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Background: Catechol-O-methyltransferase (COMT) metabolizes catecholamines in the prefrontal cortex (PFC). A common polymorphism in the COMT gene (COMT val158met) has pleiotropic effects on cognitive and emotional processing. The met allele has been associated with enhanced cognitive processing but impaired emotional processing relative to the val allele. Methods: We genotyped healthy, white men in relation to the COMT val158met polymorphism. They were given a single 4 mg dose of the selective noradrenaline reuptake inhibitor (NRI) reboxetine or placebo in a randomized, double-blind between-subjects model and then completed an emotional memory task 2 hours later. Results: We included 75 men in the study; 41 received reboxetine and 34 received placebo. In the placebo group, met/met carriers did not demonstrate the usual memory advantage for emotional stimuli that was observed in val carriers. Reboxetine restored this emotional enhancement of memory in met/met carriers, but had no significant effect in val carriers. Limitations: We studied only men, thus limiting the generalizability of our findings. We also relied on self-reported responses to screening questions to establish healthy volunteer status, and in spite of the double- blind design, participants were significantly better than chance at identifying their intervention allocation. Conclusion: Emotional memory is impaired in healthy met homozygotes and selectively improved in this group by reboxetine. This has potential translational implications for the use of reboxetine, which is currently licensed as an antidepressant in several countries, and edivoxetine, a new selective NRI currently in development., Introduction The catechol-O-methyltransferase (COMT) enzyme is responsible for degradation of catecholamines, such as dopamine (DA) and noradrenaline. The substitution of methionine (met) for valine (val) at codon 158 in the [...]

In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNVonly confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in apattern consistent with both that observed during first- episode psychosis in schizophrenia and that of structural correlates in dyslexia., Little information is available on whether or how rare CNVs conferring high risk of schizophrenia and/or autism affect physiologic function of otherwise normal brains. As none of these CNVs hitherto [...]

Although iron homeostasis is essential for brain functioning, the effects of iron levels on cognitive performance in older individuals have scarcely been investigated. In the present study, serum iron parameters and hemochromatosis (HFE) C282Y genotype were determined in 818 older individuals who participated in a 3-year randomized, placebo-controlled double-blind trial examining the effects of folic acid on carotid intima-media thickness. All participants had slightly elevated homocysteine levels and were vitamin BI2 replete. Cognitive functioning was assessed at baseline and after 3 years by means of a neuropsychological test battery. At baseline, increased serum ferritin was associated with decreased sensorimotor speed, complex speed, and information-processing speed and increased serum iron was associated with decreased sensorimotor speed. Cognitive performance over 3 years was not associated with HFE C282Y genotype or iron parameters. In conclusion, serum iron parameters do not show a straightforward relationship with cognitive functioning, although elevated iron levels may decrease cognitive speed in older individuals susceptible to cognitive impairment. Key Words: Cognitive performance--Iron parameters--HFE--Longitudinal study--Older adults. doi: 10.1093/gerona/glq149

Findings from quantitative genetic research are examined in the context of molecular genetic research. Quantitative genetic research can be used to study genetic factors for the study of learning and cognitive abilities and disabilities.

Compared with notable successes in the genetics of basic sensory transduction, progress on the genetics of higher level perception and cognition has been limited. We propose that investigating specific cognitive abilities with well-defined neural substrates, such as face recognition, may yield additional insights. In a twin study of face recognition, we found that the correlation of scores between monozygotic twins (0.70) was more than double the dizygotic twin correlation (0.29), evidence for a high genetic contribution to face recognition ability. Low correlations between face recognition scores and visual and verbal recognition scores indicate that both face recognition ability itself and its genetic basis are largely attributable to face-specific mechanisms. The present results therefore identify an unusual phenomenon: a highly specific cognitive ability that is highly heritable. Our results establish a clear genetic basis for face recognition, opening this intensively studied and socially advantageous cognitive trait to genetic investigation. behavioral genetic | face recognition | individual differences | specialist gene | generalist gene doi: 10.1073/pnas.0913053107

The goal of this first major report from the Western Reserve Reading Project Math component is to explore the etiology of the relationship among tester-administered measures of mathematics ability, reading ability, and general cognitive ability. Data are available on 314 pairs of monozygotic and same-sex dizygotic twins analyzed across 5 waves of assessment. Univariate analyses provide a range of estimates of genetic ([h.sup.2] = .00-.63) and shared ([c.sup.2] = .15-.52) environmental influences across math calculation, fluency, and problem solving measures. Multivariate analyses indicate genetic overlap between math problem solving with general cognitive ability and reading decoding, whereas math fluency shares significant genetic overlap with reading fluency and general cognitive ability. Further, math fluency has unique genetic influences. In general, math ability has shared environmental overlap with general cognitive ability and decoding. These results indicate that aspects of math that include problem solving have different genetic and environmental influences than math calculation. Moreover, math fluency, a timed measure of calculation, is the only measured math ability with unique genetic influences. Keywords: mathematics, reading, twins, genetics, environment

Little is known about the genetic contribution to individual differences in neural networks subserving cognition function. In this functional magnetic resonance imaging (fMRI) twin study, we found a significant genetic influence on brain activation in neural networks supporting digit working memory tasks. Participants activating frontal-parietal networks responded faster than individuals relying more on language-related brain networks. There were genetic influences on brain activation in language-relevant brain circuits that were atypical for numerical working memory tasks as such. This suggests that differences in cognition might be related to brain activation patterns that differ qualitatively among individuals.

RNA editing appears to be the major mechanism by which environmental signals overwrite encoded genetic information to modify gene function and regulation, particularly in the brain. We suggest that the predominance of Alu elements in the human genome is the result of their evolutionary co-adaptation as a modular substrate for RNA editing, driven by selection for higher-order cognitive function. We show that RNA editing alters transcripts from loci encoding proteins involved in neural cell identity, maturation and function, as well as in DNA repair, implying a role for RNA editing not only in neural transmission and network plasticity but also in brain development, and suggesting that communication of productive changes back to the genome might constitute the molecular basis of long-term memory and higher-order cognition.

FOXP2, the transcriptional factor genes in human brain is identified using chromatin immunoprecipitation followed by microarray analysis (ChIP-chip). The FOXP2-target genes give insights on the vital functions and pathways to explore the genetic basis of human speech and language.

The mammalian nervous system expresses numerous noncoding RNAs (ncRNAs). We propose that ncRNAs are capable of coupling the digital information universe of nucleic acids with the analog universe of cellular protein interactions, ncRNAs could contribute to the success of the organism's information processing in several ways. First, ncRNAs would allow for efficient coupling of energy with information, wherein less energy is required to represent and process more information, condensed in analog and digital form, into smaller spatial and temporal domains, ideal for the environments found in neural tissues. Second, ncRNAs would permit the rapid acquisition of information from the environment, along with the rapid flexible processing and elimination of that information when it is no longer necessary. Third, ncRNAs would facilitate accelerated evolution of an organism's information content and functional computational systems. This emerging panorama might open new dimensions of information processing in the nervous system.

Little is known about genetic regulation of the development of white matter. This knowledge is critical in understanding the pathophysiology of neurodevelopmental syndromes associated with altered cognition as well as in elucidating the genetics of normal human cognition. The hemideletion of [approximately equal to] 25 genes on chromosome 7q11.23 that causes Williams syndrome (WS) includes genes that regulate cytoskeletal dynamics in neurons, especially LIMK1 and CYLN2, and therefore offers the opportunity to investigate the role of these genes in the formation of white matter tracts. We used diffusion tensor imaging to demonstrate alteration in white matter fiber directionality, deviation in posterior fiber tract course, and reduced lateralization of fiber coherence in WS. These abnormalities are consistent with an alteration of the late stages of neuronal migration, define alterations of white matter structures underlying dissociable behavioral phenotypes in WS, and provide human in vivo information about genetic control of white matter tract formation. development | LIMK1 | neuronal growth cone | neuronal migration | tractography

Background. A decline in cognitive test scores in elderly persons can signal the beginning of a descent into dementia or may indicate only a short-term cognitive disturbance. It would be clinically useful to distinguish between the two outcomes and to identify characteristics of each. Methods. Four hundred thirty-seven community-dwelling elderly persons were given the Mini-Mental State Examination (MMSE) annually for an average of 7 years. A low score between baseline and final MMSE was identified. A low score 3 or more points lower than baseline score indicated cognitive decline. This decline was called persistent if the final MMSE score was also at least 3 points lower than baseline MMSE score; otherwise, the decline was considered transient. Results. Twenty participants (4.6%) experienced a persistent cognitive decline, 67 participants (15.3%) experienced a transient cognitive decline. Presence of the apolipoprotein [epsilon]4 allele was significantly associated with persistent cognitive decline (age-adjusted odd ratio [OR] = 11.46, p < .0001) but not with transient cognitive decline (age-adjusted OR = 1.53, p = .219). Incorrect answers on the orientation part of the MMSE at the time of cognitive decline was associated with persistent decline compared to transient decline (age-adjusted OR = 3.58, p = .058). Conclusions. Persistent cognitive decline is an infrequent occurrence in community-dwelling elderly persons. Presence of the [epsilon]4 allele and errors made by the subject on questions of orientation may be useful in determining whether a cognitive decline is likely to be persistent.

Using the classical twin design, this study investigates the influence of genetic factors on the large phenotypic variance in inspection time (IT), and whether the well established IT--IQ association can be explained by a common genetic factor. Three hundred ninety pairs of twins (184 monozygotic, MZ; 206 dizygotic, DZ) with a mean age of 16 years participated, and 49 pairs returned approximately 3 months later for retesting. As in many IT studies, the pi figure stimulus was used and IT was estimated from the cumulative normal ogive. IT ranged from 39.4 to 774.1 ms (159 ± 110.1 ms) with faster ITs (by an average of 26.9 ms) found in the retest session from which a reliability of .69 was estimated. Full-scale IQ (FIQ) was assessed by the Multidimensional Aptitude Battery (MAB) and ranged from 79 to 145 (111 ± 13). The phenotypic association between IT and FIQ was confirmed (-.35) and bivariate results showed that a common genetic factor accounted for 36% of the variance in IT and 32% of the variance in FIQ. The maximum likelihood estimate of the genetic correlation was -.63. When performance and verbal IQ (PIQ & VIQ) were analysed with IT, a stronger phenotypic and genetic relationship was found between PIQ and IT than with VIQ. A large part of the IT variance (64%) was accounted for by a unique environmental factor. Further genetic factors were needed to explain the remaining variance in IQ with a small component of unique environmental variance present. The separability of a shared genetic factor influencing IT and IQ from the total genetic variance in IQ suggests that IT affects a specific subcomponent of intelligence rather than a generalised efficiency. Keywords: IT; IQ; Heritability; Twins; Quantitative genetics, 1. Introduction In an ongoing study of the genetics of cognition, in adolescent Australian twins, inspection time (IT) was collected as part of a psychometric battery to probe processing speed. [...]

Parents and brothers of boys who are normal, those who suffer from dyslexia and those who are autistic were tested for 'central coherence'. Fathers of the autistic boys showed they processed in a piecemeal way over the test.

Information was obtained from parents and children about activities and preferences. Some of those questioned had a son with autism, some had a dyslexic son and some had no history of developmental problems.

In Williams syndrome (WS) certain physical, behavioral and cognitive abnormalities are caused by an approximately 1.5-Mb deletion on one copy of chromosome 7. Psychometric and genetic testing has been done with patients with small deletions in the WS critical region. It seems neither LIMK1 nor STX1A hemizygosity likely contributes to any part of the WS phenotype. Such patients are important in looking at subtle and very penetrant phenotypes. Studying the molecular mechanism of the phenotype may help in identification of genes important for human behavior and cognition. ELN (ital) encodes elastin and is deleted in WS, and patients with only ELN (ital) mutations had hemizygosity for elastin responsible for the cardiology problems seen in WS. LIMK1, which (ital) encodes a protein tyrosine kinase expressed in the brain during development, is missing, as are some others.

Our goal in this article is to review a debate over the evolution of language and to suggest some keys to its resolution. We begin with a review of some of the theoretical and empirical evidence for the innateness of language that has caused renewed interest in the evolution of language. in a second section we review some prominent theories of the evolution of language, focusing on the controversy over whether language could have been adapted for some purpose. We argue that for evolutionary studies of language to advance, theorists must make more persuasive arguments for the purpose of language, and, furthermore, linguists must continue to develop a detailed theory of syntax. Finally, we suggest ways that behavioral and population genetics could help to inform studies of the evolution of language. KEY WORDS: INNATENESS OF LANGUAGE, EVOLUTION OF LANGUAGE, LANGUAGE ACQUISITION, CREOLIZATION, DEAF CHILDREN, Innateness of Language Language is frequently cited as the skill that sets humans apart from other primates. As such, it is not surprising that the origins of language have been [...]

The storage of long-term memory is associated with a cellular program of gene expression, altered protein synthesis, and the growth of new synaptic connections. Recent studies of a variety of memory processes, ranging in complexity from those produced by simple forms of implicit learning in invertebrates to those produced by more complex forms of explicit learning in mammals, suggest that part of the molecular switch required for consolidation of long-term memory is the activation of a cAMP-inducible cascade of genes and the recruitment of cAMP response element binding protein-related transcription factors. This conservation of steps in the mechanisms for learning-related synaptic plasticity suggests the possibility of a molecular biology of cognition.

Hierarchical analyses of specific cognitive abilities of 145 identical twins and 135 same-sex fraternal twins using Schmid-Leiman transformations reveal that genetic influences similar to genetic g and specific to group factors such as Verbal and Performance affect individual differences in cognitive abilities. Common environmental g is not as important as the common genetic g for special cognitive abilities, and genetic factors rather than shared environmental factors influence specific cognitive abilities in individuals.

Bone loss has been found to predict cognitive decline in older women. A prospective cohort study involving 4,462 women 70 and older was carried out to investigate whether the rate of bone loss predicts cognitive decline independently of baseline bone mass and whether (ApoE) genotype explains the association.

Lifelines supports the theme that behavioral development is a fluid, life-long phenomenon. In contrast, many emotional and cognitive traits are subject to strong genetic influence, and are highly stable over many years. The manner in which neuroplasticity and trait stability co-occur needs to be modeled. An outline of such a model is provided to promote discussion of this complex issue.

Andrews et al. argue for adaptationism in cognitive research. However, the problem of evolvability brings into question the number of genes required for the evolution of cognitive mechanisms. Are there enough? Also, greater consideration should be given to alternative vicarious selection processes, which may produce cognitive mechanisms. Finally, identifying constraints with optimality arguments is more difficult than the authors think.

Much has been learned about genetic influence on cognitive abilities that might be helpful in thinking about genetic influence on other abilities such as art and sports, which have not yet been investigated using genetic research strategies. Some new findings on cognitive abilities go beyond merely demonstrating genetic influence. Misinterpretations of the meaning of genetic influence are discussed.

Heritable factors play a role in exceptional longevity since long-lived individuals have relatives that are long-lived. It has previously been found that a common functional variant (I405V) of the cholesterol [...]