Brain volume and microglial density changes are correlated in a juvenile mouse model of cranial radiation and CSF1R inhibitor treatment.

Microglia have been shown to proliferate and become activated following cranial radiotherapy (CRT), resulting in a chronic inflammatory response. We investigated the role of microglia in contributing to widespread volume losses observed in the brain following CRT in juvenile mice. To manipulate microglia, we used low-dose treatment with a highly selective CSF1R inhibitor called PLX5622 (PLX). We hypothesized that alteration of the post-CRT microglia population would lead to changes in brain development outcomes, as evaluated by structural MRI. Wild-type C57BL/6J mice were provided with daily intraperitoneal injections of PLX (25 mg/kg) or vehicle from postnatal day (P)14 to P19. Mice also received whole-brain irradiation (7 Gy) or sham irradiation (0 Gy) at 16 days of age. In one cohort of mice, immunohistochemical assessment in tissue sections was conducted to assess the impact of the selected PLX and CRT doses as well as their combination. In a separate cohort, mice were imaged using MRI at P14 (pretreatment), P19, P23, P42 and P63 in order to assess induced volume changes, which were measured based on structures from a predefined atlas. We observed that PLX and radiation treatments led to sex-specific changes in the microglial cell population. Across treatment groups, MRI-detected anatomical volumes at P19 and P63 were associated with microglia and proliferating microglia densities, respectively. Overall, our study demonstrates that low-dose PLX treatment produces a sex-dependent response in juvenile mice, that manipulation of microglia alters CRT-induced volume changes and that microglia density and MRI-derived volume changes are correlated in this model.

No evidence for a causal contribution of bioavailable testosterone to ADHD in sex-combined and sex-specific two-sample Mendelian randomization studies.

The higher prevalence of attention-deficit/hyperactivity disorder (ADHD) in males raises the question of whether testosterone is implicated in ADHD risk. However, cross-sectional studies did not identify an association between ADHD and testosterone levels. Mendelian randomization (MR) studies can overcome limitations inherent to association studies, especially of reverse causation and residual confounding. In the current study, sex-combined and sex-specific two-sample MR analyses were conducted to address whether testosterone has a causal influence on ADHD risk. Sex-combined as well as sex-specific target-genetic variants for bioavailable testosterone were derived from a large genome-wide association study (GWAS) on up to 382,988 adult white European UK Biobank study participants. In our sex-specific analyses for ADHD, including data from 14,154 males and 4,945 females with ADHD (17,948 and 16,246 controls respectively), no association between bioavailable testosterone and ADHD risk was found, neither in males (inverse-variance weighted (IVW): beta = 0.09, 95%-CI [-0.10, 0.27]) nor in females (IVW: beta=-0.01, 95%-CI [-0.20, 0.19]). However, in the sex-combined analysis, including 38,691 cases and 186,843 controls, genetically predicted bioavailable testosterone was associated with ADHD risk (IVW: beta = 0.24, 95%-CI [0.09, 0.39]). The inclusion of birth weight and/or SHBG as additional variables in multivariable MR analyses did not alter this result. However, when correcting for potential BMI-driven pleiotropy by a multivariable MR study, all effect estimates for testosterone showed non-significant results. Taken together, no robust evidence for a causal effect of bioavailable testosterone on the risk for ADHD was found.

Microglial senescence contributes to female-biased neuroinflammation in the aging mouse hippocampus: implications for Alzheimer's disease.

BACKGROUND: Microglia, the brain's principal immune cells, have been implicated in the pathogenesis of Alzheimer's disease (AD), a condition shown to affect more females than males. Although sex differences in microglial function and transcriptomic programming have been described across development and in disease models of AD, no studies have comprehensively identified the sex divergences that emerge in the aging mouse hippocampus. Further, existing models of AD generally develop pathology (amyloid plaques and tau tangles) early in life and fail to recapitulate the aged brain environment associated with late-onset AD. Here, we examined and compared transcriptomic and translatomic sex effects in young and old murine hippocampal microglia. METHODS: Hippocampal tissue from C57BL6/N and microglial NuTRAP mice of both sexes were collected at young (5-6 month-old [mo]) and old (22-25 mo) ages. Cell sorting and affinity purification techniques were used to isolate the microglial transcriptome and translatome for RNA-sequencing and differential expression analyses. Flow cytometry, qPCR, and imaging approaches were used to confirm the transcriptomic and translatomic findings. RESULTS: There were marginal sex differences identified in the young hippocampal microglia, with most differentially expressed genes (DEGs) restricted to the sex chromosomes. Both sex chromosomally and autosomally encoded sex differences emerged with aging. These sex DEGs identified at old age were primarily female-biased and enriched in senescent and disease-associated microglial signatures. Normalized gene expression values can be accessed through a searchable web interface ( https://neuroepigenomics.omrf.org/ ). Pathway analyses identified upstream regulators induced to a greater extent in females than in males, including inflammatory mediators IFNG, TNF, and IL1B, as well as AD-risk genes TREM2 and APP. CONCLUSIONS: These data suggest that female microglia adopt disease-associated and senescent phenotypes in the aging mouse hippocampus, even in the absence of disease pathology, to a greater extent than males. This sexually divergent microglial phenotype may explain the difference in susceptibility and disease progression in the case of AD pathology. Future studies will need to explore sex differences in microglial heterogeneity in response to AD pathology and determine how sex-specific regulators (i.e., sex chromosomal or hormonal) elicit these sex effects.

Impact of endocrine disruptors on peripheral blood mononuclear cells in vitro: role of gender.

Humans can be exposed to endocrine disruptors (EDs) in numerous ways. EDs can interfere with endogenous hormones at different levels, resulting in numerous adverse human health outcomes, including immunotoxicity. In this regard, this study aimed to investigate in vitro the possible effects of EDs on immune cells and possible gender differences. Peripheral blood mononuclear cells from healthy humans, both males and females, were exposed to 6 different EDs, namely atrazine (herbicide), cypermethrin (insecticide), diethyl phthalate (plasticizer), 17α-ethynylestradiol (contraceptive drug), perfluorooctanesulfonic acid (persistent organic pollutant), and vinclozolin (fungicide). We evaluated the effect of EDs on RACK1 (receptor for activated C kinase 1) expression, considering it as a bridge between the endocrine and the immune system, and putatively used as screening tool of immunotoxic effects of EDs. The exposure to EDs resulted at different extent in alteration in RACK1 expression, pro-inflammatory activity, natural killer lytic ability, and lymphocyte differentiation, with sex-related differences. In particular, diethyl phthalate and perfluorooctanesulfonic acid resulted the most active EDs tested, with gender differences in terms of effects and magnitude. The results from our study evidenced the ability of EDs to directly affect immune cells.

Ontogenesis of sociability of wild immature capuchin monkeys (Sapajus libidinosus): Sex more than personality explains interindividual variation.

Sociability is a fundamental trait that social animals need to survive and reproduce in societies. Sociability predicts how an individual can consistently interact with its conspecifics across time and situations. By studying capuchin monkeys (Sapajus libidinosus), a neotropical primate with complex social behavior and high cognitive capacity, our research aims to analyze the development of the social axis of personality of immature individuals, from birth to the third year of life. We studied wild monkeys belonging to a group with infants, juveniles, and adults of both sexes that inhabits northeastern Brazil. We analyzed the behavior of 12 immature capuchins (6 males and 6 females) in 94 h of videos recorded weekly from birth until 36 months, through daily focal sampling. We verified whether there was intraindividual consistency throughout development by fitting regression models for the effect of age on initiating affiliative social behaviors, controlling for monkey identity and sex. Our results indicate that the individuals of this study exhibit high variation in the initiation of behaviors at the beginning of infancy; there was low repeatability and high intra-individual variation during the first 3 years of life of these individuals, indicating that the social personality is not consolidated in this period. Immature females were more sociable than immature males. Therefore, differences in sociability in early life of bearded capuchin monkeys are best explained by sex rather than personality. We suggest that the high initial behavioral variation in the social axis of personality allows for plasticity influenced by the environment throughout development. The high sociability of females in infancy may be related to female philopatry and their high sociability in adulthood.

The Effect of Maternal Exposure to a Diet High in Fats and Cholesterol on the Placental Function and Phenotype of the Offspring in a Rabbit Model: A Summary Review of About 15 Years of Research.

The rates of obesity and being overweight are increasing all around the world, especially among women of childbearing age, in part due to overconsumption of lipids. The aim of this summary review was to present the cellular and molecular effects of a hyperlipidic high-cholesterol (H) diet on the maternal and offspring phenotype at the early embryonic, neonatal, weaning and adult stages while considering the effects of sex and to identify the window(s) of vulnerability linked to this exposure in a rabbit model. Before breeding, the H diet induced dyslipidemia and aortic atherosclerosis lesions and increased the number of atretic follicles. In the offspring, the H diet disrupted the embryonic phenotype and induced fetal hypotrophy associated with sex-specific disturbances of the feto-placental unit. In adulthood, the offspring of the H dams were heavier and hyperphagic and had increased blood pressure associated with disturbed gonadal development in both sexes. Vulnerability windows were explored via embryo transfers. The maternal gestational diet was shown to play a key role in the feto-placental phenotype, and preconception programming was unquestionably also observed. These two periods could represent windows of intervention in the context of obesity or being overweight to limit fetal and placental consequences.

Sex effects on carcass characteristics, meat quality traits and meat amino acid and fatty acid compositions in a novel Duroc line pig.

In-depth studies of carcass characters and meat quality could provide insight both for breeding improvement and food development in pigs. Breed and gender are two main factors affected the carcass and meat altitude, which plays important roles in pork industry. The aim of this study was to evaluate the sex effects on carcass characteristics and meat quality traits in a novel Duroc strain pig crossbred from French line, American line and Canadian line pigs. A total of 30 pigs (15 surgical-castrated males and 15 females) with similar birthweight (1.8 ± 0.13 kg) was used in experiment. During the experiment period, all pigs were fed same commercial diets. Overall, female pigs observed higher (p < 0.05) carcass weight, slaughter backfat, loin muscle area, loin muscle depth, carcass yield, pH on 45 min, meat histidine and essential amino acid (AA) compositions, and eicosenoic, unsaturation and free fatty acids (FA) compositions compared with meat from castrated males. Whereas, castrated males' meat showed better altitude (p < 0.05) on meat lightness, meat moisture content percentage, total umami AA and stearic acid and saturated FA compositions than those from female ones. In conclusion, the results of this study provide evidence on the sex effects on meat quality and carcass parameters in Duroc strain pigs. Furthermore, this study also give a reference on the relationship between sex and carcass and meat characteristics in Durco strain pigs.

Mitochondrial effects on fertility and longevity in Tigriopus californicus contradict predictions of the mother's curse hypothesis.

Strict maternal inheritance of mitochondria favours the evolutionary accumulation of sex-biased fitness effects, as mitochondrial evolution occurs exclusively in female lineages. The 'mother's curse' hypothesis proposes that male-harming mutations should accumulate in mitochondrial genomes when they have neutral or beneficial effects on female fitness. Rigorous empirical tests have largely focused on Drosophila, where support for the predictions of mother's curse has been mixed. We investigated the impact of mother's curse mutations in Tigriopus californicus, a minute crustacean. Using non-recombinant backcrosses, we introgressed four divergent mitochondrial haplotypes into two nuclear backgrounds and recorded measures of fertility and longevity. We found that the phenotypic effects of mitochondrial mutations were context dependent, being influenced by the nuclear background in which they were expressed, as well as the sex of the individual and rearing temperature. Mitochondrial haplotype effects were greater for fertility than longevity, and temperature effects were greater for longevity. However, in opposition to mother's curse expectations, females had higher mitochondrial genetic variance than males for fertility and longevity, little evidence of sexual antagonism favouring females was found, and the impacts of mitonuclear mismatch harmed females but not males. Together, this indicates that selection on mitochondrial variation has not resulted in the accumulation of male mutation load in Tigriopus californicus.

Sex, not social behavior, predicts fecal glucocorticoid metabolite concentrations in a facultatively social rodent, the highland tuco-tuco (Ctenomys opimus).

Social relationships may influence circulating glucocorticoid levels, particularly in group-living species in which individuals regularly engage in interactions with conspecifics. The effects of such interactions appear to vary, with greater social contact being associated with increased glucocorticoid concentrations in some species but decreased concentrations in others. These distinct responses raise intriguing questions regarding relationships among social behavior, individual phenotypes, and glucocorticoid physiology. To explore such relationships in a free-living mammal with a dynamic social organization, we quantified variation in baseline glucocorticoids in a population of highland tuco-tucos (Ctenomys opimus) from Jujuy Province, Argentina. These subterranean rodents are facultatively social, with lone and group-living individuals regularly occurring within the same population. To assess potential endocrine correlates of this behavioral variability, we examined differences in baseline fecal glucocorticoid metabolite (fGCm) concentrations as a function of social group size and composition as well as several metrics of social behavior derived from social network analyses. Despite marked variability in social relationships among the 37 (12 male, 25 female) free-living tuco-tucos sampled, none of the measures of social behavior examined were significant predictors of variation in fGCm concentrations. In contrast, individual variation in glucocorticoid metabolites was best explained by sex, with males having higher fGCm concentrations than females. These analyses provide the first characterization of the glucocorticoid physiology of highland tuco-tucos and underscore the potential importance of intrinsic phenotypic factors (e.g., sex) in shaping glucocorticoid variation in free-living mammals.

Sex moderates effects of alcohol and cannabis co-use on alcohol and stress reactivity.

BACKGROUND: Simultaneous or concurrent use (co-use) of alcohol and cannabis is associated with greater use of both substances over time, academic difficulties, more severe substance use consequences, and adverse impacts on cognitive functioning than the use of a single substance or no substance use. This study examined potential neural mechanisms underlying co-use behaviors in comparison to single substance use. Specifically, we compared alcohol cue reactivity and stress-cue reactivity among individuals who reported frequent same-day co-use of alcohol and cannabis and individuals who reported only alcohol use. METHODS: The sample included 88 individuals (41 women) who reported only alcohol use and 24 individuals (8 women) who reported co-use of alcohol and cannabis on at least 50% of drinking occasions. All participants completed fMRI stress and alcohol cue reactivity tasks. Because of known sex effects on stress reactivity and alcohol cue reactivity, we tested sex by co-use interactions. RESULTS: During alcohol cue presentation, co-users had less activation in the thalamus and dorsomedial prefrontal cortex than alcohol-only users, effects that were driven by differences in responses to neutral cues. Examination of stress cue reactivity revealed sex by co-use interactions in the lingual gyrus, with women co-users showing a greater difference between negative and neutral cue reactivity than all other groups. In addition, women co-users had greater connectivity between the nucleus accumbens and both the medial orbitofrontal cortex and the rostral anterior cingulate cortex during negative cue presentation than the other groups. CONCLUSIONS: These results provide preliminary evidence of enhanced stress cue reactivity in individuals reporting co-use of alcohol and cannabis, particularly women co-users.

Age Effects on Women's and Men's Dyadic and Solitary Sexual Desire.

While most studies on sexuality in later life report that sexual desire declines with age, little is known about the exact nature of age effects on sexual desire. Using self-reported dyadic sexual desire relating to a partner, dyadic sexual desire relating to an attractive person, and solitary sexual desire from a large (N > 8000) and age diverse (14.6-80.2 years) online sample, the current study had three goals: First, we investigated relationships between men and women's sexual desire and age. Second, we examined whether individual differences such as gender/sex, sexual orientation, self-rated masculinity, relationship status, self-rated attractiveness, and self-rated health predict sexual desire. Third, we examined how these associations differed across sexual desire facets. On average, the associations between age and both men and women's sexual desire followed nonlinear trends and differed between genders/sexes and types of sexual desire. Average levels of all types of sexual desire were generally higher in men. Dyadic sexual desire related positively to self-rated masculinity and having a romantic partner and solitary desire was higher in people with same-sex attraction. We discuss the results in the context of the evolutionary hypothesis that predict an increase of sexual desire and female reproductive effort prior to declining fertility. Our findings both support and challenge beliefs about gender/sex specificity of age effects on sexual desire and highlight the importance of differentiating between desire types.

Sex-specific metabolic responses to 6 hours of fasting during the active phase in young mice.

KEY POINTS: Night time/active phase food restriction for 6 h impaired glucose intolerance in young male and female mice. Females displayed increased capacity for lipogenesis and triglyceride storage in response to a short daily fast. Females had lower fasting insulin levels and an increased potential for utilizing fat for energy through ß-oxidation compared to males. The need for the inclusion of both sexes, and the treatment of sex as an independent variable, is emphasized within the context of this fasting regime. ABSTRACT: There is growing interest in understanding the mechanistic significance and benefits of fasting physiology in combating obesity. Increasing the fasting phase of a normal day can promote restoration and repair mechanisms that occur during the post-absorptive period. Most studies exploring the effect of restricting food access on mitigating obesity have done so with a large bias towards the use of male mice. Here, we disentangle the roles of sex, food intake and food withdrawal in the response to a short-term daily fasting intervention, in which food was removed for 6 h in the dark/active phase of young, 8-week-old mice. We showed that the removal of food during the dark phase impaired glucose tolerance in males and females, possibly due to the circadian disruption induced by this feeding protocol. Although both sexes demonstrated similar patterns of food intake, body composition and various metabolic markers, there were clear sex differences in the magnitude and extent of these responses. While females displayed enhanced capacity for lipogenesis and triglyceride storage, they also had low fasting insulin levels and an increased potential for utilizing available energy sources such as fat for energy through ß-oxidation. Our results highlight the intrinsic biological and metabolic disparities between male and female mice, emphasizing the growing need for the inclusion of both sexes in scientific research. Furthermore, our results illustrate sex-specific metabolic pathways that regulate lipogenesis, obesity and overall metabolic health.

Genetic and environmental influences on functional connectivity within and between canonical cortical resting-state networks throughout adolescent development in boys and girls.

The human brain is active during rest and hierarchically organized into intrinsic functional networks. These functional networks are largely established early in development, with reports of a shift from a local to more distributed organization during childhood and adolescence. It remains unknown to what extent genetic and environmental influences on functional connectivity change throughout adolescent development. We measured functional connectivity within and between eight cortical networks in a longitudinal resting-state fMRI study of adolescent twins and their older siblings on two occasions (mean ages 13 and 18 years). We modelled the reliability for these inherently noisy and head-motion sensitive measurements by analyzing data from split-half sessions. Functional connectivity between resting-state networks decreased with age whereas functional connectivity within resting-state networks generally increased with age, independent of general cognitive functioning. Sex effects were sparse, with stronger functional connectivity in the default mode network for girls compared to boys, and stronger functional connectivity in the salience network for boys compared to girls. Heritability explained up to 53% of the variation in functional connectivity within and between resting-state networks, and common environment explained up to 33%. Genetic influences on functional connectivity remained stable during adolescent development. In conclusion, longitudinal age-related changes in functional connectivity within and between cortical resting-state networks are subtle but wide-spread throughout adolescence. Genes play a considerable role in explaining individual variation in functional connectivity with mostly stable influences throughout adolescence.

Correlates of blood parasitism in a threatened marshland passerine: infection by kinetoplastids of the genus Trypanosoma is related to landscape metrics of habitat edge.

In birds, vector-borne parasites invading the bloodstream are important agents of disease, affect fitness and shape population viability, thus being of conservation interest. Here, we molecularly identified protozoan blood parasites in two populations of the threatened Aquatic Warbler Acrocephalus paludicola, a migratory passerine nesting in open marsh. We explored whether prevalence and lineage diversity of the parasites vary by population and whether infection status is explained by landscape metrics of habitat edge and individual traits (body mass, fat score, wing length and sex). Aquatic Warblers were infected by genera Plasmodium, Leucocytozoon and Trypanosoma, with seven, one and four lineages, and 29.9, 0.7 and 12.5% prevalence, respectively. No Haemoproteus infections were detected. Prevalence did not vary between the populations, but lineage diversity was higher in Polesie than in Biebrza for all the lineages pooled and for Plasmodium. Infection by Trypanosoma decreased with patch core area and increased with density of habitat edge. Infection status was not predicted by the individual traits. Our study is the first to show an association between edge-related landscape features and blood parasitism in an open habitat bird. This finding will support informed conservation measures for avian species of the globally shrinking marshland and other treeless habitats.

Diffusion tensor imaging of white matter and correlates to eye movement control and psychometric testing in children with prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can cause central nervous system dysfunction and widespread structural anomalies as detected by magnetic resonance imaging (MRI). This study focused on diffusion tensor imaging (DTI) of white matter in a large sample of PAE participants that allowed us to examine correlations with behavioral outcomes. Participants were confirmed PAE (n = 69, mean age = 12.5 ± 3.2 years) or typically developing control children (n = 67, mean age = 12.1 ± 3.2 years) who underwent brain MRI, eye movement tasks, and psychometric tests. A semi-automated tractography method extracted fractional anisotropy (FA) and mean diffusivity (MD) values from 15 white matter tracts. The PAE group displayed decreased FA compared with controls in multiple tracts including 3 corpus callosum regions, right corticospinal tract, and 3 left hemisphere tracts connecting to the frontal lobe (cingulum, uncinate fasciculus, and superior longitudinal fasciculus). Significant group by sex interactions were found for the genu, left superior longitudinal fasciculus, and the left uncinate, with females in the PAE group exhibiting lower FA compared with control females. Correlations were found between DTI and eye movement measures in the control group, but these same relationships were absent in the PAE group. In contrast, no correlations were found between DTI and any of the psychometric tests used in this study. These findings support the hypothesis that measures of eye movement control may be valuable functional biomarkers of the brain injury induced by PAE as these tasks reveal group differences that appear to be linked to deficits in white matter integrity in the brain. Hum Brain Mapp 38:444-456, 2017. © 2016 Wiley Periodicals, Inc.

Is there a sex effect in colon cancer? Disease characteristics, management, and outcomes in routine clinical practice.

INTRODUCTION: The incidence of colon cancer varies by sex. Whether women and men show differences in extent of disease, treatment, and outcomes is not well described. We used a large population-based cohort to evaluate sex differences in colon cancer. METHODS: Using the Ontario Cancer Registry, all cases of colon cancer treated with surgery in Ontario during 2002-2008 were identified. Electronic records of treatment identified use of surgery and adjuvant chemotherapy. Pathology reports for a random 25% sample of all cases were obtained, and disease characteristics, treatment, and outcomes in women and men were compared. A Cox proportional hazards model was used to identify factors associated with overall (os) and cancer-specific survival (css). RESULTS: The study population included 7249 patients who underwent resection of colon cancer; 49% (n = 3556) were women. Stage of disease and histologic grade did not vary by sex. Compared with men, women were more likely to have right-sided disease (55% vs. 44%, p ≤ 0.001). Surgical procedure and lymph node yield did not differ by sex. Adjuvant chemotherapy was delivered to 18% of patients with stage ii and 64% of patients with stage iii disease; when adjusted for patient- and disease-related factors, use of adjuvant chemotherapy was similar for women and men [relative risk: 0.99; 95% confidence interval (ci): 0.94 to 1.03]. Adjusted analyses demonstrated that os [hazard ratio (hr): 0.80; 95% ci: 0.75 to 0.86] and css (hr: 0.82; 95% ci: 0.76 to 0.90) were superior for women compared with men. CONCLUSIONS: Long-term survival after colon cancer is significantly better for women than for men, which is not explained by any substantial differences in extent of disease or treatment delivered.

A National Swedish Twin-Sibling Study of Alcohol Use Disorders.

The relationship between the genetic and environmental risk factors for alcohol use disorders (AUD) detected in Swedish medical, pharmacy, and criminal registries has not been hitherto examined. Prior twin studies have varied with regard to the detection of shared environmental effects and sex differences in the etiology of AUD. In this report, structural equation modeling in OpenMx was applied to (1) the three types of alcohol registration in a population-based sample of male-male twins and reared-together full and half siblings (total 208,810 pairs), and (2) AUD, as a single diagnosis, in male-male, female-female, and opposite-sex (OS) twins and reared-together full and half siblings (total 787,916 pairs). An independent pathway model fit best to the three forms of registration and indicated that between 70% and 92% of the genetic and 63% and 98% of the shared environmental effects were shared in common with the remainder unique to each form of AUD registration. Criminal registration had the largest proportion of unique genetic and environmental factors. The best fit model for AUD estimated the heritability to be 22% and 57%, respectively, in females and males. Both shared (12% vs. 6%) and special twin environment (29% vs. 2%) were substantially more important in females versus males. In conclusion, AUD ascertained from medical, pharmacy, and criminal Swedish registries largely share the same genetic and environmental risk factors. Large sex differences in the etiology of AUD were seen in this sample, with substantially stronger familial environmental and weaker genetic effects in females versus males.

Sex- and age-specific associations between major depressive disorder and metabolic syndrome in two general population samples in Germany.

BACKGROUND AND AIMS: Major depressive disorder (MDD) has been associated with the Metabolic Syndrome (MetS). As previous data strongly suggested sex and age effects on this association, this study aimed to analyse the association between MDD and MetS in two general population samples under explicit consideration of sex and age. METHODS: This study analysed cross-sectional data based on two independent general population samples: SHIP-0 (n = 4083; 20-81 years; 49.4% male) and SHIP-TREND-0 (n = 3957; 20-83 years; 49.0% male) that were part of the Study of Health in Pomerania. MDD (SHIP-0: 12.6%; SHIP-TREND-0: 27.2%) was assessed using the Composite International Diagnostic-Screener (CID-S) in both samples. Interview assessment of MDD diagnosis according to Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria was performed in SHIP-TREND-0 (18.1% MDD). MetS was defined by abdominal obesity, elevated blood pressure, elevated glucose, elevated triglycerides and reduced high-density lipoprotein cholesterol according to established criteria. Data analysis was performed sex- and age-stratified. RESULTS: Prevalence of MetS was high in both samples: 19.4% of females and 30.2% of males in SHIP-0 and 22.1% and 33.2% in SHIP-TREND-0, respectively. Effect modifications were observed by sex and age on the association between MDD and MetS. Particularly, younger females (20-49 years) with MDD were more often affected by MetS than younger females without MDD: OR = 2.21 (95% CI = 1.39-3.50). This association vanished in elderly participants (50-82 years). CONCLUSION: The data suggest that especially younger (presumably pre-menopausal) females with MDD are more likely to have MetS than those without major depressive disorders, and that age extenuates this association.

Evidence for litter differences in play behaviour in pre-weaned pigs.

The aim of this study was to analyse spontaneous play behaviour in litters of domestic pigs (Sus scrofa) for sources of variation at individual and litter levels and to relate variation in play to measures of pre and postnatal development. Seven litters of commercially bred piglets (n = 70) were born (farrowed) within a penning system (PigSAFE) that provided opportunities for the performance of spontaneous play behaviours. Individual behaviour was scored based on an established play ethogram for 2 days per week over the 3 week study period. We found strong evidence of litter differences in play behaviour (F(6,63) = 27.30, p < 0.001). Of the variance in total play, 50% was attributable to differences between litters with a lesser proportion (11%) to between piglets within litters. We found similar evidence of litter differences when we analysed the separate play categories (e.g. for locomotor play: F(6,63) = 27.50, p < 0.001). For social and locomotor play the variance was partitioned in a broadly similar way to total play; however for object play the variance was distributed with a more even balance across and within litters. In terms of explanatory factors we found little evidence that at the litter level differences in play were associated with differences in general activity. Of the prenatal factors measured, we found that birth weight was positively associated with total play and the play categories (e.g. with total play: F(1,64) = 12.8, p < 0.001). We also found that postnatal piglet growth up to weaning (as a percentage of birth weight) had a significant positive association with total play and the play categories (e.g. with object play: F(1,66) = 20.55, p < 0.001). As found in other studies, on average males engaged in more social play (e.g. non-injurious play fighting: F(1,63) = 39.8, p < 0.001). Males also initiated more play bouts on average than females (F(1,62) = 4.41, p = 0.040). We conclude that the study of differences between litters and individuals provides a robust approach to understanding factors potentially influencing play behaviour in the pig. This work also provides support for the use of play as a welfare indicator in pre-weaned piglets as the litter differences in play we observed were associated positively with physical development.

Interaction between sex and early-life stress: influence on epileptogenesis and epilepsy comorbidities.

Epilepsy is a common brain disorder which is characterised by recurring seizures. In addition to suffering from the constant stress of living with this neurological condition, patients also frequently experience comorbid psychiatric and cognitive disorders which significantly impact their quality of life. There is growing appreciation that stress, in particular occurring in early life, can negatively impact brain development, creating an enduring vulnerability to develop epilepsy. This aligns with the solid connections between early life environments and the development of psychiatric conditions, promoting the possibility that adverse early life events could represent a common risk factor for the later development of both epilepsy and comorbid psychiatric disorders. The influence of sex has been little studied, but recent research points to potential important interactions, particularly with regard to effects mediated by HPA axis programming. Understanding these interactions, and the underlying molecular mechanisms, will provide important new insights into the causation of both epilepsy and of psychiatric disorders, and potentially open up novel avenues for treatment.