Differential Susceptibility Framework Research Articles

Insights into the molecular genetic basis of individual differences in metacognition

There is a striking lack of studies on the molecular genetic basis of metacognition, i.e., the higher-order ability to monitor mental processes. Here, an initial step toward resolving this issue was undertaken by investigating functional polymorphisms from three genes of the dopaminergic or serotonergic systems (DRD4, COMT, and 5-HTTLPR) in relation to behaviorally assessed metacognition in six paradigms across three cognitive domains. We report evidence for a task-dependent higher average confidence level (metacognitive bias) in carriers of at least one S or LG-allele in the 5-HTTLPR genotype and integrate these findings within a differential susceptibility framework.

Frontal Brain Activity and Subjective Arousal During Emotional Picture Viewing in Nightmare Sufferers.

Nightmares are intensely negative dreams that awaken the dreamer. Frequent nightmares are thought to reflect an executive deficit in regulating arousal. Within a diathesis-stress framework, this arousal is specific to negative contexts, though a differential susceptibility framework predicts elevated arousal in response to both negative and positive contexts. The current study tested these predictions by assessing subjective arousal and changes in frontal oxyhemoglobin (oxyHB) concentrations during negative and positive picture-viewing in nightmare sufferers (NM) and control subjects (CTL). 27 NM and 27 CTL subjects aged 18–35 rated subjective arousal on a 1–9 scale following sequences of negative, neutral and positive images; changes in oxyHB were measured by Near-Infrared Spectroscopy (NIRS) using a 2 × 4 template on the frontal pole. Participants also completed the Highly Sensitive Person Scale, a trait marker for differential susceptibility; and completed a dream diary reporting negative and positive dream emotionality. The NM group had higher trait sensitivity, yet higher ratings of negative but not positive emotion in diary dreams. NM compared to CTL subjects reported higher subjective arousal in response to picture-viewing regardless of valence. Dysphoric dream distress, measured prospectively, was negatively associated with frontal activation when viewing negative pictures. Results suggest NM sufferers are highly sensitive to images regardless of valence according to subjective measures, and that there is a neural basis to level of trait and prospective nightmare distress. Future longitudinal or intervention studies should further explore positive emotion sensitivity and imagery in NM sufferers.

Testing the theory of Differential Susceptibility to nightmares: The interaction of Sensory Processing Sensitivity with the relationship of low mental wellbeing to nightmare frequency and nightmare distress.

Propensity to have nightmares has been theorised in terms of diathesis-stress models, with this propensity being seen as negative or even pathological. In contrast, a recent model proposes that nightmare propensity is due to Differential Susceptibility to stimuli, where high susceptibility can be beneficial in positive environments but detrimental in negative environments. This susceptibility to stimuli is assessed as the biobehavioural trait Sensory Processing Sensitivity, which refers to a greater responsivity to internal and external stimuli, and an increased depth of cognitive and emotional processing. To test the Differential Susceptibility Framework for nightmares, 137 participants (females=104, males=33; mean age=33.66 years), recruited from a student population and social media sites, were divided into high (n=39), medium (n=59) and low (n=39) Sensory Processing Sensitivity categories based on their score on the Highly Sensitive Person Scale. Low mental wellbeing and the presence of minor psychiatric problems, measured by the General Health Questionnaire, was found to be significantly correlated with nightmare frequency for the high and medium SPS groups (rs=.29 and .28, respectively), but not for the low Sensory Processing Sensitivity group (r=.19). General Health Questionnaire score was also significantly correlated with trait nightmare distress, for the high Sensory Processing Sensitivity group only (r=.32). These findings in favour of the Differential Susceptibility Framework have aetiology and treatment implications for nightmares that differ from diathesis-stress models.

VGLUT2 rs2290045 genotype moderates environmental sensitivity to alcohol-related problems in three samples of youths

The importance of Vesicular Glutamate Transporter 2 (VGLUT2)-mediated neurotransmission has been highlighted in studies on addiction-related phenotypes. The single nucleotide polymorphism rs2290045 in VGLUT2 has been associated with alcohol dependence, but it is unknown whether or how this association is affected by environmental factors. The present study determined whether the association of alcohol-related problems with the rs2290045 in the VGLUT2 gene was modified by negative and positive environmental factors. Three samples were included: a clinical sample of 131 adolescents followed from age 17 to 22; a general population sample of 1794 young adults; and a general population sample of 1687 adolescents followed from age 14 to 17. DNA was extracted from saliva and the rs2290045 (T/C) was genotyped. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test. Stressful life events (SLE) and parenting were assessed by questionnaires. Gene-environment interactions were investigated using a dual statistical approach. In all samples (effect sizes 0.6–6.2%), and consistent with the differential susceptibility framework, T carriers exposed to SLE reported more alcohol-related problems if they had experienced poor parenting, and lower alcohol-related problems if they had received supportive parenting. T carriers not exposed to SLE reported higher alcohol-related problems if they had received supportive parenting and lower alcohol-related problems if they had received poor parenting. Among CC carriers, alcohol-related problems did not vary as a function of negative and positive environmental factors. In conclusion, in three samples of youths, alcohol-related problems were associated with an interaction of VGLUT2 rs2290045, SLE, and parenting.

Testosterone and Proactive-Reactive Aggression in Youth: the Moderating Role of Harsh Discipline.

This study tests a biosocial model of the link between testosterone and proactive-reactive aggression in youth at varying levels of harsh discipline. Given that proactive aggression is used to gain power and status and the importance of social learning in its formation, we hypothesized that testosterone would be associated with proactive aggression at higher levels of harsh discipline, and that this relationship would be more pronounced in boys than girls. Participants (n = 445; 50% male; M age = 11.92years; 80% African-American) and their caregivers completed questionnaires including demographics, conflict tactics, and proactive-reactive aggression. Youth also provided a saliva sample for testosterone. Analyses revealed an interaction between testosterone and harsh discipline on proactive aggression in both boys and girls, and an interaction between testosterone and harsh discipline on reactive aggression in boys only. For those experiencing high levels of harsh discipline, testosterone was positively associated with proactive aggression, with the magnitude of the association increasing as harsh discipline increased. For below average levels of harsh discipline, there were protective effects of high testosterone for boy's reactive aggression and for girl's proactive aggression. The findings support basic tenets of the biosocial model which suggest that links between testosterone and aggressive behavior are dependent on contextual forces, highlighting the complex relationship between hormones, social context, and aggression. Novel findings include protective effects of high testosterone for those exposed to low levels of harsh discipline. Findings are discussed in light of the context-contingency effect and also within the differential susceptibility framework.

Cortisol Moderates the Relation Between Physical Peer Victimization and Physical Aggression in Preschoolers Attending High-Quality Child Care: Evidence of Differential Susceptibility Across Informants

We examined whether the moderating role of cortisol in the relation between physical peer victimization and physical aggression was better accounted for by a diathesis–stress model or a differential susceptibility model using a multiinformant approach (direct observations, teacher reports, and parent reports) of 198 preschool-aged children attending high-quality child care. Controlling for the influence of household income, hours per week in child care, and child age, we found that our results supported a differential susceptibility effect for boys but not for girls. This effect was replicated within reporters (observer and parent reports) and across reporters (parent-reported victimization and teacher-rated aggression) but for boys only. At higher levels of peer victimization, lower levels of basal cortisol were associated with higher levels of physical aggression, but, at lower levels of peer victimization, lower levels of basal cortisol were associated with lower levels of physical aggression. Furthermore, at higher levels of peer victimization, higher levels of basal cortisol were associated with lower levels of physical aggression, but, at lower levels of peer victimization, higher levels of basal cortisol were associated with higher levels of physical aggression. These results highlight the complex interplay between the social environment and biobehavioral systems in early childhood and the value of considering a differential susceptibility framework in peer-relations research.

Gene × Environment contributions to autonomic stress reactivity in youth.

Dysregulated physiological stress reactivity has been suggested to impact the development of children and adolescents with important health consequences throughout the life span. Both environmental adversity and genetic predispositions can lead to physiological imbalances in stress systems, which in turn lead to developmental differences. We investigated genetic and environmental contributions to autonomic nervous system reactivity to a psychosocial stressor. Furthermore, we tested whether these effects were consistent with the differential susceptibility framework. Composite measures of adverse life events combined with socioeconomic status were constructed. Effects of these adversity scores in interaction with a polygenic score summarizing six genetic variants, which were hypothesized to work as susceptibility factors, were tested on autonomic nervous system measures as indexed by heart rate and heart rate variability. Results showed that carriers of more genetic variants and exposed to high adversity manifested enhanced heart rate variability reactivity to a psychosocial stressor compared to carriers of fewer genetic variants. Conversely, the stress procedure elicited a more moderate response in these individuals compared to carriers of fewer variants when adversity was low.

Differential susceptibility effects of oxytocin gene (OXT) polymorphisms and perceived parenting on social anxiety among adolescents.

Social anxiety is one of the most commonly reported mental health problems among adolescents, and it has been suggested that parenting style influences an adolescent's level of anxiety. A context-dependent effect of oxytocin on human social behavior has been proposed; however, research on the oxytocin gene (OXT) has mostly been reported without considering contextual factors. This study investigated the interactions between parenting style and polymorphic variations in the OXT gene in association with social anxiety symptoms in a community sample of adolescents (n = 1,359). Two single nucleotide polymorphisms linked to OXT, rs4813625 and rs2770378, were genotyped. Social anxiety and perceived parenting style were assessed by behavioral questionnaires. In interaction models adjusted for sex, significant interaction effects with parenting style were observed for both variants in relation to social anxiety. The nature of the interactions was in line with the differential susceptibility framework for rs4813625, whereas for rs2770378 the results indicated a diathesis-stress type of interaction. The findings may be interpreted from the perspective of the social salience hypothesis of oxytocin, with rs4813625 affecting social anxiety levels along a perceived unsafe-safe social context dimension.

Interaction between oxytocin gene variants and perceived parenting in relation to social anxiety in adolescents: Evidence for differential susceptibility effects

IntroductionAdolescence is a period of increasing demands in independent social functioning where parenting style may have an impact on social anxiety. A context-dependent effect of oxytocin on human social behavior has been suggested, however research on the gene coding for oxytocin (OXT) has mostly been reported without considering contextual factors.AimThis study investigated interactions between parenting style and polymorphic variations in the OXT gene in association with social anxiety symptoms in a community sample of adolescents.MethodsThe study group consisted of 1359 adolescents. Two single nucleotide polymorphisms located near OXT, rs4813625 and rs2770378, were genotyped. Social anxiety and perceived parenting style were assessed by behavioral questionnaires.ResultsSignificant joint effects in line with the differential susceptibility framework were observed for rs4813625 with parenting style. The levels of social anxiety among C allele carriers were conditional on the level of supportive parenting style whereas homozygote G carriers’ levels of social anxiety were unaffected by supportive parenting style. The nature of the interactions between rs2770378 and parenting style was in line with the diatheses-stress model. However, associations of rs2770378 and parenting style with social anxiety became nonsignificant in nonlinear models.ConclusionsThe study provides preliminary evidence for a modifying effect of supportive parenting style on the relationship between rs4813625 and social anxiety symptoms in adolescents, independent of sex. The findings may be interpreted from the perspective of the social salience hypotheses of oxytocin, with rs4813625 affecting social anxiety levels along a perceived unsafe–safe social context dimension.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Interactive effects of attachment and FKBP5 genotype on school-aged children’s emotion regulation and depressive symptoms

Attachment insecurity is influenced by both environmental and genetic factors, but few studies have examined the effects of gene-environment interactions. In the context of environmental stress, a functional variant in the glucocorticoid receptor co-chaperone FKBP5 gene has been repeatedly shown to increase risk for psychiatric illness, including depression. We expand on prior work by exploring cross-sectional attachment by gene effects on both attachment insecurity and downstream physiological and behavioral measures in a diverse community sample of school-aged children (N=99, 49% girls, Mage=10.29years, 66.6% non-White) and their mothers. Specifically, we examined moderating effects of FKBP5 rs3800373 genotype on the links between parenting insensitivity (overcontrol) and child attachment. Further, we assessed whether FKBP5 moderates the links between maternal and child attachment and children’s emotion regulation self-report, respiratory sinus arrhythmia (RSA) in response to a standardized laboratory stressor, and depressive symptoms. Higher levels of overcontrol predicted lower child attachment security only in FKBP5 minor allele carriers. Among children with two minor alleles (CC), attachment security was negatively associated with emotion suppression, rumination, depressive symptoms, and RSA reactivity; similarly, for these children, maternal attachment anxiety was positively associated with depressive symptoms. The findings can be conceptualized in a differential susceptibility framework, where the FKBP5 minor allele confers either risk or resilience, depending on the parenting environment.

An Evolutionary Perspective on Family Studies: Differential Susceptibility to Environmental Influences.

An evolutionary perspective of human development provides the basis for the differential-susceptibility hypothesis which stipulates that individuals should differ in their susceptibility to environmental influences, with some being more affected than others by both positive and negative developmental experiences and environmental exposures. This paper reviews evidence consistent with this claim while revealing that temperamental and genetic characteristics play a role in distinguishing more and less susceptible individuals. The differential-susceptibility framework under consideration is contrasted to the traditional diathesis-stress view that "vulnerability" traits predispose some to being disproportionately affected by (only) adverse experiences. We raise several issues stimulated by the literature that need to be clarified in further research. Lastly, we suggest that therapy may differ in its effects depending on an individual's susceptibility.

Genetic Sensitivity to Peer Behaviors

We investigate whether the serotonin transporter-linked polymorphic region (5HTTLPR), a gene associated with environmental sensitivity, moderates the association between smoking and drinking patterns at adolescents' schools and their corresponding risk for smoking and drinking themselves. Drawing on the school-based design of the National Longitudinal Study of Adolescent Health in conjunction with molecular genetic data for roughly 15,000 respondents (including over 2,000 sibling pairs), we show that adolescents smoke more cigarettes and consume more alcohol when attending schools with elevated rates of tobacco and alcohol use. More important, an individual's susceptibility to school-level patterns of smoking or drinking is conditional on the number of short alleles he or she has in 5HTTLPR. Overall, the findings demonstrate the utility of the differential susceptibility framework for medical sociology by suggesting that health behaviors reflect interactions between genetic factors and the prevalence of these behaviors in a person's context.