
In addition, neophilic animals lived on average 200 days longer and appear to be less susceptible to cancer.4

6.2. High oxytocin receptor density in the nucleus accumbens makes us resilient to parental neglect

A high oxytocin receptor density in the nucleus accumbens resulted in an increased resistance of newborns to neglect through social isolation (a specific form of early childhood stress):5

  • Animals with low oxytocin receptor density in the nucleus accumbens
    • Without neonatal neglect
      • Strong preference as adults to spend more time with their partner than with strangers
    • And neonatal neglect
      • No preference as an adult to spend more time with their partner than with strangers
  • Animals with low oxytocin receptor density in the nucleus accumbens
    • Strong cuddle time preference for partners even with neonatal neglect

Blockade of the oxytocin receptor in the mPFC or in the nucleus accumbens (but not in the neighboring caudate nucleus or putamen) prevented the formation of a partner bond.6

6.3. Other genes that correlate with resilience

A meta-analysis found evidence that certain forms of the following genes correlate with resilience:7

  • The serotonin transporter gene a. 5-HTTLPR in SLC6A4 and b. rs25531
    • For children
      • L/L or L’/L’ genotype
      • Another study, however, found an eight times higher risk of ADHD-C or ADHD-HI with a combination of the L/L genotype and stress during pregnancy. This could be one of many possible mechanisms linking stress and genotype in the development of ADHD/CH.8
    • For adults
      • S/S or S’/S’ genotype
  • The D4 dopamine receptor gene
    • C/C and C/T from rs1800955 n ¼ 1
    • 7r/7r and 4r/7r of VNTR (in exon III)
  • The BDNF gene
    • Val/Val from rs6265
  • The CRH receptor 1 gene
    • 1 of the 2 copies of the TAT haplotype of rs110402, rs242924 and rs7209436
  • The G protein signaling 2 regulator gene (RGS2)
    • G/G from rs4606

  1. Koyuncu, Çelebi, Ertekin, Memiş, Tükel (2017): The Presence of Childhood Attention Deficit/Hyperactivity Disorder May Be Associated With Interpersonal Sensitivity in Patients With Social Anxiety Disorder. J Psychiatr Pract. 2017 Jul;23(4):254-259. doi: 10.1097/PRA.0000000000000246

  2. Hofmann (2006): Psychotraumatologie – der Stand des Wissens und die Versorgungslage, PiD 4 −2006, Seite 351 ff

  3. Meaney, Tannenbaum, Francis, et al. (1994): Early environmental programming hypothalamic-pituitary-adrenal responses to stress. Seminars in Neurosciences. 1994;6:247–259.; zitiert nach McEwen (2008): Understanding the potency of stressful early life experiences on brain and body function. Metabolism. 2008 Oct;57 Suppl 2:S11-5. doi: 10.1016/j.metabol.2008.07.006.

  4. McEwen (2008): Understanding the potency of stressful early life experiences on brain and body function. Metabolism. 2008 Oct;57 Suppl 2:S11-5. doi: 10.1016/j.metabol.2008.07.006. mit weiteren Nachweisen

  5. Walum, Young (2018): The neural mechanisms and circuitry of the pair bond. Nat Rev Neurosci. 2018 Nov;19(11):643-654. doi: 10.1038/s41583-018-0072-6. PMID: 30301953; PMCID: PMC6283620. REVIEW

  6. Young, Lim, Gingrich, Insel (2001): Cellular mechanisms of social attachment. Horm Behav. 2001 Sep;40(2):133-8. doi: 10.1006/hbeh.2001.1691. PMID: 11534973.

  7. Niitsu, Rice, Houfek, Stoltenberg, Kupzyk, Barron (2019): A Systematic Review of Genetic Influence on Psychological Resilience. Biol Res Nurs. 2019 Jan;21(1):61-71. doi: 10.1177/1099800418800396. PMID: 30223673.

  8. Grizenko N, Paci M, Joober R (2010): Is the inattentive subtype of ADHD different from the combined/hyperactive subtype? J Atten Disord. 2010 May;13(6):649-57. doi: 10.1177/1087054709347200. PMID: 19767592.

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