Sex differences in bipolar disorder:a review of neuroimaging findings and new evidence

Objectives: The sex of an individual is known to modulate the clinical presentation of bipolar disorder (BD), but little is known as to whether there are significant sex-by-diagnosis interactions on the brain structural and functional correlates of BD. Methods: We conducted a literature review of magnetic resonance imaging (MRI) studies in BD, published between January 1990 and December 2010, reporting on the effects of sex and diagnosis. In the absence of any functional MRI (fMRI) studies, this review was supplemented by original data analyses focusing on sex-by-diagnosis interactions on patterns of brain activation obtained during tasks of working memory, incentive decision-making, and facial affect processing. Results: We found no support for a sex-by-diagnosis interaction in global gray or white matter volume. Evidence regarding regional volumetric measures is limited, but points to complex interactions between sex and diagnosis with developmental and temperamental factors within limbic and prefrontal regions. Sex-by-diagnosis interactions were noted in the pattern of activation within the basal ganglia during incentive decision-making and within ventral prefrontal regions during facial affect processing. Conclusions: Potential sex-by-diagnosis interactions influencing the brain structural and functional correlates of disease expression in BD have received limited attention. Our data suggest that the sex of an individual modulates structure and function within subcortical and cortical regions implicated in disease expression. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.

Perceived and actual sex differences in attributional style for affiliative behavior

The objectives of this thesis were threefold: (1) to review the concept of attributional style, (2) to demonstrate its applicability to affiliative behavior, and (3) to document the existence of actual and perceived sex differences in attributional style for affiliative behavior. To fulfill the first two objectives the development of attributional theory was traced from the Abramson, Seligman, and Teasdale (1978) presentation of the reformulated learned helplessness model through Weiner's (1979) examination of attributional style as a motivational feature of achievement behavior to the application of attribution theory to affiliative behavior. To fulfill the third objective the evidence detailing the sex differences in achievement and affiliative attributional styles was reviewed within the framework of perceptions of sex appropriate behavior. A study was then designed to assess both actual and perceived affiliative attributional sex differences. The Escovar, Brown, and Rodriguez Attributional Style Questionnaire for Affiliative Behavior was administered to 107 male and female University of Miami and Florida International University students. Each subject answered the questionnaire twice, once for themselves and once as if they were a member of the opposite sex. The results indicated that the EBR-ASQ maintained previous levels of internal consistency and reliability. Analyses performed on the covariate of the order of perspective presentation were negative; all further analyses were performed without a covariate. The data were analyzed using a 2(Sex) X 2(Perspective) X 2(Outcome) factorial, multivariate, repeated measures design with the three attributional dimensions serving as the dependent variable repeated measures. As expected all multivariate tests revealed that each of the three factors was a significant influence over all three of the dependent variables. Of the 21 univariate tests 12 of the main effect and two-way interactions were significant and one approached significance. Examination of the means revealed that of the eight significant main effects six were in the expected direction; of the four significant two-way interactions three were in the expected direction. Although the results were not totally supportive of the hypotheses they did support the thesis that affiliation is the female sex-role appropriate analogue to male achievement behavior.

State-space modelling of geolocation data reveals sex differences in the use of management areas by breeding northern fulmars

We thank Orkney Islands Council for access to Eynhallow and Talisman Energy (UK) Ltd and Marine Scotland for fieldwork and equipment support. Handling and tagging of fulmars was conducted under licences from the British Trust for Ornithology and the UK Home Office. EE was funded by a Marine Alliance for Science and Technology for Scotland/University of Aberdeen College of Life Sciences and Medicine studentship and LQ was supported by a NERC Studentship. Thanks also to the many colleagues who assisted with fieldwork during the project, and to Helen Bailey and Arliss Winship for advice on implementing the state-space model.

State-space modelling of geolocation data reveals sex differences in the use of management areas by breeding northern fulmars

We thank Orkney Islands Council for access to Eynhallow and Talisman Energy (UK) Ltd and Marine Scotland for fieldwork and equipment support. Handling and tagging of fulmars was conducted under licences from the British Trust for Ornithology and the UK Home Office. EE was funded by a Marine Alliance for Science and Technology for Scotland/University of Aberdeen College of Life Sciences and Medicine studentship and LQ was supported by a NERC Studentship. Thanks also to the many colleagues who assisted with fieldwork during the project, and to Helen Bailey and Arliss Winship for advice on implementing the state-space model.

Sex differences in quality of life in stroke survivors. Data from the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST)

Introduction: Female sex is predictive of poor functional outcome in stroke, even after correction for prognostic factors. Poor quality of life (QoL) is observed in stroke survivors, with lower scores seen in the most disabled patients. We used data from the TAIST trial to assess the relationship between sex and QoL after ischaemic stroke. Methods: TAIST was a randomised controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1,484 patients with acute ischaemic stroke. QoL was measured at 180 days post randomisation using the short-form 36 health survey which assesses QoL across eight domains. The relationship between sex and each domain was assessed using ordinal regression, both unadjusted and adjusted for key prognostics factors. Results: Of the 1,484 patients randomised into TAIST, 216 had died at 180 days post randomisation. 1,268 survivors were included in this analysis, 694 males (55%), 574 females (45%). Females tended to score lower than males across all QoL domains (apart from general health); statistically significant lower scores were seen for physical functioning (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.47-0.72), vitality (OR 0.79, 95% CI 0.64-0.98) and mental health (OR 0.75, 95% CI 0.61-0.93). The results for physical functioning and mental health remained significant after adjustment for prognostic variables (OR 0.73, 95% CI 0.58-0.92; OR 0.76, 95% CI 0.60-0.95 respectively). Conclusions: QoL, in particular physical function and mental health domains, is lower in female patients after stroke. This difference persists even after correction for known prognostic factors such as age and stroke severity.

Sex differences in coronary artery disease severity and mortality: the impact of conventional cardiovascular risk factors

It is still unknown whether traditional risk factors may have a sex specific impact on the severity of coronary artery disease (CAD) and subsequent mortality in acute coronary syndromes (ACS). We identified 14 793 patients who underwent coronary angiography for acute coronary syndromes in the ISACS-TC (NCT01218776) registry from 2010 to 2019. The main outcome measure was the association between conventional risk factors and severity of CAD and its relationship with 30-day mortality. Risk ratios (RRs) and 95% CIs were calculated from the ratio of the absolute risks of women versus men using inverse probability of weighting. Severity of disease was categorized as obstructive (≥50% stenosis) versus nonobstructive CAD, specifically Ischemia and No Obstructive Coronary Artery disease (INOCA) and Myocardial Infarction with Non obstructive Coronary Arteries (MINOCA). The RR ratio for obstructive CAD in women versus men among people without diabetes mellitus was 0.49(95%CI,0.41–0.60) and among those with diabetes mellitus was 0.89(95% CI,0.62–1.29), with an interaction by diabetes mellitus status of P =0.002. Exposure to smoking shifted the RR ratios from 0.50 (95% CI, 0.41–0.61) in nonsmokers to 0.75 (95%CI, 0.54–1.03) in current smokers, with an interaction by smoking status of P=0.018. There were no significant sex-related interactions with hypercholesterolemia and hypertension. Women with obstructive CAD had higher 30-day mortality rates than men (RR, 1.75; 95% CI, 1.48–2.07). No sex differences in mortality were observed in patients with INOCA/MINOCA. In conclusion, obstructive CAD in women signifies a higher risk for mortality compared with men. Current smoking and diabetes mellitus disproportionally increase the risk of obstructive CAD in women. Achieving the goal of improving cardiovascular health in women still requires intensive efforts toward further implementation of lifestyle and treatment interventions.

Differences in Nevirapine Biotransformation as a Factor for its Sex-Dependent Dimorphic Profile of Adverse Drug Reactions

OBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity.

Biological monitoring of chemical exposure : toxicokinetic differences due to age and sex

Human biomonitoring is a widely used method in the assessment of occupational exposure to chemical substances and recommended biological limits are published periodically for interpretation and decision-making. However, it is increasingly recognized that a large variability is associated with biological monitoring, making interpretation less efficient than assumed. In order to improve the applicability of biological monitoring, specific factors responsible for this variability should be identified and their contribution quantified. Among these factors, age and sex are easily identifiable, and present knowledge about pharmaceutical chemicals suggests that they play an important role on the toxicokinetics of occupational chemical agents, and therefore on the biological monitoring results.The aim of the present research project was to assess the influence of age and sex on biological indicators corresponding to organic solvents. This has been done experimentally and by toxicokinetic computer simulation. Another purpose was to explore the effect of selected CYP2E1 polymorphisms on the toxicokinetic profile.Age differences were identified by numerical simulations using a general toxicokinetic model from a previous study which was applied to 14 chemicals, representing 21 specific biological entities, with, among others, toluene, phenol, lead and mercury. These models were runn with the modified parameters, indicating in some cases important differences due to age. The expected changes are mostly of the order of 10-20 %, but differences up to 50 % were observed in some cases. These differences appear to depend on the chemical and on the biological entity considered.Sex differences were quantified by controlled human exposures, which were carried out in a 12 m3 exposure chamber for three organic solvents separately: methyl ethyl ketone, 1-methoxy-2-propanol and 1,1,1-trichloroethane. The human volunteer groups were composed 12 of ten young men and fifteen young women, the latter subdivided into those with and without hormonal contraceptive. They were exposed during six hours at rest and at half of the threshold limit value. The kinetics of the parent compounds (organic volatiles) and their metabolite(s) were followed in blood, urine and expired air over time. Analyses of the solvent and their metabolites were performed by using headspace gas chromatography, CYP2E1 genotypes by using PCR-based RFLP methods. Experimental data were used to calibrate the toxicokinetic models developed for the three solvents. The results obtained for the different biomarkers of exposure mainly showed an effect on the urinary levels of several biomarkers among women due to the use of hormonal contraceptive, with an increase of about 50 % in the metabolism rate. The results also showed a difference due to the genotype CYP2E1*6, when exposed to methyl ethyl ketone, with a tendency to increase CYP2E1 activity when volunteers were carriers of the mutant allele. Simulations showed that it is possible to use simple toxicokinetic tools in order to predict internal exposure when exposed to organic solvents. Our study suggests that not only physiological differences but also exogenous sex hormones could influence CYP2E1 enzyme activity. The variability among the urinary biological indicators levels gives evidence of an interindividual susceptibility, an aspect that should have its place in the approaches for setting limits of occupational exposure.

Sex-dependent differences in the activities of acetylsalicylic acid-esterases in mouse kidneys

Acetylsalicylic acid (ASA), the most used drug worldwide, is hydrolyzed to salicylic acid and acetate by esterases present in tissues of several species including humans. Sex differences in drug metabolism by rodent liver are documented in the literature. In this paper we report a difference in the activities of the esterases (ASA-esterase I and II) in the kidneys of male and female mice. In this species there is no difference between males and females in liver ASA-esterases (ASA-esterase I: males 38.5 ± 7.9 (N = 5) and females 31.6 ± 7.6 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P>0.05; ASA-esterase II: males 77.3 ± 17.4 (N = 5) and females 61.4 ± 15.1 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P>0.05). However, in the kidneys males presented a much higher enzyme activity than females (ASA-esterase I: males 25.2 ± 6.3 (N = 5) and females 6.8 ± 0.6 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P<0.0002; ASA-esterase II: males 79.8 ± 10.1 (N = 5) and females 13.0 ± 1.1 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P<0.0001). The difference between sexes observed in mouse kidneys could serve as a model to study the molecular basis of this sex difference and also to determine the possible involvement of pituitary and gonadal hormones in this difference in ASA-esterase activities since these hormones control the sex differences in rodent liver enzyme activity.

Sex and reproductive stage differences in the growth, metabolism, feed, fecal production, excretion and energy budget of the Amazon River prawn (Macrobrachium amazonicum)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Spatial perspective taking is an embodied process, but not for everyone in the same way:differences predicted by sex and social skills score

We re-analysed visuo-spatial perspective taking data from Kessler and Thomson (2010) plus a previously unpublished pilot with respect to individual- and sex differences in embodied processing (defined as body-posture congruence effects). We found that so-called 'systemisers' (males/low-social-skills) showed weaker embodiment than so-called 'embodiers' (females/high-social-skills). We conclude that 'systemisers' either have difficulties with embodied processing or, alternatively, they have a strategic advantage in selecting different mechanisms or the appropriate level of embodiment. In contrast, 'embodiers' have an advantageous strategy of "deep" embodied processing reflecting their urge to empathise or, alternatively, less flexibility in fine-tuning the involvement of bodily representations. © 2012 Copyright Taylor and Francis Group, LLC.

Relationship Between Eccentric Hip Torque and Lower-Limb Kinematics: Gender Differences

The purposes of this study were to compare lower-limb kinematics between genders, and determine the relationships among eccentric hip abductor and lateral rotator torques and lower-limb kinematics. The movements of the pelvis, femur, and knee were calculated for 16 women and 16 men during the single-leg squat. Eccentric hip abductor and lateral rotator torques were measured using an isokinetic dynamometer. The results showed that women had greater contralateral pelvic depression, femur adduction, and knee abduction than men. The eccentric hip abductor and lateral rotator torques were correlated with coronal plane femur and knee movements in the overall sample. When the genders were analyzed separately, it was observed that women with greater eccentric hip abductor torque exhibited less femur adduction and femur medial rotation, and greater knee adduction excursion. No significant relationship was observed between the isokinetic and kinematic variables in the male group. The differences between the genders help to explain the greater rate of knee disorders observed in women. Moreover, the eccentric hip abduction action seemed to be more important in women to control the lower-limb movements.