Psoriasis localization patterns in the Swiss Psoriasis Registry (SDNTT) over 11 years: an analysis by sex and age.

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT. The localized Psoriasis Area and Severity Index (locPASI) of the head, trunk, upper and lower extremities was analyzed over two years following the start of systemic non-/biologic treatment. A total of 316 female and 517 male patients were analyzed. Male patients had a higher baseline locPASI for legs, trunk and arms (p < 0.001), but not for the head (p = 0.961). The locPASI for the head in younger female patients (18-40 years) had a higher score than those aged 55 + (p = 0.022) and after two years, middle aged (41-54) showed a lower score compared to younger patients (p = 0.045). Younger male patients revealed a lower score after two years of therapy in the leg- and arm-area compared to older (p = 0.018 and p = 0.048, respectively). Female patients on non-biologics had a fast initial response, converging with male patients' scores over 24 months. Over 75% locPASI reduction was observed for female head-area (81.4%), male trunk (82.7%) and legs (76.1%). Absolute locPASI ≤ 2 was achieved 3-6 months for all locations with interleukin (IL)-17, IL-12/23 and IL-23-inhibitors, except for the legs of male patients on anti-IL-17 and female patients on anti-IL-12/23 and -IL-23. After two years, male patients did not achieve a locPASI ≤ 2 for any biologic-treatment in the legs, nor for the arms on anti-TNF-α. Significant disparities in localized PASI were observed between female and male patients. The age, sex and severity of distinct localizations should be considered to optimize treatment goals.

Development of white matter in young adulthood: The speed of brain aging and its relationship with changes in fractional anisotropy.

White matter (WM) development has been studied extensively, but most studies used cross-sectional data, and to the best of our knowledge, none of them considered the possible effects of biological (vs. chronological) age. Therefore, we conducted a longitudinal multimodal study of WM development and studied changes in fractional anisotropy (FA) in the different WM tracts and their relationship with cortical thickness-based measures of brain aging in young adulthood. A total of 105 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort underwent magnetic resonance imaging (MRI) at the age of 23-24, and the age of 28-30 years. At both time points, FA in the different WM tracts was extracted using the JHU atlas, and brain age gap estimate (BrainAGE) was calculated using the Neuroanatomical Age Prediction using R (NAPR) model based on cortical thickness maps. Changes in FA and the speed of cortical brain aging were calculated as the difference between the respective variables in the late vs. early 20s. We demonstrated tract-specific increases as well as decreases in FA, which indicate that the WM microstructure continues to develop in the third decade of life. Moreover, the significant interaction between the speed of cortical brain aging, tract, and sex on mean FA revealed that a greater speed of cortical brain aging in young adulthood predicted greater decreases in FA in the bilateral cingulum and left superior longitudinal fasciculus in young adult men. Overall, these changes in FA in the WM tracts in young adulthood point out the protracted development of WM microstructure, particularly in men.

Sex-specific association between schizophrenia polygenic risk and subclinical schizophrenia-related traits.

BACKGROUND: According to the dimensional view of psychiatric disorders, psychosis is expressed as a continuum in the general population. However, the investigation of the putative genetic aetiological continuity between its clinical and subclinical phenotypes has yielded mixed results. We aimed to replicate previous findings regarding the association of polygenic risk for schizophrenia with subclinical traits (i.e., schizotypy traits and psychotic-like experiences), and to examine the role of sex in this association in a large nonclinical sample. METHODS: The Multidimensional Schizotypy Scale and the Community Assessment of Psychic Experiences were assessed in 919 nonclinical participants. Polygenic Risk Scores for schizophrenia (SZ-PRSs) were computed using the PRS-CS method based on the latest genome-wide association study of schizophrenia. Summary statistics derived from the total GWAS sample and stratified by sex were used. Linear regression analyses tested the associations of the SZ-PRSs with the psychometric variables, both in the total sample and by sex. RESULTS: No associations were found between the SZ-PRSs and the positive, negative or disorganized dimensions of schizotypy in the total sample. Likewise, no associations were found with psychotic-like experiences. However, the sex-stratified analyses revealed a male-specific association with positive schizotypy. Similar results were obtained with the PRSs derived from the sex-stratified summary statistics. DISCUSSION: Our results are consistent with the lack of clear evidence of an association between SZ common genetic risk and its subclinical phenotypes. Nevertheless, the male-specific association found suggests that this PRS might explain better the male phenotype, as reported in previous studies. Future studies should put a focus on the role of sex in this association to unravel its sex specificities.

Sex matters: Differences in prodromes, clinical and neuropsychological features in individuals with a first episode mania or psychosis.

OBJECTIVE: This study was aimed at identifying sex differences in patients presenting a first episode mania (FEM) or psychosis (FEP) to help shaping early treatment strategies focused on sex differences. METHODS: Patients with a FEM or FEP underwent a clinical, neuropsychological (neurocognitive functions and emotional intelligence) and functional assessment. Performance on those variables was compared between groups through general linear model, with sex and group (FEM vs FEP) as main effects and group by sex interactions. RESULTS: The total sample included 113 patients: FEM = 72 (45.83 % females) and FEP = 41 (46.34 % females). There were significant main effects for group (not for sex) for most of the clinical features (depressive, negative and positive symptoms) and psychosocial functioning (χ2 = 8.815, p = 0.003). As for neuropsychological performance, there were significant main effects for sex and group. Females performed better than males in verbal memory (χ2 = 9.038, p = 0.003) and obtained a higher emotional intelligence quotient (χ2 = 13.20, p < 0.001). On the contrary, males obtained better results in working memory (χ2 = 7.627, p = 0.006). FEP patients significantly underperformed FEM patients in most cognitive domains. There were significant group by sex interactions for few neuropsychological variables, namely processing speed (χ2 = 4.559, p = 0.033) and verbal fluency (χ2 = 8.913, p = 0.003). LIMITATIONS: Differences between sexes were evaluated, but the influence of gender was not considered. Retrospective evaluation of prodromes and substance use. No healthy control group comparator. CONCLUSION: The main finding is the presence of significant sex effect and group by sex interaction on specific neurocognitive cognition and emotional intelligence measures. Tailored sex-based early treatment strategies might be implemented.

Sex differences in DNA methylation variations according to ART conception-evidence from the Norwegian mother, father, and child cohort study.

Previous studies have shown cord-blood DNA methylation differences in newborns conceived using assisted reproductive technologies (ART) compared to those conceived naturally. However, whether these ART-related DNA methylation differences vary with children's sex is unknown. We hypothesize that the DNA methylation differences in cord blood between ART-conceived and naturally conceived newborns also varies by the sex of the child, with distinct patterns of differential methylation present in males and females. We investigated sex differences in cord-blood DNA methylation variation according to conception by ART using the Illumina MethylationEPIC platform, comparing 456 ART-conceived versus 507 naturally-conceived girls, and 503 ART-conceived and 473 naturally-conceived boys. We identified 37 differentially methylated CpGs according to ART-conception among girls, and 70 differentially methylated CpGs according to ART-conception among boys, when we used a 1% false discovery rate to account for multiple testing. Ten CpGs were differentially methylated according to conception by ART in both sexes. Among the genes that were associated with these CpGs, we found the BRCA1; NBR2 gene (two CpGs) was hypermethylated in girls while the APC2 (two CpGs) and NECAB3;ACTL10, (four CpGs) related to cellular signaling were hypomethylated in boys. These findings confirm the presence of sex-specific epigenetic differences, illustrating the nuanced impact of ART on the fetal epigenome. There is a need for further explorations into the implications for sex-specific developmental trajectories and health outcomes in ART-conceived children.

Sex-specific post-inflammatory dysbiosis mediates chronic visceral pain in colitis.

BACKGROUND: Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. Visceral pain and the microbiome exhibit sex-dependent interactions, while visceral pain in IBD shows a sex bias. Our aim was to evaluate whether post-inflammatory microbial perturbations contribute to visceral hypersensitivity in a sex-dependent manner. METHODS: Males, cycling females, ovariectomized, and sham-operated females were given dextran sodium sulfate to induce colitis and allowed to recover. Germ-free recipients received sex-appropriate and cross-sex fecal microbial transplants (FMT) from post-inflammatory donor mice. Visceral sensitivity was assessed by recording visceromotor responses to colorectal distention. The composition of the microbiota was evaluated via 16S rRNA gene V4 amplicon sequencing, while the metabolome was assessed using targeted (short chain fatty acids - SCFA) and semi-targeted mass spectrometry. RESULTS: Post-inflammatory cycling females developed visceral hyperalgesia when compared to males. This effect was reversed by ovariectomy. Both post-inflammatory males and females exhibited increased SCFA-producing species, but only males had elevated fecal SCFA content. FMT from post-inflammatory females transferred visceral hyperalgesia to both males and females, while FMT from post-inflammatory males could only transfer visceral hyperalgesia to males. CONCLUSIONS: Female sex, hormonal status as well as the gut microbiota play a role in pain modulation. Our data highlight the importance of considering biological sex in the evaluation of visceral pain.

Sex and body height influences on patellofemoral joint reaction force during stair ascent.

BACKGROUND: Females are at greater risk of developing patellofemoral pain (PFP) than males, and an excessive patellofemoral joint reaction force (PFJRF) may contribute to this discrepancy. It is unknown if the PFJRF differs between males and females during stair ascent. Additionally, body height may also influence the PFJRF. This study investigated PFJRF differences between males and females and explored relationships between body height and PFJRF during stair ascent. METHODS: Thirty males (25.6 (2.7) yr) and thirty females (23.7 (2.2) yr) ascended stairs (96 steps/min). Three-dimensional kinematics (200 Hz) and kinetics (2000 Hz) were recorded and used to calculate biomechanical dependent variables. RESULTS: Females experienced a greater PFJRF magnitude (mean difference (MD) = 3.2 N/kg; 95% CI = 0.5, 5.9; p = 0.022) and rate (MD = 23.8 N/kg/sec; 95% CI = 2.7, 45.1; p = 0.029), quadriceps muscle force (3.1 N/kg; 95% CI = 0.2, 6.0; p = 0.036), and knee flexion angle (MD = 2.3°; 95% CI = 0.3, 4.3; p = 0.026). Females exhibited shorter quadriceps lever arm length (MD = -0.1 cm; 95% CI = -0.2, 0.0; p = 0.024) and body height (MD = -16.9 cm; 95% CI = -20.5, -13.2, p < 0.001) compared to males. Body height was inversely correlated with PFJRF magnitude (r = -0.31; p = 0.017), rate (r = -0.28; p = 0.032), and knee flexion angle (r = -0.54; p < 0.001). CONCLUSION: Females experienced a greater PFJRF than males. Additionally, the PFJRF and body height were inversely correlated. This observed difference may contribute to the PFP sex discrepancy and be due, at least in part, to body height differences.

Sex differences in the molecular profile of adult diffuse glioma are shaped by IDH status and tumor microenvironment.

BACKGROUND: Sex differences in adult diffuse glioma (ADG) are well-established clinically, yet the underlying molecular mechanisms remain inadequately understood. Here, we aim to reveal molecular features and cellular compositions unique to each sex in ADG to comprehend the role of sex in disease etiology. METHODS: We quantified sex differences in transcriptome of ADG using multiple independent glioma patient datasets. Next, we delved into the single-cell landscape to examine sex differences in gene expression and cellular composition. To explore how sex influences disease progression, we analyzed paired samples from primary and recurrent ADG cases, aiming to identify sex-specific differences in molecular and cellular features. RESULTS: Our analysis revealed that mutations in isocitrate dehydrogenase (IDH) genes and the tumor microenvironment emerged as primary influencers of sex-differential molecular enrichments. In IDHwt tumors, genes in neuronal signaling pathway are found to be enriched in male tumors, while genes in hypoxia and inflammatory response pathways are enriched in female tumors. This pattern was reversed in IDHmut gliomas. We hypothesized that these distinctions could be attributed to heterogeneous cellular composition between sexes. Using single-cell data, we observed distinctive patterns of sex differences in cell states, cell composition and cell-cell interaction in IDHwt and IDHmut tumors separately. Further, by comparing molecular changes in paired primary and recurrent ADG samples, we identified sex-specific differences in molecular characteristics and cellular compositions of recurrent tumors. CONCLUSION: Our results provide a comprehensive multi-level characterization of sex differences in ADG, such findings provide novel insights into glioma disease progression in each sex.

Chinese women's years of education and subjective well-being: an empirical analysis based on ordered Logit model and coupling coordination model.

In modern society, the improvement of women's education level has become one of the important indicators of national development and social progress. Although there are many useful explorations on the relationship between education and subjective well-being, the research on women's years of education and subjective well-being is very limited. The article focuses on women's years of education to determine whether and how to affect subjective well-being. This study is based on the China general social survey in 2021. The ordered Logit model was used to analyze the impact of women's years of education on subjective well-being, and a binary coupling coordination model was constructed to test the above two variables. The results show that the longer the education years of women, the stronger the subjective well-being. The benchmark regression results show that women's years of education have positive and negative effects on subjective well-being through economic status, physical and mental health, ecological environment, social cognition and personal cognition. The analysis of coupling coordination degree shows that the coupling between the years of education and subjective well-being of women in coastal areas and economically developed areas is the strongest, and the subjective well-being is better realized by increasing the years of education. Based on the above research results, this paper provides some practical suggestions for improving women's subjective well-being, and provides some valuable references for women to effectively balance husband-wife relationship, family relationship and work relationship, improve women's years of education and better obtain happiness.

A Longitudinal Network Analysis of Emotion Regulation, Interpersonal Problems, and Eating Disorder Psychopathology in Chinese Adolescents.

OBJECTIVE: The present longitudinal study examined sex-specific, symptom-level relationships among emotion regulation (ER), interpersonal problems (IP), and eating disorder (ED) psychopathology in a large sample of Chinese adolescents. METHOD: Data were from a project with four waves of data collection (N = 1540; 710 boys and 830 girls) at 6-month intervals over 18 months. Questionnaires assessed ED psychopathology, ER, and IP at each wave of data collection. Longitudinal network analyses were conducted separately for boys and girls. Sex differences in the network structures were also examined. RESULTS: The results revealed pronounced heterogeneity in the presentation of ED psychopathology, ER, and IP across Chinese adolescent boys and girls longitudinally and intra-individually. For example, weight/shape preoccupation in ED psychopathology and awareness in ER emerged as important nodes in the temporal network for boys. However, weight/shape preoccupation and dissatisfaction in ED psychopathology were identified as the most important nodes in the temporal network for girls. Regarding bridge strength, awareness in ER emerged as the node with the highest connectivity in the temporal network for boys. At the same time, weight/shape dissatisfaction in ED psychopathology was the node with the highest connectivity for girls. DISCUSSION: The current study extended network theory to better understand the longitudinal interplay among ER, IP, and ED psychopathology in Chinese adolescents and their sex differences in the importance of symptoms. Such insights may pave the way for developing targeted prevention and treatment strategies for adolescent boys and girls in China.

Is Degradation in the Eye of the Beholder (or the Researcher)?

When people raise concerns about pornography, they most often are focused on whether pornography increases violence toward women and/or whether it degrades women. While a substantial amount of cross-cultural data suggests that there is no direct link between adult consumption and violence, the question of whether pornography is inherently degrading to women lacks clear answers. As does the question of whether behaviors in pornography that are commonly labeled as degrading are perceived that way when they take place outside pornography. To answer this question about the inherent nature of degradation, we need a better definition and understanding of what particular behaviors people consider to be degrading and whether their perception of what is degrading is influenced by the circumstance or the people involved in a non-pornography setting. To examine this, 496 individuals (247 females, 249 males) were asked to indicate their perceptions of various sexual behaviors when engaged in by males and females toward male and female partners. Results suggest that while some particular sexual behaviors are broadly viewed as degrading (e.g., watersports), perceptions of degradation for other behaviors seem to be influenced by who is doing what to whom. In this sense, the perception of degradation exists in the eye of beholder and is often not defined by the particular sexual act. Future studies of degradation should take into account the context as well as the players involved.

Sex differences in the orofacial antinociceptive effect of metformin and the role of transient receptor potential channels.

Metformin is classified as a biguanide and is used in the treatment of type 2 diabetes. It is used worldwide and has been investigated in drug repositioning. The present study aims to investigate whether there is sexual dimorphism in the orofacial antinociceptive effect of metformin and the participation of TRP channels. Acute nociceptive behavior was induced by administering cinnamaldehyde or capsaicin to the upper lip. Nociceptive behavior was assessed through orofacial rubbing, and the effects of pre-treatment with metformin (125 or 250 mg/Kg) or vehicle (control) were tested on the behavior. Nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The chronic pain model involved infraorbital nerve transection (IONX) was evaluated using Von Frey electronic filaments. Trpv1 gene expression was analyzed in the nerve ganglion. Docking experiments were performed. Metformin, but not the vehicle, produced antinociception (p < 0.0001) in all acute nociceptive behaviors in both sexes, and these effects were attenuated by the TRPV1 antagonist capsazepine and the TRPA1 antagonist HC-030031. In IONX with better (**p < 0.01, ****p < 0.0001 vs. control) results in females. TRPV1 gene expression was observed in the metformin treated group (*p < 0.05 vs. control). Docking experiments revealed that metformin may interact with TRPV1 and TRPA1 channels. Metformin promotes orofacial antinociception in both sexes in acute pain and is more effective in chronic pain in females than in males, through the modulation of TRPV1 and TRPA1 channels. These preclinical findings suggest a potential repositioning of metformin as an analgesic agent in acute and chronic orofacial pain states.

Doublecortin-immunoreactive neurons in the piriform cortex are sensitive to the long lasting effects of early life stress.

The olfactory system is a niche of continuous structural plasticity, holding postnatal proliferative neurogenesis in the olfactory bulbs and a population of immature neurons in the piriform cortex. These neurons in the piriform cortex are generated during embryonic development, retain the expression of immaturity markers such as doublecortin, and slowly mature and integrate into the olfactory circuit as the animal ages. To study how early life experiences affect this population of cortical immature neurons, we submitted mice of the C57/Bl6J strain to a protocol of maternal separation for 3 h per day from postnatal day 3 to postnatal day 21. Control mice were continuously with their mothers. After weaning, mice were undisturbed until 6 weeks of age, when they were weighted and tested in the elevated plus-maze, a standard test for anxiety-like behavior, to check for phenotypical effects. Mice were then perfused, and their brains processed for the immunofluorescent detection of doublecortin and the endogenous proliferation marker Ki67. We found that maternal separation induced a significant increase in the body weight of males, but not females. Further, maternally separated mice displayed increased exploratory-like behavior (i.e., head dipping, velocity and total distance traveled in the elevated plus maze), but no significant differences in anxiety-like behavior or corticosterone levels after behavioral testing. Finally, we observed a significant increase in the number of complex doublecortin neurons in the piriform cortex, but not in the olfactory bulbs, of mice submitted to maternal separation. Interestingly, most doublecortin neurons in the piriform cortex, but not the olfactory bulb, express the epigenetic reader MeCP2. In summary, mild early life stress results, during adolescence, in a male-specific increase in body weight, alteration of the exploratory behaviors, and an increase in doublecortin neurons in the piriform cortex, suggesting an alteration in their maturation process.

First manifestation of cardiovascular disease according to age and sex in a Mediterranean country.

Background: Cardiovascular (CV) diseases are the most common cause of death worldwide. This study aimed to investigate the incidence and type of first CV event in a broad cohort of Spaniards, focusing on age and sex differences. Methods: This was a retrospective study using the SIDIAP database. Subjects aged 30-89 years in 2010 were included. Individuals with prevalent CV disease or atrial fibrillation were excluded. Subjects were followed until the occurrence of a CV event, death, or the study end (December 2016). CV outcomes (coronary heart disease [CHD], cerebrovascular or peripheral artery disease and heart failure [HF]) during follow-up were analyzed. Clinical, anthropometrical, and laboratory data were retrieved from clinical records. Results: Overall, 3,769,563 at-risk individuals (51.2 ± 15.2 years) were followed for a median of 7 years. The cumulative incidence of a first CV event was 6.66% (men vs. women, 7.48% vs. 5.90%), with the highest incidence (25.97%) among individuals >75 years. HF (29%) and CHD (28.8%) were the most common first events overall; in men it was CHD (33.6%), while in women it was HF and cerebrovascular disease (37.4% and 27.4%). In younger age groups, CHD was more prevalent, with HF in older age groups. Baseline CV risks factors conferred more risk in younger ages and differed between men and women. Conclusions: The incidence and type of the first CV event in this Mediterranean region were significantly influenced by age and sex. This information is relevant for tailoring primary prevention strategies including the treatment of risk factors.

Sex Differences in Obstructive Patterns on Drug-Induced Sleep Endoscopy.

OBJECTIVE: To identify and characterize sex differences in collapse patterns on drug-induced sleep endoscopy (DISE) in patients with obstructive sleep apnea (OSA). STUDY DESIGN: Retrospective cohort analysis. SETTING: An outpatient tertiary care academic medical center. METHODS: A retrospective cohort study at a single tertiary care institution was performed from 2020 to 2023. All adult patients who underwent a DISE were included in this study. Univariate and multivariate analyses were used to compare differences between males and females on DISE. RESULTS: 117 patients who underwent DISE were included in this study, including 30% females (n = 35). The average age was 54.7 years (SD 15.2), mean BMI was 28.6 kg/m2 (SD 4.1), and mean apnea-hypopnea index (AHI) was 32.3 events per hour (SD 21.3). Most patients had severe OSA (48.7%). There was no difference in palatine or lingual tonsil size between sexes. On DISE, a significantly lower proportion of females demonstrated complete oropharyngeal lateral wall collapse (25.7% females vs 51.2% males, P = .008). Multivariate analysis revealed that male sex was independently associated with the presence of complete collapse at the oropharynx (odds ratio [OR] 2.55, 95% confidence interval [CI] [0.005-1.868], P = .048) but not at other levels. Additionally, higher BMI was associated with any collapse (partial or complete) at the oropharynx (OR 1.30, 95% CI [0.131-0.392], P < .001). CONCLUSION: This study demonstrates that a lower proportion of females have complete oropharyngeal lateral wall collapse even when controlling for BMI and AHI. Additional studies are needed to better understand the differences in OSA physiology between the sexes.

Unique cardiometabolic factors in women that contribute to modified cardiovascular disease risk.

Major risk factors of cardiovascular disease (CVD) include hypertension, obesity, diabetes mellitus and metabolic syndrome; all of which are considered inflammatory conditions. Women are disproportionately affected by inflammatory conditions, with sex differences emerging as early as adolescence. Hormonal fluctuations associated with reproductive events such as menarche, pregnancy and menopause, are hypothesized to promote a pro-inflammatory state in women. Moreover, women who have experienced inflammatory-type conditions such as polycystic ovarian syndrome (PCOS), gestational diabetes or pre-eclampsia, have a cardiometabolic phenotype that pre-disposes to increased risk of myocardial infarction, stroke and coronary heart disease. Women with no notable CVD risk factors are often relatively protected from CVD pre-menopause; but overtake men in risk of major cardiovascular events when the cardiovascular protective effects of oestrogen begin to wane. Sex differences and female-specific factors have long been considered challenging to study and this has led to an underrepresentation of females in clinical trials and lack of female-specific data from pre-clinical studies. However, there is now a clear prerogative to include females at all stages of research, despite inherent complexities and potential variability in data. This review explores recent advancements in our understanding of CVD in women. We summarise the underlying factors unique to women that can promote CVD risk factors, ultimately contributing to CVD burden and the emerging therapies aimed to combat this.

Sex differences in glutamate transmission and plasticity in reward related regions.

Disruptions in glutamate homeostasis within the mesolimbic reward circuitry may play a role in the pathophysiology of various reward related disorders such as major depressive disorders, anxiety, and substance use disorders. Clear sex differences have emerged in the rates and symptom severity of these disorders which may result from differing underlying mechanisms of glutamatergic signaling. Indeed, preclinical models have begun to uncover baseline sex differences throughout the brain in glutamate transmission and synaptic plasticity. Glutamatergic synaptic strength can be assessed by looking at morphological features of glutamatergic neurons including spine size, spine density, and dendritic branching. Likewise, electrophysiology studies evaluate properties of glutamatergic neurons to provide information of their functional capacity. In combination with measures of glutamatergic transmission, synaptic plasticity can be evaluated using protocols that induce long-term potentiation or long-term depression. This review will consider preclinical rodent literature directly comparing glutamatergic transmission and plasticity in reward related regions of males and females. Additionally, we will suggest which regions are exhibiting evidence for sexually dimorphic mechanisms, convergent mechanisms, or no sex differences in glutamatergic transmission and plasticity and highlight gaps in the literature for future investigation.

Sex differences in the role of sleep on cognition in older adults.

Study Objectives: The study aimed to investigate sex differences in the relationship between sleep quality (self-report and objective) and cognitive function across three domains (executive function, verbal memory, and attention) in older adults. Methods: We analyzed cross-sectional data from 207 participants with normal cognition (NC) or mild cognitive impairment (89 males and 118 females) aged over 60 years. The relationship between sleep quality and cognitive performance was estimated using generalized additive models. Objective sleep was measured with the GT9X Link ActiGraph, and self-reported sleep was measured with the Pittsburgh Sleep Quality Index. Results: We found that females exhibited lower executive function with increased objective total sleep time, with a steeper decline in performance after 400 minutes (p = .015). Additionally, longer objective sleep correlated with lower verbal memory linearly (p = .046). In males, a positive linear relationship emerged between objective sleep efficiency and executive function (p = .036). Self-reported sleep was not associated with cognitive performance in females and males with NC. However, in males with cognitive impairment, there was a nonlinear positive relationship between self-reported sleep and executive function (p < .001). Conclusions: Our findings suggest that the association between sleep parameters on cognition varies between older males and females, with executive function being most strongly associated with objective sleep for both sexes top of form. Interventions targeting sleep quality to mitigate cognitive decline in older adults may need to be tailored according to sex, with distinct approaches for males and females.

Sex Differences in Cortical Thickness and Neuropsychiatric Symptom Burden Based on APOE4 Homozygosity in Alzheimer's Disease.

Sex differences in patterns of cortical thickness and neuropsychiatric symptom (NPS) burden were examined among individuals with Alzheimer's disease (AD) and two copies (homozygote carriers) of the e4 allele of the apolipoprotein gene (APOE). A total of 752 participants with a clinical etiologic diagnosis of AD were selected from the National Alzheimer's Coordinating Center (NACC) database. Bayesian multilevel regression was used to examine both the within- and between-sex differences in gray-matter cortical thickness and total NPS burden associated with APOE homozygosity. Female homozygote carriers displayed a high probability of having reduced cortical thickness primarily in medial-lateral temporal regions and a greater burden of NPS, relative to both non-homozygous females and homozygous males. These findings support the notion that APOE4 status affects cortical thickness and symptom burden in men and women with AD differentially, with females showing more pronounced effects in brain areas known to be vulnerable in early AD. Future investigations should attempt to elucidate the proposed pattern of decline longitudinally.