Sex Differences in Intestinal Carbohydrate Metabolism Promote Food Intake and Sperm Maturation.

Physiology and metabolism are often sexually dimorphic, but the underlying mechanisms remain incompletely understood. Here, we use the intestine of Drosophila melanogaster to investigate how gut-derived signals contribute to sex differences in whole-body physiology. We find that carbohydrate handling is male-biased in a specific portion of the intestine. In contrast to known sexual dimorphisms in invertebrates, the sex differences in intestinal carbohydrate metabolism are extrinsically controlled by the adjacent male gonad, which activates JAK-STAT signaling in enterocytes within this intestinal portion. Sex reversal experiments establish roles for this male-biased intestinal metabolic state in controlling food intake and sperm production through gut-derived citrate. Our work uncovers a male gonad-gut axis coupling diet and sperm production, revealing that metabolic communication across organs is physiologically important. The instructive role of citrate in inter-organ communication might be significant in more biological contexts than previously recognized.

The gender gap in the ownership of promising land.

Using millions of observations compiled from the public administrative data of Taiwan, we find a surprising gender inequity in terms of real estate: Men own more land than women, and the annual rate of return (ROR) of men's land outperform women's by almost 1% per year. The latter finding of gender-based ROR difference is in sharp contrast to prior evidence that women outperform men in security investment, and also suggests a quantity-and-quality double jeopardy in female land ownership which, given the heavy weight of real estate in individual wealth, has important implications for wealth inequality among men and women. Our statistical analyses suggest that such a gender-based difference in land ROR cannot be attributed to individual-level factors such as liquidity preferences, risk attitudes, investment experience, and behavioral biases, as described in the literature. Rather, we hypothesize parental gender bias-a phenomenon that is still prevalent today-to be the key macrolevel factor. To test our hypothesis, we partition our observations into two groups: an experimental group in which parents can exercise gender discretion, and a control group in which parents cannot exercise such discretion. Our empirical evidence shows that the gender difference with respect to land ROR only exists in the experimental group. For many societies with long-lasting patriarchal traditions, our analysis provides a perspective to help explain gender differences in wealth distribution and social mobility.

Competitiveness among Nandi female husbands.

In the Nandi society in Kenya, custom establishes that a woman's "house property" can only be transmitted to male heirs. As not every woman gives birth to a male heir, the Nandi solution to sustain the family lineage is for the heirless woman to become the "female husband" to a younger woman by undergoing an "inversion" ceremony to "change" into a man. This biological female, now socially a man, becomes a "husband" and a "father" to the younger woman's children, whose sons become the heirs of her property. Using this unique separation of biological sex and social roles holding constant the same society, I conduct competitiveness experiments. Similar to Western cultures, I find that Nandi men choose to compete at roughly twice the rate as Nandi women. Importantly, however, female husbands compete at the same rate as males, and thus around twice as often as females. These findings are robust to controlling for several risk aversion, selection, and behavioral factors. The results provide support for the argument that social norms, family roles, and endogenous preference formation are crucially linked to differences in competitiveness between men and women.

Women and Men are the Barometers of Relationships: Testing the Predictive Power of Women's and Men's Relationship Satisfaction.

There is a longstanding belief in relationship science and popular opinion that women are the barometers in mixed-gender relationships such that their perceptions about the partnership carry more weight than men's in predicting future relationship satisfaction, but this idea has yet to be rigorously tested. We analyze data from two studies to test within-person links between men's and women's relationship satisfaction on their own and their partner's next-day and next-year satisfaction. Study 1 combined nine daily diary datasets from Canada and the United States with 901 mixed-gender couples who provided 29,541 daily reports of relationship satisfaction. Study 2 analyzed five annual waves of data from the German Family Panel (pairfam) that surveyed 3,405 mixed-gender couples who provided 21,115 relationship satisfaction reports. Latent curve models with structured residuals (LCM-SR) revealed that in both studies, men's and women's relationship satisfaction significantly predicted their own and their partner's relationship satisfaction, with no gender differences in the magnitude of these effects. Results underscore the interdependence of romantic partners' satisfaction and indicate that both men and women jointly shape romantic relationship satisfaction.

Sex-dependent phosphorylation of Argonaute 2 reduces the mitochondrial translocation of miR-181c and induces cardioprotection in females.

Obesity-induced cardiac dysfunction is growing at an alarming rate, showing a dramatic increase in global prevalence. Mitochondrial translocation of miR-181c in cardiomyocytes results in excessive reactive oxygen species (ROS) production during obesity. ROS causes Sp1, a transcription factor for MICU1, to be degraded via post-translational modification. The subsequent decrease in MICU1 expression causes mitochondrial Ca2+ accumulation, ultimately leading to a propensity for heart failure. Herein, we hypothesized that phosphorylation of Argonaute 2 (AGO2) at Ser 387 (in human) or Ser 388 (in mouse) inhibits the translocation of miR-181c into the mitochondria by increasing the cytoplasmic stability of the RNA-induced silencing complex (RISC). Initially, estrogen offers cardioprotection in pre-menopausal females against the consequences of mitochondrial miR-181c upregulation by driving the phosphorylation of AGO2. Neonatal mouse ventricular myocytes (NMVM) treated with insulin showed an increase in pAGO2 levels and a decrease in mitochondrial miR-181c expression by increasing the binding affinity of AGO2-GW182 in the RISC. Thus, insulin treatment prevented excessive ROS production and mitochondrial Ca2+ accumulation. In human cardiomyocytes, we overexpressed miR-181c to mimic pathological conditions, such as obesity/diabetes. Treatment with estradiol (E2) for 48 h significantly lowered miR-181c entry into the mitochondria through increased pAGO2 levels. E2 treatment also normalized Sp1 degradation and MICU1 transcription that normally occurs in response to miR-181c overexpression. We then investigated these findings using an in vivo model, with age-matched male, female and ovariectomized (OVX) female mice. Consistent with the E2 treatment, we show that female hearts express higher levels of pAGO2 and thus, exhibit higher association of AGO2-GW182 in cytoplasmic RISC. This results in lower expression of mitochondrial miR-181c in female hearts compared to male or OVX groups. Further, female hearts had fewer consequences of mitochondrial miR-181c expression, such as lower Sp1 degradation and significantly decreased MICU1 transcriptional regulation. Taken together, this study highlights a potential therapeutic target for conditions such as obesity and diabetes, where miR-181c is upregulated. NEW AND NOTEWORTHY: In this study, we show that the phosphorylation of Argonaute 2 (AGO2) stabilizes the RNA-induced silencing complex in the cytoplasm, preventing miR-181c entry into the mitochondria. Furthermore, we demonstrate that treatment with estradiol can inhibit the translocation of miR-181c into the mitochondria by phosphorylating AGO2. This ultimately eliminates the downstream consequences of miR-181c overexpression by mitigating excessive reactive oxygen species production and calcium entry into the mitochondria.

Sex and survival outcomes in patients with renal cell carcinoma receiving first-line immune-based combinations.

BACKGROUND: There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking. METHOD: This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy. RESULTS: A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7-44.2) in the overall study population: 40.0 months (95% CI 32.7-51.6) in males and 38.7 months (95% CI 26.4-41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0-51.6, vs. 24.8 months, 95% CI 16.8-40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8-55.7, vs. 38.7 months, 95% CI 26.0-41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4-59.0, vs. 15.3 months, 95% CI 8.9-41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 - 2.57, p = 0.008). CONCLUSIONS: Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.

Effects of sleep deprivation on language-related brain functional connectivity: differences by gender and age.

Sleep deprivation (SD) negatively affects many cognitive functions, such as language performance. However, what remains unclear is whether and how SD affects the language-related brain network based on gender and age differences. The current study of 86 healthy adults used resting-state functional magnetic resonance imaging (rs-fMRI) to measure language-related functional connectivity after full sleep or partial SD. Gender and age differences in functional connectivity were assessed across four linguistic aspects: phonetics, morphology, semantics, and syntax. The results showed that SD can affect the connectivity status of language-related brain networks, especially syntax-related networks. Furthermore, the influence of SD on the functional connectivity in language-related networks differed between male and female groups, and between younger and older groups. Specifically, there were gender differences in the temporal association cortex and age differences in the parietal association cortex, during full sleep versus partial SD. These findings highlight changes in the brain's functional connectivity in response to SD as a potential source of gender and age differences in brain function.

Gender equality in medical research: A cardiology-informed examination.

Despite a perceived increase in attention to gender differences in medicine, a comprehensive assessment of gender equality research, particularly in cardiology, remains underexplored. This observational retrospective study, focusing on documents related to "Gender Equality" according to the Sustainable Development Goals, reveals cardiology as a significant area for gender equality research, albeit with a decline in publications post-2018. The analysis highlighted a concentrated effort in the United States and a considerable impact gap between gender-focused and general cardiology research. The global academic community must intensify research into gender disparities, which is essential for achieving professional gender equality and addressing the burden of cardiovascular diseases.

Association between NTCP hepatic expression and inflammation/fibrosis as well as gender-specific differences in chronic HBV-infected patients.

To investigate the relationship between the expression of hepatitis B virus (HBV) functional receptor sodium taurocholate cotransporting polypeptide (NTCP) with disease progression and gender-specific differences in chronic HBV-infected patients. Liver samples were collected from chronic HBV-infected patients who underwent percutaneous liver biopsy or liver surgery. HBV DNA levels and the mRNA and protein expression levels of NTCP in liver tissues were determined. The relationship between NTCP expression and HBV DNA levels, inflammatory activity, fibrosis, and gender-specific differences were analyzed. A total of 94 chronic HBV-infected patients were included. Compared with patients with a METAVIR score of A0-1 or F0-1, patients with score of A2 or F2/F3 had a relatively higher level of NTCP expression. NTCP levels were positively correlated with HBV DNA levels. The inflammatory activity scores and fibrosis scores of women <50 years were significantly lower than those of women ≥50 years and age-matched males. In patients with score A0-2 or F0-3, women <50 years have lower NTCP expression level compared to women ≥50 years and age-matched males. NTCP can promote the disease progression by affecting the viral load of HBV. The NTCP expression difference may be why male and postmenopausal women are more prone to disease progression than reproductive women.

A Comprehensive Analysis of Leadership Attributes, Discrepancies, and Implications for Gender Equity in Vascular Surgery.

OBJECTIVE: Well-developed leadership skills have been associated with a better understanding of healthcare context, increased team performance, and improved patient outcomes. Surgeons, in particular, stand to benefit from leadership development. While studies have focused on investigating knowledge gaps and needs of surgeons in leadership roles, there is a noticeable gap in the literature concerning leadership in Vascular Surgery. The goal of this study was to characterize current leadership attributes of vascular surgeons and understand demographic influences on leadership patterns. METHODS: This retrospective cohort study was a descriptive analysis of vascular surgeons and their observers who took the leadership practice inventory (LPI) from 2020 to 2023. The LPI is a 30 question inventory that measures the frequency of specific leadership behaviors across five practices of leadership. RESULTS: A total of 110 vascular surgeons completed the LPI. The majority of participants were white (56%) and identified as male (60%). Vascular surgeons most frequently observed the "enabling others to act" leadership practice style (8.90 ± 0.74) by all evaluators. Vascular surgeons were most frequently above the 70th percentile in the "challenge the process" leadership practice style (49%) compared to the average of other leaders world-wide. Observers rated vascular surgeons as displaying significantly more frequent leadership behaviors than vascular surgeons rated themselves in every leadership practice style (P-value < 0.01). The only demographic variable associated with a significantly increased occurrence of achieving 70th percentile across all five leadership practice styles was the male gender: a multivariable model adjusting for objective experience showed men were at least 3.5 times more likely to be rated above the 70th percentile than women. CONCLUSIONS: Vascular surgeons under report the frequency at which they practice leadership skills across all five leadership practice styles and should recognize their strengths of enabling others to act and challenging the process. Men are recognized as exhibiting all five leadership practices more frequently than women, regardless of current position or experience level. This observation may reflect the limited leadership positions available for women, thereby restricting their opportunities to demonstrate leadership practices as frequently or recognizably as their male counterparts.

Is There a Bias Towards Males in the Diagnosis of Autism? A Systematic Review and Meta-Analysis.

Autism is more frequently diagnosed in males, with evidence suggesting that females are more likely to be misdiagnosed or underdiagnosed. Possibly, the male/female ratio imbalance relates to phenotypic and camouflaging differences between genders. Here, we performed a comprehensive approach to phenotypic and camouflaging research in autism addressed in two studies. First (Study 1 - Phenotypic Differences in Autism), we conducted a systematic review and meta-analysis of gender differences in autism phenotype. The electronic datasets Pubmed, Scopus, Web of Science, and PsychInfo were searched. We included 67 articles that compared females and males in autism core symptoms, and in cognitive, socioemotional, and behavioural phenotypes. Autistic males exhibited more severe symptoms and social interaction difficulties on standard clinical measures than females, who, in turn, exhibited more cognitive and behavioural difficulties. Considering the hypothesis of camouflaging possibly underlying these differences, we then conducted a meta-analysis of gender differences in camouflaging (Study 2 - Camouflaging Differences in Autism). The same datasets as the first study were searched. Ten studies were included. Females used more compensation and masking camouflage strategies than males. The results support the argument of a bias in clinical procedures towards males and the importance of considering a 'female autism phenotype'-potentially involving camouflaging-in the diagnostic process.

The influence of gender-specific factors influencing severe anxiety in psychotic major depression: role of thyroid hormones and depression severity.

BACKGROUND: Psychotic major depression (PMD) is characterized by major depressive disorder (MDD) accompanied by delusions or hallucinations. While the prevalence of PMD and its association with anxiety have been studied, gender-specific differences and the role of thyroid hormones in PMD-related anxiety remain less explored. METHODS: A total of 1718 first-episode and drug-naïve MDD patients was assessed for the presence of PMD and severe anxiety. Clinical assessments, including Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impressions-Severity (CGI-S) scale, were conducted to assess depression, anxiety, psychotic symptoms, and clinical severity, respectively. Blood samples were collected to measure thyroid function parameters. RESULTS: The prevalence of severe anxiety was higher in PMD patients compared to non-psychotic MDD patients (71.3% vs. 5.3%). No significant gender differences were observed in the prevalence of severe anxiety among PMD patients. However, elevated thyroid-stimulating hormone (TSH) levels and increased depression severity (HAMD scores) were identified as independent risk factors for severe anxiety in female PMD patients. In contrast, no significant risk factors were found in male PMD patients. The area under the receiver operating characteristic (AUCROC) analysis revealed that the HAMD score and TSH level showed acceptable discriminatory capacity for distinguishing between female PMD patients with and without severe anxiety. CONCLUSION: This study highlights the heightened prevalence of severe anxiety in PMD patients, with TSH levels and depression severity emerging as gender-specific risk factors for anxiety in females. These findings suggest the importance of thyroid hormone assessment and tailored interventions for managing anxiety in female PMD patients.

Research Review: A systematic review and meta-analysis of sex differences in narrow constructs of restricted and repetitive behaviours and interests in autistic children, adolescents, and adults.

BACKGROUND: Evidence that autism often manifests differently between males and females is growing, particularly in terms of social interaction and communication, but it is unclear if there are sex differences in restricted and repetitive behaviours and interests (RRBIs) when rigorously focusing on the narrow construct level (i.e., stereotyped behaviour, restricted interests, insistence on sameness, and/or sensory experiences). METHODS: We conducted a systematic review and four random effects meta-analyses investigating sex differences in narrow construct measures of RRBIs in autistic children, adolescents, and adults (Prospero registration ID: CRD42021254221). Study quality was appraised using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Forty-six studies were narratively synthesised and 25 of these were included in four random effects meta-analyses. Results found that autistic males had significantly higher levels of stereotyped behaviours (SMD = 0.21, 95% confidence interval (CI) [0.09, 0.33], p < .001) and restricted interests (SMD = 0.18, 95% CI [0.07, 0.29], p < .001) compared to autistic females. In contrast, there were no significant sex differences for sensory experiences (SMD = -0.09, 95% CI [-0.27, 0.09], p = .32) and insistence on sameness (SMD = 0.01, 95% CI [-0.03, 0.05], p = .68). The findings from the narrative synthesis were generally consistent with those from the meta-analyses and also found qualitative sex differences in the way RRBIs manifest. CONCLUSIONS: Our findings show significant differences in narrowly defined RRBIs in males and females. Practitioners need to be aware of such differences, which could be contributing to the under-recognition of autism in females and may not be captured by current diagnostic instruments.

Nightmares in Swiss elite athletes: Associated factors.

Nightmares, defined as extremely dysphoric dreams, can cause significant distress in everyday life if they occur frequently. Their aetiology is based on a disposition-stress model. As elite athletes often experience high stress levels, the present study investigated factors that might be associated with nightmare frequency in a large cohort of 2297 Swiss elite athletes (1066 women, 1231 men) with a mean age of 22.05 ± 7.53 years. In total, about 6% of the athletes reported frequent nightmares (once a week or more often). We found that well-established factors like female gender and general stress levels were related to nightmare frequency. To a smaller extent, the number of training hours, lost training days due to illness, and having early training sessions were also associated with nightmare frequency. Sport discipline was not related to nightmare frequency. An unexpected finding was the association between late alcohol intake 4 hr prior to bedtime and nightmare frequency. Our findings support the idea that stress related to practicing sports might affect nightmare frequency. Future research should study whether inventions designed for athletes suffering from frequent nightmares are beneficial for them and might even improve their athletic performance.

Gender differences in scholarly productivity of early-career transfusion medicine physicians.

BACKGROUND AND OBJECTIVES: Promotion in academic medicine requires evidence of the creation and dissemination of scholarly output, primarily through peer-reviewed publications. Studies demonstrate that scholarly activity and impact are lower for women physicians than for men physicians, especially during the early stages of their academic careers. This report reviewed physicians' academic productivity after passing their Blood Banking/Transfusion Medicine (BBTM) subspecialty exam to determine if gender discrepancies exist. METHODS: A cross-sectional analysis was designed to determine trends in scholarly activity for women physicians versus men physicians in BBTM. Indexed publications were reviewed using iCite, the National Institutes of Health (NIH) Office of Portfolio Analysis tool, from 1 January 2017 to 1 December 2021, for BBTM examinees who passed the sub-speciality fellowship exam in the years 2016 through 2018. RESULTS: Overall, women physicians had statistically significant fewer total career publications (median 6 vs. 9 cumulative papers, p = 0.03). Women published at a lower rate after passing BBTM boards, which was not statistically significant (0.7 vs. 1.3 publications per year). Other statistically significant findings include fewer early-career BBTM women physicians were first authors compared with men physicians (p = 0.03) and impact as assessed by relative citation ratio was higher for men (p = 0.01). CONCLUSIONS: This study demonstrates that there are gender differences in scholarly productivity and impact on early-career BBTM physicians. Given that this cohort of BBTM physicians are early-career professionals, the significant difference in first authorship publications between women and men physicians is especially concerning. Publication metrics should be followed to ensure equitable research environments for early-career BBTM physicians.

Gender differences in self-assessed performance and stress level during training of basic interventional radiology maneuvers.

OBJECTIVES: Gender differences have been reported to influence medical training. We investigated gender differences encountered during training in interventional radiology maneuvers. METHODS: Catheter handling was analyzed under standardized conditions in 64 participants naïve to endovascular procedures (26 women, 38 men). Objective (e.g., catheter pathway, catheter movements, required time) and subjective parameters (stress level) were recorded. The NASA-Task Load Index (NASA-TLX; 1-20 points) was used to assess participants' stress levels and perceived workload. RESULTS: In the easier tasks, no significant differences between male and female participants regarding catheter handling were observed. In the most complex task, female participants took themselves more time (688 ± 363 vs. 501 ± 230 s; p = 0.02), asked for help more frequently (n = 19 vs. n = 8) and earlier than men (203 ± 94 vs. 305 ± 142 s; p = 0.049), whereas men stood out by more agitated catheter handling (6.0 ± 1.8 vs. 4.8 ± 1.6 movements/s; p = 0.005). Overall, female participants perceived tasks to be more difficult (11.5 ± 4.2 vs. 9.6 ± 3.3; p = 0.016), perceived higher stress levels (8.9 ± 4.9 vs. 6.3 ± 4.4; p = 0.037), and rated their own performance lower (9.12 ± 3.3 vs. 11.3 ± 3.3; p = 0.009). However, female participants were able to correlate self-assessed with objective parameters correctly (r between -0.555 and -0.469; p = 0.004-0.018), whereas male participants failed to correctly rate their performance (p between 0.34 and 0.73). Stress levels correlated with objective parameters in males (r between 0.4 and 0.587; p < 0.005), but not in female participants. CONCLUSION: Perceived stress levels, self-evaluation skills, and catheter handling differ greatly between untrained male and female participants trying to solve interventional radiological tasks. These gender-specific differences should be considered in interventional radiology training. CLINICAL RELEVANCE STATEMENT: As psychological aspects may influence individual working strategies gender-specific differences in self-perception while learning interventional radiology maneuvers could be essential regarding success in teaching and treatment outcomes. KEY POINTS: • After performing standardized training, 38 male and 26 female volunteers showed significant differences regarding objective and self-assessed performance, as well as in perceived workload while performing simulated endovascular catheter maneuvers. • After solving simulated endovascular radiological tasks, female participants were able to self-assess their objective performance much more accurately than male participants. • Women took more time to solve simulated endovascular tasks and asked earlier and more frequently for help than men.

Smoking and pulmonary health in women: A narrative review and behavioral health perspective.

OBJECTIVE: Cigarette smoking prevalence has declined slower among women than men, and smoking-related pulmonary disease (PD) has risen among women. Given these trends, there is a critical need to understand and mitigate PD risk among women who smoke. The purpose of this narrative review and commentary is to highlight important evidence from the literature on smoking and PD among women. METHODS: This review focuses broadly on examining cigarette smoking and PD among women within six topic areas: (1) demographic characteristics and prevalence of smoking, (2) smoking behavior, (3) lung cancer, (4) obstructive PD, (5) diagnostic and treatment disparities, and (6) gaps in the literature and potential directions for future research and treatment. RESULTS: Growing evidence indicates that compared to men, women are at increased risk for developing smoking-related PD and poorer PD outcomes. Gender disparities in smoking-related PD may be largely accounted for by genetic differences and sex hormones contributing to PD pathogenesis and presentation, smoking behavior, nicotine dependence, and pathogen/carcinogen clearance. Moreover, gender disparities in smoking-related PD may be exacerbated by important social determinants (e.g., women with less formal education and those from minoritized groups may be at especially high risk for poor PD outcomes due to higher rates of smoking). CONCLUSION: Rising rates of smoking-related PD among women risk widening diagnostic and treatment disparities. Ongoing research is needed to explore potentially complex relationships between sex, gender, and smoking-related PD processes and outcomes, and to improve smoking-cessation and PD treatment for women.

Polygenic risk, childhood abuse and gene x environment interactions with depression development from middle to late adulthood: A U.S. national life-course study.

OBJECTIVE: Utilizing national longitudinal data, this study examines how polygenic depression risk and childhood abuse interactively influence the life-course development of depressive conditions from middle to late adulthood. METHOD: Data from 7512 participants (4323 females and 3189 males) of European ancestry aged 51-90, retrieved from the U.S. Health and Retirement Study (1992-2020), were analyzed. Childhood physical abuse and polygenic depression score were the primary predictors. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression (CESD) scale, and clinical depression risk was a binary indicator. Growth-curve linear mixed and logit mixed-effects models were conducted for analysis. RESULTS: Increasing polygenic depression scores were associated with elevated CES-D levels and potential risks of clinical depression. Males experienced more detrimental effects of childhood abuse on depression development from ages 51 to 90 years. In contract, non-maltreated females generally exhibited higher depressive symptoms and clinical depression risk than males. A significant interactive effect was found between polygenic depression risk and childhood abuse among males. Higher depression levels and clinical risk were observed with increasing polygenic depression score among maltreated males, surpassing those of females with standardized polygenic score ≥0 from age 51 to 90 years. CONCLUSIONS: The interaction between childhood abuse and genetic factors significantly shaped lifelong depression trajectories in males, while the negative impact of abusive parenting remained constant regardless of polygenic depression risk among females. Individualized prevention and intervention strategies could be crucial in mitigating lifelong depression development, especially for high-genetic-risk males with a history of childhood physical abuse.

The association between perceived social functioning and heart rate variability is mediated by subclinical depressive symptomatology and moderated by gender.

Chronic loneliness and low perceived social support have been recognized as risk factors for both mental and cardiovascular disorders. It has been proposed that their link to psychophysiological problems may involve changes in parasympathetic activity. However, the exact underlying psychopathological mechanisms and the moderating effects of gender are still not thoroughly examined. Thus, the present study investigated associations between perceived social functioning and resting vagal tone in the context of potential cognitive and subclinical mediators and gender differences. Three hundred twenty-five young adults (aged 18-35, 180 women) underwent an electrocardiogram measurement of 6-minute resting heart rate variability (HRV). They also completed questionnaires assessing loneliness, perceived social support, social cognitive biases, depressive and social anxiety symptoms, and general mental health. In men, HRV was significantly and negatively associated with poorer perceived social functioning, depressive symptoms, and self-reported social cognitive biases, while in women, there was a quadratic link between HRV and depressive symptoms and HRV and general mental health. Moderated mediation analysis revealed that depressive symptoms fully mediated the relationship between perceived social functioning and HRV in men. The results suggest that decreased resting vagal tone in lonely individuals is linked to depressive symptomatology rather than to specific social cognitive biases and that this association is significant only in men.

Greater sensitivity of the circadian system of women to bright light, but not dim-to-moderate light.

Women typically sleep and wake earlier than men and have been shown to have earlier circadian timing relative to the light/dark cycle that synchronizes the clock. A potential mechanism for earlier timing in women is an altered response of the circadian system to evening light. We characterized individual-level dose-response curves for light-induced melatonin suppression using a within-subjects protocol. Fifty-six participants (29 women, 27 men; aged 18-30 years) were exposed to a range of light illuminances (10, 30, 50, 100, 200, 400, and 2000 lux) using melatonin suppression relative to a dim control (<1 lux) as a marker of light sensitivity. Women were free from hormonal contraception. To examine the potential influence of sex hormones, estradiol and progesterone was examined in women and testosterone was examined in a subset of men. Menstrual phase was monitored using self-reports and estradiol and progesterone levels. Women exhibited significantly greater melatonin suppression than men under the 400-lux and 2000-lux conditions, but not under lower light conditions (10-200 lux). Light sensitivity did not differ by menstrual phase, nor was it associated with levels of estradiol, progesterone, or testosterone, suggesting the sex differences in light sensitivity were not acutely driven by circulating levels of sex hormones. These results suggest that sex differences in circadian timing are not due to differences in the response to dim/moderate light exposures typically experienced in the evening. The finding of increased bright light sensitivity in women suggests that sex differences in circadian timing could plausibly instead be driven by a greater sensitivity to phase-advancing effects of bright morning light.