Background: While there is clear evidence of sex-specific global and regional methylation patterns, these have yet to be examined within the context of central adiposity. We conducted a ...methylation-wide association study (MWAS) to identify cytosine-phosphate-guanine (CpG) sites that exhibit sex-specific associations with waistcircumference (WC), WC-to-hip ratio (WHR), and WC-to-height ratio (WHtR). Our study included African American (AA) adults in the Atherosclerosis Risk in Communities study (ARIC; 1,702 females; 982 males) with whole blood Illumina 450K genome-wide methylation typing data. Methods: We adjusted CpG beta values for batch effects and white blood cell proportions and used the resulting residuals in subsequent analyses. We performed sex-stratified MWAS analyses with waist traits using linear regression (or mixed model for family studies), adjusted for age, education, BMI, smoking, center, and 10 genetic principal components. Using sex-stratified results, we estimated sexinteraction methylation effects (INT) and main+interaction effects (JOINT), respectively. CpGs that reached suggestive significance (Pjoint or PINT < 1 x 10-6) were brought forward for generalization in an independent sample of European descent (EUD) adults (2,777 women; 2,299 men) from ARIC and Framingham Heart Study (FHS). Results: We identified a total of 43 non-overlapping CpGs (8 WC, 35 WHR, 20 WHtR) in our discovery analyses with evidence of sexinteraction. Of the 43 CpGs, 5 of them (cg06500161 near ABCG1, cg19693031 near TXNIP, cg00574958 near CPT1A, cg06192883 near MYO5C, cg23580000 near ADCY7) met Bonferroni-corrected significance in our generalization analyses for one or more waist traits (3 WC, 5 WHR, and 2 WHtR) in the JOINT model, including 2 CpGs (cg19693031 near TXNIP and cg06500161 in ABCG1) also significant for the INT model. Both of these CpG sites that displayed significant in INT had stronger effects in women compared to men (i.e., cg19693031 displayed ~4x effect in women (Beta = -0.23) compared to men (Beta = -0.06) for WHR) in our generalization. Conclusions: These findings underscore the importance of accounting for sex in MWAS, as differences in methylation of CpG sites in TXNIP and ABCG1 (these genes involved in glucose and lipid homeostasis) between sexes may help to explain sex differences in downstream diseases linked to obesity.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background: Testosterone (T) has been linked with insulin resistance (IR) via sex-dependent relationships; in men, low T is associated with increasing IR and visceral adipose tissue (VAT) whereas the ...opposite is reported in women, particularly in hyperandrogenic conditions. The goals of the current study were (1) examine the sex-specific effects of T on IR across a range of body weights and (2) determine the impact of diet-induced weight loss (DIWL) on these relationships in men and women with obesity (Ob). Methods: Men and women (nondiabetic and premenopausal) with a wide range of body weights (n = 55; M/F 27/28) underwent measurements of abdominal VAT by CT scan, insulin sensitivity by labeled hyperinsulinemic euglycemic clamps (Rd: mg/FFM/min), and total plasma T by radioimmunoassay. A subset of subjects (n = 32; 17/15) completed a four-month DIWL program with repeat testing. Results: Subjects with Ob (n = 40) had greater VAT and lower Rd (p < 0.05) than lean subjects (n = 15), and women had significantly lower T than men (p < 0.01). When compared to those with Ob, lean men had 40% greater (p < 0.01) and lean women had 10% lower total T (p = 0.29). T tended to correlate positively with Rd in men (r = 0.37, p = 0.06) whereas the relationship tended to be opposite in women (r = -0.26, p = 0.17). Post-DIWL, total weight was reduced by 14%, VAT by 39%, and Rd increased by 33% (all p < 0.01). When adjusted for VAT, changes in T were significantly related to changes in Rd in both men and women, despite stable T levels in males (8%; p = 0.56) and a decrease in T in females (10%; p = 0.05). Conclusions: A sexually dimorphic effect of T on IR and VAT has been reported and here, the existing knowledge was extended into a setting of DIWL. These data suggest that improvements in Rd were related to, but may not be fully explained by, changes in T. Further research is needed to elucidate the effects of sex differences in T on the development of Ob and IR, and to identify optimal interventions to alter T, reduce VAT, and improve IR.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
IntroductionDiagnostic stability is a controversial issue in first episode psychosis (FEP) due to heterogenous symptoms and unclear affective symptoms. Differencing affective and non-affective ...psychoses is important as treatment strategies are different. Initial affective symptomatology has low specificity for predicting the subsequent diagnosis of affective psychosis. Sex has proven to be relevant for clinical and functional outcomes but it remains unclear how sex may contribute to diagnosis switch of FEP.ObjectivesTo determine the role of sex in diagnostic stability in a sample of FEP after 1-year follow-up.MethodsDiagnoses of FEP patients from Hospital del Mar of Barcelona were assessed at baseline and 1 year after. Univariate analyses was perfomed for all diagnoses and dichotomic variable (affective/non-affective). Logistic regression model was perfomed to know which variables predict diagnosis switch.Results256 patients were enrolled. No differences were found at baseline between completers and non-completers (Table 1). No significant differences between men and women at baseline diagnosis were found, neither all diagnoses (p=0.274) nor the dichotomic variable affective/non-affective (p=0.829) (Table 2AB). Significant differences were found at 1-year follow-up between men and women, for all diagnoses (p=0.043) and the dichotomic variable (p=0.039). Sex was the only variable that predicted diagnosis switch (Figure 1), PANSS, CDSS, YMRS, GAF and cannabis did not.Table 1.Baseline characteristics of participantsCompleters (n=188)Non-completers (n=68)pWomen (n, %)71 (37.8)30 (44.1)0.111Age (M, IQR)24 (20-28)22 (20-28)0.899Cannabis use (M, IQR)5.5 (0-18)7 (0-21)0.231DUP (M, IQR)45 (12.5-130)36 (11.25-115.75)0.213PANSS (m, sd)44.55 (10.17)40.93 (10.42)0.761CDSS (M, IQR)2 (0-7)3 (0-5.5)0.199YMRS (m, sd)19 (9.64)17.6 (9.15)0.845GAF (M, IQR)30 (25-50)30 (25-35)0.114TABLE 2A and 2B.Diagnosis comparison (n, %)Baseline1-year follow-upMenWomenTotalMenWomenTotalPsychosis NOS69 (59)39 (54.9)108 (57.4)28 (23.9)10 (14.1)38 (20.2)Schizophreniform disorder22 (18.8)16 (22.5)38 (20.2)14 (129 (12.7)23 (12.2)Induced psychosis4 (3.4)0 (0)4 (2.1)15 (12.8)4 (5.6)19 (10.1)Affective psychosis17 (14.5)9 (12.7)26 (13.8)24 (20.5)25 (35.2)49 (26.1)Schizophrenia0 (0)0 (0)1 (0.4)30 (25.6)14 (19.7)44 (23.4)Brief psychotic disorder5 (4.3)7 (9.9)12 (6.4)6 (5.1)8 (11.3)14 (7.4)Baseline1-year follow-upMenWomenTotalMenWomenTotalAffective psychosis17 (14.5)9 (12.7)26 (13.8)24 (20.5)25 (35.2)49 (26.1)Non-affective psychosis100 (85.5)62 (87.3)162 (86.2)93 (79.5)46 (64.8)139 (73.9)Image:ConclusionsSex has proven to be the main predictor of switching initial diagnosis of FEP.Disclosure of InterestNone Declared
Background: Stimulation of energy expenditure (EE) is a common strategy in obesity treatment, and EE has several components, including that derived from spontaneous physical activity (SPA), which ...produces non-exercise activity thermogenesis (NEAT). The neuropeptide orexin A increases SPA and NEAT in several animal models. The New Zealand Obese (NZO) mouse is a polygenic animal model of obesity and diabetes, but orexin action in these mice has not been examined. Our aim was to evaluate the potential therapeutic effect of a novel orexin agonist (RTIOXA-47) for the treatment of obesity in NZO mice. We hypothesized that peripheral RTIOXA-47 administration increases SPA and attenuates obesity in NZO mice. Methods: To test this, male and female C57BL/6 WT and NZO mice (n = 24) were housed individually and randomly assigned to treatment with saline or RTIOXA47 (40 mg/kg), administered via intraperitoneal injection 5 days per week for five weeks. The current N = 3 per species, sex and treatment, but an additional cohort is in progress. Body weight (BW) and food intake (FI) were recorded weekly. Body composition (BC) and 24-hour SPA and EE were measured before and after treatment. To analyze the data, Generalized Estimated Equations (GEE) were performed followed by Bonferroni post hoc test. Significance was set at p<0.05. Results: A significant sex·strain·time·treatment interaction was observed for BW, FI, SPA, EE and fat mass (FM). Significant sex differences were seen in both NZO vs. WT across all variables. A benefit of RTIOXA-47 was seen in WT males and NZO females as both sets of treated mice had significantly lower BW and FM compared with their respective non-treated group at studys end (p <0.05). For FI, the same was observed, but only in WT females (treated < non-treated). Conclusions: These preliminary findings suggest that RTIOXA47 may help reduce BW and FM, but additional statistical power gained by inclusion of the next cohort of mice will help expand and solidify these results.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The primary aims of this literature audit were to, firstly, understand the extent of female representation in the participant populations of EIGD research; and secondly, within the studies conducted ...with females, to assess the quality of data pertaining to menstrual (and thus hormone) status of participants. Additionally, within the literature, female data (demographics and results) were typically combined with male data and reported together. ...not only is there an underrepresentation of females to begin with, but what data there is, is subsumed within the overall mean of the combined data making future analysis of sex-disaggregated data (e.g., meta-analyses) impossible. There is a need for a greater quantity of high quality data using rigorous methodology to ascertain and report menstrual status of female athletes, as well as sex-disaggregation of data, if we are to understand potential sex differences in EIGD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits and restricted and repetitive or stereotyped behaviours. The prevalence ...of ASD has been thought to be higher in men, which may reflect aspects of the own aetiology of the disorder. Still, it may also be associated with misdiagnosis or missed diagnosis of females with autism due to specific phenotypic traits.
Objectives
To explore the differences between sex/gender in autism’s clinical presentation.
Methods
Non-systematic literature review using the most relevant papers found on PubMed and Google Scholar using the following keywords: “autism spectrum disorder”, “gender differences”, and “autistic women”.
Results
Autistic women seem to have a “camouflage” phenomenon, characterized by a high level of functioning, less unusual play or restricted interests, better socio-emotional reciprocity and coping behaviours. Therefore, women with ASD commonly have an anteriority of multiple diagnoses, which delays their access to the support and care they need.
Conclusions
Professionals must be aware of the sex/gender clinical differences to prevent the misdiagnosis or missed diagnosis of females with autism. Moreover, the current clinical criteria used to diagnose ASD may underserve the female population and deserve to be reviewed.
Disclosure of Interest
None Declared
Abstract
Introduction
Studies have shown that sleep affects working memory (WM) improvement, but specific electrophysiological features are unclear (Sattari et al., 2019; MacDonald et al., 2018). In ...addition, sex differences have been found in both sleep and working memory (Mong, 2016; Harness, 2008). The goal of this study is to identify sex differences in EEG correlates of working memory over a night of sleep.
Methods
Sixty-three healthy (33 females), college-aged adults without sleep disorder were enrolled. A 32-channel electroencephalogram (EEG) cap was used to record brain activity during sleep. Operation span (OS) task was used to evaluate WM performance. Participants reported to the laboratory in the evening, performed OS before sleep (test1) and after sleep (test2). Trials were divided into easy and hard trials based on the number of letters subjects had to recall. A repeated-measure analysis of variance was conducted to examine the effects of time and trial difficulty. Paired-sample t-tests between test 1 and test 2 were conducted for males and females. Pearson’s correlations were examined between WM performance at test 1 and the difference score between test 1 and test 2 and EEG frequency bands. The Benjamini–Hochberg method was used to control for multiple comparisons.
Results
There was an increase in performance across the night in WM hard trials across all subjects (F(1,62)=4.86, p=0.03), no effect for easy trials (p>0.05). Females, but not males, showed a significant decrease in easy trials (t62= 2.40, p=0.02), while both males and females showed improvement in hard trials across the night. Females showed a positive correlation between test 1 hard trials and slow sigma, delta, slow oscillation in stage 3, this correlation is not seen in males. No correlations between overnight improvement and EEG bands were found.
Conclusion
Consistent with previous studies, participants showed better memory performance over a night of sleep, and the WM performance was associated with slow wave activity in females. Slow sigma also plays a role in the WM performance for females, indicating a possible role of sleep spindles. These associations were not shown in males, suggesting sex hormones mediate sleep’s impact on WM performance.
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