Testing differential susceptibility: Plasticity genes, the social environment, and their interplay in adolescent response inhibition

World J Biol Psychiatry. 2017 Jun;18(4):308-321. doi: 10.3109/15622975.2016.1173724. Epub 2016 May 12.


Objectives: Impaired inhibitory control is a key feature of attention-deficit/hyperactivity disorder (ADHD). We investigated gene-environment interaction (GxE) as a possible contributing factor to response inhibition variation in context of the differential susceptibility theory. This states individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments.

Methods: Behavioural and neural measures of response inhibition were assessed during a Stop-signal task in participants with (N = 197) and without (N = 295) ADHD, from N = 278 families (age M = 17.18, SD =3.65). We examined GxE between candidate plasticity genes (DAT1, 5-HTT, DRD4) and social environments (maternal expressed emotion, peer affiliation).

Results: A DRD4 × Positive peer affiliation interaction was found on the right fusiform gyrus (rFG) activation during successful inhibition. Further, 5-HTT short allele carriers showed increased rFG activation during failed inhibitions. Maternal warmth and positive peer affiliation were positively associated with right inferior frontal cortex activation during successful inhibition. Deviant peer affiliation was positively related to the error rate.

Conclusions: While a pattern of differential genetic susceptibility was found, more clarity on the role of the FG during response inhibition is warranted before firm conclusions can be made. Positive and negative social environments were related to inhibitory control. This extends previous research emphasizing adverse environments.

Keywords: ADHD; functional MRI; gene–environment interaction; response inhibition; social environment.

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity* / diagnostic imaging
  • Attention Deficit Disorder with Hyperactivity* / genetics
  • Attention Deficit Disorder with Hyperactivity* / physiopathology
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiopathology*
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Expressed Emotion / physiology
  • Female
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease
  • Humans
  • Inhibition, Psychological*
  • Interpersonal Relations*
  • Magnetic Resonance Imaging
  • Male
  • Mother-Child Relations*
  • Neuronal Plasticity / genetics*
  • Receptors, Dopamine D4 / genetics*
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Social Environment*


  • DRD4 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • SLC6A3 protein, human
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Receptors, Dopamine D4