Attenuation of Typical Sex Differences in 800 Adults with Autism vs. 3,900 Controls

Sex differences have been reported in autistic traits and systemizing (male advantage), and empathizing (female advantage) among typically developing individuals. In individuals with autism, these cognitive-behavioural profiles correspond to predictions from the “extreme male brain” (EMB) theory of autism (extreme scores on autistic traits and systemizing, below average on empathizing). Sex differences within autism, however, have been under-investigated. Here we show in 811 adults (454 females) with autism and 3,906 age-matched typical control adults (2,562 females) who completed the Empathy Quotient (EQ), the Systemizing Quotient-Revised (SQ-R), and the Autism Spectrum Quotient (AQ), that typical females on average scored higher on the EQ, typical males scored higher on the SQ-R and AQ, and both males and females with autism showed a shift toward the extreme of the “male profile” on these measures and in the distribution of “brain types” (the discrepancy between standardized EQ and SQ-R scores). Further, normative sex differences are attenuated but not abolished in adults with autism. The findings provide strong support for the EMB theory of autism, and highlight differences between males and females with autism.     

Sex Differences in the Default Mode Network with Regard to Autism Spectrum Traits: A Resting State fMRI Study

Autism spectrum traits exist on a continuum and are more common in males than in females, but the basis for this sex difference is unclear. To this end, the present study draws on the extreme male brain theory, investigating the relationship between sex difference and the default mode network (DMN), both known to be associated with autism spectrum traits. Resting-state functional magnetic resonance imaging (MRI) was carried out in 42 females (mean age ± standard deviation, 22.4 ± 4.2 years) and 43 males (mean age ± standard deviation, 23.8 ± 3.9 years) with typical development. Using a combination of different analyses (viz., independent component analysis (ICA), fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and seed-based analyses), we examined sex differences in the DMN and the relationship to autism spectrum traits as measured by autism-spectrum quotient (AQ) scores. We found significant differences between female and male subjects in DMN brain regions, with seed-based analysis revealing a significant negative correlation between default-mode resting state functional connectivity of the anterior medial prefrontal cortex seed (aMPFC) and AQ scores in males. However, there were no relationships between DMN sex differences and autism spectrum traits in females. Our findings may provide important insight into the skewed balance of functional connectivity in males compared to females that could serve as a potential biomarker of the degree of autism spectrum traits in line with the extreme male brain theory.     

Understanding and Determining the Etiology of Autism

Worldwide, the rate of autism has been steadily rising. There are several environmental factors in concert with genetic susceptibilities that are contributing to this rise. Impaired methylation and mutations of mecp2 have been associated with autistic spectrum disorders, and related Rett syndrome. Genetic polymorphisms of cytochrome P450 enzymes have also been linked to autism, specifically CYP27B1 that is essential for proper vitamin D metabolism. Vitamin D is important for neuronal growth and neurodevelopment, and defects in metabolism or deficiency have been implicated in autistic individuals. Other factors that have been considered include: maternally derived antibodies, maternal infection, heavy metal exposure, folic acid supplementation, epigenetics, measles, mumps, rubella vaccination, and even electromagnetic radiation. In each case, the consequences, whether direct or indirect, negatively affect the nervous system, neurodevelopment, and environmental responsive genes. The etiology of autism is a topic of controversial debate, while researchers strive to achieve a common objective. The goal is to identify the cause(s) of autism to understand the complex interplay between environment and gene regulation. There is optimism that specific causes and risk factors will be identified. The results of future investigations will facilitate enhanced screening, prevention, and therapy for “at risk” and autistic patients.     

Sex Differences in How Social Networks and Relationship Quality Influence Experimental Pain Sensitivity

This is the first study to examine how both structural and functional components of individuals’ social networks may moderate the association between biological sex and experimental pain sensitivity. One hundred and fifty-two healthy adults (mean age = 22yrs., 53% males) were measured for cold pressor task (CPT) pain sensitivity (i.e., intensity ratings) and core aspects of social networks (e.g., proportion of friends vs. family, affection, affirmation, and aid). Results showed consistent sex differences in how social network structures and intimate relationship functioning modulated pain sensitivity. Females showed higher pain sensitivity when their social networks consisted of a higher proportion of intimate types of relationship partners (e.g., kin vs. non kin), when they had known their network partners for a longer period of time, and when they reported higher levels of logistical support from their significant other (e.g., romantic partner). Conversely, males showed distinct patterns in the opposite direction, including an association between higher levels of logistical support from one’s significant other and lower CPT pain intensity. These findings show for the first time that the direction of sex differences in exogenous pain sensitivity is likely dependent on fundamental components of the individual’s social environment. The utility of a social-signaling perspective of pain behaviors for examining, comparing, and interpreting individual and group differences in experimental and clinical pain reports is discussed.     

Sex Differences in Exploration Behavior and the Relationship to Harm Avoidance

Venturing into novel terrain poses physical risks to a female and her offspring. Females have a greater tendency to avoid physical harm, while males tend to have larger range sizes and often outperform females in navigation-related tasks. Given this backdrop, we expected that females would explore a novel environment with more caution than males, and that more-cautious exploration would negatively affect navigation performance. Participants explored a novel, large-scale, virtual environment in search of five objects, pointed in the direction of each object from the origin, and then navigated back to the objects. We found that females demonstrated more caution while exploring as reflected in the increased amounts of pausing and revisiting of previously traversed locations. In addition, more pausing and revisiting behaviors led to degradation in navigation performance. Finally, individual levels of trait harm avoidance were positively associated with the amount of revisiting behavior during exploration. These findings support the idea that the fitness costs associated with long-distance travel may encourage females to take a more cautious approach to spatial exploration, and that this caution may partially explain the sex differences in navigation performance.     

Aging Affects the Mental Rotation of Left and Right Hands

Background

Normal aging significantly influences motor and cognitive performance. Little is known about age-related changes in action simulation. Here, we investigated the influence of aging on implicit motor imagery.

Methodology/Principal Findings

Twenty young (mean age: 23.9±2.8 years) and nineteen elderly (mean age: 78.3±4.5 years) subjects, all right-handed, were required to determine the laterality of hands presented in various positions. To do so, they mentally rotated their hands to match them with the hand-stimuli. We showed that: (1) elderly subjects were affected in their ability to implicitly simulate movements of the upper limbs, especially those requiring the largest amplitude of displacement and/or with strong biomechanical constraints; (2) this decline was greater for movements of the non-dominant arm than of the dominant arm.

Conclusions/Significance

These results extend recent findings showing age-related alterations of the explicit side of motor imagery. They suggest that a general decline in action simulation occurs with normal aging, in particular for the non-dominant side of the body.     

Mental Rotation of Faces in Healthy Aging and Alzheimer's Disease

Background

Previous research has shown that individuals with Alzheimer''s disease (AD) develop visuospatial difficulties that affect their ability to mentally rotate objects. Surprisingly, the existing literature has generally ignored the impact of this mental rotation deficit on the ability of AD patients to recognize faces from different angles. Instead, the devastating loss of the ability to recognize friends and family members in AD has primarily been attributed to memory loss and agnosia in later stages of the disorder. The impact of AD on areas of the brain important for mental rotation should not be overlooked by face processing investigations – even in early stages of the disorder.

Methodology/Principal Findings

This study investigated the sensitivity of face processing in AD, young controls and older non-neurological controls to two changes of the stimuli – a rotation in depth and an inversion. The control groups showed a systematic effect of depth rotation, with errors increasing with the angle of rotation, and with inversion. The majority of the AD group was not impaired when faces were presented upright and no transformation in depth was required, and were most accurate when all faces were presented in frontal views, but accuracy was severely impaired with any rotation or inversion.

Conclusions/Significance

These results suggest that with the onset of AD, mental rotation difficulties arise that affect the ability to recognize faces presented at different angles. The finding that a frontal view is “preferred” by these patients provides a valuable communication strategy for health care workers.     

Sex Differences in Mobility and Spatial Cognition

The fertility and parental care hypothesis interprets sex differences in some spatial-cognitive tasks as an adaptive mechanism to suppress women’s travel. In particular, the hypothesis argues that estrogens constrain travel during key reproductive periods by depressing women’s spatial-cognitive ability. Limiting travel reduces exposure to the dangers and caloric costs of navigating long distances into unfamiliar environments. Our study evaluates a collection of predictions drawn from the fertility and parental care hypothesis among the Twe and Himba people living in a remote region of Namibia. We find that nursing mothers travel more than women at any other stage of their reproductive career. This challenges the assumption that women limit travel during vulnerable and energetically demanding reproductive periods. In addition, we join previous studies in identifying a relationship between spatial ability and traveling among men, but not women. If spatial ability does not influence travel, hormonally induced changes in spatial ability cannot be used as a mechanism to reduce travel. Instead, it appears the fitness consequences of men’s travel is a more likely target for adaptive explanations of the sex differences in spatial ability, navigation, and range size.     

Individual and Developmental Differences in Interpersonal Understanding

In the study of personality as a subject reflecting knowledge, work, and interaction, the totality of internal conditions through which all external influences on the personality are refracted is a prime consideration. An individual, who for others is an object of cognition and activity, is reflected in their consciousness and determines their behavior only as "refracted" through their internal world, i.e., their set of ideas and attitudes. The same person is seen differently by people having different experiences in work, knowledge, and social interactions. In addition to our ideas concerning perception and conception of a personality, which has been formed, for example, in a young schoolchild, and in addition to the ideas of similarity between the perception and concepts of children and adults, we must always consider special features connected with the development of the youngest child as a personality, as a subject reflecting knowledge.     

Searching for Sex Differences in the Vomeronasal Pathway

The sexual differentiation of brain and behavior is reviewed from the findings of sex differences in the vomeronasal pathway. A motivational approach to sex differences in reproductive behavior is stressed by taking into account that sex differences are present in neural networks: from the receptor organ (the vomeronasal organ) to effector nuclei. Sex differences in the brain appear in two morphological patterns. In one, the male presents greater morphological measurements than the female; in the other, the opposite occurs. These two morphological patterns are actively differentiated by gonadal steroids. The functional significance of these two morphological patterns is addressed. Moreover, since the GABA_Areceptor is involved in the organization of sex differences in vomeronasal structures such as the accessory olfactory bulb and in maternal behavior, the role of membrane mechanisms, 5α reduced hormones, and neurosteroids in the sexual differentiation process is discussed.     

Morbid Jealousy and Sex Differences in Partner-Directed Violence

Previous research suggests that individuals diagnosed with morbid jealousy have jealousy mechanisms that are activated at lower thresholds than individuals with normal jealousy, but that these mechanisms produce behavior that is similar to individuals with normal jealousy. We extended previous research documenting these similarities by investigating sex differences in partner-directed violence committed by individuals diagnosed with morbid jealousy. The results support some of our predictions. For example, a greater percentage of men than women diagnosed with morbid jealousy used physical violence, attempted to kill, and actually killed their partners, and used their hands rather than an object to kill their partners. These results replicate results generated for individuals with normal jealousy. Discussion addresses implications of the current research and highlights directions for future research on the psychology of morbid jealousy.

Cognition in Males and Females with Autism: Similarities and Differences

The male bias in autism spectrum conditions (ASC) has led to females with ASC being under-researched. This lack of attention to females could hide variability due to sex that may explain some of the heterogeneity within ASC. In this study we investigate four key cognitive domains (mentalizing and emotion perception, executive function, perceptual attention to detail, and motor function) in ASC, to test for similarities and differences between males and females with and without ASC (n = 128 adults; n = 32 per group). In the mentalizing and facial emotion perception domain, males and females with ASC showed similar deficits compared to neurotypical controls. However, in attention to detail and dexterity involving executive function, although males with ASC showed poorer performance relative to neurotypical males, females with ASC performed comparably to neurotypical females. We conclude that performance in the social-cognitive domain is equally impaired in male and female adults with ASC. However, in specific non-social cognitive domains, performance within ASC depends on sex. This suggests that in specific domains, cognitive profiles in ASC are modulated by sex.     

Sex Differences in the Rapid Detection of Emotional Facial Expressions

Background

Previous studies have shown that females and males differ in the processing of emotional facial expressions including the recognition of emotion, and that emotional facial expressions are detected more rapidly than are neutral expressions. However, whether the sexes differ in the rapid detection of emotional facial expressions remains unclear.

Methodology/Principal Findings

We measured reaction times (RTs) during a visual search task in which 44 females and 46 males detected normal facial expressions of anger and happiness or their anti-expressions within crowds of neutral expressions. Anti-expressions expressed neutral emotions with visual changes quantitatively comparable to normal expressions. We also obtained subjective emotional ratings in response to the facial expression stimuli. RT results showed that both females and males detected normal expressions more rapidly than anti-expressions and normal-angry expressions more rapidly than normal-happy expressions. However, females and males showed different patterns in their subjective ratings in response to the facial expressions. Furthermore, sex differences were found in the relationships between subjective ratings and RTs. High arousal was more strongly associated with rapid detection of facial expressions in females, whereas negatively valenced feelings were more clearly associated with the rapid detection of facial expressions in males.

Conclusion

Our data suggest that females and males differ in their subjective emotional reactions to facial expressions and in the emotional processes that modulate the detection of facial expressions.     

Gonadal Steroid Hormone Receptors and Sex Differences in the Hypothalamo-Pituitary-Adrenal Axis

The rapid activation of stress-responsive neuroendocrine systems is a basic reaction of animals to perturbations in their environment. One well-established response is that of the hypothalamo-pituitary-adrenal (HPA) axis. In rats, corticosterone is the major adrenal steroid secreted and is released in direct response to adrenocorticotropin (ACTH) secreted from the anterior pituitary gland. ACTH in turn is regulated by the hypothalamic factor, corticotropin-releasing hormone. A sex difference exists in the response of the HPA axis to stress, with females reacting more robustly than males. It has been demonstrated that in both sexes, products of the HPA axis inhibit reproductive function. Conversely, the sex differences in HPA function are in part due to differences in the circulating gonadal steroid hormone milieu. It appears that testosterone can act to inhibit HPA function, whereas estrogen can enhance HPA function. One mechanism by which androgens and estrogens modulate stress responses is through the binding to their cognate receptors in the central nervous system. The distribution and regulation of androgen and estrogen receptors within the CNS suggest possible sites and mechanisms by which gonadal steroid hormones can influence stress responses. In the case of androgens, data suggest that the control of the hypothalamic paraventricular nucleus is mediated trans-synaptically. For estrogen, modulation of the HPA axis may be due to changes in glucocorticoid receptor-mediated negative feedback mechanisms. The results of a variety of studies suggest that gonadal steroid hormones, particularly testosterone, modulate HPA activity in an attempt to prevent the deleterious effects of HPA activation on reproductive function.