Exposure to early life adversity is associated with chronic stress and a range of stress-related health problems in adulthood. Since chronic stress debilitates activity in the prefrontal cortex ...(pFC), maladaptive regulatory strategies in response to stress have been proposed as one explanation for the impact of early life adversity on health outcomes in adulthood. We conducted a study to examine the impact of adverse childhood experiences (ACEs) on cognitive flexibility, a key executive function implicated in activity in the pFC, in a sample of adults (N = 486). Additionally, we investigated whether perceptions of chronic stress in adulthood would mediate the influence of ACEs on cognitive flexibility. However, stress is a subjective experience, and emotion regulation strategies can attenuate the stress response. So, we also examined if individual differences in emotion regulation strategies would modulate the relationship between ACEs and chronic stress. Our results demonstrate that early life adversity, as characterized by ACEs, is associated with decreased cognitive flexibility in adulthood. Additionally, number of ACEs was positively correlated with perceived stress, which in turn was negatively correlated with cognitive flexibility. But, individual differences in the habitual use of emotion regulation strategies moderated the influence of ACEs on chronic stress. Specifically, habitual use of cognitive reappraisal attenuated the stress levels whereas habitual use of expressive suppression exacerbated stress levels. Overall, our study highlights the importance of examining emotion regulation in individuals who have experienced early life adversity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Converging empirical evidence indicates that exposure to adversity in childhood is associated with increased vulnerability to mental health problems in adulthood. As early life adversity has the ...potential to alter an individual's appraisal of threat, we hypothesized that individuals exposed to adversity in childhood may also exhibit increased threat from environmental stressors, which in turn may impact their state anxiety levels. We examined the relations between adverse childhood experiences, assessed using the Adverse Childhood Experiences Scale (ACEs), perceived threat from COVID-19, and state anxiety in a sample of adults. Additionally, flexibility is implicated in adaptive coping with life's stressors so we also assessed participants' cognitive flexibility. Parallel mediation regression analyses revealed that both perceived threat from COVID-19 and flexibility in the appraisal of challenges mediated the influence of maltreatment, but not household dysfunction, on state anxiety. Our data indicate that experience with early life adversity in the form of maltreatment is associated with increased perceived threat from COVID-19, which results in higher anxiety levels for the individual. In contrast, childhood maltreatment is associated with reduced flexibility in appraising challenges, which in turn mediates the relationship between maltreatment and anxiety. The findings of this study adds to the limited literature on the impact of early life adversity on cognitive flexibility and highlights the psychological toll of COVID-19 on individuals who have been exposed to adverse childhood experiences.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Executive functions are cognitive processes that facilitate goal-directed behavior by enabling us to direct and control our thoughts. Cognitive flexibility is an executive function characterized by ...the ability to mentally shift between rules, strategies, or tasks. Several studies have reported that acute (brief) stress impairs cognitive flexibility. Even though an individual's perception of their chronic stress levels is shown to influence effects of future stressors, the interactive effect of acute and perceived chronic stress on cognitive flexibility is not known. We conducted two experiments to address this gap. In both studies, perceived chronic stress was measured using the Perceived Stress Scale. Acute stress was induced using the Cold Pressor Test. Number of perseverative errors on the Wisconsin Card Sorting Test was used as an indicator of cognitive flexibility. In Study 2, we also measured salivary alpha amylase as a marker of the physiological stress response. Data from our two studies are consistent with the hypothesis that an individual's perception of their chronic stress level may impact the effect of acute stress on perseveration. In Study 1, we observed a significant interaction between acute and perceived chronic stress on perseverative errors, such that only individuals who reported high levels of perceived chronic stress prior to acute stress exposure showed no change in perseveration following the acute stress manipulation. This effect did not differ based on participant sex. In Study 2, we found a similar interaction effect of acute and perceived chronic stress on perseverative errors in an all-woman sample. After identifying salivary alpha amylase responders and non-responders, we observed a strong, negative correlation between perceived chronic stress and perseverative errors amongst the responders only. Our data highlight the value in studying salivary alpha amylase in response to acute stress exposure. Additionally, perceived chronic stress emerged as a key variable in the relationship between acute stress and cognitive flexibility. Overall, our work suggests that future research interested in interrogating moderators in the relationship between acute stress and cognition would benefit from inclusion of measures of chronic stress.
The prefrontal cortex is sensitive to stress experiences and significantly impacted by early life adversity. Cognitive flexibility is an executive function that is associated with positive outcomes ...in adulthood and implicated in activity in the prefrontal cortex. The relationship between early life adversity and cognitive flexibility is underreported. Using the cumulative risk model, we conducted two studies to examine the association between early life adversity and cognitive flexibility in college students and adults (cumulative N = 510). Exposure to early life adversity was assessed using the adverse childhood experiences scale (ACEs). Cognitive flexibility was assessed using the Wisconsin Card Sorting Test (WCST). Additionally, as perceived chronic stress is associated with impaired prefrontal cortex function, we measured that as well. Higher number of ACEs was correlated with lower number of completed categories on the WCST in both college students and adults. Perceived chronic stress was not associated with cognitive flexibility, but did correlate positively with ACEs. Individuals with a higher number of ACEs were also more likely to report higher levels of perceived chronic stress. Hierarchical regression analyses indicated that exposure to adverse childhood experiences predicted lower scores on completed categories. Our findings provide further evidence that individuals with early life adversity exhibit reduced cognitive flexibility in adulthood.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent research has demonstrated that heightened motivational levels promote enhanced attention capabilities. However, the relation between attentional systems and the trait-based ability to sustain ...a motivational state long-term is less understood. Grit refers to one's ability and willingness to pursue long-term goals despite setbacks. This report presents the results of two studies conducted to examine the relation between facets of Grit-Consistency and Perseverance and attention networks, assessed using the Attention Network Test (ANT). Across both studies Grit-Perseverance was related to performance on the ANT. In Study 1, Grit-Perseverance was negatively related to alerting indicating that individuals who were high on Perseverance were more likely to show a smaller alerting effect. In particular, Grit-Perseverance was negatively correlated with reaction times in the no cue trials. In Study 2, we assessed ERP components associated with attention networks. Individuals with higher scores on Grit-Perseverance were more likely to demonstrate smaller mean difference in N1 amplitudes for double cue relative to no cue trials, suggesting an attenuated
. Our findings indicate that individuals high on Grit-Perseverance may have enhanced sustained attention. Specifically individuals with high Grit-Perseverance appear to exhibit a more efficient alerting system in the no cue trials. Implications of high levels of Grit on cognitive performance are discussed.
Polycyclic aromatic hydrocarbons (PAH) are carcinogenic, neurotoxic environmental pollutants generated during incomplete combustion of fossil fuel and other organic material. PAH exposure has been ...associated with adverse fetal development and epigenetic alterations in cord blood. Several molecular epidemiology studies have established PAH-DNA adducts as biomarkers of PAH exposure.
We investigated the relationship between LINE1 DNA methylation and PAH-DNA adduct levels in cord blood, and with neurodevelopmental outcomes.
In Tongliang County, China, the current study enrolled two population-based cohorts of nonsmoking pregnant women before (2002) and after (2005) the closure of a local coal-fired power plant in May 2004. We analyzed cord blood samples collected from mothers in the two cohorts (n=110 from 2002 cohort and n=107 from 2005 cohort) for PAH-DNA adducts and genomic LINE1 DNA methylation. Neurodevelopmental data on children were collected using the Gesell Developmental Scales (GDS) at age 2 and using the Wechsler Intelligence Scale for Children (WISC) at age 5.
A significant inverse relationship was observed between PAH-DNA adducts and LINE1 DNA methylation (β=−0.010, p<0.038). A significant, positive association between LINE1 methylation and scores on WISC full scale and verbal (β=85.31, p<0.005; β=94.36, p<0.003) but not on the GDS. Mediation analysis did not find LINE1 to be a direct mediator between PAH-DNA adducts and IQ score.
LINE1 methylation in cord blood DNA was a positive predictor of IQ at age 5 and was decreased at higher levels of prenatal PAH exposure measured by PAH-DNA adducts in cord blood. However, the adverse effects of prenatal exposure to PAH on IQ scores did not appear to be directly mediated by altered LINE1 methylation.
•PAH-DNA adducts are an integrated index of biologically effective dose of PAH exposure.•LINE1 methylation was inversely associated with PAH-DNA adduct level.•LINE1 methylation could predict IQ scores at age 5.
Cognitive processes that afford us the ability to control thoughts and achieve goal-directed behavior are known as executive functions. Empirical evidence in the past few years has demonstrated that ...executive functions can be influenced by acute stress. The impact of acute stress on cognitive flexibility, a key aspect of executive functions, has received little attention in the literature. We present the results of two experiments conducted to examine the effect of acute stress on cognitive flexibility. Acute stress was induced using the cold pressor task. Cognitive flexibility was assessed using the Wisconsin Card Sorting Test (WCST). Across both experiments acute stress had an attenuating effect on task switching on the WCST. Our findings also indicate that this effect was moderated by the participant's gender. In Study 1, we observed that following stress exposure male participants in the stress condition made more perseverative errors than participants in the control group. In Study 2, we examined the bilateral hemodynamics in the prefrontal cortex (PFC) during acute stress induction using functional near infrared spectroscopy (fNIRS). Our analysis indicated that functional oxyHb signals fluctuated with greater amplitude than systemic components for participants in the stress group relative to those in the control group. In addition, oxyHb levels post stress induction were correlated with performance on the WCST for the male participants in the stress group only. Concordant with previous reports, our findings indicate that acute stress impacts cognitive flexibility in males and females differentially. Our work also demonstrates the feasibility of using fNIRS as a practical and objective technique for the examination of hemodynamics in the PFC during acute stress.
Ocular retinoblastoma malignancies, which develop into metastatic phenotypes, result in poor prognosis and survival for infant and child patients. To improve the prognosis of metastatic ...retinoblastoma, it is important to identify novel compounds with less toxic side effects and higher therapeutic efficacy compared to existing chemotherapeutics. Piperlongumine (PL), a neuroprotective, plant-derived compound has been explored for its anticancer activities both in vitro and in vivo. Here, we analyze the potential efficacy of PL for metastatic retinoblastoma cell treatment. Our data reveal that PL treatment significantly inhibits cell proliferation in metastatic retinoblastoma Y79 cells compared to the commonly used retinoblastoma chemotherapeutic drugs carboplatin, etoposide, and vincristine. PL treatment also significantly increases cell death compared to treatment with other chemotherapeutic drugs. PL-induced cell-death signaling was associated with significantly higher caspase 3/7 activities and greater loss of mitochondrial membrane potential. PL was also internalized into Y79 cells with an estimated concentration of 0.310pM and expression analysis revealed reduced MYCN oncogene levels. We next examined extracellular vesicles derived from PL-treated Y79 cells. Extracellular vesicles in other cancers are pro-oncogenic, mediating systemic toxicities via the encapsulation of chemotherapeutic drugs. Within metastatic Y79 EV samples, an estimated PL concentration of 0.026pM was detected. PL treatment significantly downregulated Y79 EV cargo of the oncogene MYCN transcript. Interestingly, non-PL-treated Y79 cells incubated with EVs from PL-treated cells exhibited significantly reduced cell growth. These findings indicate that in metastatic Y79 cells, PL exhibits potent anti-proliferation effects and oncogene downregulation. Importantly, PL is also incorporated into extracellular vesicles released from treated metastatic cells with measurable anti-cancer effects on target cells at a distance from the site of primary treatment. The use of PL in the treatment of metastatic retinoblastoma may reduce primary tumor proliferation and inhibit metastatic cancer activity systemically via extracellular vesicle circulation.
Display omitted
•Piperlongumine (PL) decreases chemoresistant metastatic retinoblastoma (RB) MYCN expression and cell proliferation.•PL increases cell death, caspase 3/7 activities, and loss of mitochondrial membrane potential in chemoresistant RB cells.•RB cells internalize and carry PL in extracellular vesicles that decrease MYCN and cell proliferation in recipient cells.•The use of PL in RB treatment may inhibit metastatic cancer activity systemically via extracellular vesicle circulation.
Introduction
We investigated metabolites in plasma to capture systemic biochemical changes associated with Alzheimer's disease (AD).
Methods
Metabolites in plasma were measured in 59 AD cases and 60 ...healthy participants of African American (AA), Caribbean Hispanic (CH), and non‐Hispanic white (NHW) ancestry using untargeted liquid‐chromatography–based ultra‐high‐resolution mass spectrometry. Metabolite differences between AD and healthy, ethnic groups and apolipoprotein E gene (APOE) ε4 status were analyzed. Untargeted network analysis identified pathways enriched in AD‐associated metabolites.
Results
A total of 5929 annotated metabolites were measured. Partial least squares discriminant analysis (PLS‐DA) inferred that AD clustered separately from healthy controls (area under the curve AUC = 0.9816); discriminating pathways included glycerophospholipid, sphingolipid, and non‐essential amino acid (alanine, aspartate, glutamate) metabolism. Metabolic features in AA clustered differently from CH and NHW (AUC = 0.9275), and differed between APOE ε4 carriers and non‐carriers (AUC = 0.9972).
Discussion
Metabolites, specifically lipids, were associated with AD, APOE ε4, and ethnic group. Metabolite profiling can identify perturbed AD pathways, but genetic and ancestral background need to be considered.
PDF
