Variation in the µ-opioid receptor gene (OPRM1) moderates the influence of early maternal care on fearful attachment.

There is evidence that both early experience and genetic variation play a role in influencing sensitivity to social rejection. In this study, we aimed at ascertaining if the A118G polymorphism of the µ-opioid receptor gene (OPRM1) moderates the impact of early maternal care on fearful attachment, a personality trait strongly related to rejection sensitivity. In 112 psychiatric patients, early maternal care and fearful attachment were measured using the Parental Bonding Inventory and the Relationship Questionnaire (RQ), respectively. The pattern emerging from the RQ data was a crossover interaction between genotype and maternal caregiving. Participants expressing the minor 118 G allele had similar and relatively high scores on fearful attachment regardless of the quality of maternal care. By contrast, early experience made a major difference for participants carrying the A/A genotype. Those who recalled higher levels of maternal care reported the lowest levels of fearful attachment whereas those who recalled lower levels of maternal care scored highest on fearful attachment. Our data fit well with the differential susceptibility model which stipulates that plasticity genes would make some individuals more responsive than others to the negative consequences of adversity and to the benefits of environmental support and enrichment.

Social hedonic capacity is associated with the A118G polymorphism of the mu-opioid receptor gene (OPRM1) in adult healthy volunteers and psychiatric patients.

A large body of evidence links altered opioid signaling with changes in social behavior in animals. However, few studies have attempted to determine whether similar links exist in humans. Here we investigate whether a common polymorphism (A118G) in the mu-opioid receptor gene (OPRM1) is associated with alterations in personality traits linked to affiliative behavior and attachment. In a mixed sample (N = 214) of adult healthy volunteers and psychiatric patients, we analyzed the association between the A118G polymorphism of the OPRM1 and two different psychological constructs reflecting individual differences in the capacity to experience social reward. Compared to individuals expressing only the major allele (A) of the A118G polymorphism, subjects expressing the minor allele (G) had an increased tendency to become engaged in affectionate relationships, as indicated by lower scores on a self-report measure of avoidant attachment, and experienced more pleasure in social situations, as indicated by lower scores on a self-report measure of social anhedonia. The OPRM1 variation accounted for about 3.5% of the variance in the two measures. The significant association between the A118G polymorphism and social hedonic capacity was independent of the participants' mental health status. The results reported here are in agreement with the brain opioid hypothesis of social attachment and the established role of opioid transmission in mediating affiliative behavior.

Neuroculture.

Neuroscience addresses questions that, if resolved, will reveal aspects of our individuality. Therefore neuroscientific knowledge is not solely constrained within laboratories, but readily captures the attention of the public at large. Ideas, concepts and images in neuroscience widely circulate in culture and are portrayed in literature, film, works of art, the mass media and commercial products, therefore shaping social values and consumer practices. The interaction between art and science offers an opportunity to make the scientific community and the public aware of the social and ethical implications of the scientific advances in neuroscience.

Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation.

Monoamine oxidase A gene (MAOA) has earned the nickname "warrior gene" because it has been linked to aggression in observational and survey-based studies. However, no controlled experimental studies have tested whether the warrior gene actually drives behavioral manifestations of these tendencies. We report an experiment, synthesizing work in psychology and behavioral economics, which demonstrates that aggression occurs with greater intensity and frequency as provocation is experimentally manipulated upwards, especially among low activity MAOA (MAOA-L) subjects. In this study, subjects paid to punish those they believed had taken money from them by administering varying amounts of unpleasantly hot (spicy) sauce to their opponent. There is some evidence of a main effect for genotype and some evidence for a gene by environment interaction, such that MAOA is less associated with the occurrence of aggression in a low provocation condition, but significantly predicts such behavior in a high provocation situation. This new evidence for genetic influences on aggression and punishment behavior complicates characterizations of humans as "altruistic" punishers and supports theories of cooperation that propose mixed strategies in the population. It also suggests important implications for the role of individual variance in genetic factors contributing to everyday behaviors and decisions.

Identifying molecular substrates in a mouse model of the serotonin transporter x environment risk factor for anxiety and depression.

BACKGROUND: A polymorphism in the serotonin transporter (5-HTT) gene modulates the association between adverse early experiences and risk for major depression in adulthood. Although human imaging studies have begun to elucidate the neural circuits involved in the 5-HTT x environment risk factor, a molecular understanding of this phenomenon is lacking. Such an understanding might help to identify novel targets for the diagnosis and therapy of mood disorders. To address this need, we developed a gene-environment screening paradigm in the mouse. METHODS: We established a mouse model in which a heterozygous null mutation in 5-HTT moderates the effects of poor maternal care on adult anxiety and depression-related behavior. Biochemical analysis of brains from these animals was performed to identify molecular substrates of the gene, environment, and gene x environment effects. RESULTS: Mice experiencing low maternal care showed deficient gamma-aminobutyric acid-A receptor binding in the amygdala and 5-HTT heterozygous null mice showed decreased serotonin turnover in hippocampus and striatum. Strikingly, levels of brain-derived neurotrophic factor (BDNF) messenger RNA in hippocampus were elevated exclusively in 5-HTT heterozygous null mice experiencing poor maternal care, suggesting that developmental programming of hippocampal circuits might underlie the 5-HTT x environment risk factor. CONCLUSIONS: These findings demonstrate that serotonin plays a similar role in modifying the long-term behavioral effects of rearing environment in diverse mammalian species and identifies BDNF as a molecular substrate of this risk factor.

Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype.

Previous research has reported that a functional polymorphism in the monoamine oxidase A (MAOA) gene promoter can moderate the association between early life adversity and increased risk for violence and antisocial behavior. In this study of a combined population of psychiatric outpatients and healthy volunteers (N = 235), we tested the hypothesis that MAOA genotype moderates the association between early traumatic life events (ETLE) experienced during the first 15 years of life and the display of physical aggression during adulthood, as assessed by the Aggression Questionnaire. An ANOVA model including gender, exposure to early trauma, and MAOA genotype as between-subjects factors showed significant MAOAxETLE (F(1,227) = 8.20, P = 0.005) and genderxMAOAxETLE (F(1,227) = 7.04, P = 0.009) interaction effects. Physical aggression scores were higher in men who had experienced early traumatic life events and who carried the low MAOA activity allele (MAOA-L). We repeated the analysis in the subgroup of healthy volunteers (N = 145) to exclude that the observed GxE interactions were due to the inclusion of psychiatric patients in our sample and were not generalizable to the population at large. The results for the subgroup of healthy volunteers were identical to those for the entire sample. The cumulative variance in the physical aggression score explained by the ANOVA effects involving the MAOA polymorphism was 6.6% in the entire sample and 12.1% in the sub-sample of healthy volunteers. Our results support the hypothesis that, when combined with exposure to early traumatic life events, low MAOA activity is a significant risk factor for aggressive behavior during adulthood and suggest that the use of dimensional measures focusing on behavioral aspects of aggression may increase the likelihood of detecting significant gene-by-environment interactions in studies of MAOA-related aggression.