Biological Aging in Childhood and Adolescence Following Experiences of Threat and Deprivation: A Systematic Review and Meta-Analysis

Life history theory argues that exposure to early life adversity (ELA) accelerates development, although existing evidence for this varies. We present a meta-analysis and systematic review testing the hypothesis that ELA involving threat (e.g., violence exposure) will be associated with accelerated biological aging across multiple metrics, whereas exposure to deprivation (e.g., neglect, institutional rearing) and low-socioeconomic status (SES) will not. We meta-analyze 54 studies (n = 116,010) examining associations of ELA with pubertal timing and cellular aging (telomere length and DNA methylation age), systematically review 25 studies (n = 3,253) examining ELA and neural markers of accelerated development (cortical thickness and amygdala-prefrontal cortex functional connectivity) and evaluate whether associations of ELA with biological aging vary according to the nature of adversity experienced. ELA overall was associated with accelerated pubertal timing (d =-0.10) and cellular aging (d =-0.21), but these associations varied by adversity type. Moderator analysis revealed that ELA characterized by threat was associated with accelerated pubertal development (d 0.26) and accelerated cellular aging (d =-0.43), but deprivation and SES were unrelated to accelerated development. Systematic review revealed associations between ELA and accelerated cortical thinning, with threatrelated ELA consistently associated with thinning in ventromedial prefrontal cortex, and deprivation and SES associated with thinning in frontoparietal, default, and visual networks. There was no consistent association of ELA with amygdala-PFC connectivity. These findings suggest specificity in the types of early environmental experiences associated with accelerated biological aging and highlight the importance of evaluating how accelerated aging contributes to health disparities and whether this process can be mitigated through early intervention

Neural Aspects of Inhibition Following Emotional Primes in Depressed Adolescents.

Adults diagnosed with major depressive disorder (MDD) have been found to be characterized by selective attention to negative material and by impairments in their ability to disengage from, or inhibit the processing of, negative stimuli. Altered functioning in the frontal executive control network has been posited to underlie these deficits in cognitive functioning. We know little, however, about the neural underpinnings of inhibitory difficulties in depressed adolescents. We used functional magnetic resonance imaging in 18 adolescents diagnosed with MDD and 15 age- and gender-matched healthy controls (CTLs) while they performed a modified affective Go/No-Go task that was designed to measure inhibitory control in the presence of an emotional distractor. Participants were presented with either a happy or a sad face, followed by a go or a no-go target to which they either made or inhibited a motor response. A group (MDD, CTL) by valence (happy, sad) by condition (go, no-go) analysis of variance indicated that MDD adolescents showed attenuated BOLD response in the right dorsolateral prefrontal cortex (DLPFC) and in the occipital cortex bilaterally, to no-go targets that followed a sad, but not a happy, face. Adolescents diagnosed with MDD showed anomalous recruitment of prefrontal control regions during inhibition trials, suggesting depression-associated disruption in neural underpinnings of the inhibition of emotional distractors. Given that the DLPFC is associated with the maintenance of goal-relevant information, it is likely that sad faces differentially capture attention in adolescents with MDD and interfere with task demands requiring inhibition

White-Matter Tract Connecting Anterior Insula to Nucleus Accumbens Predicts Greater Future Motivation in Adolescents

The motivation to approach or avoid incentives can change during adolescence. Advances in neuroimaging allow researchers to characterize specific brain circuits that underlie these developmental changes. Whereas activity in the nucleus accumbens (NAcc) can predict approach toward incentive gain, activity in anterior insula (AIns) is associated with avoidance of incentive loss. Recent research characterized the structural white-matter tract connecting the two brain regions, but the tract has neither been characterized in adolescence nor linked to functional activity during incentive anticipation. In this study, we collected diffusion MRI and characterized the tract connecting the AIns to the NAcc for the first time in early adolescents. We then measured NAcc functional activity during a monetary incentive delay task and found that structural coherence of the AIns-NAcc tract is correlated with decreased functional activity at the NAcc terminal of the tract during anticipation of no incentives. In adolescents who completed an assessment 2 years later, we found that AIns-NAcc tract coherence could predict greater future self-reported motivation, and that NAcc functional activity could statistically mediate this association. Together, the findings establish links from brain structure to function to future motivation and provide targets to study the reciprocal development of brain structure and function

How age, sex and genotype shape the stress response

Exposure to chronic stress is a leading pre-disposing factor for several neuropsychiatric disorders as it often leads to maladaptive responses. The response to stressful events is heterogeneous, underpinning a wide spectrum of distinct changes amongst stress-exposed individuals'. Several factors can underlie a different perception to stressors and the setting of distinct coping strategies that will lead to individual differences on the susceptibility/resistance to stress. Beyond the factors related to the stressor itself, such as intensity, duration or predictability, there are factors intrinsic to the individuals that are relevant to shape the stress response, such as age, sex and genetics. In this review, we examine the contribution of such intrinsic factors to the modulation of the stress response based on experimental rodent models of response to stress and discuss to what extent that knowledge can be potentially translated to humans.FEDER through the Operational Programme Competitiveness Factors - COMPETE and National Funds through FCT - Foundation for Science and Technology under the project POCI-01-0145-FEDER-007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE, 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). We acknowledge the Portuguese Foundation for Science and Technology (FCT) for providing a post-doctoral fellowship to SR (SFRH/BPD/72710/2010), a doctoral fellowship to SM (SFRH/BD/69311/2010) and a fellowship to AN (ANR/NEU-OSD/0258/2012)info:eu-repo/semantics/publishedVersio

Figurative language processing in atypical populations: the ASD perspective

This document is protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permissionThis paper is intended to provide a critical overview of experimental and clinical research documenting problems in figurative language processing in atypical populations with a focus on the Autistic Spectrum. Research in the comprehension and processing of figurative language in autism invariably documents problems in this area. The greater paradox is that even at the higher end of the spectrum or in the cases of linguistically talented individuals with Asperger syndrome, where structural language competence is intact, problems with extended language persist. If we assume that figurative and extended uses of language essentially depend on the perception and processing of more concrete core concepts and phenomena, the commonly observed failure in atypical populations to understand figurative language remains a puzzle. Various accounts have been offered to explain this issue, ranging from linking potential failure directly to overall structural language competence (Norbury, 2005; Brock et al., 2008) to right-hemispheric involvement (Gold and Faust, 2010). We argue that the dissociation between structural language and figurative language competence in autism should be sought in more general cognitive mechanisms and traits in the autistic phenotype (e.g., in terms of weak central coherence, Vulchanova et al., 2012b), as well as failure at on-line semantic integration with increased complexity and diversity of the stimuli (Coulson and Van Petten, 2002). This perspective is even more compelling in light of similar problems in a number of conditions, including both acquired (e.g., Aphasia) and developmental disorders (Williams Syndrome). This dissociation argues against a simple continuity view of language interpretation

Exposure to Violence as an Environmental Pathway Linking Low Socioeconomic Status with Altered Neural Processing of Threat and Adolescent Psychopathology

Low childhood socioeconomic status (SES) is associated with increased risk for psychopathology, in part because of heightened exposure to environmental adversity. Adverse experiences can be characterized along dimensions, including threat and deprivation, that contribute to psychopathology via distinct mechanisms. The current study investigated a neural mechanism through which threat and deprivation may contribute to socioeconomic disparities in psychopathology. Participants were 177 youths (83 girls) aged 10–13 years recruited from a cohort followed since the age of 3 years. SES was assessed using the income-to-needs ratio at the age of 3 years. At the age of 10–13 years, retrospective and current exposure to adverse experiences and symptoms of psychopathology were assessed. At this same time point, participants also com-pleted a face processing task (passive viewing of fearful and neutral faces) during an fMRI scan. Lower childhood SES was associated with greater exposure to threat and deprivation experiences. Both threat and deprivation were associated with higher depression symptoms, whereas threat experiences were uniquely linked to posttraumatic stress disorder symp-toms. Greater exposure to threat, but not deprivation, was associated with higher activation in dorsomedial pFC to fearful compared with neutral faces. The dorsomedial pFC is a hub of the default mode network thought to be involved in internally directed attention and cognition. Experiences of threat, but not deprivation, are associated with greater engagement of this region in response to threat cues. Threat-related adversity contributes to socioeconomic disparities in adolescent psychopathology through distinct mechanisms from deprivation

Mechanism of gallic acid biosynthesis in bacteria (Escherichia coli) and walnut (Juglans regia)

Gallic acid (GA), a key intermediate in the synthesis of plant hydrolysable tannins, is also a primary anti-inflammatory, cardio-protective agent found in wine, tea, and cocoa. In this publication, we reveal the identity of a gene and encoded protein essential for GA synthesis. Although it has long been recognized that plants, bacteria, and fungi synthesize and accumulate GA, the pathway leading to its synthesis was largely unknown. Here we provide evidence that shikimate dehydrogenase (SDH), a shikimate pathway enzyme essential for aromatic amino acid synthesis, is also required for GA production. Escherichia coli (E. coli) aroE mutants lacking a functional SDH can be complemented with the plant enzyme such that they grew on media lacking aromatic amino acids and produced GA in vitro. Transgenic Nicotianatabacum lines expressing a Juglans regia SDH exhibited a 500% increase in GA accumulation. The J. regia and E. coli SDH was purified via overexpression in E. coli and used to measure substrate and cofactor kinetics, following reduction of NADP+ to NADPH. Reversed-phase liquid chromatography coupled to electrospray mass spectrometry (RP-LC/ESI–MS) was used to quantify and validate GA production through dehydrogenation of 3-dehydroshikimate (3-DHS) by purified E. coli and J. regia SDH when shikimic acid (SA) or 3-DHS were used as substrates and NADP+ as cofactor. Finally, we show that purified E. coli and J. regia SDH produced GA in vitro

Validating a self-report measure of student athletes’ perceived 2 stress reactivity: Associations with heart-rate variability and 3 stress appraisals

Student athletes experience multiple stressors relating to both their sporting and academic 25 commitments. Individual differences play a significant role in how well student athletes cope 26 with the demands they face. When assessing individual differences in stress reactivity, there 27 are a lack of valid alternatives to costly and time-consuming lab-based physiological methods 28 (e.g. cortisol sampling, cardiac variables). This paper aims to further validate a self-report 29 measure of adolescent athletes’ individual differences in perceived stress reactivity, by 30 comparing to a psycho-physiological measure of emotion regulation (heart-rate variability) 31 assessed during a socially evaluated cold pressor test. 30 student athletes and 31 student non-32 athletes completed a measure of perceived stress reactivity and took part in the socially 33 evaluated cold pressor test while their heart-rate variability was assessed, along with their 34 self-reported appraisals of stress, pain, and unpleasantness experienced during the procedure. 35 Controlling for gender and athleticism, individual differences in perceived stress reactivity 36 showed no associations with tonic or phasic levels of heart-rate variability. However, 37 perceived stress reactivity was associated with levels of self-reported stress, pain, and 38 unpleasantness experienced during the socially evaluated cold pressor test. These findings 39 therefore suggest that perceived stress reactivity is associated with cognitive responses to 40 stress (i.e. stress appraisals). However, further research is needed to confirm its relationship 41 with physiological measures and responses. This further adds to the understanding of 42 perceived stress reactivity, and validity of the perceived stress reactivity scale for adolescent 43 athletes