Individual-level Differences Research Articles

Hippocampal and motor regions contribute to memory benefits after enacted encoding: cross-sectional and longitudinal evidence.

The neurobiological underpinnings of action-related episodic memory and how enactment contributes to efficient memory encoding are not well understood. We examine whether individual differences in level (n = 338) and 5-year change (n = 248) in the ability to benefit from motor involvement during memory encoding are related to gray matter (GM) volume, white matter (WM) integrity, and dopamine-regulating genes in a population-based cohort (age range = 25-80years). A latent profile analysis identified 2 groups with similar performance on verbal encoding but with marked differences in the ability to benefit from motor involvement during memory encoding. Impaired ability to benefit from enactment was paired with smaller HC, parahippocampal, and putamen volume along with lower WM microstructure in the fornix. Individuals with reduced ability to benefit from encoding enactment over 5years were characterized by reduced HC and motor cortex GM volume along with reduced WM microstructure in several WM tracts. Moreover, the proportion of catechol-O-methyltransferase-Val-carriers differed significantly between classes identified from the latent-profile analysis. These results provide converging evidence that individuals with low or declining ability to benefit from motor involvement during memory encoding are characterized by low and reduced GM volume in regions critical for memory and motor functions along with altered WM microstructure.

Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation : A Cross-Sectional Study.

Although the population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate (mGFR) are well recognized, the magnitude and potential clinical implications of individual-level differences are unknown. To quantify the magnitude and consequences of the individual-level differences between mGFRs and eGFRs. Cross-sectional study. Four U.S. community-based epidemiologic cohort studies with mGFR. 3223 participants in 4 studies. The GFRs were measured using urinary iothalamate and plasma iohexol clearance; the eGFR was calculated from serum creatinine concentration alone (eGFRCR) and with cystatin C. All GFR results are presented as mL/min/1.73 m2. The participants' mean age was 59 years; 32% were Black, 55% were women, and the mean mGFR was 68. The population-level differences between mGFR and eGFRCR were small; the median difference (mGFR-eGFR) was -0.6 (95% CI, -1.2 to -0.2); however, the individual-level differences were large. At an eGFRCR of 60, 50% of mGFRs ranged from 52 to 67, 80% from 45 to 76, and 95% from 36 to 87. At an eGFRCR of 30, 50% of mGFRs ranged from 27 to 38, 80% from 23 to 44, and 95% from 17 to 54. Substantial disagreement in chronic kidney disease staging by mGFR and eGFRCR was present. Among those with eGFRCR of 45 to 59, 36% had mGFR greater than 60 whereas 20% had mGFR less than 45; among those with eGFRCR of 15 to 29, 30% had mGFR greater than 30 and 5% had mGFR less than 15. The eGFR based on cystatin C did not provide substantial improvement. Single measurement of mGFR and serum markers without short-term replicates. A substantial individual-level discrepancy exists between the mGFR and the eGFR. Laboratories reporting eGFR should consider including the extent of this uncertainty to avoid misinterpretation of eGFR as an mGFR replacement. National Institutes of Health.

Gender differences in campaigning under alternative voting systems: analysis of election manifestos

ABSTRACT Growing evidence reveals that candidate issue engagement differs between men and women. However, recent research suggests that individual-level differences among candidates should be small under the strategic incentives inherent in single-member district elections that encourage party rather than personal-vote seeking. We examine whether men and women candidates emphasize different issues in their electoral campaigns and if the magnitude of the gender gap varies under different electoral rules. Our analysis of 7497 Japanese election manifestos spanning more than 20 years, from 1986 to 2009, reveals significant gender differences in the issues candidates emphasize in their electoral campaigns, regardless of party affiliation or other attributes. Moreover, these differences remain salient after an extensive change from a multi-member district to single-member district electoral system.

Heterogeneous Peer Effects in the Linear Threshold Model

The Linear Threshold Model is a widely used model that describes how information diffuses through a social network. According to this model, an individual adopts an idea or product after the proportion of their neighbors who have adopted it reaches a certain threshold. Typical applications of the Linear Threshold Model assume that thresholds are either the same for all network nodes or randomly distributed, even though some people may be more susceptible to peer pressure than others. To address individual-level differences, we propose causal inference methods for estimating individual thresholds that can more accurately predict whether and when individuals will be affected by their peers. We introduce the concept of heterogeneous peer effects and develop a Structural Causal Model which corresponds to the Linear Threshold Model and supports heterogeneous peer effect identification and estimation. We develop two algorithms for individual threshold estimation, one based on causal trees and one based on causal meta-learners. Our experimental results on synthetic and real- world datasets show that our proposed models can better predict individual-level thresholds in the Linear Threshold Model and thus more precisely predict which nodes will get activated over time.

The Impact of COVID-19 Zoo Closures on Behavioural and Physiological Parameters of Welfare in Primates.

Simple SummaryZoo visitors can have a positive, negative, or neutral impact on animals. Primates are cognitively very advanced and their interactions with human visitors are complex. The COVID-19 pandemic led to a prolonged absence of visitors in zoos. This enabled an opportunity to compare how primates behaved when the zoo was open to visitors as opposed to when it was closed. We studied four primate species housed in the UK: bonobos, chimpanzees, and western lowland gorillas held at Twycross Zoo and olive baboons held at Knowsley Safari. Bonobos and gorillas spent less time alone when facilities were open to the public. Gorillas also spent less time resting when the facility was open to the public. Chimpanzees ate more and engaged more with enrichment when the zoo was open to the public. Olive baboons performed less sexual and dominance behaviour and approached visitor cars more frequently when the safari park was opened to the public than the ranger’s vehicle during closure periods. The results suggest that the zoo closures had variable impacts on the primates and that the closure periods were neither “negative” or “positive” for all of the studied species. There are likely to be differences between individuals due to prior experiences. We recommend that future work seeks to understand the impact individual differences and animal environments have on animals’ experiences with visitors. Primates are some of the most cognitively advanced species held in zoos, and their interactions with visitors are complex. The COVID-19 pandemic provided a unique opportunity to understand the impact of zoo visitors on animals, in comparison to “empty zoos”. This study sought to understand the impact of facility closures and subsequent reopenings on behavioural and physiological parameters of welfare in four primate species housed in the UK: bonobos (Pan paniscus) (n = 8), chimpanzees (Pan troglodytes) (n = 11), and western lowland gorillas (Gorilla gorilla gorilla) (n = 6) held at Twycross Zoo (TZ); and olive baboons (Papio anubis) (n = 192) held at Knowsley Safari (KS). Behavioural data were collected from April–September 2020 (KS) and November 2020–January 2021 (TZ). Faecal samples were collected during morning checks from October–November (TZ) and July–November 2020 (KS). Faecal glucocorticoid metabolites (FGMs) were measured using ELISA kits. Statistical analysis for behavioural observations was undertaken using general linear models. Enclosure usage was assessed using t-tests and Mann–Whitney U-tests as appropriate. Bonobos and gorillas spent less time alone when facilities were open to the public (p = 0.004, p = 0.02 respectively). Gorillas spent less time resting when the facility was open to the public (p = 0.04), and chimpanzees engaged in more feeding (p = 0.02) and engagement with enrichment (p = 0.03) when the zoo was open to the public than when it was closed. Olive baboons performed less sexual and dominance behaviour and approached visitor cars more frequently when the safari park was opened to the public than they did the ranger’s vehicle during closure periods. There were no significant changes in physiological parameters for any of the study species. The results suggest variable impacts of the zoo closures on zoo-housed primates. We recommend future work that seeks to understand the impact of individual-level differences on “visitor effects” and that differences between animal experiences in zoos and safari parks are further explored in a range of species.

Near transfer to an unrelated N-back task mediates the effect of N-back working memory training on matrix reasoning.

The extent to which working memory training improves performance on untrained tasks is highly controversial. Here we address this controversy by testing the hypothesis that far transfer may depend on near transfer using mediation models in three separate randomized controlled trials (RCTs). In all three RCTs, totalling 460 individuals, performance on untrained N-back tasks (near transfer) mediated transfer to Matrix Reasoning (representing far transfer) despite the lack of an intervention effect in RCTs 2 and 3. Untrained N-back performance also mediated transfer to a working memory composite, which showed a significant intervention effect (RCT 3). These findings support a model of N-back training in which transfer to untrained N-back tasks gates further transfer (at least in the case of working memory at the construct level) and Matrix Reasoning. This model can help adjudicate between the many studies and meta-analyses of working memory training that have provided mixed results but have not examined the relationship between near and far transfer on an individual-differences level.

Preferences for and perceptions about politicians’ goals and how they impact women’s and men’s political ambition

Women consistently report lower levels of nascent political ambition than men, which causes problems for the recruitment of women in politics. The aim of this study is to better understand the mechanisms behind this gender gap by simultaneously studying the extent to which gender differences in preferences for and perceptions about the typical goals attained through a political career (power, independence and communal goals) can explain gender differences in political ambition. Using data collected among Belgian political and social sciences students (N = 322), our results provide a strong confirmation of the gender gap in political ambition. We also find substantial gender differences in preferences for and perceptions about goals pursued through political careers. However, these individual-level differences in preferences and perceptions only marginally reduce the gender gap in political ambition, emphasising the need for active political recruitment.

Plasma levels of BDNF and EGF are reduced in acute stroke patients

Stroke affects almost 14 million people worldwide each year. It is the second leading cause of death and a major cause of acquired disability. The degree of initial impairment in cognitive and motor functions greatly affects the recovery, but idiosyncratic factors also contribute. These are largely unidentified, which contributes to making accurate prediction of recovery challenging. Release of soluble regulators of neurotoxicity, neuroprotection and repair are presumably essential. Here we measured plasma levels of known regulators of neuroprotection and repair in patients with mild acute ischemic stroke and compared them to the plasma levels in healthy age and gender matched controls. We found that the levels of BDNF and EGF were substantially lower in stroke patients than in healthy controls, while the levels of bFGF and irisin did not differ between the groups. The lower levels of growth factors highlight that during the acute phase of stroke, there is a mismatch between the need for neuroprotection and repair, and the brain's ability to induce these processes. Large individual differences in growth factor levels were seen among the stroke patients, but whether these can be used as predictors of long-term prognosis remains to be investigated.

Self-control in adolescence predicts forgivingness in middle adulthood.

This 33-year study examined associations between self-control development in adolescence and forgivingness, i.e., the dispositional tendency to forgive others, in middle adulthood. Participants were 1350 adults aged 45 years (50.6% female). Self-control was measured yearly from age 12 to 16, while forgivingness was measured at age 45. Results indicated significant individual differences in level and change of self-control across the adolescent years and an average mean-level increase. Individual differences in level and change in self-control were independently associated with forgivingness in middle adulthood. Individuals who either entered adolescence with higher self-control, and/or increased in self-control during the adolescent years, reported higher scores in forgivingness at age 45 compared to peers. This pattern held even after controlling for gender, socioeconomic status (SES), and conduct problems in adolescence. The current findings demonstrate that developmental processes in adolescence are important for individual differences in the dispositional tendency to forgive others in adulthood.

Implications for quantifying early life growth trajectories of term-born infants using INTERGROWTH-21st newborn size standards at birth in conjunction with World Health Organization child growth standards in the postnatal period.

The INTERGROWTH-21st sex and gestational age (GA) specific newborn size standards (IG-NS) are intended to complement the World Health Organization Child Growth Standards (WHO-GS), which are not GA-specific. We examined the implications of using IG-NS at birth and WHO-GS at postnatal ages in longitudinal epidemiologic studies. The aim of this study was to quantify the extent to which standardised measures of newborn size and growth are affected when using WHO-GS versus IG-NS at birth among term-born infants. Data from two prenatal trials in Bangladesh (n=755) and The Gambia (n=522) were used to estimate and compare size at birth and growth from birth to 3months when using WHO-GS only ('WHO-GS') versus IG-NS at birth and WHO-GS postnatally ('IG-NS'). Mean length-for-age (LAZ), weight-for-age (WAZ) and head circumference-for-age (HCAZ), and the prevalence of undernutrition (stunting: LAZ<-2SD; underweight: WAZ<-2SD; and microcephaly: HCAZ<-2SD) were estimated overall and by GA strata [early-term (370/7 -386/7 ), full-term (390/7 -406/7 ) and late-term (410/7 -430/7 )]. We used Bland-Altman plots to compare continuous indices and Kappa statistic to compare categorical indicators. At birth, mean LAZ, WAZ and HCAZ, and the prevalence of undernutrition were most similar among newborns between 39 and 40weeks of GA when using WHO-GS versus IG-NS. However, anthropometric indices were systematically lower among early-term infants and higher among late-term infants when using WHO-GS versus IG-NS. Early-term and late-term infants demonstrated relatively faster and slower growth, respectively, when using WHO-GS versus IG-NS, with the direction and magnitude of differences varying between anthropometric indices. Individual-level differences in attained size and growth, when using WHO-GS versus IG-NS, were greater than 0.2 SD in magnitude for >60% of infants across all anthropometric indices. Using IG-NS at birth with WHO-GS postnatally is acceptable for full-term infants but may give a misleading interpretation of growth trajectories among early- and late-term infants.

FlotGAIL: An operational adjustment framework for flotation circuits using generative adversarial imitation learning

In many industrial flotation processes, the operational adjustment is still manual according to individual experience. The adjustment of operational variables is mainly based on the discrimination of feed conditions and the observation of the appearance of flotation froth. Due to the limitation that partial properties of feed ore cannot be monitored online and the individual-level differences in operation experience, it is difficult to control the concentrate grade and recovery in the qualified range for a long time by manual operational adjustment. To resolve this problem, we propose FlotGAIL, an automatic operational adjustment framework based on generative adversarial imitation learning (GAIL) for the flotation circuits. From the perspective of an algorithm, this paper explores a novel way to learn operational adjustment policy. The epistemic uncertainty estimation of feed conditions provided by Bayesian neural networks is used as an additional guidance for the GAIL model to generate flotation operational trajectories, which it is just as an expert considers reducing the risk of process operation and increasing long-term rewards. In FlotGAIL, learning flotation operational adjustment from expert demonstrations is formulated as an imitation learning problem in a Markov decision process, and then the proposed model uses the signal provided by the discriminator as the reward function to guide the policy generator to complete the training process. From the perspective of engineering application, the experiments have verified that the proposed operational adjustment method has a better effect in controlling concentrate grade and recovery up to standard, and FlotGAIL can be used as an effective tool to provide decision support for operators of other similar industrial processes.

Current status and influential factors for family health management during quarantine: A latent category analysis.

ObjectiveWe aimed to explore factors affecting family health management during home quarantine as well as the effects of variations in family health management (FHM) on individuals’ health status.MethodsUsing stratified random sampling, 618 families in Wuhan as well as cities within its surrounding provinces were recruited and surveyed online. Latent class variables were extracted from four modules: disinfection, space layout, physical exercise, and food reserves. The analysis was conducted using the poLCA package in R software (v.4.1.0). Chi-squared tests, Fisher’s exact tests, and non-parametric Kruskal–Wallis tests were used to compare groups as appropriate.ResultsWe found an overall questionnaire reliability of 0.77 and a total omega of 0.92, indicating that the survey results were credible. The Bayesian information criterion and Akaike information criterion were used to identified four latent class variables, namely latent non-family health management (18.9%) and latent low, medium, and advanced FHM (30.93%, 29.49%, and 20.59%, respectively). Gender, household income level, body mass index, the presence of a nearby community hospital, and self-rated health status showed statistically significant differences with respect to latent FHM. Moreover, we found a statistically significant difference in emotional reactions when comparing latent advanced and low to mid-level latent FHM. Compared with latent non-family health managers, we detected statistically significant differences in individual energy levels between potential family health managers at latent low and medium levels. Additionally, we found statistically significant differences in individual energy levels between latent advanced and low level family health managers.ConclusionsWe found that multiple factors, including gender, household income, and body mass index, were correlated with latent FHM during home quarantine. We conclude that FHM can meaningfully improve individuals’ health. Thus, increasing social support for individuals can improve FHM as well as individuals’ health during home quarantine.

Structural Brain Imaging Predicts Individual-Level Task Activation Maps Using Deep Learning.

Accurate individual functional mapping of task activations is a potential tool for biomarker discovery and is critically important for clinical care. While structural imaging does not directly map task activation, we hypothesized that structural imaging contains information that can accurately predict variations in task activation between individuals. To this end, we trained a convolutional neural network to use structural imaging (T1-weighted, T2-weighted, and diffusion tensor imaging) to predict 47 different functional MRI task activation volumes across seven task domains. The U-Net model was trained on 591 subjects and then subsequently tested on 122 unrelated subjects. The predicted activation maps correlated more strongly with their actual maps than with the maps of the other test subjects. An ablation study revealed that a model using the shape of the cortex alone or the shape of the subcortical matter alone was sufficient to predict individual-level differences in task activation maps, but a model using the shape of the whole brain resulted in markedly decreased performance. The ablation study also showed that the additional information provided by the T2-weighted and diffusion tensor imaging strengthened the predictions as compared to using the T1-weighted imaging alone. These results indicate that structural imaging contains information that is predictive of inter-subject variability in task activation mapping and that cortical folding patterns, as well as microstructural features, could be a key component to linking brain structure to brain function.

\u2018When hunger makes everything better looking!\u2019: The effect of hunger on the aesthetic appreciation of human bodies, faces and objects

BackgroundResearch evidence suggests that physiological state of hunger might affect preference for female body weight, such that hungrier, compared to satiate, men prefer heavier body weight and rate as more attractive heavier female figures. Here, we seek to extend these findings by comparing the effects of fasting and snack on aesthetics judgements of the bodies and faces of conspecifics and of objects in a sample of female and male participants.MethodsForty-four participants (women: n = 21, mean age = 23.70 yrs ± 0.62) provided aesthetic liking judgments of round and slim human bodies, faces and objects, under at least 12 h of overnight fasting and immediately after having eaten a snack (i.e., bananas). An anthropometric measure of adiposity (i.e., Body Mass Index, BMI) was also collected from each observer.ResultsOverall, we found that participants’ aesthetic judgements were higher for slim stimuli compared to round ones. However, after fasting, participants rated round stimuli as more attractive compared to when they had a snack. This hunger-based shift in ratings not only was apparent when stimuli depicted a human body or face, but also when they depicted an object, thus suggesting a general modification of observers’ aesthetic preference related to hunger. Importantly, this effect was modulated by participants’ BMI so that only participants with a high BMI provided higher aesthetic judgements for round stimuli after fasting than after a snack.ConclusionsOur results demonstrated that both the modification of the physiological state and the individual differences in adiposity level of the observers might affect the aesthetic appreciation of the external world.

Assessing the integrity of executive functioning in chronic aphasia

ABSTRACT Background Executive functioning (EF) deficits can commonly co-occur with language impairments in aphasia. Despite recognizing the role of EF in language and aphasia treatment outcomes, the integrity of EF in aphasia remains to be comprehensively studied. Aims The present study aimed to comprehensively examine the integrity of EF skills in individuals with different types and severities of aphasia. Accordingly, we sought to compare the performances of persons with aphasia (PWA) and healthy controls on a broad range of verbal and nonverbal EF skills using an extensive battery of assessments. To fully understand the nature of deficits in the aphasia population, we aimed to evaluate EF performances both quantitatively and qualitatively in addition to examining group- and individual-level differences. Method Persons with aphasia (PWA) and age- and education-matched healthy controls (HC) completed a battery of verbal and nonverbal EF assessments. Between-group comparisons were carried out using quantitative and qualitative EF task scores. Additionally, we conducted individual-level analyses to examine performances within the aphasia group. The influence of aphasia severity and type on EF task performances were also evaluated. Results PWA differed significantly from HC on most EF measures. Individual-level analyses revealed marked variability in performances within the aphasia group indicating that most but not all PWA demonstrated EF deficits. PWA performed significantly more poorly than HC on both verbal and nonverbal measures with greater difficulty on verbal EF tasks. No consistent relationship was found between aphasia variables and EF task performances. Conclusion Our findings indicate that many PWA demonstrate domain-general EF deficits that are not necessarily related to the degree of their language impairments. The present study emphasizes the importance of evaluating EF more routinely in clinical practice to improve rehabilitation success for PWA.

Changes in Plasma Clozapine Levels after Smoking Cessation in Japanese Inpatients with Schizophrenia: A Retrospective Cohort Study.

Although reported for Caucasians, changes in plasma clozapine levels after smoking cessation in East Asians remain unclear. We here investigated plasma clozapine levels before and after smoking cessation in Japanese inpatients with schizophrenia. We conducted a retrospective chart review of 14 inpatients with schizophrenia who were being treated with clozapine between June 1, 2019, and July 31, 2019 and who were smokers as of July 1, 2019, the day on which a smoking ban was instituted in the tertiary public psychiatric hospital. The primary outcome was individual differences in plasma clozapine levels between before and after the smoking ban, which were compared using paired t-tests. The mean plasma clozapine level was significantly increased, by 213.4 ng/mL (95% CI 119.9-306.8; p<0.01) or 53.2%. Four of the 14 inpatients experienced clinically significant side effects, such as myoclonus, drooling, and amnesia, due to the development of high plasma clozapine levels. Our findings indicated that close monitoring of plasma clozapine levels before and after smoking cessation and prior dose adjustment of clozapine may be necessary, to prevent a significant risk of developing high plasma clozapine levels, even in Japanese patients.

Aspects of social behaviour and reproduction in the wild rabbit – Implications for rabbit breeding?

Further knowledge on aspects of social behaviour in the wild rabbit (Oryctolagus cuniculus), including the link to reproduction, could possibly point to new ways to improve housing and breeding conditions in rabbit farming. In this review, I present some results of our long-term study on a 2-hectare field enclosure population of wild rabbits (University of Bayreuth, Germany), exploring group-level and individual-level differences in agonistic behaviour of females and their potential associations with reproductive traits, including offspring survival. The frequency of agonistic behaviour in which females were involved, increased with increasing group size, and was lower in groups with a more heterogeneous age structure. At the individual level, reproducing females were involved in more agonistic interactions when groupmates gave birth and thus built their burrows and nests at around the same time, and higher-ranking mothers were particularly aggressive when other females approached close to their nursery burrows. Associations between females’ social environment and reproduction were evident, as the numbers of litters and offspring per female were lower at higher female densities, high-ranking females produced more offspring and had a lower offspring mortality than low-ranking ones, and cases of infanticide were lower in more stable groups, which we quantified by the more heterogeneous age structure of the females’ rank hierarchy in such groups. Furthermore, perinatal offspring mortality was increased in females with a delayed burrow and nest building activity, i.e. does that dug their nursery burrow and built their nest only during the last 24 h pre-partum, possibly driven by the more unfavourable social environment experienced by such females. Most importantly, our studies highlight the importance of the presence of litter siblings in improving an individual’s social environment, which resulted in an earlier onset of breeding in such females. Higher levels of positive social interactions with litter siblings were also associated with lower stress hormone (corticosterone) levels and with a better health status in terms of lower loads with an intestinal nematode. These findings on ameliorating effects of litter sibling presence in growing rabbits as well as in reproducing females may be a promising starting point worth further exploration in the context of group housing of domestic rabbits.

Exploring the effects of pathogen infection on tick behaviour from individuals to populations

Ticks vector a greater variety of pathogens than any other arthropod group, making them a significant threat to the public, companion animals and wildlife. Surveying wildlife habitats and areas commonly used for recreation for the presence of ticks and the pathogens that they carry is essential to the prevention of tick-borne diseases. Tick behaviour also plays an active role in transmission dynamics. We set out to study the host-seeking behaviour of Amblyomma americanum , the lone star tick, at the population level and at the individual level by collecting ticks in public parks in Gainesville, Florida, U.S.A., and by conducting behavioural assays on host-seeking behaviour (questing). We assayed a subset of the collected ticks for 3 consecutive days to determine whether ticks displayed repeatable, individual level differences in questing behaviour. Afterward, we screened ticks for two human pathogens, Rickettsia spp. and Ehrlichia spp. While we did not find differences in pathogen prevalence among the populations, we found that nymphal ticks infected with Rickettsia amblyommatis spent less time questing than uninfected nymphs. However, across all populations, we found a greater prevalence of R. amblyommatis in adult ticks. Additionally, nymphs were more likely to engage in questing behaviours than adults. Lastly, we found significant repeatability in the average height that a tick quests and the questing likelihood of a tick. These findings could fill a gap in the knowledge about trends in disease dynamics. • Ticks displayed repeatability in average heights quested and the likelihood to quest. • Infected nymphal ticks spent less time questing than uninfected nymphs. • Nymphs were more likely to engage in questing behaviours than adult ticks. • Ticks from rural sites quested higher on average compared to ticks from city parks.

Leptin Protects Against the Development and Expression of Cocaine Addiction-Like Behavior in Heterogeneous Stock Rats.

Cocaine affects food intake, metabolism and bodyweight. It has been hypothesized that feeding hormones like leptin play a role in this process. Preclinical studies have shown a mutually inhibitory relationship between leptin and cocaine, with leptin also decreasing the rewarding effects of cocaine intake. But prior studies have used relatively small sample sizes and did not investigate individual differences in genetically heterogeneous populations. Here, we examined whether the role of individual differences in bodyweight and blood leptin level are associated with high or low vulnerability to addiction-like behaviors using data from 306 heterogeneous stock rats given extended access to intravenous self-administration of cocaine and 120 blood samples from 60 of these animals, that were stored in the Cocaine Biobank. Finally, we tested a separate cohort to evaluate the causal effect of exogenous leptin administration on cocaine seeking. Bodyweight was reduced due to cocaine self-administration in males during withdrawal and abstinence, but was increased in females during abstinence. However, bodyweight was not correlated with addiction-like behavior vulnerability. Blood leptin levels after ∼6 weeks of cocaine self-administration did not correlate with addiction-like behaviors, however, baseline blood leptin levels before any access to cocaine negatively predicted addiction-like behaviors 6 weeks later. Finally, leptin administration in a separate cohort of 59 animals reduced cocaine seeking in acute withdrawal and after 7 weeks of protracted abstinence. These results demonstrate that high blood leptin level before access to cocaine may be a protective factor against the development of cocaine addiction-like behavior and that exogenous leptin reduces the motivation to take and seek cocaine. On the other hand, these results also show that blood leptin level and bodyweight changes in current users are not relevant biomarkers for addiction-like behaviors.

Effect of risk-reducing salpingo-oophorectomy on sex steroid hormone serum levels among postmenopausal women: an NRG Oncology/Gynecologic Oncology Group study

Risk-reducing salpingo-oophorectomy is an effective ovarian cancer risk reduction strategy. However, bilateral oophorectomy has also been associated with increased long-term nonneoplastic sequelae, effects suggested to be mediated through reductions in systemic sex steroid hormone levels. Currently, it is unclear whether the postmenopausal ovary contributes to the systemic hormonal milieu or whether postmenopausal ovarian volume or other factors, such as body mass index and age, affect systemic hormone levels. We examined the impact of oophorectomy on sex steroid hormone levels in postmenopausal women. Furthermore, we explored how well ovarian volume measured by transvaginal ultrasound correlated with direct ovarian measures obtained during surgical pathology evaluation and investigated the association between hormone levels and ovarian volumes. Postmenopausal women who underwent risk-reducing salpingo-oophorectomy (180 cases) or ovarian cancer screening (38 controls) enrolled in an international, prospective study of risk-reducing salpingo-oophorectomy and risk of ovarian cancer algorithm-based screening among women at increased risk of ovarian cancer (Gynecologic Oncology Group-0199) were included in this analysis. Controls were frequency matched to the cases on age at menopause, age at study entry, and time interval between blood draws. Ovarian volume was calculated using measurements obtained from transvaginal ultrasound in both cases and controls and measurements recorded in surgical pathology reports from cases. Serum hormone levels of testosterone, androstenedione, androstenediol, dihydrotestosterone, androsterone, dehydroepiandrosterone, estrone, estradiol, and sex hormone-binding globulin were measured at baseline and follow-up. Spearman correlation coefficients were used to compare ovarian volumes as measured on transvaginal ultrasound and pathology examinations. Correlations between ovarian volumes by transvaginal ultrasound and measured hormone levels were examined using linear regression models. All models were adjusted for age. Paired t tests were performed to evaluate individual differences in hormone levels before and after risk-reducing salpingo-oophorectomy. Ovarian volumes measured by transvaginal ultrasound were only moderately correlated with those reported on pathology reports (Spearman rho [ρ]=0.42). The median time interval between risk-reducing salpingo-oophorectomy and follow-up for the cases was 13.3 months (range, 6.0-19.3), and the median time interval between baseline and follow-up for the controls was 12.7 months (range, 8.7-13.4). Sex steroid levels decreased with age but were not correlated with transvaginal ultrasound ovarian volume, body mass index, or time since menopause. Estradiol levels were significantly lower after risk-reducing salpingo-oophorectomy (percentage change,-61.9 post-risk-reducing salpingo-oophorectomy vs+15.2 in controls; P=.02), but no significant differences were seen for the other hormones. Ovarian volumes measured by transvaginal ultrasound were moderately correlated with volumes directly measured on pathology specimens and were not correlated with sex steroid hormone levels in postmenopausal women. Estradiol was the only hormone that declined significantly after risk-reducing salpingo-oophorectomy. Thus, it remains unclear whether the limited post-risk-reducing salpingo-oophorectomy changes in sex steroid hormones among postmenopausal women impact long-term adverse outcomes.