Psychobiological regulation of plasma and saliva GDF15 dynamics in health and mitochondrial diseases.

GDF15 (growth differentiation factor 15) is a marker of cellular energetic stress linked to physical-mental illness, aging, and mortality. However, questions remain about its dynamic properties and measurability in human biofluids other than blood. Here, we examine the natural dynamics and psychobiological regulation of plasma and saliva GDF15 in four human studies representing 4,749 samples from 188 individuals. We show that GDF15 protein is detectable in saliva (8% of plasma concentration), likely produced by salivary glands secretory duct cells. Using a brief laboratory socio-evaluative stressor paradigm, we find that psychosocial stress increases plasma (+3.5-5.9%) and saliva GDF15 (+43%) with distinct kinetics, within minutes. Moreover, saliva GDF15 exhibits a robust awakening response, declining by ~40-89% within 30-45 minutes from its peak level at the time of waking up. Clinically, individuals with genetic mitochondrial OxPhos diseases show elevated baseline plasma and saliva GDF15, and post-stress GDF15 levels in both biofluids correlate with multi-system disease severity, exercise intolerance, and the subjective experience of fatigue. Taken together, our data establish that saliva GDF15 is dynamic, sensitive to psychological states, a clinically relevant endocrine marker of mitochondrial diseases. These findings also point to a shared psychobiological pathway integrating metabolic and mental stress.

Transgender and Gender-Diverse People's Experiences of Minority Stress, Mental Health, and Resilience in Relation to Perceptions of Sociopolitical Contexts.

Purpose: The sociopolitical context in which transgender and gender-diverse (TGD) people live has significant effects on mental health. We examined whether perceptions of context (TGD people's perceptions of how TGD people were viewed) differed across four United States (U.S.) states and associations with mental health and identity pride, the mediational effects of minority stressors, and potential buffering effects of resilience. Methods: TGD individuals in Oregon, Michigan, Nebraska, and Tennessee (n=158; ages 19-70, mean=33.06) completed questionnaires assessing their perceptions of how TGD people were viewed in their local area and in the U.S., as well as scales assessing minority stressors, pride, resilience, and mental health. Data were collected during Fall 2019 to Spring 2020. Results: Oregon participants viewed perceptions in their state the most positively, with no state-level differences in terms of broader U.S. perceptions. Tennessee participants experienced more expectations of rejection; however, there were no differences across the states in other minority stress variables, identity pride, resilience, or mental health. Participants who viewed their area as having more negative views of TGD people reported higher levels of discrimination, expectations of negative events, internalized stigma, and anxiety, as well as less pride. The effects of perceptions of local context on mental health were partially explained by enacted stigma and internalized stigma. Resilience did not buffer the effects of perceptions of the local context on mental health or pride. Conclusion: Context is important to shaping exposure to minority stressors and mental health, potentially through increasing enacted and internalized stigma.

Exploring ecosocial contexts of alcohol use and misuse during the COVID-19 pandemic among urban refugee youth in Kampala, Uganda: Multi-method findings.

Urban refugees may be disproportionately affected by socio-environmental stressors that shape alcohol use, and this may have been exacerbated by additional stressors in the COVID-19 pandemic. This multi-method study aimed to understand experiences of, and contextual factors associated with, alcohol use during the pandemic among urban refugee youth in Kampala, Uganda. We conducted a cross-sectional survey (n = 335), in-depth individual interviews (IDI) (n = 24), and focus groups (n = 4) with urban refugee youth in Kampala. We also conducted key informant interviews (n = 15) with a range of stakeholders in Kampala. We conducted multivariable logistic regression analyses with survey data to examine socio-demographic and ecosocial (structural, community, interpersonal) factors associated with ever using alcohol and alcohol misuse. We applied thematic analyses across qualitative data to explore lived experiences, and perceived impacts, of alcohol use. Among survey participants (n = 335, mean age= 20.8, standard deviation: 3.01), half of men and one-fifth of women reported ever using alcohol. Among those reporting any alcohol use, half (n = 66, 51.2 %) can be classified as alcohol misuse. In multivariable analyses, older age, gender (men vs. women), higher education, and perceived increased pandemic community violence against women and children were associated with significantly higher likelihood of ever using alcohol. In multivariable analyses, very low food security, relationship status, transactional sex, and lower social support were associated with increased likelihood of alcohol misuse. Qualitative findings revealed: (1) alcohol use as a coping mechanism for stressors (e.g., financial insecurity, refugee-related stigma); and (2) perceived impacts of alcohol use on refugee youth health (e.g., physical, mental). Together findings provide insight into multi-level contexts that shape vulnerability to alcohol mis/use among urban refugee youth in Kampala and signal the need for gender-tailored strategies to reduce socio-environmental stressors.

Associations Between Structural Stigma and Allostatic Load Among Sexual Minorities: Results From a Population-Based Study.

OBJECTIVE: Structural forms of stigma and discrimination are associated with adverse health outcomes across numerous stigmatized groups, including lesbian, gay, and bisexual (LGB) individuals. However, the biological consequences of structural stigma among LGB populations are understudied. To begin to address this gap, we assessed associations between indicators of structural stigma (i.e., state-level policies) targeting LGB individuals and allostatic load (AL) indices representing physiological dysregulations. METHODS: Pooled data from the continuous 2001-2014 National Health and Nutritional Examination Survey were analyzed (LGB: n = 864; heterosexual: n = 20,310). Ten state-level LGB-related policies (e.g., employment nondiscrimination protections, same-sex marriage) were used to operationalize structural stigma. A sex-specific AL index representing 11 immune, metabolic, and cardiovascular biomarkers was estimated. Multilevel models were used to examine associations between structural stigma and AL, net of nine individual-level characteristics (e.g., education, race/ethnicity, age, and health behaviors). RESULTS: Sexual minority men living in states with low levels of structural stigma experienced significantly lower AL ( ß = -0.45, p = .02) compared with sexual minority men living in states with high structural stigma (i.e., fewer protective policies). There was no significant association between structural stigma and AL among sexual minority women. CONCLUSIONS: By demonstrating direct associations between structural stigma and indices of physiological dysregulation, our findings provide a mechanistic understanding of how the social environment can "get under the skin and skull" for sexual minority men in the United States. Future research should explore whether these mechanisms generalize to other marginalized groups exposed to structural stigma.

Gender minority stress and diurnal cortisol profiles among transgender and gender diverse people in the United States.

The field of behavioral neuroendocrinology has only begun to explore the lived experiences of transgender and gender diverse (TGD) people exposed to stigma. In light of escalating attacks and legislation targeting TGD people in the United States, it is crucial to examine the physiological pathways through which gender minority stressors become embodied, impact health, and contribute to health inequities. The Trans Resilience and Health Study included baseline data collection from fall 2019 to spring 2020 from a sample of 124 TGD people, reflecting a diversity of gender identities (e.g., trans masculine, trans feminine, and nonbinary) and ages (range = 19-70 years old; M = 34.10), living in Michigan, Nebraska, Oregon, and Tennessee. These analyses examine experiences of gender-related enacted stigma in association with hypothalamic-pituitary-adrenal (HPA)-axis functioning. Among those experiencing the highest levels of enacted stigma, findings show a blunted cortisol awakening response and sluggish daily decline that resulted in elevated concentrations at bedtime compared to those experiencing less enacted stigma. These results of flattened diurnal activity are consistent with an emergent literature on discrimination as a social determinant of potential stress pathophysiology. In contrast, community connectedness was associated with a larger, more dynamic cortisol awakening response. These findings emphasize the importance of incorporating gender-minority stress and resilience measures when studying HPA-axis functioning among TGD people.

Associations of allostatic load with sociodemographic factors, depressive symptoms, lifestyle, and health characteristics in a large general population-based sample.

OBJECTIVE: We examined the associations between allostatic load (AL) and sociodemographic factors, depressive symptoms, lifestyle and health characteristics in a population-based sample of 4993 adults in Finland. METHODS: Thirteen biomarkers were used to construct AL. High AL was defined as scoring highly in ≥4 items. RESULTS: AL scores of 4 and above were exceeded in the age group of 45-54 years in men and 65-74 years in women. Age was the strongest predictor for belonging to the high AL score group. In addition, elevated depressive symptoms (BDI-6 ≥ 4), male sex, not engaging in physical exercise, high alcohol use and a low level of education were associated with an increased likelihood of belonging to the high AL group. CONCLUSION: The older the participants were, the greater their AL burden was. However, AL burden increased more steeply as a function of age in men. In addition to lifestyle interventions, effective prevention strategies for depression at the population level could have a major public health impact in reducing the accumulation of AL burden.

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 Signature Biobank: A longitudinal biopsychosocial repository of psychiatric emergency patients.

The Signature Biobank is a longitudinal repository of biospecimen, psychological, sociodemographic, and diagnostic data that was created in 2012. The Signature Consortium represents a group of approximately one hundred Quebec-based transdisciplinary clinicians and research scientists with various expertise in the field of psychiatry. The objective of the Signature Biobank is to investigate the multi-faceted underpinnings of psychiatric disorders among patients in crisis. The Signature Consortium is expanding and includes new active members that seek to highlight the contributions made by Signature Biobank since its inception. This article details our research protocol, directions, and summarizes contributions. To date, we have collected biological samples (n = 1,986), and questionnaire data (n = 2,085) from psychiatric emergency patients of the Institut universitaire en santé mentale de Montréal (Quebec, Canada), with a large proportion from whom both data types were collected (n = 1,926). In addition to this, a subsample of patients was followed-up at hospital discharge, and two additional outpatient clinic appointments (n = 958 with at least one follow-up). In addition, a socio-demographically matched comparison group of individuals who were not hospitalized for psychiatric disorders (n = 149) was recruited from the surrounding catchment area. To summarize, a systematic review of the literature shows that the Signature Biobank has contributed to better characterizing psychiatric comorbidities, biological profiles, and psychosocial functioning across some of the most common psychiatric disorders, including psychosis, mood, anxiety, and substance use disorders. The Signature Biobank is now one of the world's largest repositories of data collected from patients receiving care at a psychiatric emergency unit.

A step-by-step and data-driven guide to index gender in psychiatry.

Beyond sex as a binary or biological variable, within-sex variations related to sociocultural gender variables are of increasing interest in psychiatric research to better understand individual differences. Using a data-driven approach, we developed a composite gender score based on sociodemographic and psychosocial variables showing sex differences in a sample of psychiatric emergency patients upon admission (N = 1708; 39.4% birth-assigned females; mean age = 40 years; age standard deviation = 14). This gender score was extracted from a confirmatory factor analysis (CFI = 0.966; RMSEA = 0.044, SRMR = 0.030) and could predict a person's birth-assigned sex with 67% accuracy. This score allowed the further identification of differences on impulsivity measures that were absent when looking solely at birth-assigned sex. Female birth-assigned sex was also associated with higher rates of mood and personality disorder diagnoses, while higher feminine gender scores were related to higher proportions of anxiety and mood disorder diagnoses. By contrast, male birth-assigned sex and higher masculine gender scores were associated with higher proportions of psychotic and substance use disorder diagnoses. Patients with undifferentiated gender scores (i.e., scoring between masculine and feminine threshold defined by terciles) were more represented in the psychotic disorder group. Considering both sex and gender in psychiatric research is essential and can be achieved even when using secondary data to index gender comprised of demographic and psychosocial variables.

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.

Gender roles and gender norms associated with psychological distress in women and men among the Dutch general population.

Women report more psychological distress than men, which may be related to both biological sex and socio-cultural gender. We tested whether associations between gender and distress differ for women and men. The cross-sectional sample consisted of 678 Dutch people (54% women). Gender roles were assessed as masculinity and femininity. A composite gender norm score was calculated by summing gendered sociodemographics. Multivariate regressions examined sex, gender, and their interaction for depressive symptoms, anxiety, and perceived stress, additionally adjusted. Women reported more psychological distress. People scoring higher on masculine gender roles, but not feminine gender roles, reported lower psychological distress. A higher gender norm score was related to more depressive symptoms and perceived stress. This association was only present in men and was explained by health-related covariates. This research shows that there is a need to further elaborate on the discrepancies between sex and gender in health psychology research to better understand individual differences.

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.

Sex/gender differences in cognitive abilities.

Sex/gender differences in cognitive sciences are riddled by conflicting perspectives. At the center of debates are clinical, social, and political perspectives. Front and center, evolutionary and biological perspectives have often focused on 'nature' arguments, while feminist and constructivist views have often focused on 'nurture arguments regarding cognitive sex differences. In the current narrative review, we provide a comprehensive overview regarding the origins and historical advancement of these debates while providing a summary of the results in the field of sexually polymorphic cognition. In so doing, we attempt to highlight the importance of using transdisciplinary perspectives which help bridge disciplines together to provide a refined understanding the specific factors that drive sex differences a gender diversity in cognitive abilities. To summarize, biological sex (e.g., birth-assigned sex, sex hormones), socio-cultural gender (gender identity, gender roles), and sexual orientation each uniquely shape the cognitive abilities reviewed. To date, however, few studies integrate these sex and gender factors together to better understand individual differences in cognitive functioning. This has potential benefits if a broader understanding of sex and gender factors are systematically measured when researching and treating numerous conditions where cognition is altered.

COVID-19 related stress and fears of contamination: the impact of feared self-perceptions.

Specific concerns have been raised for those suffering from obsessive-compulsive disorder (OCD) during the COVID-19 pandemic, particularly those suffering from contamination fear. Investigation in non-clinical and OCD samples have reported an increase in contamination symptoms in association with the severity of the COVID-19 pandemic. In particular, stress related to COVID-19 has been found to be a major predictor of an increase in contamination symptoms. It has also been suggested that these effects may be accounted for by feared-self perceptions, that renders certain individuals more vulnerable to COVID-related stress and its effect on contamination-related symptomatology. We hypothesized that feared self-perceptions would predict COVID-19-related stress and that both feared self-perceptions and COVID-19-related stress would predict contamination symptoms while controlling for age, education and sex. To test this hypothesis, 1137 community participants completed online questionnaires. Path analysis confirmed our hypotheses highlighting the importance of feared self-perceptions during the COVID-19 pandemic in its effect on stress and ensuing symptomatology. Further, women scored higher on questionnaires, but the relationship between feared self-perceptions, COVID-19-related stress and contamination symptoms remained similar. Implications for theory and research are discussed.

Sex and gender role differences on stress, depression, and anxiety symptoms in response to the COVID-19 pandemic over time.

Introduction: Stress, depression, and anxiety symptoms have been reported during the pandemic, with important inter-individual differences. Past cross-sectional studies have found that sex and gender roles may contribute to the modulation of one's vulnerability to develop such symptoms. This longitudinal study aimed to examine the interaction of sex and psychological gender roles on stress, depression, and anxiety symptoms in adults during the COVID-19 pandemic. Methods: Following the confinement measures in March 2020 in Montreal, stress, depression, and anxiety symptoms were assessed every 3 months (from June 2020 to March 2021) with the Depression, Anxiety and Stress Scale among 103 females and 50 males. Femininity and masculinity scores were assessed with the Bem Sex Role Inventory before the pandemic and were added as predictors along with time, sex, and the interactions between these variables using linear mixed models. Results: We observed similar levels of depressive symptoms between males and females, but higher levels of stress and anxious symptoms in females. No effects of sex and gender roles on depressive symptoms were found. For stress and anxiety, an interaction between time, femininity, and sex was found. At the beginning of the pandemic, females with high femininity had more stress symptoms than males with high femininity, whereas females with low femininity had more anxiety symptoms 1 year after the confinement measures compared to males with low femininity. Discussion: These findings suggest that sex differences and psychological gender roles contribute to heterogeneous patterns of stress and anxiety symptoms over time in response to the COVID-19 pandemic.

Gender and sex in eating disorders: A narrative review of the current state of knowledge, research gaps, and recommendations.

INTRODUCTION: Eating disorders (EDs) have long been considered conditions exclusively affecting women, and studies in the ED field regularly exclude men. Research efforts are needed to better understand the role of gender and sex in EDs. This review describes the role of gender and sex in the development of EDs from a biopsychosocial perspective. METHODS: The primary hypothesis of this narrative review is that gender and sex interact to influence ED risk. The literature review was conducted using the PubMed database. RESULTS: This review first presents the general characteristics and prevalence of EDs according to gender and sex. Next, neurodevelopmental processes, neurobiology, gender roles, body image, and the minority stress model are addressed. Lastly, research perspectives to better include gender and sex in the field of EDs are discussed (e.g., representation of gender and sex diversities, development of appropriate assessment tools, and increasing awareness). CONCLUSION: Although substantial knowledge gaps remain, there is a growing recognition of the importance of integrating gender and sex in ED research that holds promise for further development in the field.