Oxytocin and intergroup relations: Goodwill is not a fixed pie

peer reviewe

Oxytocin and the stress buffering effect of social company: A genetic study in daily life

Social relationships are a crucial determinant of both mental and physical health. This effect is partly due to social buffering of stress. Animal studies suggest that social buffering is mediated via the oxytocin system, while studies in humans are sparse and limited by the low ecological validity of laboratory settings. In the present study, participants (N = 326) completed smartphone questionnaires four times a day over 4 to 5 days, measuring stressors, negative affect, and social context to assess social buffering. We found that under stress, participants reported a higher need for social company. Further, the impact of prior stressful events on momentary negative affect was attenuated by the perceived pleasantness of current social company. This social buffering effect was moderated by haplotypes of the oxytocin receptor gene, based on two well-described single nucleotide polymorphisms (rs2268498, rs53576). Effects were robust when controlling for gender and age, applying different data quality criteria, and even apparent in genotype-based analyses. Our findings demonstrate that social buffering and its modulation by oxytocin system characteristics have implications for life as lived outside the laboratory

Poverty, early care and stress reactivity in adolescence: findings from a prospective, longitudinal study in a low-middle income country

A considerable body of evidence suggests that early caregiving may affect the short-term functioning and longer-term development of the hypothalamic-pituitary adrenocortical (HPA) axis. Despite this, most research to date has been cross-sectional in nature or restricted to relatively short–term longitudinal follow-ups. More importantly, there is a paucity of research on the role of caregiving in low and middle income countries, where the protective effects of high quality care in buffering the child’s developing stress regulation systems may be crucial. In this paper, we report findings from a longitudinal study (N = 232) conducted in an impoverished peri-urban settlement in Cape Town, South Africa. We measured caregiving sensitivity and security of attachment in infancy and followed children up at age 13 years, when we conducted assessments of HPA axis reactivity, as indexed by salivary cortisol during the Trier Social Stress Test. The findings indicated that insecure attachment was predictive of reduced cortisol responses to social stress, particularly in boys, and that attachment status moderated the impact of contextual adversity on stress responses: secure children in highly adverse circumstances did not show the blunted cortisol response shown by their insecure counterparts. Some evidence was found that sensitivity of care in infancy was also associated with cortisol reactivity, but in this case insensitivity was associated with heightened cortisol reactivity, and only for girls. The discussion focuses on the potentially important role of caregiving in the long-term calibration of the stress system and the need to better understand the social and biological mechanisms shaping the stress response across development in low and middle income countries

The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity

The oxytocin receptor gene (OXTR) is of interest when investigating the effects of early adversity on DNA methylation. However, there is heterogeneity regarding the selection of the most promising CpG sites to target for analyses. The goal of this study was to determine functionally relevant clusters of CpG sites within the OXTR CpG island in 113 mother-infant dyads, with 58 of the mothers reporting childhood maltreatment (CM). OXTR DNA methylation was analyzed in peripheral/umbilical blood mononuclear cells. Different complexity reduction approaches were used to reduce the 188 CpG sites into clusters of co-methylated sites. Furthermore, associations between OXTR DNA methylation (cluster- and site-specific level) and OXTR gene expression and CM were investigated in mothers. Results showed that, first, CpG sections differed strongly regarding their statistical utility for research of individual differences in DNA methylation. Second, cluster analyses and Partial Least Squares (PLS) suggested two clusters consisting of intron1/exon2 and the protein-coding region of exon3, respectively, as most strongly associated with outcome measures. Third, cross-validated PLS regression explained 7% of variance in CM, with low cross-validated variance explained for the prediction of gene expression. Fourth, substantial mother-child correspondence was observed in correlation patterns within the identified clusters, but only modest correspondence outside these clusters. This study makes an important contribution to the mapping of the DNA methylation landscape of the OXTR CpG island by highlighting clusters of CpG sites that show desirable statistical properties and predictive value. We provide a Companion Web Application to facilitate the choice of CpG sites

Diverse physical growth trajectories in institutionalized portuguese children below age 3: relation to child, family, and institutional factors

The authors would like to thank the students involved in the data collection and coding, and especially the children, caregivers, and other institutional staff who participated in the study. Funding from Fundação para a Ciência e Tecnologia.Objective: To identify and analyze diverse longitudinal trajectories of physical growth of institutionalized children and their relation to child, family, and institutional factors. Methods: 49 institutionalized children were studied for 9 months after admission. Weight, height, and head circumference were measured on 4 occasions, beginning at admission. Data were analyzed using latent class analysis, yielding diverse patterns of growth for each feature, and relations with child characteristics, early family risk factors, and institutional relational care were investigated. Results: For each growth feature, 4 classes emerged: ‘‘Persistently Low,’’ ‘‘Improving,’’ ‘‘Deteriorating,’’ and ‘‘Persistently High.’’ Younger age at admission was a risk factor for impaired physical growth across all domains. Physical characteristics at birth were associated with trajectories across all domains. Lower prenatal risk and better institutional relational care were associated with Improving weight over time. Conclusions: Discussion highlights the role of children’s physical features at birth, prenatal risk, and caregiver’s cooperation with the child in explaining differential trajectories.This research was supported in part by grant 13/06 from Fundação BIAL and by grant PTDC/PSI-PCL/101506/2008 from Fundação para a Ciência e Tecnologia

Genetics of callous-unemotional behavior in children

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU

Epigenetic and Genetic Factors Predict Women's Salivary Cortisol following a Threat to the Social Self

10.1371/journal.pone.0048597PLoS ONE711

The relationship of serum and salivary cortisol levels to male sexual dysfunction as measured by the International Index of Erectile Function

To evaluate the biomarkers of sexual function, we investigated the relationship between questionnaire responses and biological hormones such as testosterone (T) and cortisol (F) in serum and saliva. The study population included 105 men aged 30–72 years (mean: 49±4.5, median: 49). Levels of all serum hormones (Total-T, Free-T, Bioavailable-T, Total-F and Bioavailable-F) and salivary hormones (Saliva-T and Saliva-F) were measured directly by liquid chromatography/tandem mass spectrometry. The International Index of Erectile Function (IIEF) was used as a questionnaire to evaluate sexual dysfunction. Free-T and Bioavailable-T showed significant inverse correlations with age (P<0.01). In the group not taking antidepressants, the levels of Bioavailable-F and Saliva-F showed significant inverse correlations with a portion of the IIEF score (P<0.05). However, reductions in Bioavailable-T and Saliva-T showed no association with the IIEF score. In the group taking antidepressants, these hormone levels showed no correlation with IIEF

C. elegans rrf-1 Mutations Maintain RNAi Efficiency in the Soma in Addition to the Germline

Gene inactivation through RNA interference (RNAi) has proven to be a valuable tool for studying gene function in C. elegans. When combined with tissue-specific gene inactivation methods, RNAi has the potential to shed light on the function of a gene in distinct tissues. In this study we characterized C. elegans rrf-1 mutants to determine their ability to process RNAi in various tissues. These mutants have been widely used in RNAi studies to assess the function of genes specifically in the C. elegans germline. Upon closer analysis, we found that two rrf-1 mutants carrying different loss-of-function alleles were capable of processing RNAi targeting several somatically expressed genes. Specifically, we observed that the intestine was able to process RNAi triggers efficiently, whereas cells in the hypodermis showed partial susceptibility to RNAi in rrf-1 mutants. Other somatic tissues in rrf-1 mutants, such as the muscles and the somatic gonad, appeared resistant to RNAi. In addition to these observations, we found that the rrf-1(pk1417) mutation induced the expression of several transgenic arrays, including the FOXO transcription factor DAF-16. Unexpectedly, rrf-1(pk1417) mutants showed increased endogenous expression of the DAF-16 target gene sod-3; however, the lifespan and thermo-tolerance of rrf-1(pk1417) mutants were similar to those of wild-type animals. In sum, these data show that rrf-1 mutants display several phenotypes not previously appreciated, including broader tissue-specific RNAi-processing capabilities, and our results underscore the need for careful characterization of tissue-specific RNAi tools