Sex Differences Research Articles

Sex differences in close friendships and social style

Friendships play a central role in human sociality, and are a major influence, both directly and indirectly, on our fitness. The two most important forms of friendship are the support clique and the best friend. Although the basis on which we choose friends and romantic partners have been studied in considerable detail, we know a great deal less about how individuals' own psychological traits affect whom they form relationships with. Here, we use an ethnically homogenous UK sample of 757 adults (aged 18–75 years; 56 % female) attending national science festivals to show that there are striking differences between men and women in both the structure of friendship groups and the psychological mechanisms that underpin their capacity to hold and maintain close friendships. Individual differences in the size and structure of women's cliques, and their likelihood of having a best friend, are underpinned mainly by prosocial tendencies, whereas in men they correlate negatively with anti-social, rather than prosocial, tendencies. These findings add to the evidence that male and female social worlds are organised in very different ways. This begs the evolutionary question as to why this is so.

Impact of anterior cruciate ligament injury on functional capacity and pain: an analysis differentiated by age and gender

Anterior cruciate ligament (ACL) injuries significantly impact knee function, particularly in active populations. This study explores functional capacity and pain post-ACL reconstruction in relation to age, gender, and physical activity. A total of 41 participants who underwent ACL reconstruction were analyzed. Data were collected on age, sex, physical activity level, and pain frequency/intensity. The sample included 56.10% women (n=23) with an average age of 30.27 ± 10.18 years. Among the participants, 19.51% engaged in light activity, 26.83% in moderate, 7.32% in vigorous, 24.39% in very vigorous, and 21.95% were unable to perform any activity. Significant age differences were observed in moderate activity (p = 0.017), with older women more likely to engage in moderate activity. Logistic regression revealed age as a key factor affecting activity level (p < 0.05), and sex had marginal significance (p ≈ 0.054), suggesting men may perform more intense activities. Pain frequency and intensity showed weak correlations with age (p > 0.05), but women reported higher pain levels than men. The average functional ability dropped from 8.73 before the injury to 5.80 post-surgery. Men reported more pain than women, although t-tests showed no statistically significant differences between genders in functional capacity before or after surgery. ACL reconstruction reduces knee function across genders, with men reporting higher pain intensity. Age significantly impacts activity level, emphasizing the need for targeted rehabilitation strategies. Post-surgical recovery programs should consider individual differences in age and sex to optimize outcomes and enhance recovery.

Online Health Information Seeking, eHealth Literacy, and Health Behaviors Among Chinese Internet Users: Cross-Sectional Survey Study.

The internet has become an increasingly vital platform for health-related information, especially in upper-middle-income countries such as China. While previous research has suggested that online health information seeking (OHIS) can significantly impact individuals' engagement in health behaviors, most research focused on patient-centered health communication. This study aims to examine how OHIS influences health behavior engagement among Chinese internet users, focusing on the role of eHealth literacy and perceived information quality in influencing relationships. An online cross-sectional survey was conducted in November 2021 among 10,000 Chinese internet users, using quota sampling based on sex, age, and urban and rural residence, in line with the 48th Statistical Report on Internet Development of China. Nonparametric tests were used to examine the differences in eHealth literacy across sociodemographic groups. Partial correlation analysis and stepwise linear regression were conducted to test the associations between key variables. Confirmatory factor analysis and structural equation modeling were conducted to test the hypotheses. Our study identified significant disparities in functional and critical eHealth literacy between urban and rural residents across age groups, income levels, education backgrounds, and health conditions (all P<.001). In terms of sex and regional differences, we found higher functional literacy among female users than male users, and critical literacy varied significantly across different regions. The proposed structural model showed excellent fit (χ2404=4183.6, χ2404=10.4,P<.001; root mean square error of approximation value of 0.031, 95% CI 0.030-.031; standardized root mean square residual value of 0.029; and comparative fit index value of 0.955), highlighting reciprocal associations between 2 types of eHealth literacy and OHIS. Participants' functional eHealth literacy, critical eHealth literacy, and OHIS have positive impacts on their health behavioral engagement. Perceived information quality was found to mediate the influence of OHIS on health behavior (b=0.003, 95% CI 0.002-0.003; P<.001). The study revealed the pathways linking sociodemographic factors, eHealth literacy, OHIS, and perceived information quality and how they together influenced health outcomes. The findings underscore the significance of enhancing eHealth literacy and improving information quality to promote better health outcomes among Chinese internet users.

HOUSING TEMPERATURE ALTERS BURN INDUCED HYPERMETABOLISM IN MICE.

Mice used in biomedical research are typically housed at ambient temperatures (22-24 °C) below thermoneutrality (26-31 °C). This chronic cold stress triggers a hypermetabolic response that may limit the utility of mice in modeling hypermetabolism in response to burns. To evaluate the effect of housing temperature on burn-induced hypermetabolism, mice were randomly assigned to receive sham, small, or large scald burns. Mice recovered for 21 days in metabolic phenotyping cages at 24 °C or 30 °C. Regardless of sex or sham/burn treatment, mice housed at 24 °C had greater total energy expenditure (TEE, P < 0.001), which was largely attributable to greater basal energy expenditure (BEE) when compared to mice housed at 30 °C (P < 0.001). Thermoneutral housing (30 °C) altered adipose tissue mass in a sex-dependent manner. Compared to sham and small burn groups, large burns resulted in greater water vapor loss, regardless of housing temperature (P < 0.01). Compared to sham, large burns resulted in greater BEE and TEE in mice housed at 24 °C, however, this hypermetabolic response to large burns was blunted in female mice housed at 30 °C, and absent in male mice housed at 30 °C. Locomotion was significantly reduced in mice with large burns compared to sham and small burn groups, irrespective of sex or housing temperature (P < 0.05). Housing at 30 °C revealed sexual dimorphism in terms of the impact of burns on body mass and composition, where males with large burns displayed marked cachexia, whereas females did not. Collectively, this study demonstrates a sex-dependent role for housing temperature in influencing energetics and body composition in a rodent model of burn trauma.

Sportomics Analyses of the Exercise-Induced Impact on Amino Acid Metabolism and Acute-Phase Protein Kinetics in Female Olympic Athletes

Background: Exercise can be used as a model to understand immunometabolism. Biological data on elite athletes are limited, especially for female athletes, including relevant data on acute-phase proteins and amino acid metabolism. Methods: We analyzed acute-phase proteins and amino acids collected at South American, Pan-American, and Olympic Games for 16 Olympic sports. We compared female and male elite athletes (447 vs. 990 samples) across four states (fasting, pre-exercise, post-exercise, and resting) to understand sex-specific immunometabolic responses in elite athletes. Results: Considering all states and sports, we found that elite female athletes exhibited higher concentrations of C-reactive protein, lipopolysaccharide-binding protein, myeloperoxidase, haptoglobin, and IGF1, with ratios ranging from 1.2 to 2.0 (p &lt; 0.001). Women exhibited lower concentrations of most amino acids, except for glutamate and alanine. Although almost 30% lower in women, branched-chain amino acids (BCAAs) showed a similar pattern in all states (ρ ≥ 0.9; p &lt; 0.001), while aromatic amino acids (AAAs) showed higher consumption during exercise in women. Conclusion: We established sex dimorphism in elite athletes’ metabolic and inflammatory responses during training and competition. Our data suggest that female athletes present a lower amino acid response towards central fatigue development than male athletes. Understanding these differences can lead to insights into sex-related immuno-metabolic responses in sports or other inflammatory conditions.

Genome sequence of a European Diplocarpon coronariae strain and in silico structure of the mating-type locus

Diplocarpon coronariae is a fungal pathogen that is prevalent in low-input apple production. Over the past 15 years, it has become increasingly distributed in Europe. However, comprehensive insights into its biology and pathogenicity remain limited. One particular aspect is the rarity of the sexual morph of this pathogen, a phenomenon hitherto unobserved in Europe. Diplocarpon coronariae reproduces through a heterothallic mating system requiring at least two different mating types for sexual reproduction. Genes determining the mating types are located on the mating-type locus. In this study, D. coronariae strain DC1_JKI from Dresden, Germany, was sequenced and used to unravel the structure of the mating type locus. Using short-read and long-read sequencing methods, the first gapless and near-complete telomere-to-telomere genome assembly of D. coronariae was achieved. The assembled genome spans 51.2 Mbp and comprises 21 chromosome-scale contigs of high completeness. The generated genome sequence was used to in silico elucidate the structure of the mating-type locus, identified as MAT1-2. Furthermore, an examination of MAT1-1 and MAT1-2 frequency across a diverse set of samples sourced from Europe and Asia revealed the exclusive presence of MAT1-2 in European samples, whereas both MAT loci were present in Asian counterparts. Our findings suggest an explanation for the absence of the sexual morph, potentially linked to the absence of the second mating idiomorph of D. coronariae in European apple orchards.

Lifespan of male and female APP/PS1 and APP NL-F/NL-F mouse models of Alzheimer's disease.

Alzheimer's disease (AD) disproportionately affects women, yet most preclinical research studies are male-centric. We performed lifespan analyses of male and female AD mouse models (APP/PS1 and APP NL-F/NL-F ) and their shared genetic background control (C57BL/6). Survival curves support significant sex differences between within genotypes. Minimal longevity revealed increased age in male APP/PS1, and decreased age in APP NL-F/NL-F mice. Maximal longevity revealed an increased average age in males. Furthermore, median lifespan differed between sex and genotype. This study supports sexual dimorphic survival in two mouse models of AD, emphasizing the need to examine mechanisms and treatments in both sexes.

Characterizing the progression from mild cognitive impairment to dementia: a network analysis of longitudinal clinical visits

BackgroundWith the recent surge in the utilization of electronic health records for cognitive decline, the research community has turned its attention to conducting fine-grained analyses of dementia onset using advanced techniques. Previous works have mostly focused on machine learning-based prediction of dementia, lacking the analysis of dementia progression and its associations with risk factors over time. The black box nature of machine learning models has also raised concerns regarding their uncertainty and safety in decision making, particularly in sensitive domains like healthcare.ObjectiveWe aimed to characterize the progression of health conditions, such as chronic diseases and neuropsychiatric symptoms, of the participants in Mayo Clinic Study of Aging (MCSA) from initial mild cognitive impairment (MCI) diagnosis to dementia onset through network analysis.MethodsWe used the data from the MCSA, a prospective population-based cohort study of cognitive aging, and examined the changing association among variables (i.e., participants’ health conditions) from the first visit of MCI diagnosis to the visit of dementia onset using network analysis. The number of participants for this study are 97 with the number of visits ranging from 2 visits (30 months) to 7 visits (105 months). We identified the network communities among variables from three-fold collection of instances: (i) the first MCI diagnosis, (ii) progression to dementia, and (iii) dementia diagnosis. We determine the variables that play a significant role in the dementia onset, aiming to identify and prioritize specific variables that prominently contribute towards developing dementia. In addition, we explore the sex-specific impact of variables in relation to dementia, aiming to investigate potential differences in the influence of certain variables on dementia onset between males and females.ResultsWe found correlation among certain variables, such as neuropsychiatric symptoms and chronic conditions, throughout the progression from MCI to dementia. Our findings, based on patterns and changing variables within specific communities, reveal notable insights about the time-lapse before dementia sets in, and the significance of progression of correlated variables contributing towards dementia onset. We also observed more changes due to certain variables, such as cognitive and functional scores, in the network communities for the people who progressed to dementia compared to those who does not. Most changes for sex-specific analysis are observed in clinical dementia rating and functional activities questionnaire during MCI onset are followed by chronic diseases, and then by NPI-Q scores.ConclusionsNetwork analysis has shown promising potential to capture significant longitudinal changes in health conditions, spanning from the MCI diagnosis to dementia progression. It can serve as a valuable analytic approach for monitoring the health status of individuals in cognitive impairment assessment. Furthermore, our findings indicate a notable sex difference in the impact of specific health conditions on the progression of dementia.

Cardiac Surgery-Associated Acute Kidney Injury in Cardiopulmonary Bypass: A Focus on Sex Differences and Preventive Strategies.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a high-risk complication with well-recognized increased morbidity and mortality after cardiac surgery attributable in large part to cardiopulmonary bypass (CPB) associated factors contributing to AKI including hemodilution, hypothermia, hypotension and exposure to artificial surfaces. These conditions disrupt the renal microcirculation and activate local and systemic inflammatory responses to non-pulsatile flow, and low perfusion pressure. The underlying mechanisms of CSA-AKI in CPB are not fully understood, and the incidence of CSA-AKI remains high at around 30%. Furthermore, women appear to be more vulnerable than men to the renal injury associated with CPB even though the overall incidence of cardiovascular and kidney diseases is lower in premenopausal women. Nevertheless, estrogen elicits renoprotective effects in several ways including mitigating inflammation, promoting natriuresis and endothelial protection as shown in preclinical studies. However, women have higher rates of CSA-AKI and these are exacerbated in postmenopausal women. This leads to the conundrum of whether sex, age, and hormonal status differences influence CSA-AKI. In this review, we briefly discuss the pathophysiology of CSA-AKI in CPB, and sex differences in kidney functions with a focus on the possible role of estrogen-specific effects in CPB and also possible differences in CPB in women including greater hemodilution. Further, we review strategies to prevent CSA-AKI in CPB with a highlight for potential sex-specific strategies. Improving our understanding of the impact of sex and sex hormones on CSA-AKI initiation and development will allow us to better manage the CPB strategies delivered to all patients.

Sex Differences in Human Brain Structure at Birth

BackgroundSex differences in human brain anatomy have been well-documented, though remain significantly underexplored during early development. The neonatal period is a critical stage for brain development and can provide key insights into the role that prenatal and early postnatal factors play in shaping sex differences in the brain.MethodsHere, we assessed on-average sex differences in global and regional brain volumes in 514 newborns aged 0–28 days (236 birth-assigned females and 278 birth-assigned males) using data from the developing Human Connectome Project. We also assessed sex-by-age interactions to investigate sex differences in early postnatal brain development.ResultsOn average, males had significantly larger intracranial and total brain volumes, even after controlling for birth weight. After controlling for total brain volume, females showed significantly greater total cortical gray matter volumes, whilst males showed greater total white matter volumes. After controlling for total brain volume in regional comparisons, females had significantly increased white matter volumes in the corpus callosum and increased gray matter volumes in the bilateral parahippocampal gyri (posterior parts), left anterior cingulate gyrus, bilateral parietal lobes, and left caudate nucleus. Males had significantly increased gray matter volumes in the right medial and inferior temporal gyrus (posterior part) and right subthalamic nucleus. Effect sizes ranged from small for regional comparisons to large for global comparisons. Significant sex-by-age interactions were noted in the left anterior cingulate gyrus and left superior temporal gyrus (posterior parts).ConclusionsOur findings demonstrate that sex differences in brain structure are already present at birth and remain comparatively stable during early postnatal development, highlighting an important role of prenatal factors in shaping sex differences in the brain.

Sex differences in perceived discrimination among patients with obesity.

The negative impacts of perceived discrimination on health have been documented, but how perceptions of discrimination vary by sex among people with obesity (PWO) is not well understood. This study assessed sex differences in perceived discrimination among PWO. This cross-sectional study analysed self-reported data from racially/ethnically diverse PWO attending an academic obesity program. The primary outcome was perceived discrimination, assessed by the Major Experiences of Discrimination (MED) and Everyday Discrimination Scale (EDS). Sex differences were evaluated by univariate and multivariable regression analysis adjusted for key descriptive variables. The final analytical sample included 60 PWO (62% female, 61% non-Hispanic white (NHW), 12% Hispanic, 39% non-Hispanic black (NHB), mean age 53 years, mean BMI 34 kg/m2). Women experienced everyday discrimination 59% less than men but this was not significant (OR 0.41; 95% CI 0.08-2.16; p = .29). Participant highest BMI was correlated with acute discrimination (total MED score) (r = 0.39; p = .0024) and chronic discrimination (total EDS score) (r = 0.28; p = .03). Most participants reported more chronic discrimination compared to acute discrimination (85% vs. 48%). Mean MED (β -0.18; 95% CI -0.93 to +0.56; p = .62) and EDS scores (β -0.25; 95% CI -3.37 to +2.87; p = .87) were not significantly different between women and men. Perceived discrimination was common and experienced equally between men and women with obesity. Incorporating discrimination experiences into obesity care models may be an important step to improving quality of care and outcomes.

Differences in sex and age response to single pill combination based antihypertensive therapy reflecting in blood pressure and arterial stiffness.

There are noticeable sex differences in the treatment response to antihypertensives, with limited data on the response to single pill combinations. The aim of the PRECIOUS trial was to assess the treatment response to perindopril/amlodipine and perindopril/amlodipine/indapamide dual and triple single-pill combination in men and women. Four hundred and forty adults with essential hypertension were assessed in the 16-week interventional, open-label, prospective, international, multicentre trial. Based on the previous antihypertensive therapy, patients were assigned to either perindopril/amlodipine 4/5 mg or perindopril/amlodipine/indapamide 4/5/1.25 mg, with the initial dose up-titrated in 4-week intervals in case of uncontrolled blood pressure. An additional analysis was performed for sex- and age-related differences on the blood pressure response and arterial stiffness in men and women aged 35-74 years. Women achieved better overall blood pressure control in all age groups, except for the 35-44 age group. Women presented higher average 24 h aortic augmentation indexes than men, but had more pronounced decreasing trends. The pulse wave velocity was only age-dependent, with reductions slightly greater in women. Both the aortic augmentation index and pulse wave velocity were significantly decreased in all groups compared to baseline. The results of the PRECIOUS trial contribute significant data to the expanding body of evidence on sex differences in hypertension, including the aspect of age-related changes during the life course of women. The differences between same-aged men and women tend to be smaller with advancing age, but with a greater treatment response in women in all age groups for all observed blood pressure parameters and arterial stiffness. ClinicalTrials.gov identifier NCT03738761.

A new metric method for sex estimation using three-dimensional imaging of the nuchal crest.

In Walker's nonmetric method, the nuchal crest serves as the representative region for indicating sexual dimorphism in cranial bones. However, the accuracy of sex estimation using the nuchal crest is lower than that using other anatomical regions. Furthermore, because of the protruding processes and structurally challenging features characterized by uneven and rough surfaces, there is a lack of metric methods for sex estimation, making quantification challenging. In this study, we aimed to validate a derived metric method for sex estimation by reconstructing the nuchal crest region in three-dimensional (3D) images obtained from computed tomography scans of cranial bones and compare its accuracy with that of the nonmetric method. A total of 648 images were collected, with 100 randomly selected for use in the nonmetric method. We applied our metric method to the remaining 548 images. Our findings showed that the surface area of the nuchal crests was greater in male individuals than in female individuals. The nuchal crest surface area quantified by the metric method increased the accuracy of sex estimation by 48% compared with that by the nonmetric method. Our metric method for sex estimation, which quantifies the nuchal crest surface area using 3D images of the skull, led to a high sex estimation accuracy of 93%. Future studies should focus on proposing and quantifying new measurement methods for areas showing sexual characteristics in the skull that are difficult to measure, thereby enhancing the accuracy and reliability of sex estimation in human skeletal identification across various fields.

Female Specific Restrictive Cardiomyopathy and Metabolic Dysregulation in transgenic mice expressing a Peptide of the Amino-Terminus of GRK2.

Cardiovascular disease and heart failure are a major health challenge, with sex differences in pathophysiology and treatment responses critically influencing patient outcomes. G protein-coupled receptor (GPCR) kinase 2 (GRK2) is a pivotal regulator of cellular signaling whose elevation is a hallmark of heart failure progression. Its complex network of protein interactions impact a wide range of physiological and pathophysiological processes including cardiac function. In this study, we examined the effects of cardiac-restricted expression of an amino-terminal peptide of GRK2 (βARKnt) in female mice subjected to acute and chronic pressure overload. Our findings reveal that that βARKnt affects hypertrophy development and cardiac function differently in female mice than in males, leading to a transition to heart failure not observed in control females or βARKnt males. Notably, the βARKnt female mice exhibited baseline hypertrophy with distinct left atrial morphology, increased fibrosis, and immune cell infiltration compared to the controls, which progressed under chronic stress, indicating adverse cardiac remodeling. Furthermore, βARKnt female mice, unlike males, exhibit impaired tissue respiration following acute pressure overload and altered glucose sensitivity and insulin tolerance, highlighting significant remodeling of cardiac and systemic metabolism.

Baseline differences in cardiorespiratory fitness by gonadotropin releasing hormone agonist treatment converge after testosterone in transgender adolescents.

There are known sex differences in cardiorespiratory fitness (CRF). Little is known about the impact of pubertal blockade with a gonadotropin releasing hormone agonist (GnRHa) followed by hormone therapy on CRF for transgender adolescents. We aimed to (1) determine the effect of GnRHa monotherapy on CRF and mitochondrial function and associations with metabolomic profiles, and (2) evaluate for changes after 1 and 12 months of testosterone therapy among transgender adolescents . Participants assigned female at birth (n=19, baseline age 15.0+1.0 years) from two groups: GnRHa+ (n=8) and GnRHa- (n=11) were examined at baseline and 1- and 12-months post-testosterone therapy in a longitudinal observational study to assess cardiorespiratory fitness, mitochondrial respiration and metabolic profile. Fasted morning labs including assessment of metabolomics and peripheral blood mononuclear cell mitochondrial respiration and degree of mitochondrial coupling (respiratory control ratio, RCR). A graded cycle ergometer test was performed. Baseline differences were evaluated between groups. Changes were compared with mixed linear regression models evaluating time (baseline, 1 and 12 months), group (GnRHa treatment yes/no), and their interaction. At baseline GnRHa+ individuals had higher relative VO2peak (30.1+4.83 vs. 25.24+4.47 ml/kg/min, p=0.042) than GnRHa- individuals. In regression models, GnRHa+ individuals had a significant increase in peak watts (p=0.011) and total exercise time (p=0.005)after 12 months of testosterone (p=0.012), but not GnRHa- individuals. GnRHa+ individuals have significantly higher RCR under carbohydrate (p=0.0007) and lipid (p=0.0002) conditions than GnRHa+ individuals. Pretreatment with GnRHa positively influences peak CRF and mitochondrial respiration in adolescent transgender males undergoing testosterone therapy.

Corrigendum: Sex difference in the association between creatinine-to-cystatin C ratio and metabolic syndrome among Chinese adults

Corrigendum: Sex difference in the association between creatinine-to-cystatin C ratio and metabolic syndrome among Chinese adults

Trends in smoking initiation, sex, and regional differences: a repeat cross-sectional study in the European Union between 1940 and 2019

Trends in smoking initiation, sex, and regional differences: a repeat cross-sectional study in the European Union between 1940 and 2019

Impact of biological sex on heart transplant patients admitted to cardiac rehabilitation: A 10-year retrospective cohort study

IntroductionHeart transplantation (HTx) serves as the gold-standard therapy for end-stage heart failure, yet patients often experience physical deconditioning and cognitive impairments post-surgery. Cardiac rehabilitation (CR) has shown promise in the HTx context. However, uncertainty surrounds the impact of biological sex. Accordingly, the aim of this paper was to investigate the impact of biological sex in a cohort of patients with HTx early admitted to a residential CR program. MethodsThis was a retrospective analysis involving patients who underwent HTx at Niguarda Hospital and who subsequently participated in a CR program at IRCCS Fondazione Don Gnocchi, Milan, Italy, between 2010 and 2022. The primary endpoint was time to event (in months), with an event defined as a composite outcome of whichever occurred first of death, allograft rejection, or cardiac allograft vasculopathy up to 30 months follow-up. ResultsIn a total of 129 patients, 60 % male, and 40 % female, baseline characteristics presented comparably between the sexes. At 6 months, no significant sex differences were observed for the primary composite outcome. However, at 30 months, females exhibited a significantly lower incidence of the primary composite outcome and an increased survival rate. Multivariable analysis confirmed a protective effect of female sex against mortality (F vs. M, HR 0.164, 95 % CI 0.038–0.716, P = 0.0161). ConclusionsDespite limitations, our findings emphasize that sex affects post-HTx long-term follow-up following CR discharge, with more favorable outcomes for female recipients. In an era of tailored management algorithms, it is imperative to take into account the gender gap even in cardiac rehabilitation.

Sex differences in prelimbic cortex calcium dynamics during stress and fear learning

In recent years, research has progressively increased the importance of considering sex differences in stress and fear memory studies. Many studies have traditionally focused on male subjects, potentially overlooking critical differences with females. Emerging evidence suggests that males and females can exhibit distinct behavioral and neurophysiological responses to stress and fear conditioning. These differences may be attributable to variations in hormone levels, brain structure, and neural circuitry, particularly in regions such as the prefrontal cortex (PFC). In the present study, we explored sex differences in prelimbic cortex (PL) calcium activity in animals submitted to immobilization stress (IMO), fear conditioning (FC), and fear extinction (FE). While no significant sex differences were found in behavioral responses, we did observe differences in several PL calcium activity parameters. To determine whether these results were related to behaviors beyond stress and fear memory, we conducted correlation studies between the movement of the animals and PL activity during IMO and freezing behavior during FC and FE. Our findings revealed a clear correlation between PL calcium activity with movement during stress exposure and freezing behavior, with no sex differences observed in these correlations. These results suggest a significant role for the PL in movement and locomotion, in addition to its involvement in fear-related processes. The inclusion of both female and male subjects is crucial for studies like this to fully understand the role of the PFC and other brain areas in stress and fear responses. Recognizing sex differences enhances our comprehension of brain function and can lead to more personalized and effective approaches in the study and treatment of stress and fear-related conditions.

A Systematic Review on Sex Differences in Prepulse Inhibition of Startle

Abstract: Prepulse inhibition of the startle response is defined as the inhibition of the startle reflex to an intense contextual stimulus (named pulse) when a weaker stimulus (named prepulse) precedes it and is considered a measure of sensorimotor gating. Consistent with recent research, it has been observed that this measure might exhibit sex differences in studies of both humans and rodents, although the results in the literature appear to be inconsistent. Therefore, this systematic review aims to analyze the sexual differences observed in human and nonhuman animal studies from a comparative perspective. A comprehensive search was conducted from the inception to the present in the Web of Science, PubMed, and PsycInfo databases. Following the search, 58 studies were included in the review. The average age in human studies ( n = 32) was 31.45 years (range = 4–69), while among nonhuman animal studies ( n = 26), the average age was 75.5 postnatal days (range = 7–360). The results indicated no clear sexual differences in the startle response magnitude. However, consistent sex differences in prepulse inhibition were found, revealing that males exhibited higher levels of sensorimotor gating compared to females in both humans (78.79% of the studies) and nonhuman animal studies (69.23% of the studies). Therefore, the findings corroborate the sex differences of prepulse inhibition and underscore the value of this paradigm in comparative science, emphasizing the importance of considering sex as an independent variable when studying this phenomenon.