Sex Differences In Response Research Articles

Efficacy of aerobic exercise following concussion: a narrative review

Concussion is a type of mild traumatic brain injury which results in symptoms within the physical, cognitive, emotional, and sleep domains. Historically, guidelines established by expert opinion have recommended rest during the initial stages of recovery following a concussion until symptom resolution. However, recent recommendations have shifted to advise an initial period of 24-48 h of rest immediately following concussion with the gradual introduction of light-to-moderate intensity aerobic exercise thereafter. Given the relatively recent transition in recommendations, the aim of this review is to provide an overview of the current literature on the efficacy of aerobic exercise following concussion. The current literature is limited to studies assessing the impact of standardized aerobic exercise following concussion. Upon review, literature suggests participating in aerobic exercise below the point of symptom exacerbation is safe in both the acute and chronic post-concussion symptom stages of recovery and does not delay time to medical clearance. Future large-scale randomized controlled trials assessing the impact of aerobic exercise and differences between males and females would help support the current evidence suggesting aerobic exercise could improve time to recovery following concussion and identify any sex differences in response. As well, future studies with the purpose of identifying optimal aerobic exercise volume and intensity in the treatment of concussion could improve the specificity of the current guidelines.

EPCO-22. SINGLE CELL ANALYSIS TO UNDERSTAND SEX DIFFERENCES IN GBM OUTCOME

Abstract Males have a higher incidence and mortality in certain cancers compared to females. The same is true in glioblastoma (GBM) regardless of age, suggesting that cell-intrinsic factors rather than extrinsic factors such as circulating sex hormones are causing these sex differences. Our lab has demonstrated cell-intrinsic sex differences with respect to growth, clonogenicity, and in vivo tumorigenesis using an isogenic murine astrocyte cell culture model of GBM (Nf1 -/-; DNp53). Male astrocytes are more likely to adapt and grow when exposed to irradiation-induced stress compared to female astrocytes, which are more likely to undergo growth arrest after the same exposures. These sex differences in response to treatment can be explained by the different chromatin and transcriptional profiles established from the moment of fertilization that can result in different levels of transcriptional heterogeneity, a well-established cause for resistance to induced stress in GBM. However, so far sex has not been considered when exploring transcriptional heterogeneity. As such, we used 10x Genomics technology to extract single nuclei RNA (snRNA) and ATAC (snATAC) sequencing from the same nuclei and identified different levels of transcriptional heterogeneity in male and female astrocytes cells from our model. We also identified different chromatin profiles of crucial genes, such as Sox2, an important TF for the reprogramming of differentiated GBM into stem-like cells, which can then form tumors in vivo. We expect for the male astrocytes to be more effective in escaping growth arrest and adapting to irradiation-induced stress because of these different transcriptional and chromatin profiles. Our work will identify epigenetic mechanisms by which male cells are more able to adapt to treatment-induced stress compared to female cells and will further advance our understanding of sex differences in treatment-response in GBM and cancer overall, while giving avenues for the development of novel treatments.

Integrated analyses reveal evolutionarily conserved and specific injury response genes in dorsal root ganglion

Rodent dorsal root ganglion (DRG) is widely used for studying axonal injury. Extensive studies have explored genome-wide profiles on rodent DRGs under peripheral nerve insults. However, systematic integration and exploration of these data still be limited. Herein, we re-analyzed 21 RNA-seq datasets and presented a web-based resource (DRGProfile). We identified 53 evolutionarily conserved injury response genes, including well-known injury genes (Atf3, Npy and Gal) and less-studied transcriptional factors (Arid5a, Csrnp1, Zfp367). Notably, we identified species-preference injury response candidates (e.g. Gpr151, Lipn, Anxa10 in mice; Crisp3, Csrp3, Vip, Hamp in rats). Temporal profile analysis reveals expression patterns of genes related to pre-regenerative and regenerating states. Finally, we found a large sex difference in response to sciatic nerve injury, and identified four male-specific markers (Uty, Eif2s3y, Kdm5d, Ddx3y) expressed in DRG. Our study provides a comprehensive integrated landscape for expression change in DRG upon injury which will greatly contribute to the neuroscience community.

Sex differences in acetylcholinesterase modulation during spatial and fear memory extinction in the amygdala; an animal study in the single prolonged stress model of PTSD.

Men and women show different reactions to trauma and that is believed to be the reason behind the higher prevalence of post-traumatic stress disorder (PTSD) in women. Cholinergic signaling has long been known to be involved in the processing of fear-related information and the amygdala is a critical center for fear modulation. The main goal of the current research was to find (a) whether trauma results in different learning/extinction of fear or spatial-related information among male and female rats and (b) if trauma is associated with different acetylcholinesterase (AchE) activity in the amygdala. We used single prolonged stress (SPS) as a PTSD model in this study. Normal and SPS animals of both sexes were tested in contextual and spatial tasks (learning and extinction). AchE activity in the amygdala was also measured during each process. Results indicated that fear and spatial learning were impaired in SPS animals. SPS animals also had deficits in fear and spatial memory extinction and the effect was significantly higher in female- SPS than in the male-SPS group. In the enzymatic tests, AchE activity was increased during the fear extinction test and incremental changes were more significant in the female-SPS group. Collectively, these findings provided evidence that sex differences in response to trauma were at least partly related to less fear extinction potential in female subjects. It also indicated that the extinction deficit was associated with reduced cholinergic activity in the amygdala of female animals.

Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection.

Male sex is a major risk factor for SARS-CoV-2 infection severity. To understand the basis for this sex difference, we studied SARS-CoV-2 infection in a young adult cohort of United States Marine recruits. Among 2,641 male and 244 female unvaccinated and seronegative recruits studied longitudinally, SARS-CoV-2 infections occurred in 1,033 males and 137 females. We identified sex differences in symptoms, viral load, blood transcriptome, RNA splicing, and proteomic signatures. Females had higher pre-infection expression of antiviral interferon-stimulated gene (ISG) programs. Causal mediation analysis implicated ISG differences in number of symptoms, levels of ISGs, and differential splicing of CD45 lymphocyte phosphatase during infection. Our results indicate that the antiviral innate immunity set point causally contributes to sex differences in response to SARS-CoV-2 infection. A record of this paper's transparent peer review process is included in the supplemental information.

Sex difference in the expression of PD-1 of non-small cell lung cancer.

Evidence increasingly indicated that lung cancer incidence in female individuals continue to rise, and women have a higher risk to develop adenocarcinoma than men. Male and female individuals differ in their innate and adaptive immune responses, and there are sex differences in response to the PD-1/PD-L1-dependent blocking immunotherapy. Whether the differential expression of PD-1 between genders affect the response to blocking treatment is currently unknown. In this study, we examined sex differences in serum sPD-1, mPD-1 expression on T cells, and sex hormone levels in non-small cell lung cancer (NSCLC) patients. Our results revealed a higher level of sPD-1 and expression of PD-1 on CD4+T cell in female patients than in male patients; we identified that serum sPD-1 level and the expression of mPD-1 on T cells were significantly reduced in NSCLC; we also found that serum testosterone level increased in female patients compared with control subjects and that increased testosterone downregulated the expression of mPD-1 on T cell. These findings provide a better understanding of the differences in PD-1 expression between genders in NSCLC patients and the effect of sex hormones on PD-1 expression and supply evidence for early lung cancer diagnosis and responsiveness to immune checkpoint inhibitors.

Sexual segregation occurs in bats within fragmented remnant woodlands in an agricultural landscape.

Species‐specific responses to landscape configuration and landscape composition have been studied extensively. However, little work has been done to compare intraspecific differences in habitat preferences. Bats have potential as good bioindicator taxa in woodland habitats. Therefore, studying sex differences in responses to woodland and the wider landscape can allow us to gain insight into the relative importance of these habitats for both bats and other taxa. In this study, we aimed to test the predictions that (i) habitat type and connectivity will influence the probability of recording female bats in woodlands and (ii) sex differences in response to habitat type and connectivity will be species‐specific. Bat capture data was collected in 206 woodlands over 3 years in England. The probability of detecting females relative to males was modeled in response to a range of woodland characteristics and landscape metrics for six bat species. We recorded sex differences in responses to landscape features in three species. We found a higher probability of capturing female Myotis nattereri in woodlands that were surrounded by a higher proportion of improved grasslands, whereas female Myotis mystacinus were less likely to be recorded in woodlands surrounded by semi‐natural vegetation. Female Plecotus auritus were more likely to be recorded in isolated woodlands with less connectivity to other woodlands and where agriculture dominated the surrounding landscape. Our findings indicate that sexual segregation occurs across several UK bat species in response to landscape connectivity and composition. Sexual segregation in response to landscape characteristics in bats should therefore be an important consideration in the management of fragmented agricultural landscapes.

Investigating the “two-hit hypothesis”: Effects of prenatal maternal immune activation and adolescent cannabis use on neurodevelopment in mice

Prenatal exposure to maternal immune activation (MIA) and chronic adolescent cannabis use are both risk factors for neuropsychiatric disorders. However, exposure to a single risk factor may not result in major mental illness, indicating that multiple exposures may be required for illness onset. Here, we examine whether combined exposure to prenatal MIA and adolescent delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, lead to enduring neuroanatomical and behavioural changes in adulthood.Mice were prenatally exposed to viral mimetic, poly I:C (5 mg/kg), or vehicle at gestational day (GD) 9, and postnatally exposed to chronic THC (5 mg/kg, intraperitoneal) or vehicle during adolescence (postnatal day [PND]28–45). Longitudinal magnetic resonance imaging (MRI) was performed pre-treatment, PND 25, post-treatment, PND 50, and in adulthood, PND85, followed by behavioural tests for anxiety-like, social, and sensorimotor gating. Post-mortem assessment of cannabinoid (CB)1 and 2 receptor expressing cells was performed in altered regions identified by MRI (anterior cingulate and somatosensory cortices, striatum, and hippocampus).Subtle deviations in neurodevelopmental trajectory and subthreshold anxiety-like behaviours were observed in mice exposed to both risk factors. Sex-dependent effects were observed in patterns of shared brain-behaviour covariation, indicative of potential sex differences in response to MIA and THC. Density of CB1 and CB2 receptor positive cells was significantly decreased in all mice exposed to MIA, THC, or both.These findings suggest that there may be a cumulative effect of risk factor exposure on gross neuroanatomical development, and that the endocannabinoid system may be sensitive to both prenatal MIA, adolescent THC, or the combination.

Examining sex differences in responses to footshock stress and the role of the metabotropic glutamate receptor 5: an [18F]FPEB and positron emission tomography study in rats.

Clinical investigations suggest involvement of the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of fear learning that underlies trauma-related disorders. Here, we utilized a 4-day fear learning paradigm combined with positron emission tomography (PET) to examine the relationship between mGluR5 availability and differences in the response of rats to repeated footshock exposure (FE). Specifically, on day 1, male (n = 16) and female (n = 12) rats received 15 footshocks and were compared with control rats who did not receive footshocks (n = 7 male; n = 4 female). FE rats were classified as low responders (LR) or high responders (HR) based on freezing to the context the following day (day 2). PET with [18F]FPEB was used to calculate regional mGluR5 binding potential (BPND) at two timepoints: prior to FE (i.e., baseline), and post-behavioral testing. Additionally, we used an unbiased proteomics approach to assess group and sex differences in prefrontal cortex (PFC) protein expression. Post-behavioral testing we observed decreased BPND in LR females, but increased BPND in HR males relative to baseline. Further, individuals displaying the greatest freezing during the FE context memory test had the largest increases in PFC BPND. Males and females displayed unique post-test molecular profiles: in males, the greatest differences were between FE and CON, including upregulation of mGluR5 and related molecular networks in FE, whereas the greatest differences among females were between the LR and HR groups. These findings suggest greater mGluR5 availability increases following footshock exposure may be related to greater contextual fear memory. Results additionally reveal sex differences in the molecular response to footshock, including differential involvement of mGluR5-related molecular networks.

Sex-Related Differences in Voluntary Alcohol Intake and mRNA Coding for Synucleins in the Brain of Adult Rats Prenatally Exposed to Alcohol.

Maternal alcohol consumption is one of the strong predictive factors of alcohol use and consequent abuse; however, investigations of sex differences in response to prenatal alcohol exposure (PAE) are limited. Here we compared the effects of PAE throughout gestation on alcohol preference, state anxiety and mRNA expression of presynaptic proteins α-, β- and γ-synucleins in the brain of adult (PND60) male and female Wistar rats. Total RNA was isolated from the hippocampus, midbrain and hypothalamus and mRNA levels were assessed with quantitative RT-PCR. Compared with naïve males, naïve female rats consumed more alcohol in “free choice” paradigm (10% ethanol vs. water). At the same time, PAE produced significant increase in alcohol consumption and preference in males but not in females compared to male and female naïve groups, correspondingly. We found significantly lower α-synuclein mRNA levels in the hippocampus and midbrain of females compared to males and significant decrease in α-synuclein mRNA in these brain areas in PAE males, but not in females compared to the same sex controls. These findings indicate that the impact of PAE on transcriptional regulation of synucleins may be sex-dependent, and in males’ disruption in α-synuclein mRNA expression may contribute to increased vulnerability to alcohol-associated behavior.

No Sex Differences In Common Carotid Artery Stiffness Response Following Maximal Oxygen Consumption Test

No Sex Differences in Common Carotid Artery Stiffness Response Following Maximal Oxygen Consumption Test HEYSEL MORALES, MICHAEL DIAZ, ZARIA OPARA, STEVEN HAWKINS, LOUISE KELLY, ALLAN KNOX. PURPOSE: Previous investigations have reported sex differences in the time course of age-related arterial stiffness, with postmenopausal women presenting increased risk of cardiovascular diseases. Using sex as a biological variable has identified differences between males and females in physiological responses to equivalent doses of exercise. The purpose of this study was to determine if sex differences exist in arterial stiffness response to a maximum oxygen consumption (VO2max) exercise test. METHODS: VO2max was measured by indirect calorimetry. Body composition was measured by air displacement plethysmography (BODPOD). Indices of common carotid artery (CCA) stiffness (Peterson’s elastic modulus [Ep], Beta stiffness [B1], distensibility [DIST], and diameter compliance [DC]) were calculated before and within 5 minutes following VO2max. CCA’s were imaged for 1 minute by duplex Doppler ultrasound approximately 2-3cm below bifurcation and stored for offline analysis of velocities and diameters. Brachial blood pressures were captured by automated cuff. RESULTS: Males (n=14) and females (n=15) were matched for age (p=0.549), fat mass (p =0.775), body fat percentage (p=0.08), fat free mass percentage (p=0.087), and VO2max (p=0.349). Males had higher body mass (p < 0.001) and fat free mass (p<0.001). No sex differences were observed before or after exercise for Ep, B1, DIST, and DC (p >0.05 for all). No sex differences were identified for delta changes in any CCA stiffness indices (p >0.05). CONCLUSION: The CCA response to VO2max test is equivalent in males and females who are matched for baseline VO2max, despite males presenting high fat free masses. Previously reported sex differences in response to equivalent exercise dose may not be evident in the CCA stiffness characteristics.

P9. Sex differences in response to recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat posterolateral fusion spine model

<h3>BACKGROUND CONTEXT</h3> Estrogen modulates bone activity largely through inhibition of osteoclast bone resorption and bone morphogenetic protein-2 (BMP-2) signaling pathways in osteoblasts. Minimal data exist concerning potential sex-dependent differences in BMP-2-mediated bone regeneration. Here, we aimed to quantify sex-dependent differences in the bone healing response to recombinant human BMP-2 (rhBMP-2) treatment in a rat posterolateral spinal fusion model. <h3>METHODS</h3> A total of 48 female and male Sprague-Dawley rats (N=24/group), underwent L4-L5 posterolateral fusion with bilateral placement of absorbable collagen sponges, loaded with 5 µg of rhBMP-2 (10 µg/animal). At 8 weeks postoperatively, 10 specimens of each sex were tested in flexion-extension with quantification of range of motion (ROM) and stiffness. The remaining specimens were evaluated for new bone growth and fusion via radiography, blinded manual palpation and microcomputed tomography (microCT). Laboratory microCT quantified bone microarchitecture and synchrotron microCT examined bone microstructure. On histology, the number of adipocytes within a standardized field of view was counted for both male and female fusion masses. <h3>RESULTS</h3> Manual palpation scores differed significantly between sexes, with mean fusion scores of 2.4±0.4 in females vs 3.1±0.6 in males, p < 0.001. Biomechanical stiffness did not differ between sexes, but ROM was significantly greater and more variable for females vs males (3.7°±5.6° vs 0.27°±0.15°,p < 0.005, respectively. Laboratory microCT showed significantly smaller volumes of fusion masses in females vs males (262±87 mm³ vs 732±238 mm³, respectively, p < 0.001) but significantly higher bone volume fraction (0.27±0.08 vs 0.12±0.05, respectively, p < 0.001). Mean trabecular thickness was not different, but trabecular number was significantly greater in females (3.1±0.5 mm-1vs 1.5±0.4 mm-1, respectively, p<0.001). Synchrotron microCT showed fine bone structures developing in both sexes at the 8-week time point. Adipocyte density was found to be significantly higher in male fusion masses than in female fusion masses. <h3>CONCLUSIONS</h3> This study demonstrates that sex-based factors may influence both the quantity and quality of bone formation in patients receiving rhBMP-2 for a variety of orthopedic applications. We found that male rats had significantly higher fusion scores, greater fusion-mass volume, and lower ratio of new bone volume to total volume compared to female rats. Male and female mean trabecular thicknesses were equal, but the female fusion masses were more densely filled with trabeculae (higher trabecular number) than those of males. MicroCT results suggested that the male trabeculae were more rod-like and the female more plate-like, although the methods that were used are generally considered less accurate for trabecular bone, which has a high degree of concavity. The incomplete fusions on three female rats, evidenced by high ROM and small gaps on microCT, suggest that females may have a more variable response to rhBMP-2. Investigation into whether these sex-based differences are specific to rhBMP-2-induced bone formation or are more general to bone regeneration/healing is prudent. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Editor's Choice – Sex Differences in Response to Administration of Heparin During Non-Cardiac Arterial Procedures

Females are more prone to complications during non-cardiac arterial procedures (NCAPs) than males. The current study investigated the difference in the effect of peri-procedural prophylactic heparin in males and females, using the activated clotting time (ACT). This was a retrospective analysis of a prospective multicentre cohort study. All patients undergoing elective NCAP using heparin and ACT measurements between January 2016 and March 2020 were included. Two heparin dosage protocols were used: weight based dosing of 100 IU/kg (international units per kilogram) or a bolus of 5 000 IU. The primary outcome was the anticoagulatory effect of heparin after five minutes, measured by ACT. Secondary outcomes were the effect of heparin after 30 minutes, bleeding complications, and arterial thromboembolic complications (ATECs). A total of 778 patients were included; 26% were female. After 100 IU/kg (n= 300), females more often reached longer ACT (< 200 seconds: 22% vs. 25%, p= .62; 200 - 250 seconds: 41% vs. 53%, p= .058; 251 - 280 seconds, 26% vs. 15%, p= .030). The mean ACT after 100 IU/kg heparin was 233 seconds (95% confidence interval [CI] 224 - 243) for females and 226 seconds (95% CI 221 - 231) for males (p= .057). After a bolus of 5 000 IU of heparin (n= 411), females reached significantly higher levels of anticoagulation than males (mean ACT 204 seconds vs. 190 seconds: p ≤ .001; ACT < 200 seconds: 44% vs. 66%; p < .001; ACT 200 - 250 seconds: 47% vs. 30%, p= .001; ACT 251 - 280 seconds: 7.8% vs. 2.3%, p= .009). Thirty minutes after heparin administration, 58% of all patients had an ACT < 200 seconds. ATECs did not differ between females and males (6.9% vs. 5.1%, p= .33) but bleeding complications were higher in females (27% vs. 16%, p= .001). Heparin leads to significantly longer ACT in females during NCAP. Further research is needed to investigate whether individually based heparin protocols lead to fewer bleeding complications and lower incidence of ATECs.

Differences between men and women in response to antiseizure medication use and the likelihood of developing treatment resistant epilepsy.

The prevalence of epilepsy is slightly higher in women than in men and sensitivity to seizure stimuli differs between sexes. Some evidence suggests sex differences in response to antiseizure medications exist mainly due to inconsistent pharmacokinetic differences; however, there is a lack of real-world evidence examining differences in response to antiseizure medications between men and women. This was a retrospective population-based cohort study in five large US healthcare databases. The population included adult patients with epilepsy, newly exposed to levetiracetam, and naive to antiseizure medication. The first exposure to levetiracetam was the index date. The requirement that all patients received the same medication was done to avoid potential confounding due to differences in index treatment. The outcome was the development of treatment resistant epilepsy (TRE), defined as having at least three distinct antiseizure medications in 1 year. The proportion of patients who developed TRE within 1 year following the index date was calculated. To compare the risk of developing TRE between sexes, relative risks (RR) and 95% confidence intervals (CI) were calculated, and estimates were pooled using meta-analytic techniques stratified by gender and age. A total of 147 334 subjects were included in the databases, 50.8% were women, and 4.27% developed TRE. The comorbid profile differed greatly between men and women; however, the types of epilepsy syndromes observed during baseline were similar between the two groups. Across all databases, women were more likely to develop TRE than men (pooled RR 1.27, 95% CI 1.17-1.38). Results remained similar when stratified by age. This study assessed sex differences in response to antiseizure medications using the development of TRE as a proxy for effectiveness. Women newly exposed to levetiracetam were 27% more likely to develop TRE than men, independent of age.

Sex differences in cognitive flexibility are driven by the estrous cycle and stress-dependent.

Stress is associated with psychiatric disorders such as post-traumatic stress disorder, major depressive disorder, anxiety disorders, and panic disorders. Women are more likely to be diagnosed with these stress-related psychiatric disorders than men. A key phenotype in stress-related psychiatric disorders is impairment in cognitive flexibility, which is the ability to develop new strategies to respond to different patterns in the environment. Because gonadal hormones can contribute to sex differences in response to stress, it is important to consider where females are in their cycle when exposed to stress and cognitive flexibility testing. Moreover, identifying neural correlates involved in cognitive flexibility could not only build our understanding of the biological mechanisms behind this crucial skill but also leads to more targeted treatments for psychiatric disorders. Although previous studies have separately examined sex differences in cognitive flexibility, stress effects on cognitive flexibility, and the effect of gonadal hormones on cognitive flexibility, many of the findings were inconsistent, and the role of the estrous cycle in stress-induced impacts on cognitive flexibility is still unknown. This study explored potential sex differences in cognitive flexibility using an operant strategy shifting-paradigm after either control conditions or restraint stress in freely cycling female and male rats (with estrous cycle tracking in the female rats). In addition, we examined potential neural correlates for any sex differences observed. In short, we found that stress impaired certain aspects of cognitive flexibility and that there were sex differences in cognitive flexibility that were driven by the estrous cycle. Specifically, stress increased latency to first press and trials to criterion in particular tasks. The female rats demonstrated more omissions and perseverative errors than the male rats; the sex differences were mostly driven by proestrus female rats. Interestingly, the number of orexinergic neurons was higher in proestrus female rats than in the male rats under control conditions. Moreover, orexin neural count was positively correlated with number of perseverative errors made in cognitive flexibility testing. In sum, there are sex differences in cognitive flexibility that are driven by the estrous cycle and are stress-dependent, and orexin neurons may underlie some of the sex differences observed.

Sex differences in rTMS treatment response: A deep learning-based EEG investigation.

IntroductionThe present study aimed to investigate sex differences in response to repetitive transcranial magnetic stimulation (rTMS) in Major Depressive Disorder (MDD) patients. Identifying the factors that mediate treatment response to rTMS in MDD patients can guide clinicians to administer more appropriate, reliable, and personalized interventions.MethodsIn this paper, we developed a novel pipeline based on convolutional LSTM‐based deep learning (DL) to classify 25 female and 25 male patients based on their rTMS treatment response.ResultsFive different classification models were generated, namely pre‐/post‐rTMS female (model 1), pre‐/post‐rTMS male (model 2), pre‐rTMS female responder versus pre‐rTMS female nonresponders (model 3), pre‐rTMS male responder vs. pre‐rTMS male nonresponder (model 4), and pre‐rTMS responder versus nonresponder of both sexes (model 5), achieving 93.3%, 98%, 95.2%, 99.2%, and 96.6% overall test accuracy, respectively.ConclusionThese results indicate the potential of our approach to be used as a response predictor especially regarding sex‐specific antidepressant effects of rTMS in MDD patients.

The effect of an acute bout of high intensity intermittent exercise on neural growth factors in young adults: Sex differences

The neurophysiological response to exercise on cognition is modulated through chemical pathways which involve several neurotrophic factors and the sex of the individual determines this effect. We examined sex differences in the concentration of neural growth factors (NGF); brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and insulin like growth factor-I (IGF- I) in response to acute high intensity intermittent exercise (HIIE). We also evaluated the relationship of NGF with gonadal hormones before and after the HIIE session. Forty healthy young adults (22 males and 18 females) performed HIIE (4 bouts of 4 minutes at 90–95% HR max with 3min active recovery at 70% HRmax). Venous blood was drawn before and immediately after the exercise session and was analyzed for the concentration of serum BDNF, VEGF, IGF-I, cortisol, estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone, using ELISA method. A significant sex difference (p&lt;0.05) was observed for BDNF concentration in response to HIIE and a significant increase was found in males but not in females. A significant (p&lt;0.005) positive correlation of BDNF with FSH and LH and a significant (p&lt;0.05) negative correlation of BDNF and VEGF with testosterone were found. Other NGFs (VEGF and IGF-I) did not show sex differences in response to HIIE. In conclusion, a single session of HIIE increases the serum concentration of BDNF in males and IGF-I in females and the response of NGF is different in males and females.

Scoping review on environmental enrichment: Are critical periods and sex differences adequately studied?

BackgroundDecades of research have shown the robust behavioral, structural, and molecular effects of environmental enrichment (EE) which predominantly improves neuropathological conditions. However, systematic examination of age and sex influences in response to EE is limited. ObjectiveExamine the use of EE and evaluate where sex differences (or similarities) are described and whether critical developmental periods are addressed. A critical examination of review articles about EE will establish a framework for the context of the findings of EE-induced effects, improve the impact of future EE studies and improve translatability. Eligibility criteriaNarrative, systematic reviews (not original reports) and meta-analyses of any animal species published during 2011 to 2021. Clinical and farming studies were excluded. Sources of evidenceIndexed review articles in Pubmed and Psychinfo. ResultsMost studies examine EE during adulthood such as following an injury or following repeated addictive drug exposure. However, in various genetic models of disease states, little attention is paid to effects of EE at different ages. Only some reviews acknowledge that sex differences exist even when the disease state under study is known to be sexually dimorphic. Identified issues include lack of systematic reporting; status of the “control group” (i.e., isolation or pair housing); the use and reporting of proper statistical analyses. ConclusionReviews have concluded that EE is most effective when administered early in life but that EE during adulthood is certainly effective. Too few review studies have compared sexes for the effects of EE to make a statement about sex differences. Overall, articles reflect a lack of integration of information on age and sex differences in response to EE. Future studies of EE should examine both sexes and consider critical periods of the lifespan in the experimental models to facilitate the adequate translation of EE as a non-pharmaceutical intervention.

Deep learning approach to evaluate sex differences in response to neuromodulation in Major Depressive Disorder

IntroductionIdentifying the factors that mediate treatment response to rTMS in MDD patients can guide clinicians to administer more appropriate, reliable, and personalized interventions.ObjectivesThe present study aimed to investigate sex differences in response to repetitive transcranial magnetic stimulation (rTMS) in Major Depressive Disorder (MDD) patients.MethodsIn this paper, we developed a novel pipeline based on convolutional LSTM-based deep learning (DL) to classify 25 female and 25 male subjects based on their rTMS treatment response.ResultsFive different classification models were generated, namely pre/post-rTMS female (model 1), pre/post-rTMS male (model 2), pre-rTMS female responder vs. pre-rTMS female non-responders (model 3), pre-rTMS male responder vs. pre-rTMS male non-responder (model 4), and pre-rTMS responder vs. non-responder of both sexes (model 5), achieving 93.3%, 98%, 95.2%, 99.2%, and 96.6% overall test accuracy, respectively.ConclusionsThese results indicate the potential of our approach to be used as a response predictor especially regarding sex-specific antidepressant effects of rTMS in MDD patients.DisclosureNo significant relationships.

ID:15886 Deep Learning Approach to Evaluate Sex Differences in Response to Neuromodulation in Major Depressive Disorder

Major depressive disorder (MDD) affects women more severely than men1, particularly in Iran where prevalence is two-fold.2 There is no current research available for such sex differences in repetitive transcranial magnetic stimulation (rTMS), an efficacious MDD treatment.3 Electroencephalography (EEG) serves as biomarker for rTMS treatment given its high temporal resolution, non-invasiveness, and relative affordability. 4,5 Deep learning (DL) algorithms can further classify these EEG signals to predict treatment responses.6 In this study, five different EEG-based deep learning (DL) models were created to classify male and female subjects using their pre- and post-TMS raw EEG data.