Interindividual Factors Research Articles

Exploring gender differences in pharmacokinetics of central nervous system related medicines based on a systematic review approach.

Due to the inevitable differences in physiological and/or genetic factors between genders, the possibility that differences in pharmacokinetics between genders may occur when exposed to the same dose of the same drug is subject to reasonable inference and suspicion. Nevertheless, a significant number of medicines still rely on empirical usage and uniform clinical application without consideration of inter-individual diversity factors. In particular, in the pharmacokinetic diversity of medicines related to central nervous system (CNS) activity, consideration of gender factors and access to comparative analysis are very limited. The purpose of this study was to conduct an integrated analysis and review of differences in pharmacokinetics between genders that have not been specifically reported to date for medicines related to CNS effects, which are a group of drugs with relatively significant concerns about systemic side effects. This study was accessible through extensive data collection and analyzes using a web-based scientific literature search engine of pharmacokinetic results of CNS-related drugs performed on humans, taking gender into account. As a result, significant differences in pharmacokinetics between genders were identified for many drugs related to CNS. And most of the pharmacokinetic differences between genders suggested a higher in vivo exposure in females. This study suggests that consideration of gender factors cannot be ignored and will be an important point of interest in the precision medicine application of CNS-related medicines.

Probing erythrocytes as sensitive and reliable sensors of metabolic disturbances in the crosstalk between childhood obesity and insulin resistance: findings from an observational study, in vivo challenge tests, and ex vivo incubation assays

BackgroundAlthough insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified.MethodsTo get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis.ResultsChildren with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals’ metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels.ConclusionsThus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms.

Formed in context: A mixed-methods study of medical students' mindsets in an Eastern culture.

Mindsets have become an important focus in the fields of social and cognitive psychology. When holding a growth mindset, people appear more likely to engage in hard work and effort to foster success, seeing setbacks as necessary for learning. When holding a fixed mindset, in contrast, people tend to believe success comes from innate ability, seeing setbacks as evidence of inability. As such, mindsets affect students' learning, resilience and personal development. There is little empirical evidence, however, regarding how medical students perceive mindsets and the fundamental determinants of mindset formation, especially in non-Western contexts. This study investigated medical students' mindsets and perceptions of mindset formation with the aim of broadening the cross-cultural understanding of self-theories. Using a convergent mixed-methods approach at a medical school in China, the authors conducted a survey and four focus groups with medical students in first to third years. Quantitatively, we used the Dweck Mindset Scale to describe medical students' mindsets in the domains of intelligence and talent. Qualitatively, we analysed focus group data using a grounded theory approach to develop a descriptive model. Survey results included 464 responses for quantitative analysis. Multivariable regression found that Year 3 students had more fixed mindsets for intelligence and talent (p< 0.05) compared with Year 1 students. Rural students reported a more mixed mindset for intelligence compared to urban students (p< 0.05). Qualitative analysis of focus group data yielded four major categories: beliefs about mindsets, conceptualization of mindsets, achievement motivation and source of mindset formation. We developed a Mindset Basis Model to depict connections among the factors students perceived to influence mindset formation-intra- and interindividual factors; contextual factors; and micro-, meso- and macro-system factors-and students' motivation regarding achievement. The study describes medical students' mindsets for the domains of intelligence and talent and explores how they conceptualised these mindsets. The findings indicate that factors influencing mindsets do not operate in isolation but through intricate interactions among multilevel factors embedded within a context.

Meta-analysis of variance in tDCS effects on response inhibition

Deficiencies in response inhibition are associated with numerous mental health conditions, warranting innovative treatments. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, modulates cortical excitability and has shown promise in improving response inhibition. However, tDCS effects on response inhibition often yield contradictory findings. Previous research emphasized the importance of inter-individual factors that are mostly ignored in conventional meta-analyses of mean effects. We aimed to fill this gap and promote the complementary use of the coefficient of variation ratio and standardized mean effects. The systematic literature search included single-session and sham-controlled tDCS studies utilizing stop-signal task or Go-NoGo tasks, analyzing 88 effect sizes from 53 studies. Considering the impact of inter-individual factors, we hypothesized that variances increase in the active versus sham tDCS. However, the results showed that variances between both groups did not differ. Additionally, analyzing standardized mean effects supported previous research showing an improvement in the stop-signal task but not in the Go-NoGo task following active tDCS. These findings suggest that inter-individual differences do not increase variances in response inhibition, implying that the heterogeneity cannot be attributed to higher variance in response inhibition during and after active tDCS. Furthermore, methodological considerations are crucial for tDCS efficacy.

Protocol for a Study Investigating Context-Specific Sedentary Behaviors and Cardiometabolic Health in College-Based Young Adults (CONTEXT-SB).

Sedentary behavior (SB) is detrimental to cardiometabolic disease (CMD) risk, which can begin in young adulthood. To devise effective SB-CMD interventions in young adults, it is important to understand which context-specific sedentary behaviors (CS-SB) are most detrimental for CMD risk, the lifestyle behaviors that co-exist with CS-SBs, and the socioecological predictors of CS-SB. This longitudinal observational study will recruit 500 college-aged (18-24 years) individuals. Two laboratory visits will occur, spaced 12 months apart, where a composite CMD risk score (e.g., arterial stiffness, metabolic and inflammatory biomarkers, heart rate variability, and body composition) will be calculated, and questionnaires to measure lifestyle behaviors and different levels of the socioecological model will be administered. After each visit, total SB (activPAL) and CS-SB (television, transportation, academic/ occupational, leisure computer, "other"; ecological momentary assessment) will be measured across seven days. It is hypothesized that certain CS-SB will show stronger associations with CMD risk, compared to T-SB, even after accounting for coexisting lifestyle behaviors. It is expected that a range of intra-individual, inter-individual, and physical environment socioecological factors will predict CS-SB. The findings from this study will support the development of an evidence-based, multi-level intervention to target SB reduction and mitigate CMD risk in CBYA.

Exploring the contribution of inter-individual factors to the development of physiological heat strain in older adults exposed to simulated indoor overheating.

Older adults are at elevated risk of heat-related mortality due to age-associated declines in thermoregulatory and cardiovascular function. However, the inter-individual factors that exacerbate physiological heat strain during heat exposure remain unclear, making it challenging to identify more heat-vulnerable subgroups. We therefore explored factors contributing to inter-individual variability in physiological responses of older adults exposed to simulated hot weather. Thirty-seven older adults (61-80 years, 16 females) rested for 8 h in 31 and 36 °C (45% relative humidity). Core (rectal) temperature, heart rate (HR), HR variability, mean arterial pressure (MAP), and cardiac autonomic responses to standing were measured at baseline and end-exposure. Bootstrapped least absolute shrinkage and selection operator regression was used to evaluate whether variation in these responses was related to type 2 diabetes (T2D, n=10), hypertension (n=18), age, sex, body morphology, habitual physical activity levels, and/or heat-acclimatization. T2D was identified as a predictor of end-exposure HR (with vs. without: 13 beats/min (bootstrap 95% confidence interval: 6, 23)), seated MAP (-7mmHg (-18, 1)), and the systolic pressure response to standing (20mmHg (4, 36)). HR was also influenced by sex (female vs. male: 8 beats/min (1, 16)). No other predictors were identified. The inter-individual factors explored did not meaningfully contribute to the variation in body temperature responses in older adults exposed to simulated indoor overheating. By contrast, cardiovascular responses were exacerbated in females and individuals with T2D. These findings improve understanding of how inter-individual differences contribute to heat-induced physiological strain in older persons.

Association between childhood obesity, trace elements, and heavy metals: Recent discoveries and future perspectives.

Trace elements and heavy metals play pivotal roles in health status by regulating a myriad of vital biological functions. Abnormal metal homeostasis has been linked to a constellation of pathogenic complications, including oxidative stress, inflammatory processes, dyslipidemia, and impaired insulin-mediated metabolism of carbohydrates, thereby increasing the odds of developing childhood obesity and related comorbidities. Herein, we provide a comprehensive revision of recent literature on the association between childhood obesity, trace elements, and heavy metals. Further, we emphasize on the crucial importance of addressing the influence that interindividual variability factors (e.g., sex, age, genetic determinants, concomitance of comorbidities, and environmental factors) may have in modulating the susceptibility to disease development. Altogether, this review article represents a concise guide to better understand the involvement of metals in childhood obesity pathogenesis and discusses future needs with the aim of establishing robust biomarkers in the context of precision medicine.

Cognitive reserve predicts episodic memory enhancement induced by transcranial direct current stimulation in healthy older adults

Episodic memory shows the largest degree of age-related decline. Anodal transcranial Direct Current Stimulation (tDCS) can enhance episodic memory in aging but there is also evidence of response variability even when using identical stimulation parameters. To explore which inter-individual factors (i.e. age, education, encoding performance, cognitive reserve, tDCS group and timing of tDCS application) may directly and/or indirectly modulate verbal memory recall, we used data from our previous tDCS studies that showed enhanced episodic memory recall in 80 healthy older adults. In these studies we used the same paradigm and stimulation parameters but tDCS was applied during different memory stages. Memory recall was tested 48 hours and 30 days after encoding. Univariate regression models showed that tDCS group (Anodal vs. Sham) predicted memory recall, indicating higher scores in the Anodal group than in the Sham group. Encoding performance predicted memory recall in both tDCS groups. Multiple regression models revealed that cognitive reserve, measured with a life experience questionnaire, predicted memory recall only for the Anodal group. Higher cognitive reserve was linked to better memory recall. Accounting for individual differences in cognitive reserve at baseline helps to explain tDCS responsiveness. This knowledge may contribute to optimize its use in older adults.

Mattering and Self-Esteem as Bulwarks Against the Consequences of Financial Strain for Loneliness in Later Life: Differentiating Between- and Within-Person Processes.

Financial strain likely constitutes a principal risk for loneliness in later-life, but a strong sense of mattering and self-esteem may mitigate these consequences by both offsetting and buffering the influence of financial strain. We test these arguments using data from a national longitudinal survey of older adults gathered between 2021 and 2022 (N = 2384), as nations emerged from the COVID-19 pandemic. Application of a within-between modelling strategy facilitates differentiation of inter-individual (i.e., between-person) and intra-individual (i.e., within-person) factors. Between-person financial strain is associated with greater loneliness, but within- and between-person mattering and self-esteem offset this association by forestalling loneliness. Between-person mattering buffers between-person financial strain, but between-person self-esteem buffers within-person financial strain. Consequently, within-person financial strain is associated with greater loneliness only at low levels of between-person self-esteem. In summary, accruing a strong sense of worth contributes to protecting older adults from the adverse consequences of financial strain for loneliness.

WITHIN- AND BETWEEN-PERSON DIFFERENCES IN ACTIVITY FACTOR STRUCTURE: RESULTS FROM AN EMA STUDY

Abstract Analyses of activity participation scales are typically based on single time points and resulting factors focus on differences between participants. However, as real-world activity engagement varies at more micro-timescales, these analyses provide little insight into how activities cluster together within a person across moments or days. Ecological momentary assessment (EMA) studies capture within-person fluctuations in activity engagement and allow us to compare within-person variability to that observed across persons. Using multilevel factor analysis we examined the factor structure of activity participation within-persons (i.e., across days) and between participants. Using tablet-based assessments, 81 adults aged 41 to 94 years (M=61.26, SD=12.12) reported the activities they completed in the past 3-4 hours 5 times per day (4 at semi-randomly scheduled intervals and 1 at bedtime) for 14 days. Multilevel factor analysis simultaneously computed both intra-individual factors (within-person structure of activity in daily life) and inter-individual factors (between-person structure of activity engagement). A solution of 4 within-person and 4 between-person factors provided the best model fit, with three common factors across levels: 1) cognitive (e.g., read, write, computer tasks); 2) social (e.g., events, mentoring, providing care); and 3) passive (e.g., TV, games) factors. There were notable differences in the fourth factor however. Although there are similarities, the factor structure of activity participation between individuals is different than factors describing activity participation within persons from day to day. Researchers should be aware that common between-person activity factors will not unilaterally fit EMA within-person data and should conduct additional preparatory factor analyses.

Evidence for a Negative Loss Spiral between Co-Worker Social Support and Burnout: Can Psychosocial Safety Climate Break the Cycle?

Previous research suggests that co-worker social support predicts burnout, but this relationship may be far more complex, with the potential for a reciprocal cycle of loss. Leading research on loss spirals has explicitly called for more research on interindividual factors such as social support and, by extension, how interventions that operate on these interpersonal resources could play a role in primary and secondary prevention (i.e., intervening in cycles of loss). In this study, we explore the reciprocal relationship between burnout and co-worker social support, with psychosocial safety climate (PSC) as an upstream predictor and moderator of this relationship. Using hierarchical linear modelling (N = 380 frontline healthcare workers, nested within N = 63 teams) on longitudinal data, we found a reciprocal relationship between burnout and co-worker support, which was both triggered and moderated by PSC. These findings provide initial evidence for a social support-burnout loss spiral, wherein individuals with poor co-worker support are more likely to become burnt-out, and in this depleted state they are subsequently less likely to reach out for those social supports when available, which would, in turn, lead to further burnout. This social support-burnout loss spiral is exacerbated when working in a low-PSC context, as the environment does not send positive safety signals about resource scarcity and replenishment. Therefore, PSC may be a potential target for intervention both in primary prevention (i.e., stopping the loss spiral in the first instance) and in secondary intervention, as high PSC signals to workers already in the burnout-support loss cycle when it is safe to reinvest resources or engage in recovery behavior.

How far are we from reliable metabolomics-based biomarkers? The often-overlooked importance of addressing inter-individual variability factors

Metabolomics has proven great potential to unravel the molecular basis of diseases. However, most attempts aimed at identifying reliable metabolomics-based biomarkers for diagnosis, prediction, and prognosis of diseases have repeatedly failed because of inconsistent results and unsatisfactory replication in independent cohorts. This review article explores the possible causes behind this reproducibility crisis, with special focus on the role that inter-individual variability factors play in modulating the susceptibility to disease development. Furthermore, we provide future perspectives on the applicability of metabolomics in biomedical research and its translatability into clinical practice.

Inter-individual exposure variability interpretation through reflection of biological age algorithm in physiologically based toxicokinetic model: Application to human risk assessment of di-isobutyl-phthalate

Age-related changes and interindividual variability in the degree of exposure to hazardous substances in the environment are pertinent factors to be considered in human risk assessment. Existing risk assessments remain in a one-size-fits-all approach, often without due consideration of inter-individual toxicokinetic variability factors, such as age. The purpose of this study was to advance from the existing risk assessment of hazardous substances based on toxicokinetics to a precise human risk assessment by additionally considering the effects of physiologic and metabolic fluctuations and interindividual variability in age. Qualitative age-associated physiologic and metabolic changes in humans, obtained through a meta-analysis, were quantitatively modeled to produce the final biological age algorithm (BAA). The developed BAAs (for males) were extended and applied to the reported testicular reproductive toxicity-focused di-isobutyl-phthalate (DiBP)−mono-isobutyl-phthalate (MiBP) physiologically based toxicokinetic (PBTK) model in males. The advanced PBTK model combined with the BAA was applied to the human risk assessment based on MiBP biomonitoring data. As a result, the specialized DiBP external exposure values for each age could be estimated. Additionally, by applying the Monte Carlo simulation, the distribution of internal exposure diversity among individuals according to the same external exposure dose could be estimated. The contributions of physiologic and metabolic factors to the age-dependent toxicokinetic changes were approximately 93.41–99.99 and 0.01−6.59%, respectively. In addition, the relative contribution of metabolic factors was major in infants and continued to decrease as age increased (up to about age 30 years). This study provides a step-by-step platform that can be widely applied to overcome the limitations of existing toxicokinetic models that still require interindividual pharmacokinetic variability explanations. This will be important for the rationalization and explanation of inter-individual variability in the pharmacokinetics of many substances.

Understanding the Complexities of Adolescent Bullying: The Interplay between Peer Relationships, Emotion Regulation, and Victimization

Bullying is a major social problem that is receiving increased attention in society and research. The overarching goal of the current study was to identify risk and protective factors of bullying examining direct effects between peer relationship, emotion regulation, and bullying involvement. Therefore, a cross-sectional study was conducted with N = 201 students (55.7% female) between the ages of 10 and 15 ( M = 12.86 ; SD = 1.29 ). Path model analysis revealed that trust had a negative effect on victimization, dysfunctional emotion regulation had a positive effect on perpetration and victimization, alienation had a positive effect on dysfunctional emotion regulation, and victimization and communication had a positive effect on functional emotion regulation. Additionally, dysfunctional emotion regulation strategies mediate the path from alienation to bullying and to victimization. Study results underline the importance of considering the bullying dynamic from a combined perspective of intra- and interindividual factors. The results partially confirmed the hypotheses and contribute to our knowledge about individual and contextual correlates of bullying in adolescents. The present findings suggest that group facilitation with the entire class in team building could be a useful intervention to strengthen peer relationships as well as the relationships between classmates and teachers and students.

The influence of emotion regulation strategies and sleep quality on depression and anxiety

Chronic stress is a major risk factor for a number of mental health disorders, including depression and pathological anxiety. Adaptive cognitive emotion regulation (CER) strategies (i.e. positively-focused thought processes) can help to prevent psychiatric disturbance when enduring unpleasant and stressful experiences, but little is known about the inter-individual factors that govern their success. Sleep plays an important role in mental health, and may moderate the effectiveness of adaptive CER strategies by maintaining the executive functions on which they rely. In this study, we carried out a secondary analysis of self-reported mental health and sleep data acquired during a protracted and naturally-occurring stressor – the COVID-19 pandemic – to firstly test the hypothesis that adaptive CER strategy use is associated with positive mental health outcomes and secondly, that the benefits of adaptive CER strategy use for mental health are contingent on high-quality sleep. Using established self-report tools, participants estimated their depression (N = 551) and anxiety (N = 590)22Due to a minor coding error that resulted in an incorrectly computed predictor measure, we have more missing data than was originally reported in our Stage 1 Registered Report. Our total sample size therefore differs from that reported in our Stage 1 Registered Report for both the pilot study (from n = 118 to n = 117 for the depression sample and from n = 123 to n = 122 for the anxiety sample) and the main study (from n = 562 to n = 551 for the depression sample and from n = 604 to n = 590 for the anxiety sample). These corrections received editorial approval on 30th November 2022. levels, sleep quality and tendency to engage in adaptive and maladaptive CER strategies during the Spring and Autumn of 2020. Using a linear mixed modelling approach, we found that greater use of adaptive CER strategies and higher sleep quality were independently associated with lower self-reported depression and anxiety. However, adaptive CER strategy use was not a significant predictor of self-reported anxiety when accounting for sleep quality in our final model. The positive influence of adaptive CER strategy use on depression was observed at different levels of sleep quality. These findings highlight the importance of adaptive CER strategy use and good sleep quality in promoting resilience to depression and anxiety when experiencing chronic stress.

Beyond heat exposure — new methods to quantify and link personal heat exposure, stress, and strain in diverse populations and climates: The journal Temperature toolbox

ABSTRACT Fine-scale personal heat exposure (PHE) information can help prevent or minimize weather-related deaths, illnesses, and reduced work productivity. Common methods to estimate heat risk do not simultaneously account for the intensity, frequency, and duration of thermal exposures, nor do they include inter-individual factors that modify physiological response. This study demonstrates new whole-body net thermal load estimations to link PHE to heat stress and strain over time. We apply a human-environment heat exchange model to examine how time-varying net thermal loads differ across climate contexts, personal attributes, and spatiotemporal scales. First, we investigate summertime climatic PHE impacts for three US cities: Phoenix, Miami, and New York. Second, we model body morphology and acclimatization for three profiles (middle-aged male/female; female >65 years). Finally, we quantify model sensitivity using representative data at synoptic and micro-scales. For all cases, we compare required and potential evaporative heat losses that can lead to dangerous thermal exposures based on (un)compensable heat stress. Results reveal misclassifications in heat stress or strain due to incomplete environmental data and assumed equivalent physiology and activities between people. Heat strain is most poorly represented by PHE alone for the elderly, non-acclimatized, those engaged in strenuous activities, and when negating solar radiation. Moreover, humid versus dry heat across climates elicits distinct thermal responses from the body. We outline criteria for inclusive PHE evaluations connecting heat exposure, stress, and strain while using physiological-based methods to avoid misclassifications. This work underlines the value of moving from “one-size-fits-all” thermal indices to “fit-for-purpose” approaches using personalized information.

Americans’ COVID-19 risk perceptions and risk perception predictors changed over time

Identifying and understanding risk perceptions—“how bad are the harms” to humans or to what they value that people see as potentially or actually arising from entities or events—has been critical for risk analysis, both for its own sake, and for expected associations between risk perceptions and subsequent outcomes, such as risky or protective behavior, or support for hazard management policies. Cross-sectional surveys have been the dominant method for identifying and understanding risk perceptions, yielding valuable data. However, cross-sectional surveys are unable to probe the dynamics of risk perceptions over time, which is critical to do while living in a dynamically hazardous world and to build causal understandings. Building upon earlier longitudinal panel studies of Americans’ Ebola and Zika risk perceptions using multi-level modeling to assess temporal changes in these views and inter-individual factors affecting them, we examined patterns in Americans’ COVID-19 risk perceptions in six waves across 14 months. The findings suggest that, in general, risk perceptions increased from February 2020 to April 2021, but with varying trends across different risk perception measures (personal, collective, affective, affect, severity, and duration). Factors in baseline risk perceptions (Wave 1) and inter-individual differences across waves differed even more: baseline ratings were associated with how immediate the threat is (temporal distance) and how likely the threat would affect people like oneself (social distance), and following the United States news about the pandemic. Inter-individual trend differences were shaped most by temporal distance, whether local coronavirus infections were accelerating their upward trend, and subjective knowledge about viral transmission. Associations of subjective knowledge and risk trend with risk perceptions could change signs (e.g. from positive to negative) over time. These findings hold theoretical implications for risk perception dynamics and taxonomies, and research design implications for studying risk perception dynamics and their comparison across hazards.

Individual response to transcranial direct current stimulation as a function of working memory capacity and electrode montage.

Attempts to improve cognitive abilities via transcranial direct current stimulation (tDCS) have led to ambiguous results, likely due to the method's susceptibility to methodological and inter-individual factors. Conventional tDCS, i.e., using an active electrode over brain areas associated with the targeted cognitive function and a supposedly passive reference, neglects stimulation effects on entire neural networks. We investigated the advantage of frontoparietal network stimulation (right prefrontal anode, left posterior parietal cathode) against conventional and sham tDCS in modulating working memory (WM) capacity dependent transfer effects of a single-session distractor inhibition (DIIN) training. Since previous results did not clarify whether electrode montage drives this individual transfer, we here compared conventional to frontoparietal and sham tDCS and reanalyzed data of 124 young, healthy participants in a more robust way using linear mixed effect modeling. The interaction of electrode montage and WM capacity resulted in systematic differences in transfer effects. While higher performance gains were observed with increasing WM capacity in the frontoparietal stimulation group, low WM capacity individuals benefited more in the sham condition. The conventional stimulation group showed subtle performance gains independent of WM capacity. Our results confirm our previous findings of WM capacity dependent transfer effects on WM by a single-session DIIN training combined with tDCS and additionally highlight the pivotal role of the specific electrode montage. WM capacity dependent differences in frontoparietal network recruitment, especially regarding the parietal involvement, are assumed to underlie this observation.

Predictors for reactogenicity and humoral immunity to SARS-CoV-2 following infection and mRNA vaccination: A regularized, mixed-effects modelling approach.

The influence of pre-existing humoral immunity, inter-individual demographic factors, and vaccine-associated reactogenicity on immunogenicity following COVID vaccination remains poorly understood. Ten-fold cross-validated least absolute shrinkage and selection operator (LASSO) and linear mixed effects models were used to evaluate symptoms experienced by COVID+ participants during natural infection and following SARS-CoV-2 mRNA vaccination along with demographics as predictors for antibody (AB) responses to recombinant spike protein in a longitudinal cohort study. In previously infected individuals (n=33), AB were more durable and robust following primary vaccination when compared to natural infection alone. Higher AB were associated with experiencing dyspnea during natural infection, as was the total number of symptoms reported during the COVID-19 disease course. Both local and systemic symptoms following 1st and 2nd dose (n=49 and 48, respectively) of SARS-CoV-2 mRNA vaccines were predictive of higher AB after vaccination. Lastly, there was a significant temporal relationship between AB and days since infection or vaccination, suggesting that vaccination in COVID+ individuals is associated with a more robust immune response. Experiencing systemic and local symptoms post-vaccine was suggestive of higher AB, which may confer greater protection.

Imbalanced weighting of proactive and reactive control as a marker of risk-taking propensity.

According to the dual mechanisms of control (DMC), reactive and proactive control are involved in adjusting behaviors when maladapted to the environment. However, both contextual and inter-individual factors increase the weight of one control mechanism over the other, by influencing their cognitive costs. According to one of the DMC postulates, limited reactive control capacities should be counterbalanced by greater proactive control to ensure control efficiency. Moreover, as the flexible weighting between reactive and proactive control is key for adaptive behaviors, we expected that maladaptive behaviors, such as risk-taking, would be characterized by an absence of such counterbalance. However, to our knowledge, no studies have yet investigated this postulate. In the current study, we analyzed the performances of 176 participants on two reaction time tasks (Simon and Stop Signal tasks) and a risk-taking assessment (Balloon Analog Risk Taking, BART). The post-error slowing in the Simon task was used to reflect the spontaneous individuals' tendency to proactively adjust behaviors after an error. The Stop Signal Reaction Time was used to assess reactive inhibition capacities and the duration of the button press in the BART was used as an index of risk-taking propensity. Results showed that poorer reactive inhibition capacities predicted greater proactive adjustments after an error. Furthermore, the higher the risk-taking propensity, the less reactive inhibition capacities predicted proactive behavioral adjustments. The reported results suggest that higher risk-taking is associated with a smaller weighting of proactive control in response to limited reactive inhibition capacities. These findings highlight the importance of considering the imbalanced weighting of reactive and proactive control in the analysis of risk-taking, and in a broader sense, maladaptive behaviors.