Sex and gender correlates of sexually polymorphic cognition.

BACKGROUND: Sexually polymorphic cognition (SPC) results from the interaction between biological (birth-assigned sex (BAS), sex hormones) and socio-cultural (gender identity, gender roles, sexual orientation) factors. The literature remains quite mixed regarding the magnitude of the effects of these variables. This project used a battery of classic cognitive tests designed to assess the influence of sex hormones on cognitive performance. At the same time, we aimed to assess the inter-related and respective effects that BAS, sex hormones, and gender-related factors have on SPC. METHODS: We recruited 222 adults who completed eight cognitive tasks that assessed a variety of cognitive domains during a 150-min session. Subgroups were separated based on gender identity and sexual orientation and recruited as follows: cisgender heterosexual men (n = 46), cisgender non-heterosexual men (n = 36), cisgender heterosexual women (n = 36), cisgender non-heterosexual women (n = 38), gender diverse (n = 66). Saliva samples were collected before, during, and after the test to assess testosterone, estradiol, progesterone, cortisol, and dehydroepiandrosterone. Psychosocial variables were derived from self-report questionnaires. RESULTS: Cognitive performance reflects sex and gender differences that are partially consistent with the literature. Interestingly, biological factors seem to better explain differences in male-typed cognitive tasks (i.e., spatial), while psychosocial factors seem to better explain differences in female-typed cognitive tasks (i.e., verbal). CONCLUSION: Our results establish a better comprehension of SPC over and above the effects of BAS as a binary variable. We highlight the importance of treating sex as a biological factor and gender as a socio-cultural factor together since they collectively influence SPC.

Many studies show sex differences in cognitive abilities. In general, women outperform men in verbal tasks and fine motor skills, while men outperform women in spatial orientation and mental rotation tasks. These differences underlie research on sexually polymorphic cognition, a concept influenced by sex hormones (estradiol, progesterone, and testosterone) as well as birth-assigned sex. In addition to these biological factors, socio-cultural gender factors such as gender identity (the gender we feel and embody), gender roles (masculine and feminine expressions based on stereotypes), as well as sexual orientation are all known to influence cognition as well. We provide a broader understanding by accounting for both sex and gender factors. Our team recruited 222 adults separated into 5 sub-groups based on birth-assigned sex, gender identity, and sexual orientation. Each participant completed eight sexually polymorphic cognitive tasks. In this 150-min experimental protocol, saliva samples were collected before, during, and after the test to assess testosterone, estradiol, progesterone, cortisol, and dehydroepiandrosterone. Psychosocial variables were derived from self-report questionnaires. Results showed that spatial cognition was better explained by biological sex factors, while verbal cognition was better explained by socio-cultural gender factors. Taken together, our findings demonstrate the importance of considering sex-based and gender-based factors collectively and, respectively, when studying sex differences in cognition.

The role of sex hormones, oral contraceptive use, and its parameters on visuospatial abilities, verbal fluency, and verbal memory.

Sex hormones can cross the blood-brain barrier and access brain regions underlying higher-order cognition. Containing synthetic sex hormones, oral contraceptives (OC) have been found to modulate visuospatial and verbal abilities, though inconsistencies have been found in the literature. Among possible explanations, certain OC use parameters (progestin androgenicity, synthetic hormone levels, duration of use) have not received consistent consideration. Thus, the objectives were to (1) examine group differences between men, combined OC users, and naturally cycling women (NC women; not using OC) in visuospatial abilities, verbal fluency, and verbal memory and (2) investigate the contribution of endogenous and exogenous sex hormones on these effects. We also aimed to (3) identify OC use parameters relevant to cognitive outcomes. In total, 70 combined OC users, 53 early follicular (EF) women, 43 pre-ovulatory (PO) women, and 47 men underwent cognitive tests. Performance was compared based on hormonal milieus (OC, EF, PO, men) and OC users' contraceptive androgenicity (anti, low, high). Correlations between performance, hormone levels and OC use duration were also conducted. OC use dampened the sex difference that typically favors men in 3D visuospatial abilities, whereas its duration of use positively predicted verbal fluency. Androgenicity and hormone levels did not predict performance in any task. These results highlight the importance of considering OC use duration. Results also did not support a role for androgenicity in cognition. Importantly, combined OC use (including prolonged use) does not impair visuospatial, verbal, and memory functions in a healthy young sample.

Spousal Synchrony in Allostatic Load Among Older Couples in the Health and Retirement Study.

OBJECTIVE: Using national data from the Health and Retirement Study, this study examined interpartner associations of allostatic load (AL) among 2338 different-sex couples ( N = 4676 individuals) over a 4-year period among older American couples from a dyadic approach. METHODS: AL was indexed by immune (C-reactive protein), metabolic (high-density lipoprotein cholesterol, total cholesterol, and glycosylated hemoglobin), renal (cystatin C), cardiovascular (systolic and diastolic blood pressures, pulse rate), and anthropometric (waist and body mass index) parameters using the traditional count-based formulation. Actor-partner interdependence models were used to assess interpartner concordance in AL. RESULTS: Higher partners' baseline AL was significantly associated with higher own AL both at baseline and 4 years later. In addition, partners' baseline AL was significantly associated with own AL 4 years later only in women but not men. Lastly, we did not observe any significant moderating effect of relationship quality on interpartner AL concordance. CONCLUSIONS: The findings suggest that older couples' physiological responses to environmental stress are not only linked concurrently, but the associations persist after 4 years, alluding to long-term impacts of couples' psychosocial context and physiology on each other.

Health risk behaviours and allostatic load: A systematic review.

Health risk behaviours (HRB) across the lifespan have been associated with higher cumulative physiological burden as measured by allostatic load (AL). This study examines the contribution of HRB and their effects on multisystem biological risk associated with morbidity and early mortality. We systematically reviewed the literature to assess the links between HRB and AL. Twenty-six eligible human studies were included in our assessment of the current literature investigating the association of different HRB that included overeating/obesity, alcohol, smoking, drug use, physical inactivity and sleep impairments in relation to AL. We found that 50 % of obesity and substance abuse, 75 % of sleep and 62.5 % of combined HRB studies showed a significant association with AL. Lifestyle coping behaviours therefore have a significant contribution to AL. This study is among the first to explore multiple domains of HRB in relation to AL. Further research should focus on evaluating lifestyle factors that adapt HRB as a strategy to cope with chronic stress to help decrease AL and resulting long-term negative health consequences.

Increased frequency of mind wandering in healthy women using oral contraceptives.

Oral contraceptive (OC) is the most common type of contraceptive method used in industrialized countries. A recent epidemiological study showed that OC use was associated with the onset of depression in young women. Mind wandering, a cognitive process associated with spontaneous thoughts unrelated to the task at-hand, has previously been associated with depressive thinking. Consequently, mind wandering might be a precursor for cognitive vulnerability in individuals who are at-risk for mood disorders. The purpose of this study was to examine the frequency and nature of mind wandering in women using OC in comparison to two control groups: naturally cycling women and men. We recruited 71 participants (28 women currently using OC, 14 naturally cycling women in the luteal phase of their menstrual cycle and 29 men) aged between 18 and 35 years, and measured the frequency and nature (guilt/fear oriented and positive) of mind wandering using the short version of the Imaginal Process Inventory. In all analyses, we controlled for depressive symptoms to delineate the unique association between OC use and mind wandering. We also measured estradiol, progesterone and testosterone to confirm expected group differences in sex hormones concentrations. Results show that women using OC presented increased frequency of mind wandering when compared to naturally cycling women and men who did not differ between each other. The three groups did not differ in terms of the nature of mind wandering. These results show that OC use is associated with increased frequency of mind wandering and suggest that the association between OC use and dysphoric mood described in previous studies may be partially explained by the impact of OC use on cognitive processes underlying mind wandering.

Elevated allostatic load in individuals presenting at psychiatric emergency services.

OBJECTIVE: Individuals requiring psychiatric emergency services are often highly distressed and intoxicated. To provide an objective and comprehensive measure of their stress-related physiological dysregulations, we indexed allostatic load with 14 biomarkers collected within 24 h of patients' admission to the largest psychiatric hospital in the Canadian province of Quebec. METHODS: This study (N = 278) combines data for emergency patients (n = 76; 65.8% women; M age = 44.97, SE = 1.6) and hospital workers who served as sex- and age-matched controls (n = 202; 70.8% women; M age = 40.10, SE = 0.83). Sex-specific allostatic load indices summarized neuroendocrine (cortisol), immune (tumor necrosis factor-α, interleukin-6, c-reactive protein), metabolic (insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, body mass index), and cardiovascular (heart rate, systolic and diastolic blood pressure) functioning. Well-validated questionnaires assessed substance (ab)use. RESULTS: Individuals presenting at psychiatric emergency showed elevated allostatic load, drug abuse, and tobacco use compared to controls. Elevated allostatic load in emergency patients was driven by elevated cortisol, interleukin-6, systolic blood pressure, and heart rate; however, allostatic load was not explained by substance (ab)use or demographic variables. Sub-group analyses revealed that emergency patients primarily diagnosed with bipolar, depressive, or anxiety disorders showed higher allostatic load than those diagnosed with personality disorder(s). CONCLUSIONS: This study demonstrates that individuals presenting at psychiatric emergency services show physiological dysregulations associated with chronic stress. Future research should explore the clinical utility of allostatic load in predicting comorbidities among psychiatric patients.

Allostatic load is associated with psychotic symptoms and decreases with antipsychotic treatment in patients with schizophrenia and first-episode psychosis.

Current pathophysiological models of schizophrenia suggest that stress contributes to the etiology and trajectory of the disorder. We investigated if allostatic load (AL), an integrative index of neuroendocrine, immune and metabolic dysregulation in response to chronic stress, is elevated in patients with schizophrenia (SCZ) and first-episode psychosis (FEP) and related to psychotic symptoms and social and occupational functioning. Additionally, we assessed the temporal dynamics of AL in response to treatment with second-generation antipsychotics. AL, psychotic symptoms and psychosocial functioning were assessed in a longitudinal design in patients with SCZ (n = 28), FEP (n = 28), and healthy controls (n = 53) at baseline and 6 and 12 weeks after commencement of antipsychotic therapy. AL at baseline was higher in patients with SCZ and FEP relative to controls, but not different between patients with SCZ and FEP. Adjusting for age and smoking, we found that positive symptoms were positively correlated with AL and psychosocial functioning was negatively correlated with AL at trend level. Linear mixed model analysis demonstrated that AL decreased after treatment was commenced in patients with SCZ and FEP between the baseline assessment and the 6 and 12-week follow-up. AL was not predictive of treatment response or symptomatic remission. Our data provide evidence for cumulative physiological dysregulation in patients with SCZ and FEP that is linked to the experience of current positive psychotic symptoms. AL could be a useful tool to monitor biological signatures related to chronic stress and unhealthy behaviors in schizophrenia.

Gonads and strife: Sex hormones vary according to sexual orientation for women and stress indices for both sexes.

This study assessed sexual orientation and psychobiological stress indices in relation to salivary sex hormones as part of a well-validated laboratory-based stress paradigm. Participants included 87 healthy adults that were on average 25 years old who self-identified as lesbian/bisexual women (n=20), heterosexual women (n=21), gay/bisexual men (n=26), and heterosexual men (n=20). Two saliva samples were collected fifteen minutes before and fifteen minutes after exposure to a modified Trier Social Stress Test to determine testosterone, estradiol, and progesterone concentrations via enzyme-immune assaying. Mean sex hormones were further tested in association to stress indices related to cortisol systemic output (area under the curve with respect to ground) based on ten measures throughout the two-hour visit, allostatic load indexed using 21 biomarkers, and perceived stress assessed using a well-validated questionnaire. Results revealed that lesbian/bisexual women had higher overall testosterone and progesterone concentrations than heterosexual women, while no differences were found among gay/bisexual men in comparison to heterosexual men. Lesbian/bisexual women and heterosexual men showed positive associations between mean estradiol concentrations and allostatic load, while gay/bisexual men and heterosexual women showed positive associations between mean testosterone and cortisol systemic output. In summary, sex hormone variations appear to vary according to sexual orientation among women, but also as a function of cortisol systemic output, allostatic load, and perceived stress for both sexes.

Psychosocial determinants of diurnal alpha-amylase among healthy Quebec workers.

Salivary alpha-amylase (sAA) is a stress-sensitive biomarker the shows promise as an indirect proxy of sympathetic-adrenal-medullary axis activities that are otherwise difficult to discern non-invasively. This comprehensive study investigated diurnal sAA in association with numerous psychosocial characteristics related to mental health, work stress, and non-work stress. Participants included 395 workers (56.1% women, age: M=41.3, SD=10.81) from across 34 distinct workplaces. Diurnal sAA was sampled over two non-consecutive work days at awakening, 30 min after awakening, 14h00, 16h00, and bedtime. Well-validated psychometrics and survey items were used to measure mental health (psychological distress, depression, burnout, work characteristics) (task design, demands, social relations, gratifications), and non-work characteristics (marital/parental status, economic statuses, marital and parental stress, work-family conflicts). Preliminary results revealed that men showed occasionally higher sAA concentrations than women. Multilevel regressions were used to analyze sAA concentrations nested according to levels (i) for each time-point, (ii) between workers, and (iii) across workplaces while covarying for time of awakening, sex, age, cigarette smoking, alcohol consumption, regular physical activity, psychotropic drug use, and body mass index. Main results revealed that psychological demands, support from colleagues, interpersonal conflicts, job recognition and job insecurity appear to be associated with diurnal sAA, while non-work factors did not. Our findings showing a distinct diurnal profile for sAA replicate and expand those of Nater et al. (2007, Psychoneuroendocrinology 32, 392-401), providing further evidence that sAA is associated to subjective psychosocial factors.

Sex hormones adjust "sex-specific" reactive and diurnal cortisol profiles.

Sex differences in stress hormone functions are presumed to depend on sex hormones. And yet, surprisingly few psychoneuroendocrine studies actually assess within-sex variations of testosterone, estradiol, and progesterone when investigating sex-specific activities of the hypothalamic-pituitary-adrenal axis. In this methodological study of 204 healthy adults (60 men), we assessed whether cortisol profiles would differ between the sexes when unadjusted or adjusted for basal sex hormones among both sexes. Reactive cortisol was sampled using 6 saliva samples measured every 10-min as part of the Trier Social Stress Test that generally activates cortisol among men more than women. Diurnal cortisol was sampled over two days at (1) awakening, (2) 30-min thereafter, (3) 1400 h, (4) 1600 h, and (5) bedtime. Sex hormones were collected at baseline before the psychosocial stressor and on two occasions during diurnal cortisol assessment. Repeated-measures analysis of covariance controlled for key covariates in analyses unadjusted or adjusted for sex hormones. Results revealed that men had higher reactive cortisol than women in unadjusted analysis, but this sex difference was attenuated when adjusting for sex hormones. While diurnal cortisol showed no sex differences in unadjusted models, adjusting for sex hormones revealed that women have higher morning cortisol. Correlations using area under the curve formulae revealed intriguing sex-specific associations with progesterone in men and testosterone in women that we propose have implications for social and affective neuroscience. In summary, our results reveal that adjusting for sex hormones alters "sex-specific" reactive and diurnal cortisol profiles.

Mental health consequences of stress and trauma: allostatic load markers for practice and policy with a focus on Indigenous health.

OBJECTIVE: Mental health, well-being, and social life are intimately related as is evident from the higher incidence of psychiatric illness in individuals exposed to social stress and adversity. Several biological pathways linking social adversity to health outcomes are heavily investigated in the aims of facilitating early identification and prevention of adverse health outcomes. We provide a practice-orientated overview of the allostatic load model and how it relates to metabolic and cardiovascular comorbidity in psychiatric disorders. CONCLUSIONS: Allostatic load brings together a set of neuroendocrine, metabolic, immune and cardiovascular biomarkers that are elevated in individuals with adverse early life experiences and are predictive of cardiovascular and metabolic risk in psychiatric illness of critical importance for Indigenous Australians.

Sexual orientation modulates endocrine stress reactivity.

BACKGROUND: Biological sex differences and sociocultural gender diversity influence endocrine stress reactivity. Although numerous studies have shown that men typically activate stronger stress responses than women when exposed to laboratory-based psychosocial stressors, it is unclear whether sexual orientation further modulates stress reactivity. Given that lesbian, gay, and bisexual (LGB) individuals frequently report heightened distress secondary to stigma-related stressors, we investigated whether cortisol stress reactivity differs between LGB individuals and heterosexual individuals in response to a well-validated psychosocial stressor. METHODS: The study population comprised 87 healthy adults (mean age, 25 years) who were grouped according to their biological sex and their gendered sexual orientation: lesbian/bisexual women (n = 20), heterosexual women (n = 21), gay/bisexual men (n = 26), and heterosexual men (n = 20). Investigators collected 10 salivary cortisol samples throughout a 2-hour afternoon visit involving exposure to the Trier Social Stress Test modified to maximize between-sex differences. RESULTS: Relative to heterosexual women, lesbian/bisexual women showed higher cortisol stress reactivity 40 min after exposure to the stressor. In contrast, gay/bisexual men displayed lower overall cortisol concentrations throughout testing compared with heterosexual men. Main findings were significant while adjusting for sex hormones (estradiol-to-progesterone ratio in women and testosterone in men), age, self-esteem, and disclosure status (whether LGB participants had completed their "coming out"). CONCLUSIONS: Our results provide novel evidence for gender-based modulation of cortisol stress reactivity based on sexual orientation that goes beyond well-established between-sex differences. This study raises several important avenues for future research related to the physiologic functioning of LGB populations and gender diversity more broadly.