Sex differences in the brain: implications for explaining autism

‘Empathizing’ is the capacity to predict and to respond to the behavior of agents (usually people) by inferring their mental states and responding to these with an appropriate emotion. ‘Systemizing’ is the capacity to predict and to respond to the behavior of non-agentive, deterministic systems, by analyzing input-operation-output relations and inferring the rules that govern such systems. At a population level, females are stronger empathizers and males stronger systemizers. The ‘extreme male brain’ theory posits that autism represents an extreme of the male pattern (impaired empathizing and enhanced systemizing). Here we suggest that specific aspects of autistic neuropathology may also be extremes of typical male neuroanatomy

Why Are Autism Spectrum Conditions More Prevalent in Males?

Autism Spectrum Conditions (ASC) are much more common in males, a bias that may offer clues to the etiology of this condition. Although the cause of this bias remains a mystery, we argue that it occurs because ASC is an extreme manifestation of the male brain. The extreme male brain (EMB) theory, first proposed in 1997, is an extension of the Empathizing-Systemizing (E-S) theory of typical sex differences that proposes that females on average have a stronger drive to empathize while males on average have a stronger drive to systemize. In this first major update since 2005, we describe some of the evidence relating to the EMB theory of ASC and consider how typical sex differences in brain structure may be relevant to ASC. One possible biological mechanism to account for the male bias is the effect of fetal testosterone (fT). We also consider alternative biological theories, the X and Y chromosome theories, and the reduced autosomal penetrance theory. None of these theories has yet been fully confirmed or refuted, though the weight of evidence in favor of the fT theory is growing from converging sources (longitudinal amniocentesis studies from pregnancy to age 10 years old, current hormone studies, and genetic association studies of SNPs in the sex steroid pathways). Ultimately, as these theories are not mutually exclusive and ASC is multi-factorial, they may help explain the male prevalence of ASC.</p

Fetal testosterone and autistic traits

Studies of amniotic testosterone in humans suggest that fetal testosterone (fT) is related to specific (but not all) sexually dimorphic aspects of cognition and behaviour. It has also been suggested that autism may be an extreme manifestation of some male-typical traits, both in terms of cognition and neuroanatomy. In this paper, we examine the possibility of a link between autistic traits and fT levels measured in amniotic fluid during routine amniocentesis. Two instruments measuring number of autistic traits (the Childhood Autism Spectrum Test (CAST) and the Child Autism Spectrum Quotient (AQ-Child)) were completed by these women about their children (N = 235), ages 6-10 years. Intelligence Quotient (IQ) was measured in a subset of these children (N = 74). fT levels were positively associated with higher scores on the CAST and AQ-Child. This relationship was seen within sex as well as when the sexes were combined, suggesting this is an effect of fT rather than of sex per se. No relationships were found between overall IQ and the predictor variables, or between IQ and CAST or AQ-Child. These findings are consistent with the hypothesis that prenatal androgen exposure is related to children exhibiting more autistic traits. These results need to be followed up in a much larger sample to test if clinical cases of ASC have elevated fT.</p

TGFb-facilitated optic fissure fusion and the role of bone morphogenetic protein antagonism

The optic fissure is a transient gap in the developing vertebrate eye, which must be closed as development proceeds. A persisting optic fissure, coloboma, is a major cause for blindness in children. Although many genes have been linked to coloboma, the process of optic fissure fusion is still little appreciated, especially on a molecular level. We identified a coloboma in mice with a targeted inactivation of transforming growth factor β2 (TGFβ2). Notably, here the optic fissure margins must have touched, however failed to fuse. Transcriptomic analyses indicated an effect on remodelling of the extracellular matrix (ECM) as an underlying mechanism. TGFβ signalling is well known for its effect on ECM remodelling, but it is at the same time often inhibited by bone morphogenetic protein (BMP) signalling. Notably, we also identified two BMP antagonists among the downregulated genes. For further functional analyses we made use of zebrafish, in which we found TGFβ ligands expressed in the developing eye, and the ligand binding receptor in the optic fissure margins where we also found active TGFβ signalling and, notably, also gremlin 2b ( grem2b ) and follistatin a ( fsta ), homologues of the regulated BMP antagonists. We hypothesized that TGFβ is locally inducing expression of BMP antagonists within the margins to relieve the inhibition from its regulatory capacity regarding ECM remodelling. We tested our hypothesis and found that induced BMP expression is sufficient to inhibit optic fissure fusion, resulting in coloboma. Our findings can likely be applied also to other fusion processes, especially when TGFβ signalling or BMP antagonism is involved, as in fusion processes during orofacial development. </jats:p

Anionic polymerization of a series of cyclocarbosiloxanes

A study has been made on the anionic polymerization of a series of cyclocarbosiloxanes of the type: [IMAGE] where n was varied from 2 to 8. The polymerization reaction in benzene, was initiated using cesium trihexyl silanolate, a unique organic soluble liquid catalysts. Benzene served as both a solvent and to shift the position of the NMR SiCH3 polymer peak away from the monomer peak making it feasible to follow the kinetics on a Varian EM-360 Nuclear Magnetic Resonance Spectrometer. Hexamethylphosphoramide (HMPA) was used as a promoter to solvate the initiator ions and thus increasing the polymerization rate. It was found that water present in the system decreased the polymerization rate and brought about a decrease in the molecular weight of the polymer. The polymerization rate was found to vary with the one-half power of initiator concentration, while molecular weight dropped with increasing initiator concentration. The effect of temperature was to increase the rate of polymerization. The activation energies were found to be approximately 10 kcal/mole for all of the systems studied --Abstract, pages ii-iii

Liver Transplantation Prevents Progressive Neurological Impairment in Argininemia

Argininemia is a rare hereditary disease due to a deficiency of hepatic arginase, which is the last enzyme of the urea cycle and hydrolyzes arginine to ornithine and urea. The onset of the disease is usually in childhood, and clinical manifestations include progressive spastic paraparesis and mental retardation. Liver involvement is less frequent and usually not as severe as observed in other UCDs. For this reason, and because usually there is a major neurological disease at diagnosis, patients with argininemia are rarely considered as candidates for OLT despite its capacity to replace the deficient enzyme by an active one. We report on long-term follow-up of two patients with argininemia. Patient 1 was diagnosed by the age of 20 months and despite appropriate conventional treatment progressed to spastic paraparesis with marked limp. OLT was performed at 10 years of age with normalization of plasmatic arginine levels and guanidino compounds. Ten years post-OLT, under free diet, there is no progression of neurological lesions. The second patient (previously reported by our group) was diagnosed at 2 months of age, during a neonatal cholestasis workup study. OLT was performed at the age of 7 years, due to liver cirrhosis with portal hypertension, in the absence of neurological lesions and an almost-normal brain MRI. After OLT, under free diet, there was normalization of plasmatic arginine levels and guanidino compounds. Twelve years post-OLT, she presents a normal neurological examination. We conclude that OLT prevents progressive neurological impairment in argininemia and should be considered when appropriate conventional treatment fails

The Rank and File Movement: The Relevance of Radical Social Work Traditions to Modern Social Work Practice

Social work, like many fields, has sometimes suffered from an inadequate and distorted understanding of its own history. A profession\u27s inattention to its past is an unfortunate thing. As Clark Chambers has noted, the study of social work history provides models for social work practice and yields insights into social processes (31 11-22). Works like Cloward and Piven\u27s Regulating the Poor have demonstrated the rich potential of the social welfare case study for social analyses (4). In addition, examination of goals and motivations of specific social workers in the past have served to further our understanding of professional issues and problems of the present (see for example, 16, 21)

A structural MRI study of human brain development from birth to two years

pre-printBrain development in the first 2 years after birth is extremely dynamic and likely plays an important role in neurodevelopmental disorders, including autism and schizophrenia. Knowledge regarding this period is currently quite limited. We studied structural brain development in healthy subjects from birth to 2. Ninety-eight children received structural MRI scans on a Siemens head-only 3T scanner with magnetization prepared rapid gradient echo T1-weighted, and turbo spin echo, dual-echo (proton density and T2 weighted) sequences: 84 children at 2- 4 weeks, 35 at 1 year and 26 at 2 years of age. Tissue segmentation was accomplished using a novel automated approach. Lateral ventricle, caudate, and hippocampal volumes were also determined. Total brain volume increased 101% in the first year, with a 15% increase in the second. The majority of hemispheric growth was accounted for by gray matter, which increased 149% in the first year; hemispheric white matter volume increased by only 11%. Cerebellum volume increased 240% in the first year. Lateral ventricle volume increased 280% in the first year, with a small decrease in the second. The caudate increased 19% and the hippocampus 13% from age 1 to age 2. There was robust growth of the human brain in the first two years of life, driven mainly by gray matter growth. In contrast, white matter growth was much slower. Cerebellum volume also increased substantially in the first year of life. These results suggest the structural underpinnings of cognitive and motor development in early childhood, as well as the potential pathogenesis of neurodevelopmental disorders

Evaluating progestin-based protocols to control estrous cycles of beef heifers prior to timed artificial insemination

The recent development of split-time artificial insemination as a breeding strategy improved reproductive outcomes following treatment with the 14d CIDR[copyright]-PG protocol; however, STAI has not been evaluated with other protocols designed to synchronize estrus in beef heifers. Two experiments (Chapter 2) were designed to evaluate estrous response and pregnancy rates resulting from fixed-time (FTAI) or split-time (STAI) artificial insemination among beef heifers. Experiment 1 (Chapter 2) evaluated FTAI and STAI following administration of the melengestrol acetate (MGA[copyright]) prostaglandin F[super script 2a] protocol. Experiment 2 (Chapter 2) evaluated FTAI and STAI following administration of the 7d CO-Synch + controlled internal drug release (CIDR[copyright]) estrus synchronization protocol. Heifers (n = 524) in Experiment 1 (Chapter 2) were managed in 10 pens and assigned within pen to balanced treatments based on weight and reproductive tract score (RTS; Scale 1-5). Heifers were fed MGA[copyright] (0.5 mg x animal[superscript -1]d[superscript -1]) in a 1.8 kg grain carrier for 14 d. Prostaglandin F[subscript 2a] (PG; 250 [mu]g im cloprostenol sodium) was administered 19 d after MGA[copyright] withdrawal. Estrus detection aids (Estrotect[copyright]) were applied at PG. Estrous status was recorded at 72 h after PG for heifers assigned to FTAI, and 72 and 96 h after PG for heifers assigned to STAI. Estrus was defined as removal of [greater than or equal to] 50% of the coating from the Estrotect[copyright] patch. Heifers assigned to FTAI were inseminated 72 h after PG and gonadotropin-releasing hormone (GnRH; 100 [mu]g im gonadorelin acetate) was administered at AI. Heifers in the STAI treatment that exhibited estrus by 72 h after PG were inseminated at 72 h; however, AI was postponed until 96 h for heifers that were non-estrous at 72 h. Only heifers that failed to exhibit estrus by 96 h received GnRH at AI. Estrous response 72 h after PG did not differ between treatments; however, total estrous response was increased (P < 0.001) among heifers assigned to STAI (88%, STAI; 72%, FTAI). Pregnancy rates resulting from AI were greater (P < 0.04) for heifers assigned to STAI compared to FTAI (55% vs 46%, respectively), and were enhanced (P < 0.05) among heifers that exhibited estrus. Heifers (n=456) in Experiment 2 (Chapter 2) were managed at one location in three pens and assigned within pen to one of two balanced treatments based on weight and reproductive tract score (RTS; Scale 1-5). All heifers were subject to the 7d CO-Synch + controlled internal drug release (CIDR[copyright]) estrus synchronization protocol and managed in two synchronization groups. Gonadotropin-releasing hormone (100 [mu]g im gonadorelin acetate) was administered and an EAZI-Breed CIDR[copyright] [1.38g progesterone (P[subscript 4]); Zoetis, Madison, NJ] inserted in heifers at the start of the protocol. The CIDR[copyright] inserts were removed after 7 d. Prostaglandin F[subscript 2a] (PG; 250 [mu]g im cloprostenol sodium) was administered and estrus detection aids (Estrotect[copyright]) were applied concurrent with CIDR[copyright] removal. Estrous status was recorded at 54 h after PG for heifers assigned to FTAI, and 54 and 78 h after PG for heifers assigned to STAI. Estrous was defined as removal of [greater than or equal to]50% of the grey coating from the Estrotect[copyright] patch. Heifers assigned to FTAI were inseminated 54 h after PG and GnRH (100 [mu]g im gonadorelin acetate) was administered at AI. Heifers in the STAI treatment were inseminated when considered estrous by 54 h after PG; however, AI was postponed until 78 h for heifers that were non-estrous at 54 h. Only heifers that failed to exhibit estrus by 78 h received GnRH at AI. Estrous response 54 h after PG did not differ between treatments; however, total estrous response was increased (P < 0.001) among heifers assigned to STAI (74%, STAI; 47%, FTAI). Pregnancy rates resulting from AI were not different for heifers assigned to STAI compared to FTAI (48% and 46%, respectively; P=0.6), and were enhanced (P < 0.05) among heifers in the STAI treatment that exhibited estrus. In summary of Experiment 1 (Chapter 2), STAI has potential to improve estrous response and pregnancy rate to AI following the MGA [copyright]PG protocol. When compared to FTAI in Experiment 2 (Chapter 2), STAI enhanced estrous response following the 7d CO-Synch + CIDR[copyright],however, this did not result in an increase in pregnancy rate to AI.Includes bibliographical reference