Design and methods of the mobile assessment of cognition, environment, and sleep (MACES) feasibility study in newly diagnosed breast cancer patients.

Endocrine therapy (ET) for breast cancer treatment is associated with cognitive complaints, but their etiology is poorly understood. To address this, we developed and implemented an ambulatory assessment protocol consisting of wearable activity monitors, brief surveys of affect, context, and perceived impairments, and ultra-brief performance-based measures of cognition. Newly diagnosed, ER/PR+, stage 0-III, female breast cancer patients, were recruited. Ambulatory assessments were conducted on smart phones and wearable activity monitors were used to monitor sleep and physical activity. Participants were asked to complete five 7-day measurement bursts (one before starting ET and one each month for 4 consecutive months while on ET). We observed a consent rate of 36%, 27 women completed the study. Of the women that withdrew, 91% dropped prior to the midpoint of follow up. There were no significant differences in demographics, clinical breast cancer characteristics, sleep or physical activity patterns, or measures of cognition between women who completed versus withdrew. Women who did not complete the study provided fewer valid days of baseline data. In conclusion, while some women may be overwhelmed with their cancer diagnosis, we did not identify any predictive characteristics of women whom did not complete the study. This novel method enables the prospective study of psychological changes associated with cancer treatment, capturing a wide array of information about behavior, experience, and cognition, thus providing a picture of the lived experiences of cancer patients before and during exposure to ET.

Prenatal androgen influences on the brain: A review, critique, and illustration of research on congenital adrenal hyperplasia.

Sex hormones, especially androgens, contribute to sex and gender differences in the brain and behavior. Organizational effects are particularly important because they are thought to be permanent, reflecting hormone exposure during sensitive periods of development. In human beings, they are often studied with natural experiments in which sex hormones are dissociated from other biopsychosocial aspects of development, such as genes and experiences. Indeed, the greatest evidence for organizational effects on sex differences in human behavior comes from studies of females with congenital adrenal hyperplasia (CAH), who have heightened prenatal androgen exposure, female-typical rearing, and masculinized toy play, activity and career interests, spatial skills, and some personal characteristics. Interestingly, however, neuroimaging studies of females with CAH have revealed few neural mechanisms underlying these hormone-behavior links, with the exception of emotion processing; studies have instead shown reduced gray matter volumes and reduced white matter integrity most consistent with other disease-related processes. The goals of this narrative review are to: (a) describe methods for studying prenatal androgen influences, while offering a brief overview of behavioral outcomes; (b) provide a critical methodological review of neuroimaging research on females with CAH; (c) present an illustrative analysis that overcomes methodological limitations of previous work, focusing on person-specific neural reward networks (and their associations with sensation seeking) in women with CAH and their unaffected sisters in order to inform future research questions and approaches that are most likely to reveal organizational hormone effects on brain structure and function.

Vision contributes to sex differences in spatial cognition and activity interests.

Sex differences in a variety of psychological characteristics are well-documented, with substantial research focused on factors that affect their magnitude and causes. Particular attention has focused on mental rotation, a measure of spatial cognition, and on activity interests. We studied whether sex differences in visual perception-luminance contrast thresholds and motion duration thresholds-contribute to sex differences in mental rotation and interest in male-typed activities. We confirmed sex differences in vision, mental rotation, and activity interests in a sample of 132 college students. In novel findings, we showed that vision correlated with mental rotation performance in women, that vision was a better predictor of individual differences in mental rotation than sex, and that contrast thresholds correlated with women's interest in male-typed activities. These results suggest that sex differences in spatial cognition and activity interests may have their roots in basic perceptual processes.

Family environmental antecedents of pubertal timing in girls and boys: A review and open questions.

Across nonhuman species, pubertal timing is affected by the social environment, with consequences for reproductive success and behavior. In human beings, variations in pubertal timing have not been systematically examined in relation to social environmental antecedents, although their psychological consequences are well documented. This paper focuses on links in human beings between pubertal timing and the childhood social environment, with several sections: A review of studies relating pubertal timing to the family context, a key aspect of the social environment; challenges in studying the issue; and opportunities for future work that takes advantage of and creates links with evidence in other species. The review shows that pubertal timing in girls is accelerated by adversity in aspects of the early family social context, with effects small in size; data in boys are not sufficient to enable conclusions. Inferences from existing studies are limited by variations in conceptualizations and measurement of relevant aspects of puberty and of the family social environment, and by methodological issues (e.g., reliance on existing data, use of retrospective reports, nonrandom missing data). Open questions remain about the nature, mechanisms, and specificity of the links between early family social environment and pubertal timing (e.g., form of associations, consideration of absence of positive experiences, role of timing of exposure). Animal studies provide a useful guide for addressing these questions, by delineating potential hormonal mechanisms that underlie links among social context, pubertal timing, and behavior, and encouraging attention to aspects of the social environment outside the family, especially peers.

Family Experiences and Parent Personality as Antecedents of Pubertal Timing in Girls and Boys.

Pubertal timing may be influenced by typical variations in early family environmental events, but questions remain concerning the roles of specific parenting factors, developmental age of exposure to events, moderation by child temperament, and comparability of effects for girls and boys. This study focused on these questions utilizing longitudinal data from 733 same-sex twins (45% girls) in the U.S.; family context was measured at ages 1-3, 4-5, and 6-7 years and pubertal status was assessed annually via self-report at ages 9-15, enabling estimates of pubertal timing. Home environment at ages 4-5 years predicted pubertal timing better than home environment at other ages for both girls and boys, but parent personality was more predictive than home experiences (e.g., divorce, parental harshness, family conflict). Thus, effects of family environment must be considered within the context of parent characteristics, encouraging caution in implicating early environmental experiences as direct influences on early pubertal timing.

Evidence and Implications from a Natural Experiment of Prenatal Androgen Effects on Gendered Behavior.

Sex and gender are key to people's lives, and are the focus of scientific and popular interest and controversy. Sex-related psychological characteristics reflect more than socialization; they are influenced by sex hormones present during sensitive periods of development, particularly prenatal androgens. Studies of females with congenital adrenal hyperplasia (CAH) show how prenatal androgens affect behavior across the life span, with large effects on gendered activity interests and engagement, moderate effects on spatial abilities, and relatively small (or no) effects on gender identity, gender cognitions, and gendered peer involvement. In addition to showing the complexity of androgen effects on gendered behavior, studies of females with CAH provide an opportunity to test theories of gender development, understand how nature and nurture work together, and examine mechanisms of development. The implications of this work have often been misunderstood, so we consider what it means - and does not mean - for biology to influence gender-related behavior.

Consensus Parameter: Research Methodologies to Evaluate Neurodevelopmental Effects of Pubertal Suppression in Transgender Youth.

Purpose: Pubertal suppression is standard of care for early pubertal transgender youth to prevent the development of undesired and distressing secondary sex characteristics incongruent with gender identity. Preliminary evidence suggests pubertal suppression improves mental health functioning. Given the widespread changes in brain and cognition that occur during puberty, a critical question is whether this treatment impacts neurodevelopment. Methods: A Delphi consensus procedure engaged 24 international experts in neurodevelopment, gender development, puberty/adolescence, neuroendocrinology, and statistics/psychometrics to identify priority research methodologies to address the empirical question: is pubertal suppression treatment associated with real-world neurocognitive sequelae? Recommended study approaches reaching 80% consensus were included in the consensus parameter. Results: The Delphi procedure identified 160 initial expert recommendations, 44 of which ultimately achieved consensus. Consensus study design elements include the following: a minimum of three measurement time points, pubertal staging at baseline, statistical modeling of sex in analyses, use of analytic approaches that account for heterogeneity, and use of multiple comparison groups to minimize the limitations of any one group. Consensus study comparison groups include untreated transgender youth matched on pubertal stage, cisgender (i.e., gender congruent) youth matched on pubertal stage, and an independent sample from a large-scale youth development database. The consensus domains for assessment includes: mental health, executive function/cognitive control, and social awareness/functioning. Conclusion: An international interdisciplinary team of experts achieved consensus around primary methods and domains for assessing neurodevelopmental effects (i.e., benefits and/or difficulties) of pubertal suppression treatment in transgender youth.

Does puberty affect the development of behavior problems as a mediator, moderator, or unique predictor?

Pubertal timing matters for psychological development. Early maturation in girls is linked to risk for depression and externalizing problems in adolescence and possibly adulthood, and early and late maturation in boys are linked to depression. It is unclear whether pubertal timing uniquely predicts problems; it might instead mediate the continuity of behavior problems from childhood to adolescence or create psychological risk specifically in youth with existing problems, thus moderating the link. We investigated these issues in 534 girls and 550 boys, measuring pubertal timing by a logistic model fit to annual self-report measures of development and, in girls, age at menarche. Prepuberty internalizing and externalizing behavior problems were reported by parents. Adolescent behavior problems were reported by parents and youth. As expected, behavior problems were moderately stable. Pubertal timing was not predicted by childhood problems, so it did not mediate the continuity of behavior problems from childhood to adolescence. Pubertal timing did not moderate links between early and later problems for girls. For boys, early maturation accentuated the link between childhood problems and adolescent substance use. Overall, the replicated links between puberty and behavior problems appear to reflect the unique effects of puberty and child behavior problems on the development of adolescent behavior problems.

Evidence needed to understand gender identity: Commentary on Turban & Ehrensaft (2018).

Turban and Ehrensaft (2018) have provided a thoughtful review of transgender identity in children and adolescents, emphasizing the benefits of the affirmative approach in maintaining positive psychological health in transgender individuals. The review reveals significant gaps in our understanding of gender identity regarding its nature, development, plasticity, causes, and links with other aspects of gender, and of the long-term benefits and costs of childhood social transitions. A full understanding of transgender identity requires studying cisgender identity too, and recognition that gender identity is continuous, develops across time and is not synonymous with gender expression or variations in gender-typed characteristics. Considerable evidence is needed before we can be confident that we are providing optimal treatment for children who are gender variant.

From Genes to Behavior Through Sex Hormones and Socialization: The Example of Gender Development.

Irving Gottesman is known primarily for his work in psychopathology, but he also had a long-standing interest in understanding psychological development generally (typical and atypical). Through his mentorship, he also influenced work in gender development. Characteristics related to sex and gender are ideally suited to study the interplay of genes and environment across development. We discuss how gender development is influenced by gonadal hormones present during early life, but not in a simple way. We describe some of the challenges and opportunities to extend our understanding of the complexity of gender development. Throughout, we consider the kinds of questions Gottesman would likely have asked and emphasize his influence on our work.

Beyond Pink and Blue: The Complexity of Early Androgen Effects on Gender Development.

Why do girls and women differ from boys and men? Gender development is typically considered to result from socialization, but sex hormones present during sensitive periods of development, particularly prenatal androgens, play an important role. Data from natural experiments, especially from females with congenital adrenal hyperplasia, show the complexity of the effects of androgens on behavior: Prenatal androgens apparently have large effects on interests and engagement in gendered activities; moderate effects on spatial abilities; and relatively small or no effects on gender identity, gender cognitions, and gendered peer involvement. These differential effects provide an opportunity to move beyond identifying sources of variation in behavior to understanding developmental processes. These processes include links among gendered characteristics, psychological and neural mechanisms underlying development, and the joint effects of biological predispositions and social experiences.

Gendered Peer Involvement in Girls with Congenital Adrenal Hyperplasia: Effects of Prenatal Androgens, Gendered Activities, and Gender Cognitions.

A key question in understanding gender development concerns the origins of sex segregation. Children's tendencies to interact with same-sex others have been hypothesized to result from gender identity and cognitions, behavioral compatibility, and personal characteristics. We examined whether prenatal androgen exposure was related to time spent with boys and girls, and how that gendered peer involvement was related to sex-typed activities and gender identity and cognitions. We studied 54 girls with congenital adrenal hyperplasia (CAH) aged 10-13 years varying in degree of prenatal androgen exposure: 40 girls with classical CAH (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical CAH (NC-CAH) exposed to low, female-typical, prenatal androgens. Home interviews and questionnaires provided assessments of gendered activity interests and participation, gender identity, and gender cognitions. Daily phone calls over 7 days assessed time spent in gendered activities and with peers. Girls with both C-CAH and NC-CAH interacted more with girls than with boys, with no significant group differences. The groups did not differ significantly in gender identity or gender cognitions, but girls with C-CAH spent more time in male-typed activities and less time in female-typed activities than did girls with NC-CAH. Time spent with girls reflected direct effects of gender identity/cognitions and gender-typed activities, and an indirect effect of prenatal androgens (CAH type) through gender-typed activities. Our results extend findings that prenatal androgens differentially affect gendered characteristics and that gendered peer interactions reflect combined effects of behavioral compatibility and feelings and cognitions about gender. The study also shows the value of natural experiments for testing hypotheses about gender development.

Linking Prenatal Androgens to Gender-Related Attitudes, Identity, and Activities: Evidence From Girls With Congenital Adrenal Hyperplasia.

Key questions for developmentalists concern the origins of gender attitudes and their implications for behavior. We examined whether prenatal androgen exposure was related to gender attitudes, and whether and how the links between attitudes and gendered activity interest and participation were mediated by gender identity and moderated by hormones. Gender attitudes (i.e., gender-role attitudes and attitudes about being a girl), gender identity, and gender-typed activities were reported by 54 girls aged 10-13 years varying in degree of prenatal androgen exposure, including 40 girls with classical congenital adrenal hyperplasia (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical (NC) CAH exposed to low, female-typical, prenatal androgens. Both girls with C-CAH and NC-CAH reported positive attitudes about being a girl and egalitarian gender attitudes, consistent with their female-typical gender identity. In contrast, girls with C-CAH had more male-typed activity interest and participation than girls with NC-CAH. Gender attitudes were linked to activities in both groups, with gender identity mediating the links. Specifically, gender-role attitudes and positive attitudes about being a girl were associated with feminine gender identity, which in turn was associated with decreased male-typed activity interests and participation, and increased female-typed activity interests. Our results are consistent with schema theories, with attitudes more closely associated with gender identity than with prenatal androgens.

Gender Assignment, Reassignment and Outcome in Disorders of Sex Development: Update of the 2005 Consensus Conference.

BACKGROUND: Societal changes are increasingly moving the conceptualization of gender from a set of binary categories towards a bimodal continuum, which along with the cautious conclusions resulting from the 2005 Consensus Conference influences gender-related clinical work with patients with disorders of sex development. OBJECTIVE: This article provides an update of these developments over the past decade along with an overview of pertinent new data. CONCLUSION: Considerably more research is needed on larger sample sizes with systematic long-term follow-up to ground the emerging trends in clinical management of the highly diverse disorders of sex development syndromes in a solid empirical basis.

How Early Hormones Shape Gender Development.

Many important psychological characteristics show sex differences, and are influenced by sex hormones at different developmental periods. We focus on the role of sex hormones in early development, particularly the differential effects of prenatal androgens on aspects of gender development. Increasing evidence confirms that prenatal androgens have facilitative effects on male-typed activity interests and engagement (including child toy preferences and adult careers), and spatial abilities, but relatively minimal effects on gender identity. Recent emphasis has been directed to the psychological mechanisms underlying these effects (including sex differences in propulsive movement, and androgen effects on interest in people versus things), and neural substrates of androgen effects (including regional brain volumes, and neural responses to mental rotation, sexually arousing stimuli, emotion, and reward). Ongoing and planned work is focused on understanding the ways in which hormones act jointly with the social environment across time to produce varying trajectories of gender development, and clarifying mechanisms by which androgens affect behaviors. Such work will be facilitated by applying lessons from other species, and by expanding methodology. Understanding hormonal influences on gender development enhances knowledge of psychological development generally, and has important implications for basic and applied questions, including sex differences in psychopathology, women's underrepresentation in science and math, and clinical care of individuals with variations in gender expression.

Sex differences in resting state brain function of cigarette smokers and links to nicotine dependence.

Sex--a marker of biological and social individual differences--matters for drug use, particularly for cigarette smoking, which is the leading cause of preventable death in the United States. More men than women smoke, but women are less likely than men to quit. Resting state brain function, or intrinsic brain activity that occurs in the absence of a goal-directed task, is important for understanding cigarette smoking, as it has been shown to differentiate between smokers and nonsmokers. But, it is unclear whether and how sex influences the link between resting state brain function and smoking behavior. In this study, the authors demonstrate that sex is indeed associated with resting state connectivity in cigarette smokers, and that sex moderates the link between resting state connectivity and self-reported nicotine dependence. Using functional MRI and behavioral data from 50 adult daily smokers (23 women), the authors found that women had greater connectivity than men within the default mode network, and that increased connectivity within the reward network was related to increased nicotine tolerance in women but to decreased nicotine tolerance in men. Findings highlight the importance of sex-related individual differences reflected in resting state connectivity for understanding the etiology and treatment of substance use problems.

Oral contraceptives and cognition: A role for ethinyl estradiol.

This article is part of a Special Issue "Estradiol and cognition". Estrogens have been seen to play a role in human cognitive abilities, but questions remain about the cognitive impact of ethinyl estradiol, which is contained in many oral contraceptives (OCs). Inconsistencies in past studies likely reflect small samples and heterogeneous groups of OC users. The aims of the present work were to examine OC effects on sex-typed spatial and verbal abilities by (a) comparing mental rotations and expressional fluency in normally-cycling (NC) women and men to OC users considered as a heterogeneous group and then to homogeneous groups of OC users created by classifying pills according to their active constituents, and (b) determining the relation between synthetic hormone doses in OCs and mental rotations and expressional fluency. Participants were 136 men, 93 NC women, and 148 OC users, including homogeneous monophasic (n = 55) and triphasic (n = 43) OC groups, aged 18 to 30 years. Significant effects of OC use were seen in homogeneous group comparisons but not when OC users were considered as a heterogeneous group. On mental rotations, men outperformed women, and monophasic OC users outperformed NC women. The latter difference may be attributable to estradiol, as ethinyl estradiol was inversely related to spatial ability among OC users and was lower in monophasic than in triphasic users. On expressional fluency, NC women and monophasic OC users outperformed men, and monophasic users outperformed triphasic users. Thus, results show the importance of ethinyl estradiol and of considering pill constituents when studying the cognitive effects of OCs.

Genetic influences on pubertal development and links to behavior problems.

Genetic influences on adolescent psychological development are likely to be mediated and moderated by pubertal hormones. Combining genetic analyses with advanced models of pubertal development, we extended work on the measurement and psychological significance of puberty. We examined how genetic and environmental influences on puberty vary by the way that development is described (logistic versus linear models versus traditional methods) and the different aspects of puberty (adrenarche vs. gonadarche), and how genes and environment contribute to the covariation between different descriptions and aspects of puberty, and between pubertal development and behavior problems (substance use, age at sexual initiation). We also considered how puberty moderated the heritability of psychological outcomes (internalizing and externalizing problems), and sex differences. Participants from the Colorado Longitudinal Twin Study (403 girls, 395 boys) reported their pubertal development annually from ages 9 through 15; they and their parents reported their behavior in mid-to-late adolescence. There was a large genetic contribution to pubertal timing for both sexes no matter how it was measured, but findings for pubertal tempo varied by method. Genetic covariation accounted for most of the phenotypic correlations among different indicators of pubertal timing, and between pubertal timing and psychological outcome. We consider the implications of our results for understanding how pubertal hormones mediate or moderate genetic and environmental influences on psychological development.