Effects of growth hormone on cognitive function

Whether growth hormone deficiency (GHD) and/or treatment in childhood and adolescence influences cognitive outcome in children with GHD or girls with Turner syndrome (TS) is controversial. Previous studies also suggest that quality of life (QoL) is reduced in adults with GHD, particularly in the areas of social isolation and fatigue. Baseline QoL scores were significantly lower in patients with GHD than in the general population of the same age, gender, and nationality. Unfortunately, few data are available describing QoL in children with GHD. TS is a genetic disorder characterized by short stature, gonadal dysgenesis, and a particular neurocognitive profile of normally developed language abilities (particularly verbal intelligence quotients) and impaired visual-spatial and/or visual-perceptual abilities. This study evaluated the effects of GH treatment on neurocognitive function in girls with TS who were enrolled in a long-term, double-blind, placebo-controlled trial of the effects of GH treatment on final adult height. Treatment duration ranged from 1 to 7 years. The major result of this study was the absence of GH treatment effects on cognitive function in girls with TS. GHD and/or treatment in childhood and adulthood influences cognitive and/or QoL outcomes in some but not all studies. This study did not support a role for GH in influencing the characteristic nonverbal neurocognitive deficits associated with TS. However, evaluation of QoL should be a part of the routine clinical management of patients with GHD or TS.     

Associations between Skeletal Growth in Childhood and Cognitive Function in Mid-Life in a 53-Year Prospective Birth Cohort Study

Background

Several studies have found that shorter stature (height and limb length) in late life is associated with dementia and cognitive impairment. The extent to which childhood environment and early life cognitive function accounts for these associations is not clear.

Methods

We investigated associations of adult trunk height and leg length with cognitive function in middle age, analysing data from the MRC National Survey of Health and Development: a cohort followed from birth to age 53, 1677 of whom had data on all covariates. The four cognitive tests measured verbal ability, word list memory, verbal fluency and speed/concentration. Early life environmental measures included parental education, poverty, parental divorce, physical health, cognitive ability at age 15, own education and own adult social class.

Results

After adjusting for gender, shorter trunk length was associated with lower cognitive function on all four tests and shorter leg length with lower verbal intelligence and word list memory. These associations were only partially attenuated following adjustment for childhood adversity/health but were substantially accounted for by cognitive ability at age 15.

Conclusions

Shorter stature was associated with lower cognitive function at age 53, the majority of this association being accounted for by cognitive function at age 15. Reduced cognitive reserve may well account for later associations between anthropometric measures and dementia.     

Human behavioural genetics of cognitive abilities and disabilities

Although neither the genome nor the environment can be manipulated in research on human behaviour, some of the new tools of molecular genetics can be brought to bear on human behavioural disorders (e.g. cognitive disabilities) and quantitative traits (e.g. cognitive abilities). The inability to manipulate the human genome experimentally has had the positive effect of focusing attention on naturally occuring genetic variation responsible for behavioural differences among individuals in all their complex multifactorial splendour. Genes in such complex multiple-gene systems are called quantitative trait loci (QTLs), which merge the two worlds of genetic research, quantitative genetics and molecular genetics. Although most genetic research on complex human behaviour has focused on severe mental disorders, cognitive abilities and disabilities may be even more immediately relevant to neuroscience. For example, verbal ability and spatial ability are two of the most heritable cognitive abilities, and reading disability is the first behavioural disability for which replicated QTL linkage has been found. The purpose of this essay is to provide an overview of the genetics of cognitive abilities and disabilities as an example of the impending merger of quantitative genetics and molecular genetics in QTL analysis of complex traits.     

Sexual Differentiation of Cognitive Abilities in Women Exposed to Diethylstilbestrol (DES) Prenatally

In nonhuman animals, prenatal exposure to androgens or estrogens enhances development of male-typical characteristics (masculinizes) and impairs development of female-typical characteristics (defeminizes). We investigated the hypothesis that prenatal exposure to the synthetic estrogen, diethylstilbestrol (DES), similarly masculinizes or defeminizes cognitive development in women. Forty-two DES-exposed women and 26 of their unexposed sisters were studied. No group differences were seen for abilities at which females excel on average (verbal fluency, perceptual speed and accuracy, and associative memory), for abilities at which males excel on average (visuospatial abilities), or for abilities that do not show sex differences (vocabulary, nonverbal intelligence). The time of prenatal exposure to DES correlated with visuospatial performance with later exposure associated with better performance. However, the subgroup of women exposed to DES late in gestation did not differ from unexposed women on these measures. Results support the conclusion that prenatal exposure to DES has little or no influence on cognitive development in women. However, they do not preclude other types of early hormonal influences on human cognition, such as prenatal influences of androgen or influences of androgens or estrogens during the early postnatal period.     

Genotype differences in cognitive functioning in Noonan syndrome

Noonan syndrome (NS) is an autosomal-dominant genetic disorder associated with highly variable features, including heart disease, short stature, minor facial anomalies and learning disabilities. Recent gene discoveries have laid the groundwork for exploring whether variability in the NS phenotype is related to differences at the genetic level. In this study, we examine the influence of both genotype and nongenotypic factors on cognitive functioning. Data are presented from 65 individuals with NS (ages 4–18) who were evaluated using standardized measures of intellectual functioning. The cohort included 33 individuals with PTPN11 mutations, 6 individuals with SOS1 mutations, 1 individual with a BRAF mutation and 25 participants with negative, incomplete or no genetic testing. Results indicate that genotype differences may account for some of the variation in cognitive ability in NS. Whereas cognitive impairments were common among individuals with PTPN11 mutations and those with unknown mutations, all of the individuals with SOS1 mutations exhibited verbal and nonverbal cognitive skills in the average range or higher. Participants with N308D and N308S mutations in PTPN11 also showed no (or mild) cognitive delays. Additional influences such as hearing loss, motor dexterity and parental education levels accounted for significant variability in cognitive outcomes. Severity of cardiac disease was not related to cognitive functioning. Our results suggest that some NS-causing mutations have a more marked impact on cognitive skills than others.     

Seoul Twin Family Study: design, sampling, assessments, and future directions.

The Seoul Twin Family Study seeks to investigate genetic and environmental influences on the development of cognitive abilities and other psychological traits among children and adolescents in Seoul, South Korea. In November, 2001 with the assistance of the Seoul Metropolitan Office of Education, we began to solicit all private and public schools in Seoul to obtain names, addresses, and telephone numbers of the twins enrolled in schools in Seoul. The vast majority of the recruited twins were between 6 and 18 years old. The recruited twins and their non-twin siblings and parents will undergo comprehensive assessment of cognitive abilities, interests, daily activities, personality, and familial and non-familial environments. We plan to reassess the twins and their families every two years as the twins progress through major changes that characterize childhood, adolescence, and adulthood. In addition, medical records of the twins during the prenatal period will be examined to determine the effects of intrauterine environment on individual differences in cognitive abilities and other psychological traits. We also plan to undertake molecular genetic studies to identify genes involved in specific cognitive abilities.     

Practicing a musical instrument in childhood is associated with enhanced verbal ability and nonverbal reasoning

Background

In this study we investigated the association between instrumental music training in childhood and outcomes closely related to music training as well as those more distantly related.

Methodology/Principal Findings

Children who received at least three years (M = 4.6 years) of instrumental music training outperformed their control counterparts on two outcomes closely related to music (auditory discrimination abilities and fine motor skills) and on two outcomes distantly related to music (vocabulary and nonverbal reasoning skills). Duration of training also predicted these outcomes. Contrary to previous research, instrumental music training was not associated with heightened spatial skills, phonemic awareness, or mathematical abilities.

Conclusions/Significance

While these results are correlational only, the strong predictive effect of training duration suggests that instrumental music training may enhance auditory discrimination, fine motor skills, vocabulary, and nonverbal reasoning. Alternative explanations for these results are discussed.     

Shared Cognitive Impairments and Aetiology in ADHD Symptoms and Reading Difficulties

BackgroundTwin studies indicate that the frequent co-occurrence of attention deficit hyperactivity disorder (ADHD) symptoms and reading difficulties (RD) is largely due to shared genetic influences. Both disorders are associated with multiple cognitive impairments, but it remains unclear which cognitive impairments share the aetiological pathway, underlying the co-occurrence of the symptoms. We address this question using a sample of twins aged 7–10 and a range of cognitive measures previously associated with ADHD symptoms or RD.MethodsWe performed multivariate structural equation modelling analyses on parent and teacher ratings on the ADHD symptom domains of inattention and hyperactivity, parent ratings on RD, and cognitive data on response inhibition (commission errors, CE), reaction time variability (RTV), verbal short-term memory (STM), working memory (WM) and choice impulsivity, from a population sample of 1312 twins aged 7–10 years.ResultsThree cognitive processes showed significant phenotypic and genetic associations with both inattention symptoms and RD: RTV, verbal WM and STM. While STM captured only 11% of the shared genetic risk between inattention and RD, the estimates increased somewhat for WM (21%) and RTV (28%); yet most of the genetic sharing between inattention and RD remained unaccounted for in each case.ConclusionWhile response inhibition and choice impulsivity did not emerge as important cognitive processes underlying the co-occurrence between ADHD symptoms and RD, RTV and verbal memory processes separately showed significant phenotypic and genetic associations with both inattention symptoms and RD. Future studies employing longitudinal designs will be required to investigate the developmental pathways and direction of causality further.     

Twins early development study (TEDS): a multivariate, longitudinal genetic investigation of language, cognition and behavior problems in childhood.

The Twins Early Development Study (TEDS) focuses on the early development of the three most common psychological problems in childhood: communication disorders, mild mental impairment and behavior problems. The TEDS twins were assessed longitudinally at 2, 3, 4 and 7 years of age in order to investigate genetic and environmental contributions to change and continuity in language and cognitive development; it is multivariate in order to examine the origins of comorbidity; and it uses a large sample in order to study abnormal development in the context of normal development. The twins were identified from birth records of twins born in the UK in 1994-96. More than 15,000 pairs of twins have been enrolled in TEDS and the participating families are representative of the UK. The measures at 2, 3 and 4 years are administered by parents. At 7 years, children are assessed for language and cognitive development using telephone testing, parents and children are interviewed about behavior problems, and teachers also assess behavior problems as well as academic achievement. One set of findings is that the same genes largely contribute to both language and cognitive problems and the same genes affect normal and abnormal development, a result that suggests that general impairment may be a better target for genetic research than specific language impairment independent of nonverbal cognitive problems. DNA has been obtained so far for more than 4000 pairs and is being used initially in molecular genetic studies of language problems and hyperactivity.     

Cognitive Functions in Middle Aged Individuals Are Related to Metabolic Disturbances and Aerobic Capacity: A Cross-Sectional Study

Aims

Metabolic disturbances may contribute to cognitive dysfunction in patients with type 2 diabetes. We investigated the relation between cognitive impairment and metabolic deteriorations, low physical fitness, low-grade inflammation and abdominal obesity in middle aged individuals.

Methods

We conducted a cross-sectional study including 40 to 65 year-old patients with type 2 diabetes and limited co morbidity (N = 56), age-matched individuals with impaired glucose tolerance (N = 56) as well as age-matched controls with normal glucose tolerance (N = 72). Specific cognitive functions were assessed with focus on verbal memory, processing speed, executive functions, and a composite overall mean score. Oral glucose tolerance test, VO₂max test, systemic inflammation, DXA scanning and abdominal MRI were measured.

Results

Multiple linear regression analyses adjusting for age, gender and verbal intelligence demonstrated that a low score in processing speed, executive functions and overall cognitive function were related to high fasting C-peptide, as well as low insulin sensitivity, beta-cell function and VO₂max. Measurements of blood glucose, obesity and inflammation were not associated with cognitive function.

Conclusion

Low cognitive scores are seen in middle aged individuals with hyperinsulinemia, low insulin sensitivity, beta-cell function and low aerobic capacity. These findings emphasize the importance of appropriate lifestyle and not only blood glucose control in prevention of cognitive disability.     

A perspective on Darwinian psychology: The importance of domain-general mechanisms,plasticity, and individual differences

In this paper a theory of Darwinian psychological adaptations as motive dispositions with an affective core is developed, and it is argued that 1) there is significant plasticity in these mechanisms; 2) in addition to domain-specific evolved motive dispositions, there are a variety of domain-general cognitive and emotional mechanisms; 3) humans are capable of developing motive dispositions which are not adaptations; 4) the relationship between evolved motive dispositions and behavior is very tenuous so that the explanatory power of Darwinian psychology is very weak; 5) individual differences in human psychological characteristics are evolutionarily meaningful and are linked to mechanisms which assess the resource value of intraspecific genetic and phenotypic diversity.     

Examining the relationships between early childhood experiences and adolescent and young adult health status in a resource-limited population: A cohort study

BackgroundAdolescence is a critical point in the realization of human capital, as health and educational decisions with long-term impacts are made. We examined the role of early childhood experiences on health, cognitive abilities, and educational outcomes of adolescents followed up from a longitudinal cohort study in Pakistan, hypothesizing that early childhood experiences reflecting poverty would manifest in reduced health and development in adolescence.Methods and findingsAdolescents/young adults previously followed as children aged under 5 years were interviewed. Childhood data were available on diarrhea, pneumonia, and parental/household characteristics. New data were collected on health, anthropometry, education, employment, and languages spoken; nonverbal reasoning was assessed. A multivariable Bayesian network was constructed to explore structural relationships between variables. Of 1,868 children originally enrolled, 1,463 (78.3%) were interviewed as adolescents (range 16.0–29.3 years, mean age 22.6 years); 945 (65%) lived in Oshikhandass. While 1,031 (70.5%) of their mothers and 440 (30.1%) of their fathers had received no formal education, adolescents reported a mean of 11.1 years of education. Childhood diarrhea (calculated as episodes/child-year) had no association with nonverbal reasoning score (an arc was supported in just 4.6% of bootstrap samples), health measures (with BMI, 1% of bootstrap samples; systolic and diastolic blood pressure, 0.1% and 1.6% of bootstrap samples, respectively), education (0.7% of bootstrap samples), or employment (0% of bootstrap samples). Relationships were found between nonverbal reasoning and adolescent height (arc supported in 63% of bootstrap samples), age (84%), educational attainment (100%), and speaking English (100%); speaking English was linked to the childhood home environment, mediated through maternal education and primary language. Speaking English (n = 390, 26.7% of adolescents) was associated with education (100% of bootstrap samples), self-reported child health (82%), current location (85%) and variables describing childhood socioeconomic status. The main limitations of this study were the lack of parental data to characterize the home setting (including parental mental and physical health, and female empowerment) and reliance on self-reporting of health status.ConclusionsIn this population, investments in education, especially for females, are associated with an increase in human capital. Against the backdrop of substantial societal change, with the exception of a small and indirect association between childhood malnutrition and cognitive scores, educational opportunities and cultural language groups have stronger associations with aspects of human capital than childhood morbidity.

In a cohort study, Zeba A Rasmussen and colleagues examine the relationship between early childhood experiences on health, cognitive abilities and education, and health outcomes in adolescents and young adults in Pakistan.     

A Genetic Deconstruction of Neurocognitive Traits in Schizophrenia and Bipolar Disorder

Background

Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function in healthy individuals and in the dysfunction observed in psychiatric disorders.

Methods

Sets of genes associated with a range of cognitive functions often impaired in schizophrenia and bipolar disorder were generated from a genome-wide association study (GWAS) on a sample comprising 670 healthy Norwegian adults who were phenotyped for a broad battery of cognitive tests. These gene sets were then tested for enrichment of association in GWASs of schizophrenia and bipolar disorder. The GWAS data was derived from three independent single-centre schizophrenia samples, three independent single-centre bipolar disorder samples, and the multi-centre schizophrenia and bipolar disorder samples from the Psychiatric Genomics Consortium.

Results

The strongest enrichments were observed for visuospatial attention and verbal abilities sets in bipolar disorder. Delayed verbal memory was also enriched in one sample of bipolar disorder. For schizophrenia, the strongest evidence of enrichment was observed for the sets of genes associated with performance in a colour-word interference test and for sets associated with memory learning slope.

Conclusions

Our results are consistent with the increasing evidence that cognitive functions share genetic factors with schizophrenia and bipolar disorder. Our data provides evidence that genetic studies using polygenic and pleiotropic models can be used to link specific cognitive functions with psychiatric disorders.     

Genetic foundations of human intelligence

Individual differences in intelligence (cognitive abilities) are a prominent aspect of human psychology, and play a substantial role in influencing important life outcomes. Their phenotypic structure—as described by the science of psychometrics—is well understood and well replicated. Approximately half of the variance in a broad range of cognitive abilities is accounted by a general cognitive factor (g), small proportions of cognitive variance are caused by separable broad domains of mental function, and the substantial remainder is caused by variance that is unique to highly specific cognitive skills. The heritability of g is substantial. It increases from a low value in early childhood of about 30%, to well over 50% in adulthood, which continues into old age. Despite this, there is still almost no replicated evidence concerning the individual genes, which have variants that contribute to intelligence differences. Here, we describe the human intelligence phenotype, summarise the evidence for its heritability, provide an overview of and comment on molecular genetic studies, and comment on future progress in the field.     

眼睛注视线索对物体认知加工的影响及其机制

眼睛注视作为一种重要的非语言社会线索,不仅可以传达他人丰富的注意方向信息,并且能够诱发独特的社会性注意行为.近年来,研究者利用改编的社会性注意任务发现,眼睛注视线索还可以进一步影响我们对各种不同种类物体(用具、符号、面孔等)的感知觉加工,以及主观评价、记忆等其他高级认知加工过程.眼睛注视线索对物体加工的这种影响受到诸多因素的调节,如面孔属性、数量以及注视模式等.特别地,眼睛注视线索对物体加工的这一调制作用能够在无意识水平发生,具有一定的特异性.此外,针对这一调制作用背后机制的研究暗示心理理论和观点采择可能参与其中,但仍有待进一步探究.眼睛注视对物体加工影响的研究有助于我们深入理解社会互动的方式以及人类与环境的交互过程,因此具有重要的理论意义和社会应用价值.     

First Genome-Wide Association Study on Anxiety-Related Behaviours in Childhood

Background

Twin studies have shown that anxiety in a general population sample of children involves both domain-general and trait-specific genetic effects. For this reason, in an attempt to identify genes responsible for these effects, we investigated domain-general and trait-specific genetic associations in the first genome-wide association (GWA) study on anxiety-related behaviours (ARBs) in childhood.

Methods

The sample included 2810 7-year-olds drawn from the Twins Early Development Study (TEDS) with data available for parent-rated anxiety and genome-wide DNA markers. The measure was the Anxiety-Related Behaviours Questionnaire (ARBQ), which assesses four anxiety traits and also yields a general anxiety composite. Affymetrix GeneChip 6.0 DNA arrays were used to genotype nearly 700,000 single-nucleotide polymorphisms (SNPs), and IMPUTE v2 was used to impute more than 1 million SNPs. Several GWA associations from this discovery sample were followed up in another TEDS sample of 4804 children. In addition, Genome-wide Complex Trait Analysis (GCTA) was used on the discovery sample, to estimate the total amount of variance in ARBs that can be accounted for by SNPs on the array.

Results

No SNP associations met the demanding criterion of genome-wide significance that corrects for multiple testing across the genome (p<5×10⁻⁸). Attempts to replicate the top associations did not yield significant results. In contrast to the substantial twin study estimates of heritability which ranged from 0.50 (0.03) to 0.61 (0.01), the GCTA estimates of phenotypic variance accounted for by the SNPs were much lower 0.01 (0.11) to 0.19 (0.12).

Conclusions

Taken together, these GWAS and GCTA results suggest that anxiety – similar to height, weight and intelligence − is affected by many genetic variants of small effect, but unlike these other prototypical polygenic traits, genetic influence on anxiety is not well tagged by common SNPs.     

Relation of visual evoked potentials to the integral characteristics of cognitive activity in 8- to 9-year-old children

Amplitude and temporal parameters of evoked potentials (EPs) in response to a checkerboard pattern, picture of a house, the Russian word "dom", meaning house, combination of letters "DMO" and a number of other stimuli, correlated with indices of the verbal, nonverbal, and general intelligence as well as with those of the cognitive style "field dependence-independence". Maximum number of statistically significant correlations was found in the course of comparison of integrative cognitive characteristics and parameters of EPs to stimuli with increased semantic complexity. No interhemispheric differences were found in the character of interrelations between cognitive characteristics and parameters of EPs to verbal and spatially structured stimuli.     

Genome-wide quantitative trait locus association scan of general cognitive ability using pooled DNA and 500K single nucleotide polymorphism microarrays

General cognitive ability ( g ), which refers to what cognitive abilities have in common, is an important target for molecular genetic research because multivariate quantitative genetic analyses have shown that the same set of genes affects diverse cognitive abilities as well as learning disabilities. In this first autosomal genome-wide association scan of g , we used a two-stage quantitative trait locus (QTL) design with pooled DNA to screen more than 500 000 single nucleotide polymorphisms (SNPs) on microarrays, selecting from a sample of 7000 7-year-old children. In stage 1, we screened for allele frequency differences between groups pooled for low and high g . In stage 2, 47 SNPs nominated in stage 1 were tested by individually genotyping an independent sample of 3195 individuals, representative of the entire distribution of g scores in the full 7000 7-year-old children. Six SNPs yielded significant associations across the normal distribution of g , although only one SNP remained significant after a false discovery rate of 0.05 was imposed. However, none of these SNPs accounted for more than 0.4% of the variance of g , despite 95% power to detect associations of that size. It is likely that QTL effect sizes, even for highly heritable traits such as cognitive abilities and disabilities, are much smaller than previously assumed. Nonetheless, an aggregated 'SNP set' of the six SNPs correlated 0.11 ( P  < 0.00000003) with g . This shows that future SNP sets that will incorporate many more SNPs could be useful for predicting genetic risk and for investigating functional systems of effects from genes to brain to behavior.     

Magnitude Representations in Williams Syndrome: Differential Acuity in Time,Space and Number Processing

For some authors, the human sensitivity to numerosities would be grounded in our ability to process non-numerical magnitudes. In the present study, the developmental relationships between non numerical and numerical magnitude processing are examined in people with Williams syndrome (WS), a genetic disorder known to associate visuo-spatial and math learning disabilities. Twenty patients with WS and 40 typically developing children matched on verbal or non-verbal abilities were administered three comparison tasks in which they had to compare numerosities, lengths or durations. Participants with WS showed lower acuity (manifested by a higher Weber fraction) than their verbal matched peers when processing numerical and spatial but not temporal magnitudes, indicating that they do not present a domain-general dysfunction of all magnitude processing. Conversely, they do not differ from non-verbal matched participants in any of the three tasks. Finally, correlational analyses revealed that non-numerical and numerical acuity indexes were both related to the first mathematical acquisitions but not with later arithmetical skills.     

THE EVOLUTION OF ENDOTHERMY: TESTING THE AEROBIC CAPACITY MODEL

One of the most important events in vertebrate evolution was the acquisition of endothermy, the ability to use metabolic heat production to elevate body temperature above environmental temperature. Several verbal models have been proposed to explain the selective factors leading to the evolution of endothermy. Of these, the aerobic capacity model has received the most attention in recent years. The aerobic capacity model postulates that selection acted mainly to increase maximal aerobic capacity (or associated behavioral abilities) and that elevated resting metabolic rate evolved as a correlated response. Here we evaluate the implicit evolutionary and genetic assumptions of the aerobic capacity model. In light of this evaluation, we assess the utility of phenotypic and genetic correlations for testing the aerobic capacity model. Collectively, the available intraspecific data for terrestrial vertebrates support the notion of a positive phenotypic correlation between resting and maximal rates of oxygen consumption within species. Interspecific analyses provide mixed support for this phenotypic correlation. We argue, however, that assessments of phenotypic or genetic correlations within species and evolutionary correlations among species (from comparative data) are of limited utility, because they may not be able to distinguish between the aerobic capacity model and plausible alternatives, such as selection acting directly on aspects of thermoregulatory abilities. We suggest six sources of information that may help shed light on the selective factors important during the evolution of high aerobic metabolic rates and, ultimately, the attainment of endothermy. Of particular interest will be attempts to determine, using a combination of mechanistic physiological and quantitative-genetic approaches, whether a positive genetic correlation between resting and maximal rates of oxygen consumption is an ineluctable feature of vertebrate physiology.