189926223
Sex Hormones and Gender Role Relate to Gray Matter Volumes in Sexually Dimorphic Brain Areas
The present study investigates the relationship of circulating sex hormone levels and gender role to gray matter volumes in sexually dimorphic brain areas and explores, whether these relationships are modulated by biological sex (as assigned at birth based on sexual anatomy) or oral contraceptive (OC) use. It was hypothesized that testosterone and masculinity relate positively to gray matter volumes in areas that are typically larger in men, like the hippocampus or cerebellum, while estradiol/progesterone and femininity relate positively to gray matter volumes in the frontal cortex. To that end, high resolution structural MRI scans, sex hormone levels and gender role self-assessments were obtained in a large sample 89 men, 89 naturally cycling (NC) women, and 60 OC users. Men showed larger regional gray matter volumes than women in the cerebellum and bilateral clusters spanning the putamen and parts of the hippocampi/parahippocampi and fusiform gyri. In accordance with our hypotheses, a significant positive association of testosterone to hippocampal volumes was observed in women irrespective of OC use. Participant’s self-reported femininity was significantly positively associated with gray matter volumes in the left middle frontal gyrus (MFG) in men. In addition several differences between OC-users and NC women were identified.
10144646
Evolving Knowledge of Sex Differences in Brain Structure, Function, and Chemistry
Clinical and epidemiologic evidence demonstrates sex differences in the prevalence and course of various psychiatric disorders. Understanding sex-specific brain differences in healthy individuals is a critical first step toward understanding sex-specific expression of psychiatric disorders. Here, we evaluate evidence on sex differences in brain structure, chemistry, and function using imaging methodologies, including functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and structural magnetic resonance imaging (MRI) in mentally healthy individuals. MEDLINE searches of English-language literature (1980-November 2006) using the terms sex, gender, PET, SPECT, MRI, fMRI, morphometry, neurochemistry, and neurotransmission were performed to extract relevant sources. The literature suggests that while there are many similarities in brain structure, function, and neurotransmission in healthy men and women, there are important differences that distinguish the male from the female brain. Overall, brain volume is greater in men than women; yet, when controlling for total volume, women have a higher percentage of gray matter and men a higher percentage of white matter. Regional volume differences are less consistent. Global cerebral blood flow is higher in women than in men. Sex-specific differences in dopaminergic, serotonergic, and gamma-aminobutyric acid (GABA)ergic markers indicate that male and female brains are neurochemically distinct. Insight into the etiology of sex differences in the normal living human brain provides an important foundation to delineate the pathophysiological mechanisms underlying sex differences in neuropsychiatric disorders and to guide the development of sex-specific treatments for these devastating brain disorders.
206237430
Sex influences on the neurobiology of learning and memory.
In essentially every domain of neuroscience, the generally implicit assumption that few, if any, meaningful differences exist between male and female brain function is being challenged. Here we address how this development is influencing studies of the neurobiology of learning and memory. While it has been commonly held that males show an advantage on spatial tasks, and females on verbal tasks, there is increasing evidence that sex differences are more widespread than previously supposed. Differing performance between the sexes have been observed on a number of common learning tasks in both the human and animal literature, many neither purely spatial nor verbal. We review sex differences reported in various areas to date, while attempting to identify common features of sexually dimorphic tasks, and to place these differences in a neurobiological context. This discussion focuses on studies of four classes of memory tasks for which sex differences have been frequently reported: spatial, verbal, autobiographical, and emotional memory. We conclude that the female verbal advantage extends into numerous tasks, including tests of spatial and autobiographical abilities, but that a small but significant advantage may exist for general episodic memory. We further suggest that for some tasks, stress evokes sex differences, which are not normally observed, and that these differences are mediated largely by interactions between stress and sex hormones.
13790333
A meta-analysis of sex differences in human brain structure☆
Highlights • This is the first meta-analysis of sex differences in the typical human brain.• Regional sex differences overlap with areas implicated in psychiatric conditions.• The amygdala, hippocampus, planum temporale and insula display sex differences.• On average, males have larger brain volumes than females.• Most articles providing sex differences in volume are in the ‘mature’ category.
207093123
Sex differences in brain and behavior in adolescence: Findings from the Philadelphia Neurodevelopmental Cohort
Sex differences in brain and behavior were investigated across the lifespan. Parameters include neurobehavioral measures linkable to neuroanatomic and neurophysiologic indicators of brain structure and function. Sexual differentiation of behavior has been related to organizational factors during sensitive periods of development, with adolescence and puberty gaining increased attention. Adolescence is a critical developmental period where transition to adulthood is impacted by multiple factors that can enhance vulnerability to brain dysfunction. Here we highlight sex differences in neurobehavioral measures in adolescence that are linked to brain function. We summarize neuroimaging studies examining brain structure, connectivity and perfusion, underscoring the relationship to sex differences in behavioral measures and commenting on hormonal findings. We focus on relevant data from the Philadelphia Neurodevelopmental Cohort (PNC), a community-based sample of nearly 10,000 clinically and neurocognitively phenotyped youths age 8-21 of whom 1600 have received multimodal neuroimaging. These data indicate early and pervasive sexual differentiation in neurocognitive measures that is linkable to brain parameters. We conclude by describing possible clinical implications.
708124
Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants
Abstract Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44–77 years). Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function.
28876076
Sex differences in spatial cognition: advancing the conversation.
The existence of a sex difference in spatial thinking, notably on tasks involving mental rotation, has been a topic of considerable research and debate. We review this literature, with a particular focus on the development of this sex difference, and consider four key questions: (1) When does the sex difference emerge developmentally and does the magnitude of this difference change across development? (2) What are the biological and environmental factors that contribute to sex differences in spatial skill and how might they interact? (3) How malleable are spatial skills, and is the sex difference reduced as a result of training? and (4) Does 'spatializing' the curriculum raise the level of spatial thinking in all students and hold promise for increasing and diversifying the STEM pipeline? Throughout the review, we consider promising avenues for future research.
144368987
Sex differences in the causes of self-control: An examination of mediation, moderation, and gendered etiologies
Sex is one of the most robust predictors of self-control, with a consistent finding that girls score higher on a variety of measures of self-control. In this research, we investigate three possible reasons for why this is true: first, we examine whether current predictors of self-control mediate the effect of sex on self-control, second, we examine whether sex moderates the effect of current predictors on self-control and third, we examine the possibility that the causes of self-control are gendered, necessitating different causal models for boys and girls. Using data from the Children of the National Longitudinal Survey of Youth79, we assess three, related questions: Is the sex effect on self-control mediated by current predictors of self-control? Does sex moderate the effects of current predictors of self-control? Does the causal model predicting self-control differ for boys and girls? We find that the sex effect on self-control is robust; does not moderate the etiology of self-control; and although partially mediated by etiological variables, remains a significant predictor of self-control. We also find that current predictors do a poor job of explaining girls' acquisition of self-control, suggesting a gendered etiology of self-control.
3496647
Sex differences in self-regulation: an evolutionary perspective
Bjorklund and Kipp (1996) provide an evolutionary framework predicting that there is a female advantage in inhibition and self-regulation due to differing selection pressures placed on males and females. The majority of the present review will summarize sex differences in self-regulation at the behavioral level. The neural and hormonal underpinnings of this potential sexual dimorphism will also be investigated and the results of the experiments summarized will be related to the hypothesis advanced by Bjorklund and Kipp (1996). Paradoxically, sex differences in self-regulation are more consistently reported in children prior to the onset of puberty. In adult cohorts, the results of studies examining sex differences in self-regulation are mixed. A few recent experiments suggesting that females are less impulsive than males only during fertile stages of the menstrual cycle will be reviewed. A brief discussion of an evolutionary framework proposing that it is adaptive for females to employ a self-regulatory behavioral strategy when fertile will follow.
5144570
Hippocampal structural changes across the menstrual cycle
Magnetic resonance imaging (MRI) in association with Jacobian‐modulated voxel‐based morphometry (VBM) was used to test for regional variation in gray matter over the menstrual cycle. T1‐weighted anatomical images were acquired using a spoiled gradient recalled acquisition sequence in 21 women. Each subject was scanned twice: once during the postmenstrual late‐follicular phase (Days 10–12 after onset of menses), and once during the premenstrual late‐luteal phase (1–5 days before the onset of menses). Gray matter was relatively increased in the right anterior hippocampus and relatively decreased in the right dorsal basal ganglia (globus pallidus/putamen) in the postmenstrual phase. Verbal declarative memory was increased in the postmenstrual vs. premenstrual phase. This first report of human brain structural plasticity associated with the endogenous menstrual cycle extends well‐established animal findings of hormone‐mediated hippocampal plasticity to humans, and has implications for understanding alterations in cognition and behavior across the menstrual cycle. © 2008 Wiley‐Liss, Inc.
3267324
Differential effects of androgenic and anti-androgenic progestins on fusiform and frontal gray matter volume and face recognition performance
Effects of oral hormonal contraceptives (OC) on human brain structure and behavior have only recently become a focus of research. Two explorative reports observed larger regional gray matter (GM) volumes in OC users within the prefrontal cortex, ACC and fusiform gyri, as well as parahippocampal gyri, hippocampus and cerebellum. These studies did however not control for the androgenicity of the progestin compound of OC, did not take into consideration how long OC users had been on their OC, and did not control for age differences between the OC group and the naturally cycling group. We compared 20 naturally cycling women during their early follicular cycle phase to 18 users of OC containing androgenic progestins and 22 users of OC containing anti-androgenic progestins. When controlling for age, we found that in users of anti-androgenic progestins relative GM volumes within the bilateral fusiform gyri, fusiform face area (FFA), parahippocampal place area (PPA) and cerebellum, were significantly larger than in naturally cycling women, while in users of androgenic progestins, relative as well as absolute volumes within the bilateral middle and superior frontal gyri were significantly smaller compared to naturally cycling women. These morphological changes were related to performance in a face recognition task. Face recognition performance was significantly better in users of anti-androgenic progestins compared to the other groups and significantly related to absolute as well as relative GM volumes in the FFA and PPA. Total GM volume, as well as absolute GM volumes within the bilateral fusiform gyri, FFA, hippocampus, parahippocampus, PPA, middle frontal gyri and ACC were significantly larger, the longer the duration of OC use, particularly in users of androgenic progestins. Morphological differences between active and inactive pill phase were observed in users of androgenic progestins. These findings suggest differential effects of androgenic and anti-androgenic progestins on human brain structure.
24582593
Menstrual cycle and hormonal contraceptive use modulate human brain structure
Sex differences in human brain structure have repeatedly been described, but results are inconsistent. However, these studies hardly controlled for cycle phase of women or the use of hormonal contraceptives. Our study shows that these factors are not negligible, but have a considerable influence on human brain structure. We acquired high-resolution structural images from the brains of 14 men, 14 women, who did not use, and 14 women, who did use hormonal contraceptives. Women, who did not use hormonal contraceptives, were scanned twice, once during their early follicular and once during their mid-luteal cycle-phase. Regional gray matter volumes were compared by voxel-based morphometry. Men had larger hippocampi, parahippocampal and fusiform gyri, amygdalae and basal ganglia than women. Women showed larger gray matter volumes in the prefrontal cortex, pre- and postcentral gyri. These sex-dependent effects were modulated by menstrual cycle phases and hormonal contraceptives. We found larger volumes in the right fusiform/parahippocampal gyrus during early follicular compared to mid-luteal cycle phase. Women using hormonal contraceptives showed significantly larger prefrontal cortices, pre- and postcentral gyri, parahippocampal and fusiform gyri and temporal regions, compared to women not using contraceptives.
27880568
Gender Differences in Brain and Behavior Hormonal and Neural Bases
This article briefly discusses the difficulties in determining the brain-behavior relationship and reviews the literature on some potential mechanisms underlying gender differences in behavioral responses. Mechanisms that are discussed include genetic effects, organizational effects of gonadal hormones, genomic actions of steroids, nongenomic effects of steroids, and environmental influences. The review is an introduction to the articles presented in this special volume on gender differences in brain and behavior.
5966454
Hippocampal volume and functional connectivity changes during the female menstrual cycle
Hippocampal volume has been shown to be sensitive to variations in estrogen and progesterone levels across rodents' estrous cycle. However, little is known about the covariation of hormone levels and brain structure in the course of the human menstrual cycle. Here, we examine this covariation with a multi-method approach that includes several brain imaging methods and hormonal assessments. We acquired structural and functional scans from 21 naturally cycling women on four time points during their cycles (early follicular phase, late follicular phase, ovulation and luteal phase). Hormone blood concentrations and cognitive performance in different domains were assessed on each of the measurement occasions. Structural MRI images were processed by means of whole-brain voxel-based morphometry and FreeSurfer. With either method, bilateral increases in hippocampal volume were found in the late follicular phase relative to the early follicular phase. The gray matter probability in regions of hippocampal volume increase was associated with lower mean diffusivity in the same region. In addition, we observed higher functional connectivity between the hippocampi and the bilateral superior parietal lobe in the late follicular phase. We did not find any reliable cycle-related performance variations on the cognitive tasks. The present results show that hormonal fluctuations covary with hippocampal structure and function in the course of the human menstrual cycle.
368056
In-vivo Dynamics of the Human Hippocampus across the Menstrual Cycle
Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies suggests similar subtle fluctuations in hippocampal structure, predominantly linked to estrogen. Hippocampal abnormalities have been observed in several neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential impact of subtle sex-hormonal fluctuations on human hippocampal structure in health is unclear. We tested the feasibility of longitudinal neuroimaging in conjunction with rigorous menstrual cycle monitoring to evaluate potential changes in hippocampal microstructure associated with physiological sex-hormonal changes. Thirty longitudinal diffusion weighted imaging scans of a single healthy female subject were acquired across two full menstrual cycles. We calculated hippocampal fractional anisotropy (FA), a measure sensitive to changes in microstructural integrity, and investigated potential correlations with estrogen. We observed a significant positive correlation between FA values and estrogen in the hippocampus bilaterally, revealing a peak in FA closely paralleling ovulation. This exploratory, single-subject study demonstrates the feasibility of a longitudinal DWI scanning protocol across the menstrual cycle and is the first to link subtle endogenous hormonal fluctuations to changes in FA in vivo. In light of recent attempts to neurally phenotype single humans, our findings highlight menstrual cycle monitoring in parallel with highly sampled individual neuroimaging data to address fundamental questions about the dynamics of plasticity in the adult brain.
2089438
Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods
Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo.
27493794
Changing your sex changes your brain: influences of testosterone and estrogen on adult human brain structure
Objective: Sex hormones are not only involved in the formation of reproductive organs, but also induce sexually-dimorphic brain development and organization. Cross-sex hormone administration to transsexuals provides a unique possibility to study the effects of sex steroids on brain morphology in young adulthood. Methods: Magnetic resonance brain images were made prior to, and during, cross-sex hormone treatment to study the influence of anti-androgen + estrogen treatment on brain morphology in eight young adult male-to-female transsexual human subjects and of androgen treatment in six female-to-male transsexuals. Results: Compared with controls, anti-androgen + estrogen treatment decreased brain volumes of male-to-female subjects towards female proportions, while androgen treatment in female-to-male subjects increased total brain and hypothalamus volumes towards male proportions. Conclusions: The findings suggest that, throughout life, gonadal hormones remain essential for maintaining aspects of sex-specific differences in the human brain.
6793632
A Review of the Status of Brain Structure Research in Transsexualism
The present review focuses on the brain structure of male-to-female (MtF) and female-to-male (FtM) homosexual transsexuals before and after cross-sex hormone treatment as shown by in vivo neuroimaging techniques. Cortical thickness and diffusion tensor imaging studies suggest that the brain of MtFs presents complex mixtures of masculine, feminine, and demasculinized regions, while FtMs show feminine, masculine, and defeminized regions. Consequently, the specific brain phenotypes proposed for MtFs and FtMs differ from those of both heterosexual males and females. These phenotypes have theoretical implications for brain intersexuality, asymmetry, and body perception in transsexuals as well as for Blanchard’s hypothesis on sexual orientation in homosexual MtFs. Falling within the aegis of the neurohormonal theory of sex differences, we hypothesize that cortical differences between homosexual MtFs and FtMs and male and female controls are due to differently timed cortical thinning in different regions for each group. Cross-sex hormone studies have reported marked effects of the treatment on MtF and FtM brains. Their results are used to discuss the early postmortem histological studies of the MtF brain.
2911710
The relationship of male testosterone to components of mental rotation
Studies suggest that higher levels of testosterone (T) in males contribute to their advantage over females in tests of spatial ability. However, the mechanisms that underlie the effects of T on spatial ability are not understood. We investigated the relationship of salivary T in men to performance on a computerized version of the mental rotation task (MRT) developed by [Science 171 (3972) (1971) 701]. We studied whether T is associated specifically with the ability to mentally rotate objects or with other aspects of the task. We collected hormonal and cognitive data from 27 college-age men on 2 days of testing. Subjects evaluated whether two block objects presented at different orientations were the same or different. We recorded each subject's mean response time (RT) and error rate (ER) and computed the slopes and intercepts of the functions relating performance to angular disparity. T level was negatively correlated with ER and RT; these effects arose from correlations with the intercepts but not the slopes of the rotation functions. These results suggest that T may facilitate male performance on MRTs by affecting cognitive processes unrelated to changing the orientation of imagined objects; including encoding stimuli, initiating the transformation processes, making a comparison and decision, or producing a response.
17448245
Virtual navigation in humans: the impact of age, sex, and hormones on place learning
Certain cognitive processes, including spatial ability, decline with normal aging. Spatial ability is also a cognitive domain with robust sex differences typically favoring males. However, tests of spatial ability do not seem to measure a homogeneous class of processes. For many, mentally matching rotated three-dimensional images is the gold standard for measuring spatial cognition in humans, while the Morris water task (MWT) is a preferred method in the domain of nonhuman animal research. The MWT is sensitive to hippocampal damage, a structure critical for normal learning and memory and often implicated in age-related cognitive decline. A computerized (virtual) version of the MWT (VMWT) appears to require and engage human hippocampal circuitry, and has proven useful in studying sex differences and testing spatial learning theories. In Experiment 1, we tested participants (20-90 years of age) in the VMWT and compared their performance to that on the Vandenberg Mental Rotation Test. We report an age-related deficit in performance on both tasks. In Experiment 2, we tested young (age 20-39) and elderly (age >60) participants in the VMWT and correlated their performance to the circulating levels of testosterone and cortisol. Our findings indicate that the persistence of male spatial advantage may be related to circulating testosterone, but not cortisol levels, and independent of generalized age-related cognitive decline.
6955664
Interactive effects of sex hormones and gender stereotypes on cognitive sex differences—A psychobiosocial approach
Biological and social factors have been shown to affect cognitive sex differences. For example, several studies have found that sex hormones have activating effects on sex-sensitive tasks. On the other hand, it has been shown that gender stereotypes can influence the cognitive performance of (gender-) stereotyped individuals. However, few studies have investigated the combined effects of both factors. The present study investigated the interaction between sex hormones and gender stereotypes within a psychobiosocial approach. One hundred and fourteen participants (59 women) performed a battery of sex-sensitive cognitive tasks, including mental rotation, verbal fluency, and perceptual speed. Saliva samples were taken immediately after cognitive testing. Levels of testosterone (T) were analysed using chemiluminescence immunoassay (LIA). To activate gender stereotypes, a questionnaire was applied to the experimental group that referred to the cognitive tasks used. The control group received an identical questionnaire but with a gender-neutral content. As expected, significant sex differences favouring males and females appeared for mental rotation and verbal fluency tasks, respectively. The results revealed no sex difference in perceptual speed. The male superiority in the Revised Vandenberg and Kuse Mental Rotations Tests (MRT-3D) was mainly driven by the stereotype-active group. No significant sex difference in MRT-3D appeared in the control group. The MRT-3D was also the task in which a strong gender-stereotype favouring males was present for both males and females. Interestingly, T levels of the stereotype-activated group were 60% higher than that of male controls. The results suggest that sex hormones mediate the effects of gender stereotypes on specific cognitive abilities.
14632876
Sex hormones and mental rotation: An intensive longitudinal investigation
The present study used an intensive longitudinal design to examine whether mental rotation performance varies according to a monthly cycle in both males and females and whether these variations are related to variations in progesterone, estradiol, and testosterone levels. We collected reaction time and accuracy data for 10 males and seven females each workday over eight weeks using 136 pairs of mental rotation stimuli/day, and measured sexual hormones concentrations in the saliva twice a week. A mixed linear model statistical analysis revealed that all females and seven males showed significant cycle effects in mental rotation performance. The female cycle showed an amplitude that was twice as large compared with the amplitude found in males. For males and females, estradiol and testosterone were significantly linearly and quadratically related to interindividual variation in performance at the beginning of the study (progesterone was linearly related to performance for females). The association between testosterone and performance differed across sexes: for males, it had an inverse U-shape, for females it was U-shaped. Towards the end of the study, none of the hormones were significantly related to performance anymore. Thus, the relationship between hormones and mental rotation performance disappeared with repeated testing. Only estradiol levels were significantly elevated at the lowest point of the cycle in mental rotation performance in females. In conclusion, in this intensive longitudinal study spanning two months, a monthly cycle in mental rotation performance was found among both males and females, with a larger cycle's amplitude for females.
42403127
The measurement of psychological androgyny.
This article describes the development of a new sex-role inventory that treats masculinity and femininity as two independent dimensions, thereby making it possible to characterize a person as masculine, feminine, or "androgynous" as a function of the difference between his or her endorsement of masculine and feminine personality characteristics. Normative data are presented, as well as the results of various psychometric analyses. The major findings of conceptual interest are: (a) the dimensions of masculinity and femininity are empirically as well as logically independent; (6) the concept of psychological androgyny is a reliable one; and (c) highly sex-typed scores do not reflect a general tendency to respond in a socially desirable direction, but rather a specific tendency to describe oneself in accordance with sex-typed standards of desirable behavior for men and women. Both in psychology and in society at large, masculinity and femininity have long been conceptualized as bipolar ends of a single continuum; accordingly, a person has had to be either masculine or feminine, but not both. This sex-role dichotomy has served to obscure two very plausible hypotheses: first, that many individuals might be "androgynous" ; that is, they might be both masculine and feminine, both assertive and yielding, both instrumental and expressive—depending on the situational appropriateness of these various behaviors; and conversely, that strongly sex-typed individuals might be seriously limited in the range of behaviors available to them as they move from situation to situation. According to both Kagan (1964) and Kohlberg (1966), the highly sex-typed individual is motivated to keep his behavior consistent with an internalized sex-role standard, a goal that he presumably accomplishes by suppressing any behavior that might be con
10328126
Depression, Sex and Gender Roles in Older Adult Populations: The International Mobility in Aging Study (IMIAS)
Objectives To assess the associations between gender roles and depression in older men and women and whether gender roles are independent risk factors for depression. Methods International cross-sectional study of adults between 65 and 74 years old (n = 1,967). Depression was defined by a score of 16 or over in the Center for Epidemiologic Studies Depression Scale (CES-D). A validated 12-item Bem Sex Role Inventory (BSRI) was used to classify participants in gender roles (Masculine, Feminine, Androgynous, and Undifferentiated) using research site medians of femininity and masculinity as cut-off points. Poisson regressions were fitted to estimate the prevalence ratios (PR) of depression for each gender role compared to the masculine role, adjusting for sex, sufficiency of income, education, marital status, self-rated health, and chronic conditions. Results Among men, 31.2% were androgynous, 26% were masculine, 14.4% were feminine, and 28.4% were undifferentiated; among women, the corresponding percentages were 32.7%, 14.9%, 27%, and 25.4%. Both in men and in women, depressive symptoms (CES-D≥16) were more prevalent in those endorsing the undifferentiated type, compared to masculine, feminine or androgynous groups. However, after adjusting for potential confounders, compared to the masculine group only those endorsing the androgynous role were 28% less likely to suffer from depression: PR of 0.72 (95% CI: 0.55–0.93). In fully adjusted models, prevalence rates of depression were not different from masculine participants in the two other gender groups of feminine and undifferentiated. Conclusions Androgynous roles were associated with lower rates of depression in older adults, independently of being a man or a woman.
143564917
Gender-Role Differences in Spatial Ability: A Meta-Analytic Review
Although gender-related differences in highly gender typed cognitive abilities are of considerable interest to educators and cognitive researchers alike, relatively little progress has been made in understanding the psychological processes that lead to them. Nash (1979) proposed a gender-role mediation hypothesis for such differences, with particular emphasis on spatial ability. However, changes in gender equality and gender stereotypes in the decades since merit a re-examination of whether a gender-role association still holds (Feingold 1988). A meta-analysis of 12 studies that examined gender-role identity and mental rotation performance was conducted. These included studies from the United Kingdom, Canada, Poland, Croatia, and the United States of America. The mean effect size for masculinity was r = .30 for men and r = .23 for women; no association was found between femininity and mental rotation. This effect size was slightly larger than that found previously by Signorella and Jamison (1986), and exceeds many other factors known to influence spatial ability. The implications of gender-role mediation of gender differences are discussed and future research directions are identified.
1510889
Reproductive toxicology. Di-n-octylphthalate.
1 Section of Sexual Medicine, Christian-Albrechts University, Kiel, Germany, 2 Department of Neurology, Christian-Albrechts University, Kiel, Germany, 3 NeuroImage Nord, Hamburg-Kiel-Lübeck, Germany, 4 Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom, 5 Department of Neurology, University Freiburg, Freiburg, Germany, 6 Section of Neuroradiology, Department of Neurosurgery, ChristianAlbrechts University, Kiel, Germany, 7 Department of Neurosurgery, Christian-Albrechts University, Kiel, Germany
19012014
Sexual Orientation Related Differences in Cortical Thickness in Male Individuals
Previous neuroimaging studies demonstrated sex and also sexual orientation related structural and functional differences in the human brain. Genetic information and effects of sex hormones are assumed to contribute to the male/female differentiation of the brain, and similar effects could play a role in processes influencing human's sexual orientation. However, questions about the origin and development of a person's sexual orientation remain unanswered, and research on sexual orientation related neurobiological characteristics is still very limited. To contribute to a better understanding of the neurobiology of sexual orientation, we used magnetic resonance imaging (MRI) in order to compare regional cortical thickness (Cth) and subcortical volumes of homosexual men (hoM), heterosexual men (heM) and heterosexual women (heW). hoM (and heW) had thinner cortices primarily in visual areas and smaller thalamus volumes than heM, in which hoM and heW did not differ. Our results support previous studies, which suggest cerebral differences between hoM and heM in regions, where sex differences have been reported, which are frequently proposed to underlie biological mechanisms. Thus, our results contribute to a better understanding of the neurobiology of sexual orientation.
46875093
Cerebral sex dimorphism and sexual orientation
The neurobiology of sexual orientation is frequently discussed in terms of cerebral sex dimorphism (defining both functional and structural sex differences). Yet, the information about possible cerebral differences between sex‐matched homo and heterosexual persons is limited, particularly among women. In this multimodal MRI study, we addressed these issues by investigating possible cerebral differences between homo and heterosexual persons, and by asking whether there is any sex difference in this aspect. Measurements of cortical thickness (Cth), subcortical volumes, and functional and structural resting‐state connections among 40 heterosexual males (HeM) and 40 heterosexual females (HeF) were compared with those of 30 homosexual males (HoM) and 30 homosexual females (HoF). Congruent with previous reports, sex differences were detected in heterosexual controls with regard to fractional anisotropy (FA), Cth, and several subcortical volumes. Homosexual groups did not display any sex differences in FA values. Furthermore, their functional connectivity was significantly less pronounced in the mesial prefrontal and precuneus regions. In these two particular regions, HoM also displayed thicker cerebral cortex than other groups, whereas HoF did not differ from HeF. In addition, in HoM the parietal Cth showed “sex‐reversed” values, not observed in HoF. Homosexual orientation seems associated with a less pronounced sexual differentiation of white matter tracts and a less pronounced functional connectivity of the self‐referential networks compared to heterosexual orientation. Analyses of Cth suggest that male and female homosexuality are not simple analogues of each other and that differences from heterosexual controls are more pronounced in HoM.
6993817
Increased Cortical Thickness in Male-to-Female Transsexualism.
BACKGROUND
The degree to which one identifies as male or female has a profound impact on one's life. Yet, there is a limited understanding of what contributes to this important characteristic termed gender identity. In order to reveal factors influencing gender identity, studies have focused on people who report strong feelings of being the opposite sex, such as male-to-female (MTF) transsexuals.


METHOD
To investigate potential neuroanatomical variations associated with transsexualism, we compared the regional thickness of the cerebral cortex between 24 MTF transsexuals who had not yet been treated with cross-sex hormones and 24 age-matched control males.


RESULTS
Results revealed thicker cortices in MTF transsexuals, both within regions of the left hemisphere (i.e., frontal and orbito-frontal cortex, central sulcus, perisylvian regions, paracentral gyrus) and right hemisphere (i.e., pre-/post-central gyrus, parietal cortex, temporal cortex, precuneus, fusiform, lingual, and orbito-frontal gyrus).


CONCLUSION
These findings provide further evidence that brain anatomy is associated with gender identity, where measures in MTF transsexuals appear to be shifted away from gender-congruent men.
12651216
Surface-based morphometry reveals the neuroanatomical basis of the five-factor model of personality
Abstract The five-factor model (FFM) is a widely used taxonomy of human personality; yet its neuro anatomical basis remains unclear. This is partly because past associations between gray-matter volume and FFM were driven by different surface-based morphometry (SBM) indices (i.e. cortical thickness, surface area, cortical folding or any combination of them). To overcome this limitation, we used Free-Surfer to study how variability in SBM measures was related to the FFM in n = 507 participants from the Human Connectome Project. Neuroticism was associated with thicker cortex and smaller area and folding in prefrontal–temporal regions. Extraversion was linked to thicker pre-cuneus and smaller superior temporal cortex area. Openness was linked to thinner cortex and greater area and folding in prefrontal–parietal regions. Agreeableness was correlated to thinner prefrontal cortex and smaller fusiform gyrus area. Conscientiousness was associated with thicker cortex and smaller area and folding in prefrontal regions. These findings demonstrate that anatomical variability in prefrontal cortices is linked to individual differences in the socio-cognitive dispositions described by the FFM. Cortical thickness and surface area/folding were inversely related each others as a function of different FFM traits (neuroticism, extraversion and consciousness vs openness), which may reflect brain maturational effects that predispose or protect against psychiatric disorders.
26052169
Effect of four different oral contraceptives on various sex hormones and serum-binding globulins.
In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on various hormone parameters and serum-binding globulins was investigated. Four groups with 25 volunteers each (18-35 years of age) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). The study was completed by 91 subjects. Blood samples were taken after at least 12 h of fasting on Day 21-26 of the preceding control cycle and on Day 18-21 of the first, third and sixth treatment cycle. The serum concentrations of free testosterone were significantly decreased by about 40-60% in all four groups, while those of dehydroepiandrosterone sulfate (DHEAS) showed a time-dependent decrease during treatment. Except for EE/EV/DNG, which increased prolactin significantly during the third and sixth cycles, no change was observed with the EE-containing preparations. There was a significant increase in the levels of serum-binding globulins during treatment, which differed according to the composition of the OCs used. The rise in sex hormone-binding globulin (SHBG) was highest during intake of 30EE/DNG (+320%) and lowest with EE/LNG (+80%), while the effect of 20EE/DNG and EE/EV/DNG was similar (+270%). The thyroxine-binding globulin (TBG) levels increased significantly, by 50-60%, during treatment with the DNG-containing formulations, while the effect of EE/LNG was less significant (+30%). The rise in corticosteroid-binding globulin (CBG), which occurred in all groups, was most pronounced in women treated with 30EE/DNG (+90%) and least with EE/EV/DNG (+55%), indicating a strong influence of EE and no effect of the progestogen component. In all treatment groups, the frequency of intracyclic bleeding rose in the first treatment cycle and decreased thereafter. Cycle control was significantly better with 30EE/DNG or EE/LNG than with 20EE/DNG or EE/EV/DNG. There was no significant change in blood pressure, body mass index or pulse rate throughout the study. In conclusion, the DNG-containing OCs caused a higher rise in SHBG and TBG levels than the LNG-containing preparation. The effects on CBG suggest a lesser hepatic effect of 2 mg EV as compared to 20 or 30 microg EE. In contrast to EE, the use of estradiol in OCs appeared to increase prolactin release, while the cycle control was better with the OC containing 30 microg EE.
42665313
Oral contraceptive pill use is associated with localized decreases in cortical thickness
Oral contraceptive pills (OCs), which are used to prevent pregnancy by the majority of women in the United States, contain steroid hormones that may affect the brain's structure and function. In this investigation, we tested the hypothesis that OC use is associated with differences in brain structure using a hypothesis‐driven, surface‐based approach. In 90 women, (44 OC users, 46 naturally‐cycling women), we compared the cortical thickness of brain regions that participate in the salience network and the default mode network, as well as the volume of subcortical regions in these networks. We found that OC use was associated with significantly lower cortical thickness measurements in the lateral orbitofrontal cortex and the posterior cingulate cortex. These regions are believed to be important for responding to rewards and evaluating internal states/incoming stimuli, respectively. Further investigations are needed to determine if cortical thinning in these regions are associated with behavioral changes, and also to identify whether OC use is causally or only indirectly related to these changes in brain morphology. Hum Brain Mapp 36:2644–2654, 2015. © 2015 Wiley Periodicals, Inc.
13128066
Interactive effects of culture and sex hormones on the sex role self-concept
Sex role orientation, i.e., a person's masculinity or femininity, influences cognitive and emotional performance, like biological sex. While it is now widely accepted that sex differences are modulated by the hormonal status of female participants (menstrual cycle, hormonal contraceptive use), the question, whether hormonal status and sex hormones also modulate participants sex role orientation has hardly been addressed previously. The present study assessed sex role orientation and hormonal status as well as sex hormone levels in three samples of participants from two different cultures (Northern American, Middle European). Menstrual cycle phase did not affect participant's masculinity or femininity, but had a significant impact on reference group. While women in their follicular phase (low levels of female sex hormones) determined their masculinity and femininity in reference to men, women in their luteal phase (high levels of female sex hormones) determined their masculinity and femininity in reference to women. Hormonal contraceptive users rated themselves as significantly more feminine and less masculine than naturally cycling women. Furthermore, the impact of biological sex on the factorial structure of sex role orientation as well as the relationship of estrogen to masculinity/femininity was modulated by culture. We conclude that culture and sex hormones interactively affect sex role orientation and hormonal status of participants should be controlled for when assessing masculinity and/or femininity.
8912381
Hormonal contraception usage is associated with altered memory for an emotional story
Substantial evidence now documents sex-related influences on the neurobiology of emotional memory. Robust sex influences exist, for example, on the amygdala's role in emotional memory formation, as well as on retention of central information (gist) and detail for an emotional event. Evidence also suggests that the well-documented effects of stress hormones on memory depend upon sex hormone levels. Since hormonal contraception alters sex hormone levels, and must by extension alter sex/stress hormone interactions in memory, we examined whether the use of hormonal contraception also alters memory for an emotional story. Two groups of healthy female subjects--one naturally cycling, one using hormonal contraception--viewed either a brief, emotionally arousing story, or a closely matched, but more emotionally neutral story. Each subject's eye movements and pupil dilation changes were recorded as they viewed the story. Additionally, saliva samples were taken throughout the experimental session to examine salivary alpha-amylase, a biomarker for norepinephrine. A surprise free recall test one week later measured story memory in all subjects. Naturally cycling women exhibited enhanced memory of story details, but not of central information (gist), in the emotional compared with neutral story conditions. In contrast, women using hormonal contraception exhibited enhanced memory of gist, but not story details, in the emotional compared with neutral story conditions. Analysis of eye movements made while watching the stories indicated that the differences in memory could not be attributed either to a differential attention focus or to the degree of arousal induced by the stories in the two groups. These findings suggest that the use of hormonal contraception alters memory for an emotional event, perhaps by altering sex/stress hormone interactions in memory formation. They also suggest that further investigation of the mnemonic effects of these very widely used treatments is warranted.
24328169
Hormonal contraceptives masculinize brain activation patterns in the absence of behavioral changes in two numerical tasks
The aim of the present study was to identify, whether and how oral hormonal contraceptives (OCs) alter women's number processing. Behavioral performance and brain activation patterns (BOLD-response) of 14 OC-users were evaluated during two distinct numerical tasks (number comparison, number bisection) and compared to 16 men (high testosterone), and 16 naturally cycling women, once during their follicular (low hormone levels) and once during their luteal cycle phase (high progesterone). For both tasks, reliable sex differences and menstrual cycle dependent modulation have previously been described. If progestogenic effects of the synthetic progestins contained in OC play a predominant role, OC-users should be comparable to luteal women. If androgenic effects of the synthetic steroids exert the progestogenic actions, OC-users should be comparable to men. Likewise, if neither of the above are the case, the reduction of endogenous steroids by OCs should make OC-users comparable to follicular women. Our findings suggest that OC-users resemble follicular women in their behavioral performance, but show male-like brain activation patterns during both tasks. Analysis of brain-behavior relationships suggests that OC-users differ from naturally cycling women in the way they recruit their neural resources to deal with challenges of the tasks. We conclude that OCs, which are used by 100 million women worldwide, may have profound effects on cognition that have not been recognized so far.
24016339
Neuroimaging supports behavioral personality assessment: Overlapping activations during reflective and impulsive risk taking
Personality assessment has been challenged by the fact that different assessment methods (implicit measures, behavioral measures and explicit rating scales) show little or no convergence in behavioral studies. In this neuroimaging study we address for the first time, whether different assessment methods rely on separate or overlapping neuronal systems. Fifty nine healthy adult participants completed two objective personality tests of risk propensity: the more implicit Balloon Analogue Risk Task (BART) and the more explicit Game of Dice Task (GDT). Significant differences in activation, as well as connectivity patterns between both tasks were observed. In both tasks, risky decisions yielded significantly stronger activations than safe decisions in the bilateral caudate, as well as the bilateral Insula. The finding of overlapping brain areas validates different assessment methods, despite their behavioral non-convergence. This suggests that neuroimaging can be an important tool of validation in the field of personality assessment.
18564619
Sex differences in number processing: Differential systems for subtraction and multiplication were confirmed in men, but not in women
Neuroimaging studies suggest segregated neuronal systems underlying number magnitude processing (e.g. subtraction) and arithmetic fact retrieval (e.g. multiplication). While number magnitude processing is thought to rely on the intraparietal sulcus (IPS) bilaterally, arithmetic fact retrieval is thought to rely on the left angular gyrus (AG). However, evidence from brain damaged patients and brain stimulation challenges this view and suggests considerable overlap between the systems underlying number magnitude processing and arithmetic fact retrieval. This study investigates, whether sex differences in number processing can account for these conflicting findings. A subtraction and a multiplication task were administered to 40 men and 34 women in their luteal phase during functional MRI. Replicating previous studies in men, we found the IPS to be more strongly activated during subtraction than multiplication, and the AG to be more strongly activated during multiplication than subtraction. However, no differences between the two tasks were observed in women.
33155690
Ratings of self and peers on sex role attributes and their relation to self-esteem and conceptions of masculinity and femininity.
Male (N = 248) and female (N = 282) subjects were given the Personal Attributes Questionnaire consisting of 55 bipolar attributes drawn from the Sex Role Stereotype Questionnaire by Rosenkrantz, Vogel, Bee, Broverman, and Broverman and were asked to rate themselves and then to compare directly the typical male and female college student. Self-ratings were divided into male-valued (stereotypically masculine attributes judged more desirable for both sexes), female-valued, and sex-specific items. Also administered was the Attitudes Toward Women Scale and a measure of social self-esteem. Correlations of the self-ratings with stereotype scores and the Attitudes Toward Women Scale were low in magnitude, suggesting that sex role expectations do not distort self-concepts. For both men and women, "femininity" on the female-valued self items and "masculinity" on the male-valued items were positively correlated, and both significantly related to self-esteem. The implications of the results for a concept of masculinity and femininity as a duality, characteristic of all individuals, and the use of the self-rating scales for measuring masculinity, femininity, and androgyny were discussed.
4437764
Why can't a man be more like a woman? Sex differences in Big Five personality traits across 55 cultures.
Previous research suggested that sex differences in personality traits are larger in prosperous, healthy, and egalitarian cultures in which women have more opportunities equal with those of men. In this article, the authors report cross-cultural findings in which this unintuitive result was replicated across samples from 55 nations (N = 17,637). On responses to the Big Five Inventory, women reported higher levels of neuroticism, extraversion, agreeableness, and conscientiousness than did men across most nations. These findings converge with previous studies in which different Big Five measures and more limited samples of nations were used. Overall, higher levels of human development--including long and healthy life, equal access to knowledge and education, and economic wealth--were the main nation-level predictors of larger sex differences in personality. Changes in men's personality traits appeared to be the primary cause of sex difference variation across cultures. It is proposed that heightened levels of sexual dimorphism result from personality traits of men and women being less constrained and more able to naturally diverge in developed nations. In less fortunate social and economic conditions, innate personality differences between men and women may be attenuated.
2254100
Testing Predictions From Personality Neuroscience
We used a new theory of the biological basis of the Big Five personality traits to generate hypotheses about the association of each trait with the volume of different brain regions. Controlling for age, sex, and whole-brain volume, results from structural magnetic resonance imaging of 116 healthy adults supported our hypotheses for four of the five traits: Extraversion, Neuroticism, Agreeableness, and Conscientiousness. Extraversion covaried with volume of medial orbitofrontal cortex, a brain region involved in processing reward information. Neuroticism covaried with volume of brain regions associated with threat, punishment, and negative affect. Agreeableness covaried with volume in regions that process information about the intentions and mental states of other individuals. Conscientiousness covaried with volume in lateral prefrontal cortex, a region involved in planning and the voluntary control of behavior. These findings support our biologically based, explanatory model of the Big Five and demonstrate the potential of personality neuroscience (i.e., the systematic study of individual differences in personality using neuroscience methods) as a discipline.
10113394
Correlations Between Personality and Brain Structure: A Crucial Role of Gender
Previous studies have shown that males and females differ in personality and gender differences have also been reported in brain structure. However, effects of gender on this "personality-brain" relationship are yet unknown. We therefore investigated if the neural correlates of personality differ between males and females. Whole brain voxel-based morphometry was used to investigate the influence of gender on associations between NEO FFI personality traits and gray matter volume (GMV) in a matched sample of 182 males and 182 females. In order to assess associations independent of and dependent on gender, personality-GMV relationships were tested across the entire sample and separately for males and females. There were no significant correlations between any personality scale and GMV in the analyses across the entire sample. In contrast, significant associations with GMV were detected for neuroticism, extraversion, and conscientiousness only in males. Interestingly, GMV in left precuneus/parieto-occipital sulcus correlated with all 3 traits. Thus, our results indicate that brain structure-personality relationships are highly dependent on gender, which might be attributable to hormonal interplays or differences in brain organization between males and females. Our results thus provide possible neural substrates of personality-behavior relationships and underline the important role of gender in these associations.
8545091
Sex Differences in the Flexibility of Sexual Orientation: A Multidimensional Retrospective Assessment
The flexibility of sexual orientation in men and women was examined by assessing self-reported change over time for three dimensions of sexual orientation (sexual fantasy, romantic attraction, and sexual behavior) across three categorical classifications of current sexual orientation (heterosexual, bisexual, and gay). The primary purpose of the study was to determine if there were sex differences in the flexibility (i.e., change over time) of sexual orientation and how such differences were manifested across different dimensions of orientation over the lifespan. Retrospective, life-long ratings of sexual orientation were made by 762 currently self-identified heterosexual, bisexual, and gay men and women, aged 36 to 60, via a self-report questionnaire. Cumulative change scores were derived for each of the three dimensions (fantasy, romantic attraction, and sexual behavior) of orientation by summing the differences between ratings over consecutive 5-year historical time periods (from age 16 to the present). Sex differences were observed for most, but not all, classification groups. There were significant sex differences in reported change in orientation over time for gays and heterosexuals, with women reporting greater change in orientation over time than did men. Bisexual men and women did not differ with respect to self-reported change in orientation.