The Contribution of a Polygenic Risk Score to Individual Differences in Aggressive Behavior: The Moderating and Mediating Roles of Stressful Events

Although aggression can be beneficial in certain situations (e.g. playing sports, self-defense), excessive and inappropriate aggression can lead to adverse physical and psychological health outcomes in both perpetrators and victims. Genetic susceptibility to negative environments can increase the likelihood of aggressive behavior in the context of situational risk factors. Low efficiency of serotonin neurotransmission and exposure to stress appear to play a prominent role in the etiology of aggressive behavior. A set of three studies assessed the contribution of polygenic risk (TPH2 rs4570625, SLC6A4 5-HTTLPR+rs25531, HTR1B rs13212041, MAOA uVNTR) to aggressive behavior, including alcohol-related aggression, in university students at varying reported levels of childhood stress (i.e. exposure to childhood trauma, lack of social support). Additionally, the mediating role of acute stress on the association between the polygenic risk score and aggression was examined using both self-report measures and experimental manipulation. It was expected that increased genetic susceptibility would predict higher aggressive behavior resulting from stress, and that the association would be greater as level of exposure to childhood stress increased. Hypotheses for the study were partially supported. Findings showed that individuals with higher genetic susceptibility (i.e. high polygenic risk score) reported engaging in more aggression if they reported experiencing higher levels of childhood trauma and reported engaging in less aggression if they reported experiencing lower levels of childhood trauma. In women only, higher genetic susceptibility and higher reported levels of childhood trauma also predicted more aggression indirectly via higher acute perceived stress. However, these results did not generalize to alcohol-related aggression. The pattern of results is consistent with the Differential Susceptibility Model based on a visual inspection and suggests that individuals with genetic risk who have experienced childhood trauma may benefit from intervention and prevention strategies. Because the association in women between the polygenic risk score and aggression was mediated by stress, intervention and prevention strategies that focus on teaching adaptive coping techniques may be particularly useful in reducing aggressive behavior in women that occurs as a result of stress. Adviser: Scott F. Stoltenber

The Role of Vocal Hostility on Mood: Initial Development of an Alternative Stress Paradigm

Maltreatment, such as physical or emotional abuse, can alter one’s later emotional regularity and responses to stimuli. To be able to study the effect of maltreatment on later stimuli response, appropriate laboratory paradigms need to be available, which is not currently true. The purpose of the study was to investigate the effect of vocal hostility stimuli on mood change as preliminary steps toward the creation of a laboratory paradigm. Participants were recruited from a regional university in southeast United States and asked to react to recorded audio with a hostile tone. Study 1 found that participants’ mood did not differ based on the level of hostility they were exposed to, although participants indicated they would expect a more negative mood had the situation been real. Additionally, participants could not always differentiate between the hostility levels, indicating adjustments to the study stimuli might be needed. Study 2 investigated whether longer exposure to hostility might impact the relationship between hostility and mood. Results of Study 2 replicated Study 1, suggesting other factors would need to be considered in the adjustment of our stimuli to create a useful paradigm

Oxytocin Receptor (\u3ci\u3eOXTR\u3c/i\u3e) Single Nucleotide Polymorphisms Indirectly Predict Prosocial Behavior through Perspective Taking and Empathic Concern

Engaging in prosocial behavior can provide positive outcomes for self and others. Prosocial tendencies contribute to the propensity to engage in prosocial behavior.The oxytocin receptor gene (OXTR) has also been associated with prosocial tendencies and behaviors. There has been little research, however, investigating whether the relationship between OXTR and prosocial behaviors is mediated by prosocial tendencies.This relationship may also vary among different types of prosocial behavior. The current study examines the relationship between OXTR, gender, prosocial tendencies, and both altruistic and public prosocial behavior endorsement. Students at a midwestern university (N = 398; 89.2% Caucasian; Mage = 20.76; 26.6% male) provided self-report measures of prosocial tendencies and behaviors and buccal cells for genotyping OXTR polymorphisms. Results indicated that OXTR single nucleotide polymorphism (SNP) rs2268498 genotype significantly predicted empathic concern, whereas gender moderated the association between several other OXTR SNPs and prosocial tendencies. Increased prosocial tendencies predicted increased altruistic prosocial behavior endorsement and decreased public prosocial behavior endorsement. Our findings suggest an association between genetic variation in OXTR and endorsement of prosocial behavior indirectly through prosocial tendencies, and that the pathway is dependent on the type of prosocial behavior and gender

Serotonin System Gene Polymorphisms Are Associated with Impulsivity in a Context Dependent Manner

Impulsivity is a risk factor for adverse outcomes and characterizes several psychiatric disorders and risk for suicide. There is strong evidence that genetic variation influences individual differences in impulsivity, but the details are not yet understood. There is growing interest in better understanding the context dependency of genetic effects that is reflected in studies examining gender specificity, gene × environment interaction and epistasis (gene-gene interaction). In a cross-sectional study we examined whether polymorphisms in six serotonin system candidate genes and the experience of early life trauma (age 0–12) were associated with individual differences in impulsivity in a nonclinical sample of Caucasian university students (N = 424). We specifically tested potential gender specific, gene-gene, and gene × environment (early life trauma) effects. In our main analyses with Barratt Impulsiveness Scale (BIS-11) total score, there were significant (i.e., p \u3c .01 and False Discovery Rate \u3c .10) interactions between (1) gender and TPH2 (rs1386483) genotype; (2) gender and HTR2A (rs6313) genotype; and epistatic interactions among (3) 5-HTTLPR and MAOA uVNTR; (4) 5-HTTLPR and rs6313 and (5) HTR1B (rs6296) and rs6313 genotypes. Our results strongly support the explicit investigation of context-dependent genetic effects on impulsivity and may help to resolve some of the conflicting reports in the literature

Gender differences in the relationship between impulsivity and disordered eating behaviors and attitudes

Objective: We investigated relationships among gender, impulsivity and disordered eating in healthy college students. Method: Participants (N = 1223) were healthy, undergraduate men (28.5%) and women (71.5%), who completed the Barratt Impulsiveness Scale — Version 11 (BIS-11) and a four-factor version of the Eating Attitudes Test (EAT-16). Results: As predicted, mean scores on all four EAT-16 factors were significantly higher for women than for men. Attentional impulsivity was related to poorer self-perception of body shape, more dieting, and a greater preoccupation with food for the sample as a whole. Moreover, motor impulsivity was related to poorer self-perceptions of body shape and a greater preoccupation with food. However, no gender differences emerged in the relationship between impulsivity and disordered eating attitudes. Discussion: This study elucidates the role of impulsivity in disordered eating behaviors among non-clinical college students. For both women and men, attentional and motor impulsivity were related to disordered eating attitudes and behaviors. Overall, these findings suggest that different facets of impulsivity are related to disordered eating attitudes and behaviors in a non-clinical college population

Associations among types of impulsivity, substance use problems and \u3ci\u3eNeurexin-3\u3c/i\u3e polymorphisms

Background—Some of the genetic vulnerability for addiction may be mediated by impulsivity. This study investigated relationships among impulsivity, substance use problems and six neurexin-3 (NRXN3) polymorphisms. Neurexins (NRXNs) are presynaptic transmembrane proteins that play a role in the development and function of synapses. Methods—Impulsivity was assessed with the Barratt Impulsiveness Scale Version 11 (BIS-11), the Boredom Proneness Scale (BPS) and the TIME paradigm; alcohol problems with the Michigan Alcoholism Screening Test (MAST); drug problems with the Drug Abuse Screening Test (DAST-20); and regular tobacco use with a single question. Participants (N = 439 Caucasians, 64.7% female) donated buccal cells for genotyping. Six NRXN3 polymorphisms were genotyped: rs983795, rs11624704, rs917906, rs1004212, rs10146997 and rs8019381. A dual luciferase assay was conducted to determine whether allelic variation at rs917906 regulated gene expression. Results—In general, impulsivity was significantly higher in those who regularly used tobacco and/or had alcohol or drug problems. In men, there were modest associations between rs11624704 and attentional impulsivity (p = .005) and between rs1004212 and alcohol problems (p = .009). In women, there were weak associations between rs10146997 and TIME estimation (p = .03); and between rs1004212 and drug problems (p = .03). The dual luciferase assay indicated that C and T alleles of rs917906 did not differentially regulate gene expression in vitro. Conclusions—Associations between impulsivity, substance use problems and polymorphisms in NRXN3 may be gender specific. Impulsivity is associated with substance use problems and may provide a useful intermediate phenotype for addiction

Associations among types of impulsivity, substance use problems and \u3ci\u3eNeurexin-3\u3c/i\u3e polymorphisms

Background—Some of the genetic vulnerability for addiction may be mediated by impulsivity. This study investigated relationships among impulsivity, substance use problems and six neurexin-3 (NRXN3) polymorphisms. Neurexins (NRXNs) are presynaptic transmembrane proteins that play a role in the development and function of synapses. Methods—Impulsivity was assessed with the Barratt Impulsiveness Scale Version 11 (BIS-11), the Boredom Proneness Scale (BPS) and the TIME paradigm; alcohol problems with the Michigan Alcoholism Screening Test (MAST); drug problems with the Drug Abuse Screening Test (DAST-20); and regular tobacco use with a single question. Participants (N = 439 Caucasians, 64.7% female) donated buccal cells for genotyping. Six NRXN3 polymorphisms were genotyped: rs983795, rs11624704, rs917906, rs1004212, rs10146997 and rs8019381. A dual luciferase assay was conducted to determine whether allelic variation at rs917906 regulated gene expression. Results—In general, impulsivity was significantly higher in those who regularly used tobacco and/or had alcohol or drug problems. In men, there were modest associations between rs11624704 and attentional impulsivity (p = .005) and between rs1004212 and alcohol problems (p = .009). In women, there were weak associations between rs10146997 and TIME estimation (p = .03); and between rs1004212 and drug problems (p = .03). The dual luciferase assay indicated that C and T alleles of rs917906 did not differentially regulate gene expression in vitro. Conclusions—Associations between impulsivity, substance use problems and polymorphisms in NRXN3 may be gender specific. Impulsivity is associated with substance use problems and may provide a useful intermediate phenotype for addiction

Afraid to Help: Social Anxiety Partially Mediates the Association between 5-HTTLPR Triallelic Genotype and Prosocial Behavior

There is growing evidence that the serotonin system influences prosocial behavior. We examined whether anxiety mediated the association between variation in the serotonin transporter gene regulatory region (5-HTTLPR) and prosocial behavior. We collected self-reported tendencies to avoid certain situations and history of helping others using standard instruments and buccal cells for standard 5-HTTLPR genotyping from 398 undergraduate students. Triallelic 5-HTTLPR genotype was significantly associated with prosocial behavior and the effect was partially mediated by social anxiety, such that those carrying the S′ allele reported higher levels of social avoidance and lower rates of helping others. These results are consistent with accounts of the role of serotonin on anxiety and prosocial behavior and suggest that targeted efforts to reduce social anxiety in S′ allele carriers may enhance prosocial behavior

Oxytocin Receptor (\u3ci\u3eOXTR\u3c/i\u3e) Single Nucleotide Polymorphisms Indirectly Predict Prosocial Behavior through Perspective Taking and Empathic Concern

Engaging in prosocial behavior can provide positive outcomes for self and others. Prosocial tendencies contribute to the propensity to engage in prosocial behavior.The oxytocin receptor gene (OXTR) has also been associated with prosocial tendencies and behaviors. There has been little research, however, investigating whether the relationship between OXTR and prosocial behaviors is mediated by prosocial tendencies.This relationship may also vary among different types of prosocial behavior. The current study examines the relationship between OXTR, gender, prosocial tendencies, and both altruistic and public prosocial behavior endorsement. Students at a midwestern university (N = 398; 89.2% Caucasian; Mage = 20.76; 26.6% male) provided self-report measures of prosocial tendencies and behaviors and buccal cells for genotyping OXTR polymorphisms. Results indicated that OXTR single nucleotide polymorphism (SNP) rs2268498 genotype significantly predicted empathic concern, whereas gender moderated the association between several other OXTR SNPs and prosocial tendencies. Increased prosocial tendencies predicted increased altruistic prosocial behavior endorsement and decreased public prosocial behavior endorsement. Our findings suggest an association between genetic variation in OXTR and endorsement of prosocial behavior indirectly through prosocial tendencies, and that the pathway is dependent on the type of prosocial behavior and gender

Serotonin System Gene Polymorphisms Are Associated with Impulsivity in a Context Dependent Manner

Impulsivity is a risk factor for adverse outcomes and characterizes several psychiatric disorders and risk for suicide. There is strong evidence that genetic variation influences individual differences in impulsivity, but the details are not yet understood. There is growing interest in better understanding the context dependency of genetic effects that is reflected in studies examining gender specificity, gene × environment interaction and epistasis (gene-gene interaction). In a cross-sectional study we examined whether polymorphisms in six serotonin system candidate genes and the experience of early life trauma (age 0–12) were associated with individual differences in impulsivity in a nonclinical sample of Caucasian university students (N = 424). We specifically tested potential gender specific, gene-gene, and gene × environment (early life trauma) effects. In our main analyses with Barratt Impulsiveness Scale (BIS-11) total score, there were significant (i.e., p \u3c .01 and False Discovery Rate \u3c .10) interactions between (1) gender and TPH2 (rs1386483) genotype; (2) gender and HTR2A (rs6313) genotype; and epistatic interactions among (3) 5-HTTLPR and MAOA uVNTR; (4) 5-HTTLPR and rs6313 and (5) HTR1B (rs6296) and rs6313 genotypes. Our results strongly support the explicit investigation of context-dependent genetic effects on impulsivity and may help to resolve some of the conflicting reports in the literature