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

Abstract

Objectives Impaired inhibitory control is a key feature of Attention-Deficit/Hyperactivity Disorder (ADHD). We investigated 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 Behavioral 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 x 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.

Children’s DAT1 Polymorphism Moderates the Relationship Between Parents’ Psychological Profiles, Children’s DAT Methylation, and Their Emotional/Behavioral Functioning in a Normative Sample

“…Finally, given that several studies have shown that gene–environment interactions can be confounded by the presence of gene–environment correlations (rGE; [83,84]), as suggested by Richards et al [85], we primarily carried out Pearson correlation analyses. Then, a hierarchical regression was carried out to verify if children’s DAT1 polymorphisms moderated the relationship between parents’ psychological profile (independent variable) and children’s emotional/behavioral functioning (dependent variable).…”

Gene-Environment Interactions in Psychiatry: Recent Evidence and Clinical Implications

“…A review of the last 4.5 years of the literature included 34 studies that focused on ADHD diagnosis and related symptoms. A majority of studies focused their environmental exposure on related to psychosocial [67][68][69][70][71][72][73][74][75][76][77], stress and adversity [27,75,[77][78][79][80][81][82][83][84], and trauma-related exposures [85]. Very few focused on toxicant exposure such as blood lead levels [86, 87••, 88], phthalate metabolites [89], and organophosphate pesticide exposure [90].…”

Individual differences in sensitivity to positive home environment among children “at risk” for attention-deficit/hyperactivity disorder: A review

“…It should be noted that additional susceptibility factors involved in the development of EF that have been found in these mentioned studies include temperamental reactivity (38), physiological reactivity (19), difficult temperament (143), candidate genes such as the 5-HTTLRP, DAT1, DRD4 (20), and neonatal brain volume (18). All these studies suggested that children with susceptibility factors were more sensitive to both negative and positive aspects of the home environment or parenting; children showed poor EF under less optimal environments but outperformed their non-susceptible peers in supportive environments.…”

“…All these studies suggested that children with susceptibility factors were more sensitive to both negative and positive aspects of the home environment or parenting; children showed poor EF under less optimal environments but outperformed their non-susceptible peers in supportive environments. Other environmental aspects that children showed sensitivity to, for better and worst, were adversity and low family income (19,38), maternal behaviors such as sensitivity and the quality of mother-infant interactions (18,143), and peer affiliation (20).…”

“…For example, individuals at such risk, who also experience a low-quality home environment, would be at higher risk to manifest the disorder's symptoms, compared to individuals who are not at such risk (14,16). However, individuals at risk who experience a very supportive environment might disproportionally benefit from this experience, and even, for certain developmental outcomes, outperform their peers who are not at such risk (12, [17][18][19][20][21][22]. Therefore, these individual factors have been suggested to be susceptibility factors, rather than simply risk factors (23).…”