Socioeconomic status in early adolescence predicts blunted stress responses in adulthood.

Individuals who grow up in families with lower socioeconomic status (SES) tend to experience disproportionate rates of chronic stress. The "freeze" response, characterized by blunted cardiovascular reactivity and reduced engagement with the environment, is associated with chronic stress and may be utilized when an individual is unable to escape or overcome environmental stressors. Using a diverse community sample of 184 adolescents followed from the age of 13 to 29 years, along with their friends and romantic partners, this study examined links between family SES and stress responses in adulthood. Low family SES at the age of 13 years directly predicted blunted heart rate responding and fewer attempts to answer math problems during a modified version of the Trier Social Stress Task at the age of 29 years. Indirect effects were found from low family SES to blunted respiratory sinus arrhythmia responding and the number of words spoken during a speech task. SES at the age of 29 years mediated many of these relations. Findings held after accounting for a number of potential confounds, including adolescent academic and attachment functioning and body mass index. We interpret these findings as evidence that low familial SES may predict freezing-type responses in adulthood.

OXTR DNA methylation moderates the developmental calibration of neural reward sensitivity.

The Adaptive Calibration Model of Stress Responsivity (ACM) suggests that developmental experiences predictably tune biological systems to meet the demands of the environment. Particularly important is the calibration of reward systems. Using a longitudinal sample (N = 184) followed since adolescence, this study models the dimensions of early life stress and their effects on epigenetic modification of the oxytocin receptor gene (OXTR) and individual differences in neural response to reward anticipation. We first created a latent variable model of developmental context using measures collected when participants were 13 years old. As adults, two subsets of participants completed a reward anticipation fMRI paradigm (N = 82) and agreed to have their blood assayed for (OXTR) DNA methylation (N = 112) at two CpG sites. Three latent constructs of developmental context emerged: Neighborhood Harshness, Family Harshness, and Abuse and Disorder. Greater OXTR DNA methylation at CpG sites -924 and -934 blunted the association between greater Neighborhood Harshness and increased neural activation in caudate in anticipation of rewards. Interaction effects were also found outside of reward-related areas for all three latent constructs. Results indicate an epigenetically derived differential susceptibility model whereby high methylation coincides with decreased association between developmental environment and neural reward anticipation.

A low-rank multivariate general linear model for multi-subject fMRI data and a non-convex optimization algorithm for brain response comparison.

The focus of this paper is on evaluating brain responses to different stimuli and identifying brain regions with different responses using multi-subject, stimulus-evoked functional magnetic resonance imaging (fMRI) data. To jointly model many brain voxels' responses to designed stimuli, we present a new low-rank multivariate general linear model (LRMGLM) for stimulus-evoked fMRI data. The new model not only is flexible to characterize variation in hemodynamic response functions (HRFs) across different regions and stimulus types, but also enables information "borrowing" across voxels and uses much fewer parameters than typical nonparametric models for HRFs. To estimate the proposed LRMGLM, we introduce a new penalized optimization function, which leads to temporally and spatially smooth HRF estimates. We develop an efficient optimization algorithm to minimize the optimization function and identify the voxels with different responses to stimuli. We show that the proposed method can outperform several existing voxel-wise methods by achieving both high sensitivity and specificity. We apply the proposed method to the fMRI data collected in an emotion study, and identify anterior dACC to have different responses to a designed threat and control stimuli.

A semi-parametric nonlinear model for event-related fMRI.

Nonlinearity in evoked hemodynamic responses often presents in event-related fMRI studies. Volterra series, a higher-order extension of linear convolution, has been used in the literature to construct a nonlinear characterization of hemodynamic responses. Estimation of the Volterra kernel coefficients in these models is usually challenging due to the large number of parameters. We propose a new semi-parametric model based on Volterra series for the hemodynamic responses that greatly reduces the number of parameters and enables "information borrowing" among subjects. This model assumes that in the same brain region and under the same stimulus, the hemodynamic responses across subjects share a common but unknown functional shape that can differ in magnitude, latency and degree of interaction. We develop a computationally-efficient strategy based on splines to estimate the model parameters, and a hypothesis test on nonlinearity. The proposed method is compared with several existing methods via extensive simulations, and is applied to a real event-related fMRI study.

Yielding to social presence as a bioenergetic strategy.

All life must strategically conserve and allocate resources in order to meet the challenges of living. Social Baseline Theory suggests that, for humans, social context and the social resources therein are a central ecology in human phylogeny. In ontogeny, this manifests in flexible bioenergetic strategies that vary in the population based on social history. We introduce yielding, a conservation process wherein we relax physiological investment in response to a challenge when in the presence of a relational partner. The availability of these conserved resources then impact response to subsequent challenges while alone and if this pattern is habitual, it can reciprocally influence strategies used to solve or cope with typical stress. We discuss neural targets of this resource conservation and reframe our lab's previous studies on the social regulation of neural threat responding within this framework. We then show functional magnetic resonance imaging (fMRI) data indicating the presence of relational partners decreases blood-oxygen-level-dependent (BOLD) response to threat in key targets of resource conservation (e.g, dlPFC, dACC, and insula) and that stronger signal reduction in these areas coincide with less BOLD in pre-frontal (vmPFC, dlPFC) and visuo-sensory integration (occipital cortex, precuneus, superior parietal lobule) regions during ostracism. Finally, we show that these neural relationships are associated with less use of self-regulation-based coping strategies two years post scanning. Taken together, we show the utility of yielding both as a concept and as a bioenergetic process which helps to conserve energy in this social primate.

Oxytocin receptor genotype and low economic privilege reverses ventral striatum-social anxiety association.

Oxytocin receptor gene (OXTR) polymorphisms, lower ventral striatum (VS) response to social stimuli, and lower economic privilege have been independently associated with depression and anxiety. However, the interactions between these risk factors are unknown. One hundred and fifty-seven healthy adult participants genotyped for OXTR rs237915 completed a common emotion-matching task during functional magnetic resonance imaging. Past economic privilege and depression and anxiety symptoms were concurrently assessed through validated self-report measures. The data revealed an interaction between rs237915 genotype and economic privilege on the neural response to negative faces. C-carriers showed decreased VS activation and increased connectivity between the VS and ventromedial prefrontal cortex with increased economic privilege. TT homozygotes showed the reverse pattern. Low VS response to negative faces predicted increased social anxiety, but only for those with either lower economic privilege or the C allele. For those with both, low VS response was associated with paradoxically lower social anxiety. Findings suggest that economic privilege and OXTR rs237915 genotype may calibrate social motivational neural systems for better or worse. While lower VS response to negative faces may generally constitute a risk factor for social anxiety, lower response to social cues may be a benefit for those with dual risk.

Relationship status and perceived support in the social regulation of neural responses to threat.

Strong social ties correspond with better health and well being, but the neural mechanisms linking social contact to health remain speculative. This study extends work on the social regulation of brain activity by supportive handholding in 110 participants (51 female) of diverse racial and socioeconomic origins. In addition to main effects of social regulation by handholding, we assessed the moderating effects of both perceived social support and relationship status (married, cohabiting, dating or platonic friends). Results suggest that, under threat of shock, handholding by familiar relational partners attenuates both subjective distress and activity in a network associated with salience, vigilance and regulatory self-control. Moreover, greater perceived social support corresponded with less brain activity in an extended network associated with similar processes, but only during partner handholding. In contrast, we did not observe any regulatory effects of handholding by strangers, and relationship status did not moderate the regulatory effects of partner handholding. These findings suggest that contact with a familiar relational partner is likely to attenuate subjective distress and a variety of neural responses associated with the presence of threat. This effect is likely enhanced by an individual's expectation of the availability of support from their wider social network.

Lower neighborhood quality in adolescence predicts higher mesolimbic sensitivity to reward anticipation in adulthood.

Life history theory suggests that adult reward sensitivity should be best explained by childhood, but not current, socioeconomic conditions. In this functional magnetic resonance imaging (fMRI) study, 83 participants from a larger longitudinal sample completed the monetary incentive delay (MID) task in adulthood (∼25 years old). Parent-reports of neighborhood quality and parental SES were collected when participants were 13 years of age. Current income level was collected concurrently with scanning. Lower adolescent neighborhood quality, but neither lower current income nor parental SES, was associated with heightened sensitivity to the anticipation of monetary gain in putative mesolimbic reward areas. Lower adolescent neighborhood quality was also associated with heightened sensitivity to the anticipation of monetary loss activation in visuo-motor areas. Lower current income was associated with heightened sensitivity to anticipated loss in occipital areas and the operculum. We tested whether externalizing behaviors in childhood or adulthood could better account for neighborhood quality findings, but they did not. Findings suggest that neighborhood ecology in adolescence is associated with greater neural reward sensitivity in adulthood above the influence of parental SES or current income and not mediated through impulsivity and externalizing behaviors.

Adolescent neighborhood quality predicts adult dACC response to social exclusion.

Neuroimaging studies using the social-exclusion paradigm Cyberball indicate increased dorsal anterior cingulate cortex (dACC) and right insula activity as a function of exclusion. However, comparatively less work has been done on how social status factors may moderate this finding. This study used the Cyberball paradigm with 85 (45 females) socio-economically diverse participants from a larger longitudinal sample. We tested whether neighborhood quality during adolescence would predict subsequent neural responding to social exclusion in young adulthood. Given previous behavioral studies indicating greater social vigilance and negative evaluation as a function of lower status, we expected that lower adolescent neighborhood quality would predict greater dACC activity during exclusion at young adulthood. Our findings indicate that young adults who lived in low-quality neighborhoods in adolescence showed greater dACC activity to social exclusion than those who lived in higher quality neighborhoods. Lower neighborhood quality also predicted greater prefrontal activation in the superior frontal gyrus, dorsal medial prefrontal cortex and the middle frontal gyrus, possibly indicating greater regulatory effort. Finally, this effect was not driven by subsequent ratings of distress during exclusion. In sum, adolescent neighborhood quality appears to potentiate neural responses to social exclusion in young adulthood, effects that are independent of felt distress.