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 predisposition due to hereditary / familial 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
• 6.2. High oxytocin receptor density in the nucleus accumbens makes people resilient to parental neglect
• 6.3. Other genes that correlate with resilience

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 people 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
• NR3C1, which encodes the glucocorticoid receptor (GR)
  • GR plays a key role in mediating the switch-off of the HPA axis (stress axis) after stress-induced activation
  • Reduced expression is associated with impaired deactivation of the HPA axis after activation
  • In the Brazilian high-risk cohort, reduced NR3C1 expression correlated with increased internalizing symptoms⁹