Influence of X Chromosome and Hormones on Human Brain Development: A Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy Study of Turner Syndrome

Cutter, William; Daly, Eileen; Robertson, Dene; Chitnis, Xavier; Amelsvoort, Thérèse van; Simmons, Andrew; Ng, Virginia; Williams, Benjamin; Shaw, Philip; Conway, Gerard S.; Skuse, David; Collier, David; Craig, Michael C.; Murphy, Declan

doi:10.1016/j.biopsych.2005.06.026

Cited by 102 publications

(117 citation statements)

References 57 publications

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“…The increase in amygdala size is even greater than the relative difference normally found between males and females (58) implying that haploinsufficiency for one or more dosage sensitive genes might contribute to sexual dimorphism in this structure. Replication, of the volumetric differences in the amygdala of Turner subjects, has been found by some investigators (59) but not by all (60). Other structural brain changes in X monosomy include the parieto-occipital region (possibly related to the visuospatial and arithmetic difficulties), the cerebellum and the basal ganglia and the superior temporal gyrus (60).…”

Section: Human X Monosomymentioning

confidence: 99%

“…Replication, of the volumetric differences in the amygdala of Turner subjects, has been found by some investigators (59) but not by all (60). Other structural brain changes in X monosomy include the parieto-occipital region (possibly related to the visuospatial and arithmetic difficulties), the cerebellum and the basal ganglia and the superior temporal gyrus (60). The superior temporal gyrus has efferent connections with the parietal lobes and the prefrontal cortex, both of which are structurally anomalous in XO females; so sexual dimorphism in the cortical thickness of certain regions could reflect the actions of X-linked genes (61).…”

Section: Human X Monosomymentioning

confidence: 99%

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Sexual dimorphism in cognition and behaviour: the role of X-linked genes

Skuse¹

2006

eur j endocrinol

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Chimpanzees and humans last shared a common ancestor between 5 and 7 million years ago; 99% of the two species' DNA is identical. Yet, since the paths of primate evolution diverged, there have been remarkable developments in the behavioural and cognitive attainments of our species, which ultimately reflect subtle differences in gene structure and function. These modifications have occurred despite evolutionary constraints upon the diversity of genetic influences, on the development and function of neural tissue. Significant species differences can be observed both at the levels of function (gene expression) and structure (amino acid sequence). Protein evolution is driving an accelerating increase in brain complexity and size. Playing centre stage, in terms of the proportion of genes involved in brain development and cognitive function, is the X chromosome. Recently, it has become clear that a long-standing theory, implicating X-linked genes in a sexually antagonistic evolutionary role, is probably correct. Genes on the sex chromosomes can directly influence sexual dimorphism in cognition and behaviour, independent of the action of sex steroids. Mechanisms by which sexchromosomal effects, due to X-linked genes, influence neural development or function are reviewed. These include the biased expression of genes subject to X-inactivation, haploinsufficiency (in males) for non-inactivated genes with no Y homology, sex-specific brain functions and genomic imprinting of Xlinked loci. Evidence supporting each of these mechanisms is available from both human and animal models. Recently, the first candidate genes have been discovered.European Journal of Endocrinology 155 S99-S106

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Section: Human X Monosomymentioning

confidence: 99%

Section: Human X Monosomymentioning

confidence: 99%

Sexual dimorphism in cognition and behaviour: the role of X-linked genes

Skuse¹

2006

eur j endocrinol

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“…Many parameters of brain function and structure vary between men and women (eg Gur et al, 1995;Murphy et al, 1996;De Courten-Myers, 1999;De Bellis et al, 2001;Goldstein et al, 2001;Preece and Cairns, 2003;De Vries, 2004), and most psychiatric disorders show sex differences in one or more variables including incidence, age at onset, clinical features, and outcome (eg Lensi et al, 1996;Tamminga, 1997;Piccinelli and Wilkinson, 2000;Aleman et al, 2003;Baron-Cohen et al, 2005). These dimorphisms are usually ascribed primarily to the influence of sex hormones (Collaer and Hines, 1995;Rubinow and Schmidt, 1996;Seeman, 1997;Kelly et al, 1999), as well as to the actions of sex chromosome genes (Vawter et al, 2004;Cutter et al, 2006;Davies and Wilkinson, 2006). Sex differences in epigenetic mechanisms, such as DNA methylation and chromatin modifications, predisposing to these phenotypes may also play a major role (Kaminsky et al, 2006).…”

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confidence: 99%

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

Harrison

Tunbridge

2007

Neuropsychopharmacol

278

217

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Sex differences in the genetic epidemiology and clinical features of psychiatric disorders are well recognized, but the individual genes contributing to these effects have rarely been identified. Catechol-O-methyltransferase (COMT), which metabolizes catechol compounds, notably dopamine, is a leading candidate. COMT enzyme activity, and the neurochemistry and behavior of COMT null mice, are both markedly sexually dimorphic. Genetic associations between COMT and various psychiatric phenotypes frequently show differences between men and women. Many of these differences are unconfirmed or minor, but some appear to be of reasonable robustness and magnitude; eg the functional Val 158 Met polymorphism in COMT is associated with obsessive-compulsive disorder in men, with anxiety phenotypes in women, and has a greater impact on cognitive function in boys than girls. Sex-specific effects of COMT are usually attributed to transcriptional regulation by estrogens; however, additional mechanisms are likely to be at least as important. Here we review the evidence for a sexually dimorphic influence of COMT upon psychiatric phenotypes, and discuss its potential basis. We conclude that despite the evidence being incomplete, and lacking a unifying explanation, there are accumulating and in places compelling data showing that COMT differentially impacts on brain function and dysfunction in men and women. Since sex differences in the genetic architecture of quantitative traits are the rule not the exception, we anticipate that additional evidence will emerge for sexual dimorphisms, not only in COMT but also in many other autosomal genes.

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“…Additional research will shed light on the many factors not reviewed in this article, including the biological mechanisms potentially leading to mathematics difficulties in Turner syndrome. These include direct and indirect effects linked to karyotype [Ross et al, 2000], hormone deficiency and treatment [Ross et al, 2006], and imprinting [e.g., Cutter et al, 2005].…”

Section: Do Girls With Turner Syndrome Have Mld?mentioning

confidence: 99%

Mathematical learning disability in girls with Turner syndrome: A challenge to defining MLD and its subtypes

Mazzocco

2009

Dev Disabil Res Revs

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Turner syndrome is a common disorder with a prevalence of 1:2,500 live female births. Although not associated with mental retardation, there is an increased risk of learning difficulties in this population. In particular, mathematical learning difficulties among girls with Turner syndrome are prevalent, significant, and persistent. As such, the study of mathematical performance in girls with Turner syndrome presents opportunities to advance our knowledge of mathematics ability, disability, and disability subtypes. Moreover, the Turner syndrome phenotype illustrates the challenges faced when defining mathematical learning disability (MLD) and characterizing MLD subtypes because the cognitive phenotype is aligned with several proposed MLD subtypes. There is some evidence linking MLD in Turner syndrome with spatial deficits, with executive dysfunction, and with deficient numerosity skills. Yet there is also conflicting evidence as to whether any of these explanations underlies MLD in Turner syndrome. Most mathematical difficulties in girls with Turner syndrome, as a group, occur on timed tests or on complex problems. On untimed tests, achievement test scores may be age appropriate. Therefore, the inclusion of MLD in the Turner syndrome cognitive phenotype reminds us that we cannot rule out MLD solely on the basis of performance on an untimed calculations subtest, and it poses a challenge to the widespread practice in which many researchers engage, that is, defining MLD on the basis of broad mathematics achievement test outcomes.

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Influence of X Chromosome and Hormones on Human Brain Development: A Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy Study of Turner Syndrome

Cited by 102 publications

References 57 publications

Sexual dimorphism in cognition and behaviour: the role of X-linked genes

Sexual dimorphism in cognition and behaviour: the role of X-linked genes

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

Mathematical learning disability in girls with Turner syndrome: A challenge to defining MLD and its subtypes

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