Social Cognition,the Male Brain and the Autism Spectrum

Behavioral studies have shown that, at a population level, women perform better on tests of social cognition and empathy than men. Furthermore Autism Spectrum Disorders (ASDs), which are characterized by impairments in social functioning and empathy, occur more commonly in males than females. These findings have led to the hypothesis that differences in the functioning of the social brain between males and females contribute to the greater vulnerability of males to ASD and the suggestion that ASD may represent an extreme form of the male brain. Here we sought to investigate this hypothesis by determining: (i) whether males and females differ in social brain function, and (ii) whether any sex differences in social brain function are exaggerated in individuals with ASD. Using fMRI we show that males and females differ markedly in social brain function when making social decisions from faces (compared to simple sex judgements) especially when making decisions of an affective nature, with the greatest sex differences in social brain activation being in the inferior frontal cortex (IFC). We also demonstrate that this difference is exaggerated in individuals with ASD, who show an extreme male pattern of IFC function. These results show that males and females differ significantly in social brain function and support the view that sex differences in the social brain contribute to the greater vulnerability of males to ASDs.     

Practice Variation in the Management of Girls and Boys with Delayed Puberty

Objective: Delayed puberty is a common condition, and typical management includes “watchful waiting” and/or sex-steroid therapy. We sought to characterize treatment practices and to assess provider comfort with the management of delayed puberty in girls and boys.Methods: A national survey of pediatric endocrine providers assessed definitions of delayed puberty, practices around sex-steroid therapy, reasons for treatment, and comfort in managing delayed puberty in girls and boys.Results: Of 184 respondents (12% participation rate), 64% and 71% used the traditional age cutoffs for defining delayed puberty of 13 years for girls and 14 years for boys, respectively. Nearly half (45%) of providers would treat boys relatively earlier than girls, compared to 18% who would treat girls relatively earlier (P<.0001). Providers were more likely to cite bone density as a reason to treat girls and alleviating patient and parental distress, accelerating growth, and “jump starting” puberty as reasons to treat boys. Greater experience in endocrine practice was associated with greater comfort managing delayed puberty in both boys and girls. Approximately 80% of providers agreed that clinical guidelines are needed for the management of delayed puberty.Conclusion: There is a high degree of variability in the clinical management of delayed puberty, and our results suggest that providers are more hesitant to treat girls compared to boys and have different reasons for treating each. It remains to be determined if these discrepancies in treatment are justified by biologic differences between girls and boys or represent nonevidence-based disparities in care.Abbreviation: U.S. = United States     

Brain Transcriptional and Epigenetic Associations with Autism

BackgroundAutism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic.Conclusions/SignificanceThis work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.     

Boys and Girls Come Out to Play: The Molecular Biology of Dioecious Plants

The majority of the world's flowering plants are hermaphroditebut many of them encourage cross pollination by means of spatialor temporal separation of eggs and pollen, or by genetically-controlledphysiological incompatibility. A minority of species has takenthe avoidance of self-pollination to its logical conclusionby evolving two distinct and sexually different forms (dioecy).In a very small number of plants, dioecy has been accompaniedby the development of sex chromosomes. From the study of thedevelopment of male and female flowers of different speciesit is clear that there is no common underlying mechanism andthat sex determination systems leading to dioecy have originatedindependently many times in evolution. This Botanical Briefinghighlights new information from recent molecular approachesin the study of dioecy.Copyright 2000 Annals of Botany Company Review, sex determination, dioecy, sex chromosome     

The Combined Effects of Pre- and Post-Insemination Sexual Selection on Extreme Variation in Male Body Size

Orb-weaving spiders of the genus Nephila are notable for their sexual size dimorphism, with dwarf males and giant females. However, less well known is the extreme size polymorphism of males that is characteristic of some species. For example, adult male body size in N. edulis varies by an order of magnitude. Previous experiments reveal that male mating behaviour covaries with body size, suggesting the size variation is maintained by opposing pre- and post-insemination sexual selection pressures. Here, we test this idea by allowing males of different sizes to compete directly and simultaneously for access to females. Using the sterile-male technique for paternity assessment, we show that two competing males drawn from the extremes of size variations, split paternity the same way as two males of the same size drawn from the intermediate sizes. The paternity of a large male dropped from 50% to 30% on average if he competed against two instead of one small male. The large male increased his mating frequency when there were more rivals but required a much lower total duration of copulation to achieve the same paternity share. These data are consistent with the idea that opposing pre- and post-insemination selection pressures at least partly explain the variation in male body size. Co-ordinating editor: L.D. Hurst     

Extreme Costs of Mating for Male Two-Spot Ladybird Beetles

Male costs of mating are now thought to be widespread. The two-spot ladybird beetle (Adalia bipunctata) has been the focus of many studies of mating and sexual selection, yet the costs of mating for males are unknown. The mating system of A. bipunctata involves a spermatophore nuptial gift ingested by females after copulation. In this study, we investigate the cost to males of mating and of transferring spermatophores in terms of lifespan, ejaculate production and depletion of nutritional reserves. We found that males faced a strong trade-off between mating and survival, with males that were randomly assigned to mate a single time experiencing a 53% reduction in post-mating lifespan compared to non-mating males. This is among the most severe survival costs of a single mating yet reported. However, spermatophore transfer did not impact male survival. Instead, the costs associated with spermatophores appeared as a reduced ability to transfer spermatophores in successive matings. Furthermore, males ingested more food following spermatophore transfer than after matings without spermatophores, suggesting that spermatophore transfer depletes male nutritional reserves. This is to our knowledge the first report of an effect of variation in copulatory behaviour on male foraging behaviour. Overall, our study highlights the advantages of assessing mating costs using multiple currencies, and suggests that male A. bipunctata should exhibit mate choice.     

Dose-Dependent Adverse Effects of Salinomycin on Male Reproductive Organs and Fertility in Mice

Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis. Spermatogenesis was however observed in testis 28 days after Salinomycin withdrawal. The results indicate reversible dose-dependent adverse effects of Salinomycin on male reproductive system of mice.     

The Home Dreams and Waking Fantasies of Boys and Girls Between Ages 9 and 15: A Longitudinal Study

In this longitudinal developmental study, 12 boys and 12 girls provided home dreams and waking fantasies at 3 age levels: 9–11, 11–13, and 13–15. A total of 299 dreams and 286 fantasies were coded by 2 independent raters using Hall and Van de Castle (1966) content categories. In addition, word counts and bizarreness ratings were completed. There were very few changes in the dreams or waking fantasies of either boys or girls, but dream reports were longer at ages 13–15, the aggression/friendliness percent increased over the course of the study, joint-sex peer groups became more frequent, and girls showed a decline in animal percent. The tendency in a wide range of societies for men to dream mostly about other men and for women to dream equally of women and men was found in both the dreams and waking fantasies. Dreams and fantasies differed markedly, with dreams containing more outdoor and unfamiliar settings, and more bizarreness. In dreams the children tended to portray themselves as victims of aggression and recipients of friendliness, but in fantasies they took a more active role as aggressors and befrienders. It is suggested that the children in this study portrayed themselves in their dreams as they conceived of themselves in everyday life, while in their waking fantasies they imagined themselves as they would have liked to be.     

自闭症个体道德推理的心理机制及其脑机制

社交障碍是自闭症个体主要的临床症状之一,对他们的道德推理状况进行研究有助于我们解释这一现象.研究表明,自闭症个体在进行道德推理时和常人之间有所不同,而道德推理任务中经常包含有心理理解和移情方面的信息,提示我们自闭症个体的心理推理和移情能力可能是影响他们道德推理的内在心理机制.自闭症个体能够区分道德违背和习俗违背,但是他们经常判断不是故意造成的伤害是有意的.他们对伤害者的情绪线索也不太敏感,不能理解他人的感受,这种移情能力和道德推理能力之间的表现是相关的.此外,自闭症个体对道德推理的解释和言语发展水平之间也存在关联,他们经常通过重复故事情节、引述具体后果来解释道德推理,而缺乏对抽象道德规则的描述.脑成像研究表明,自闭症个体进行道德推理时在眶额叶皮质、杏仁核、脑岛、额下回、前扣带回、内侧前额叶皮质、默认网络模式、右颞顶联合区等部位的激活程度与常人存在着显著差异,这些部位同时也是心理理论或移情能力的重要脑区.自闭症个体在句子加工任务中言语功能联合区的激活程度也与常人存在差异,这可能是他们在对道德推理进行解释时存在困难的内部原因.未来研究需要考察心理理论、移情和言语能力对自闭症道德推理的交互作用,并采取非言语的方式对自闭症个体的道德推理进行研究,同时可通过脑损伤技术和激素水平的分析对影响他们道德推理的生理机制进行更加全面的考察.     

Testosterone and Androgen Receptor Sensitivity in Relation to Hyperactivity Symptoms in Boys with Autism Spectrum Disorders

Introduction

Autism spectrum disorders (ASD) and hyperactivity symptoms exhibit an incidence that is male-biased. Thus androgen activity can be considered a plausible biological risk factor for these disorders. However, there is insufficient information about the association between increased androgen activity and hyperactivity symptoms in children with ASD.

Methods

In the present study, the relationship between parameters of androgenicity (plasmatic testosterone levels and androgen receptor sensitivity) and hyperactivity in 60 boys (age 3–15) with ASD is investigated. Given well documented differences in parent and trained examiners ratings of symptom severity, we employed a standardized parent`s questionnaire (Nisonger Child Behavior Rating Form) as well as a direct examiner`s rating (Autism diagnostic observation schedule) for assessment of hyperactivity symptoms.

Results

Although it was found there was no significant association between actual plasmatic testosterone levels and hyperactivity symptoms, the number of CAG triplets was significantly negatively correlated with hyperactivity symptoms (R² = 0.118, p = 0.007) in the sample, indicating increased androgen receptor sensitivity in association with hyperactivity symptoms. Direct trained examiner´s assessment appeared to be a relevant method for evaluating of behavioral problems in the investigation of biological underpinnings of these problems in our study.

Conclusions

A potential ASD subtype characterized by increased rates of hyperactivity symptoms might have distinct etiopathogenesis and require a specific behavioral and pharmacological approach. We propose an increase of androgen receptor sensitivity as a biomarker for a specific ASD subtype accompanied with hyperactivity symptoms. Findings are discussed in terms of their implications for practice and future research.     

Autism as the Low-Fitness Extreme of a Parentally Selected Fitness Indicator

Siblings compete for parental care and feeding, while parents must allocate scarce resources to those offspring most likely to survive and reproduce. This could cause offspring to evolve traits that advertise health, and thereby attract parental resources. For example, experimental evidence suggests that bright orange filaments covering the heads of North American coot chicks may have evolved for this fitness-advertising purpose. Could any human mental disorders be the equivalent of dull filaments in coot chicks—low-fitness extremes of mental abilities that evolved as fitness indicators? One possibility is autism. Suppose that the ability of very young children to charm their parents evolved as a parentally selected fitness indicator. Young children would vary greatly in their ability to charm parents, that variation would correlate with underlying fitness, and autism could be the low-fitness extreme of this variation. This view explains many seemingly disparate facts about autism and leads to some surprising and testable predictions.     

Co-expression Profiling of Autism Genes in the Mouse Brain

Autism spectrum disorder (ASD) is one of the most prevalent and highly heritable neurodevelopmental disorders in humans. There is significant evidence that the onset and severity of ASD is governed in part by complex genetic mechanisms affecting the normal development of the brain. To date, a number of genes have been associated with ASD. However, the temporal and spatial co-expression of these genes in the brain remain unclear. To address this issue, we examined the co-expression network of 26 autism genes from AutDB (http://mindspec.org/autdb.html), in the framework of 3,041 genes whose expression energies have the highest correlation between the coronal and sagittal images from the Allen Mouse Brain Atlas database (http://mouse.brain-map.org). These data were derived from in situ hybridization experiments conducted on male, 56-day old C57BL/6J mice co-registered to the Allen Reference Atlas, and were used to generate a normalized co-expression matrix indicating the cosine similarity between expression vectors of genes in this database. The network formed by the autism-associated genes showed a higher degree of co-expression connectivity than seen for the other genes in this dataset (Kolmogorov–Smirnov P = 5×10⁻²⁸). Using Monte Carlo simulations, we identified two cliques of co-expressed genes that were significantly enriched with autism genes (A Bonferroni corrected P<0.05). Genes in both these cliques were significantly over-expressed in the cerebellar cortex (P = 1×10⁻⁵) suggesting possible implication of this brain region in autism. In conclusion, our study provides a detailed profiling of co-expression patterns of autism genes in the mouse brain, and suggests specific brain regions and new candidate genes that could be involved in autism etiology.     

Evaluation of Metabolic Risk in Prepubertal Girls Versus Boys in Relation to Fitness and Physical Activity

BackgroundLow levels of cardiorespiratory fitness (CRF) and physical activity (PA) are associated with a risk of the development of metabolic syndrome. Contradictory findings are reported in the literature regarding the influence of sex and CRF and PA on metabolic changes.ObjectiveThe aim of this study was to analyze the effects of CRF and PA on lipid and carbohydrate metabolism biomarkers in boys and girls.MethodsA total of 82 prepubertal boys and 55 girls (7–12 years of age) were classified according to sex, low or high CRF, and performance or nonperformance of PA. Anthropometric and blood pressure (BP) measurements, plasma lipid profile values, glucose and insulin levels, and homeostasis model assessment for insulin resistance were analyzed.ResultsThe percentage of boys with high CRF and performance of PA was higher than that of girls (P < 0.05). When children of the same sex were compared, higher values for body mass index and waist circumference z-scores were found for boys with low CRF compared with boys with high CRF (P < 0.001) without differences between girls, and in all groups classified by PA. Systolic and diastolic BPs were higher in boys than in girls, in both CRF and PA groups (P < 0.05). In the low CRF and no PA groups, girls had higher plasma glucose, total cholesterol, and low-density lipoprotein cholesterol levels than boys, with higher high-density lipoprotein cholesterol and apolipoprotein A levels (P < 0.05).ConclusionsSex in relation to CRF and PA could affect the plasma lipid profile. These changes in girls are associated with low CRF and low levels of PA. Considering these results, we suggest the need to improve CRF and promote PA, especially in girls, to reduce metabolic risk.     

The Earliest Case of Extreme Sexual Display with Exaggerated Male Organs by Two Middle Jurassic Mecopterans

Background

Many extant male animals exhibit exaggerated body parts for display, defense or offence in sexual selection, such as male birds of paradise showing off colorful and elegant feathers and male moose and reindeers bearing large structured antlers. For insects, male rhinoceros and stag beetles have huge horn-like structure for fighting and competition and some male Leptopanorpa scorpionflies have very long abdominal terminal segments for sexual display and competition. Fossil records of insects having exaggerated body parts for sexual display are fairly rare. One example is two male holcorpids with elongate abdominal segments from sixth (A6) to eighth (A8) and enlarged male genitalia from Eocene, suggesting evolution of these characters occurred fairly late.

Principal Findings

We document two mecopterans with exaggerated male body parts from the late Middle Jurassic Jiulongshan Formation in northeastern China. Both have extremely extended abdominal segments from A6 to A8 and enlarged genitalia, which might have been used for sexual display and, to less extent, for fighting with other males in the competition for mates. Although Fortiholcorpa paradoxa gen. et sp. nov. and Miriholcorpa forcipata gen. et sp. nov. seem to have affinities with Holcorpidae, we deem both as Family Incertae sedis mainly due to significant differences in branching pattern of Media (M) veins and relative length of A8 for F. paradoxa, and indiscernible preservation of 5-branched M veins in hind wing for M. forcipata.

Conclusions/Significance

These two new taxa have extended the records of exaggerated male body parts of mecopterans for sexual display and/or selection from the Early Eocene to the late Middle Jurassic. The similar character present in some Leptopanorpa of Panorpidae suggests that the sexual display and/or sexual selection due to extremely elongated male abdominal and sexual organs outweigh the negative impact of bulky body and poor mobility in the evolutionary process.     

1例雄性朱鹮脑内脑啡肽的免疫组织化学分布

用免疫组织化学方法研究脑啡肽(ENK)在极危物种朱(Nipponia nippon)脑内的分布,结合计算机图像分析仪检测免疫阳性细胞和末梢的灰度值。ENK阳性细胞、纤维和终末分布如下:发声核团有原纹状体中间区腹部、丘脑背内侧核外侧部、中脑丘间核、中脑背内侧核、延髓舌下神经核。听觉中枢有丘脑卵圆核壳区、中脑背外侧核壳区、脑桥外侧丘系腹核、上橄榄核、耳蜗核等。内分泌核团有视前区前核、旧纹状体增加部、下丘脑外侧核、下丘脑腹内侧核等。结果表明,朱脑内ENK可能对发声、听觉和下丘脑内分泌的生理活动有一定的调制作用。