Cognitive development among children with early‐treated phenylketonuria

Previous research supports the notion that children with early‐treated classical phenylketonuria (PKU) have specific cognitive deficits in executive function skills. These deficits may relate to depressed levels of dopamine, due to defective tyrosine synthesis. We investigated whether deficits reported for preschoolers with early‐treated PKU are manifested also among school‐age children with PKU, and whether cognitive performance among the latter group is related to phenylalanine level at time of testing. Seventeen children with PKU and 17 age‐, sex‐, and IQ‐matched controls were tested individually on measures of executive functions. The results demonstrate that executive function deficits reported for preschoolers with PKU were not manifested in the school‐age PKU children included in this study. The authors discuss the implications of these findings for theories of the development of executive function skills.     

Speed of processing and individual differences in IQ in schizophrenia: General or specific cognitive deficits?

Introduction. The aim of this study was to re‐examine the role of cognitive processing speed in the vulnerability to schizophrenia, using an inspection time (IT) task that does not require a speeded manual response. Since IT consistently correlates with intelligence, the relationship between IT and general intelligence was also explored.

Methods. Patients with schizophrenia were compared with unaffected siblings of schizophrenia patients and healthy controls on a visual IT task. Both speed and variability of IT performance were examined. Current intellectual ability (IQ) was estimated with the Shipley Institute of Living Scale (SILS), which yields separate assessments of verbal and abstraction abilities.

Results. Schizophrenia patients produced ITs that were significantly slower and more variable than either unaffected siblings or healthy controls. These results are not related to demographic or clinical variables. A significant negative correlation was obtained between IT and IQ; specifically, longer IT values were associated with abstraction scores only.

Conclusions. These findings confirm that basic cognitive processing efficiency is impaired in patients with schizophrenia. In contrast, ITs in unaffected siblings did not differ from healthy controls, in line with their better IQ test scores. Implica tions for models of general and specific heritable dimensions in schizophrenia are discussed.     

Further antinociceptive effects of myricitrin in chemical models of overt nociception in mice

Neurocognitive de?cits are recognized as core features of schizophrenia. The aim of this study was to compare the cognitive performance of antipsychotic, drug-naive patients with first-episode schizophrenia (FES patients) to their healthy siblings and to healthy controls from the Han Chinese population for exploring potential endophenotypes for the early detection of schizophrenia. A battery of cognitive assessment tools was used to measure seven cognitive domains in matched groups consisting of 56 subjects each. Cognitive tests included the grooved pegboard test (GPT), the category fluency test (CFT), the trail making test A (TMT-A), the Wechsler memory scale-III spatial span test (WMS-III SST), the Hopkins verbal learning test-revised (HVLT-R), the brief visuospatial memory test-revised (BVMT-R), the paced auditory serial addition test (PASAT), and the Wisconsin card sorting test-64 cards version (WCST-64). The performances of FEP patients were inferior to normal controls on all neuropsychological tests, while siblings were lower than healthy controls in many of the same tasks. Patients’ performances were lower than siblings’ on all tests except for the CFT, the WMS-III SST backward test, and four subtests of the WCST-64. Our data suggest that FEP patients exhibited pronounced impairment of fine motor skills, speed of processing, attention, verbal memory, visual memory, and executive function, while siblings exhibited deficits intermediate between those of schizophrenic patients and the control group. Semantic fluency function and executive function may be potential endophenotypes for the early diagnosis of schizophrenia.     

Neurobehavioral correlates of sleep-disordered breathing in children

The effects of sleep-disordered breathing (SDB) on neurobehavioral function were examined in two matched groups of children from the general population. Thirty-five children with polysomnographically confirmed SDB were matched for ethnicity, age, gender, maternal educational attainment, and maternal smoking, to healthy children with no evidence of SDB. Children with SDB had significantly lower mean scores on the Differential Ability Scales for General Conceptual Ability (similar to IQ) and for the Non-verbal Cluster. On the neuropsychology assessment battery (NEPSY), children with SDB scored significantly lower than the control group on the attention/executive function domain and two subtests within that domain, one measuring visual attention and the other executive function. In addition, children with SDB scored significantly lower than the controls on one subtest from the NEPSY language domain: Phonological Processing. This subtest measures phonological awareness, a skill that is critical for learning to read. No differences in behavior, as measured by the Child Behavior Checklist (CBCL) or the Conners' Parent Rating Scale, were found between the two groups. Using a novel algorithm to assess sleep pressure, we found that children with SDB were significantly sleepier than controls. Furthermore, total arousal index was negatively correlated with neurocognitive abilities, suggesting a role for sleep fragmentation in pediatric SDB-induced cognitive dysfunction.     

Association of copy number variation across the genome with neuropsychiatric traits in the general population

Copy number variants (CNVs) are associated with psychiatric conditions in clinical populations. The relationship between rare CNV burden and neuropsychiatric traits in young, general populations is underexplored. A total of 6,807 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) were studied. CNVs were inferred from single nucleotide polymorphism‐array data using PennCNV. After excluding children with known candidate CNVs for schizophrenia (SCZ), rare (<1%) CNV burden (total number of genes affected by CNVs, total length of CNVs, and largest CNV carried) was analyzed in relation to: psychotic experiences (PEs) and anxiety/depression in adolescence; autism spectrum disorder (ASD) and attention‐deficit hyperactivity disorder (ADHD), ASD and ADHD traits, and cognitive measures during childhood. Outcomes were also assessed in relation to known SCZ CNVs. The number of genes affected by rare CNVs was associated with a continuous measure of ASD: the standardized mean difference [SMD] per gene affected was increased by 0.018 [95%CI 0.011,0.025], p = 3e‐07 for duplications and by 0.021 [95%CI 0.010, 0.032], p = 1e‐04 for deletions. In line with our published results on educational attainment in ALSPAC, intelligence quotient (IQ) was associated with CNV burden: the SMD per gene affected was −0.017 [95%CI −0.025, −0.008] p = 1e‐04 for duplications and −0.023 [95%CI −0.037, −0.009], p = .002 for deletions. Associations were also observed for measures of coherence, attention, memory, and social cognition. SCZ‐associated deletions were associated with IQ (SMD: −0.617 [95%CI −0.936, −0.298], p = 2e‐04), but not with PEs or other traits. We found that rare CNV burden and known SCZ candidate CNVs are associated with neuropsychiatric phenotypes in a nonclinically ascertained sample of young people.     

Does asthma or treatment with theophylline limit children's academic performance?

BACKGROUND. Asthma is a major cause of morbidity in childhood, restricting activity and causing absences from school. Theophylline, although effective in managing chronic asthma, has been reported to cause deficits in cognitive functioning and school performance. We therefore examined the effect of asthma and its treatment on academic achievement in a large, representative population of school-age children; matched sibling controls were used for comparison. METHODS. We identified 255 consecutive children with asthma (mean age, 12.0 years) who had taken nationally standardized scholastic achievement tests administered routinely by the schools. One hundred one of these children had siblings without asthma with whom comparisons could be made in reading, mathematics, and a composite measure of achievement. RESULTS. Academic achievement among the children with asthma was similar to normative standards in Iowa and higher than national standards, as reflected in a mean composite T-score of 57.1 (expected mean [+/- SD], 50 +/- 10). For the 101 children with sibling controls, composite T-scores were 58.3 for the children with asthma and 57.5 for the siblings. Eighty-five of these 101 children with asthma were receiving daily maintenance medication for chronic asthma; 72 of these were receiving theophylline. The mean composite T-scores were 58.5 for the theophylline-treated patients and 58.4 for their siblings without asthma. None of the differences between the children with asthma and the sibling controls were statistically significant. CONCLUSIONS. Academic achievement among children with asthma, at least those whose status is closely monitored in a structured treatment program, generally appears to be unaffected by asthma or by its treatment with appropriate doses of theophylline.     

Disrupted cortical network as a vulnerability marker for obsessive–compulsive disorder

Morphological alterations of brain structure are generally assumed to be involved in the pathophysiology of obsessive–compulsive disorder (OCD). Yet, little is known about the morphological connectivity properties of structural brain networks in OCD or about the heritability of those morphological connectivity properties. To better understand these properties, we conducted a study that defined three different groups: OCD group with 30 subjects, siblings group with 19 subjects, and matched controls group with 30 subjects. A structural brain network was constructed using 68 cortical regions of each subject within their respective group (i.e., one brain network for each group). Both small-worldness and modularity were measured to reflect the morphological connectivity properties of each constructed structural brain network. When compared to the matched controls, the structural brain networks of patients with OCD indeed exhibited atypical small-worldness and modularity. Specifically, small-worldness showed decreased local efficiency, and modularity showed reduced intra-connectivity in Module III (default mode network) and increased interconnectivity between Module I (executive function) and Module II (cognitive control/spatial). Intriguingly, the structured brain networks of the unaffected siblings showed similar small-worldness and modularity as OCD patients. Based on the atypical structural brain networks observed in OCD patients and their unaffected siblings, abnormal small-worldness and modularity may indicate a candidate endophenotype for OCD.     

Huntingtin gene CAG repeat size affects autism risk: Family‐based and case–control association study

The Huntingtin (HTT) gene contains a CAG repeat in exon 1, whose expansion beyond 39 repeats consistently leads to Huntington's disease (HD), whereas normal‐to‐intermediate alleles seemingly modulate brain structure, function and behavior. The role of the CAG repeat in Autism Spectrum Disorder (ASD) was investigated applying both family‐based and case–control association designs, with the SCA3 repeat as a negative control. Significant overtransmission of “long” CAG alleles (≥17 repeats) to autistic children and of “short” alleles (≤16 repeats) to their unaffected siblings (all p < 10^?5) was observed in 612 ASD families (548 simplex and 64 multiplex). Surprisingly, both 193 population controls and 1,188 neurological non‐HD controls have significantly lower frequencies of “short” CAG alleles compared to 185 unaffected siblings and higher rates of “long” alleles compared to 548 ASD patients from the same families (p < .05–.001). The SCA3 CAG repeat displays no association. “Short” HTT alleles seemingly exert a protective effect from clinically overt autism in families carrying a genetic predisposition for ASD, while “long” alleles may enhance autism risk. Differential penetrance of autism‐inducing genetic/epigenetic variants may imply atypical developmental trajectories linked to HTT functions, including excitation/inhibition imbalance, cortical neurogenesis and apoptosis, neuronal migration, synapse formation, connectivity and homeostasis.     

高智商注意缺陷多动障碍男性儿童的生态学执行功能特点

目的:探讨高智商注意缺陷多动障碍(ADHD)男性儿童生态学执行功能特点。方法:对50名7～14岁符合美国精神障碍诊断与统计手册第4版(DSM-IV)诊断标准的高智商(总智商≥120)ADHD男性儿童与50名年龄匹配的高智商正常男性儿童、723名一般人群男性儿童对照,用执行功能行为评定量表父母版(BRIEF)进行测评生态学执行功能。结果:高智商ADHD组的BRIEF评分,经多重检验校正后,抑制、转换、感情控制、任务启动、工作记忆、计划、组织、监控8个因子,行为管理指数、元认知指数2个维度得分及总分均高于高智商正常对照组和一般人群对照组[总分,(150±22)vs.(108±20),(104±21),P'0.05]。结论:本研究显示高智商ADHD男性患儿生态学执行功能在各层面均差于正常儿童。     

Differential genetic etiology of reading component processes as a function of IQ

Results obtained from previous studies of word recognition, reading component skills, and reading composite measures suggest that genetic factors may be more important as a cause for reading disability among children with higher IQ scores than among those with lower IQ scores. To investigate the genetic etiology of reading disability further, measures of word recognition, phonological decoding, orthographic coding, and phoneme awareness were obtained from a total of 465 twin pairs with a positive school history of reading problems. The basic and extended DeFries and Fulker (DF) multiple regression models for the analysis of selected twin data were employed to investigate the etiology of group deficits in reading and language skills, as well as to assess differential genetic etiology for the reading-related measures as a function of IQ. Data from 168 sibling pairs (drawn from the twins' families), including fraternal twin pairs and their siblings, as well as non-twin siblings of identical twins were subjected to single-marker analyses using the DF basic linkage model to examine evidence for linkage of a quantitative-trait locus (QTL) for reading and language deficits to the short arm of chromosome 6. Lastly, to investigate the possible differential influence of this QTL as a function of IQ, the sibling pair data were fitted to an extension of the DF basic linkage model. Results indicated that reading and language deficits are significantly heritable and that differential genetic influences as a function of IQ are evident for measures of word recognition and phonological decoding. Results obtained from linkage analyses confirmed the presence of a QTL on chromosome 6p that influences phonological and orthographic skills, as well as phoneme awareness measures, and suggest that this QTL may influence phoneme awareness differentially as a function of IQ: however, future analyses with considerably larger samples are needed to test the hypothesis of differential QTL influence more rigorously.     

Do seizures in children cause intellectual deterioration?

We studied whether the occurrence of seizures in childhood affected intellectual performance. We compared the full-scale IQs at seven years of age of children who had experienced one or more nonfebrile seizures with the IQs of their seizure-free siblings who were tested at the same age in a large longitudinal study. Among 98 children with seizures, the mean score on IQ tests at seven years was not significantly different from the mean score of their siblings. Mental retardation was more common among the children with seizures, but the excess was accounted for by children who had neurologic abnormalities before the first seizure. We also examined the IQ before and after the onset of seizures in 62 children whose first seizure occurred in the interval between psychometric examinations given at four and seven years of age. The IQ at seven years in the children with seizures did not differ significantly from that in controls matched for IQ (as determined at the four-year assessment), sex, race, and socioeconomic status. Thus, in both the sibling-control comparison and the comparisons made between controls and subjects before and after the onset of seizures, the occurrence of nonfebrile seizures was not associated with a significant change in full-scale IQ.     

The Impact of ADHD on the Cognitive and Academic Functioning of Children With NF1

We compared cognitive functioning, academic ability, and the predictors of academic underachievement in children with neurofibromatosis type 1 (NF1) (n?=?132), children with NF1 and comorbid attention deficit hyperactivity disorder (NF1 + ADHD) (n?=?60), and unaffected controls (n?=?52). Results indicate the presence of ADHD burdens some aspects of cognitive functioning and learning in NF1. Inattention and executive dysfunction are general characteristics of the NF1 cognitive phenotype and significantly undermine academic achievement across children with NF1.     

Executive dysfunction and its relation to language ability in verbal school-age children with autism

This study examined executive dysfunction and its relation to language ability in verbal school-age children with autism. Participants were 37 children with autism and 31 nonautistic comparison participants who were matched on age and on verbal and nonverbal IQ but not on language ability, which was lower in the autism group. Children with autism exhibited deficits compared to the comparison group across all 3 domains of executive function that were assessed including working memory (Block Span Backward; Isaacs & Vargha-Khadem, 1989), working memory and inhibitory control (NEPSY Knock-Tap; Korkman, Kirk, & Kemp, 1998), and planning (NEPSY Tower; Korkman et al., 1998). Children with autism were less developed than the comparison group in their language skills, but correlational analyses revealed no specific association between language ability and executive performance in the autism group. In contrast, executive performance was positively correlated with language ability in the comparison group. This pattern of findings suggest that executive dysfunction in autism is not directly related to language impairment per se but rather involves an executive failure to use of language for self-regulation.     

Executive function and attention deficit hyperactivity disorder: stimulant medication and better executive function performance in children.

BACKGROUND: Executive function deficits have been reported repeatedly in children with Attention Deficit Hyperactivity Disorder (ADHD). Stimulant medication has been shown to be effective in improving cognitive performance on most executive function tasks, but neuropsychological tests of executive function in this population have yielded inconsistent results. Methodological limitations may explain these inconsistencies. This study aimed to measure executive function in medicated and non-medicated children with ADHD by using a computerized battery, the Cambridge Neuropsychological Test Automated Battery (CANTAB), which is sensitive to executive function deficits in older patients with frontostriatal neurological impairments. METHODS: Executive function was assessed in 30 children with ADHD: 15 were stimulant medication naive and 15 were treated with stimulant medication. These two groups were compared to 15 age, sex and IQ matched controls. RESULTS: The unmedicated children with ADHD displayed specific cognitive impairments on executive function tasks of spatial short-term memory, spatial working memory, set-shifting ability and planning ability. Impairments were also seen on spatial recognition memory and delayed matching to sample, while pattern recognition memory remained intact. The medicated children with ADHD were not impaired on any of the above executive function tasks except for deficits in spatial recognition memory. CONCLUSIONS: ADHD is associated with deficits in executive function. Stimulant medication is associated with better executive function performance. Prospective follow-up studies are required to examine these effects.     

Cognitive function of 6-year old children exposed to mold-contaminated homes in early postnatal period. Prospective birth cohort study in Poland

In the last decade, the neurologic effects of various air pollutants have been the focus of increasing attention. The main purpose of this study was to assess the potential impact of early childhood exposure to indoor molds on the subsequent cognitive function of 6-year old children. The results of this study are based on the six-year follow-up of 277 babies born at term to mothers participating in a prospective cohort study in Krakow, Poland. The study participants are all non-smoking pregnant women who were free of chronic diseases such as diabetes and hypertension.The presence of visible mold patches on indoor walls was monitored at regular time intervals over gestation and after birth up to the age of five. The Wechsler Intelligence Scale for Children (WISC-R) was administered to children at age 6. The exposure effect of living in mold-contaminated homes on the IQ scores of children was adjusted for major confounders, known to be important for the cognitive development of children such as maternal education, the child's gender, breastfeeding practices in infancy, the presence of older siblings and the prenatal exposure to lead and environmental tobacco smoke (ETS).The adjusted IQ deficit attributed to longer exposures to indoor molds (> 2 years) was significantly lower on the IQ scale (beta coeff. = − 9.16, 95%CI: −15.21, −3.10) and tripled the risk of low IQ scoring (OR = 3.53; 95%CI: 1.11-11.27) compared with references. While maternal education (beta coeff. = 0.61, 95%CI: 0.05, 1.17) and breastfeeding (beta coeff. = 4.0; 95%CI: 0.84, 7.17) showed a significant positive impact on cognitive function, prenatal ETS exposure (beta coeff. = −0.41; 95%CI: −0.79, −0.03) and the presence of older siblings (beta coefficient = −3.43; 95%CI: −5.67, −1.20) were associated with poorer cognitive function in children.In conclusion, the results of this study draw attention to the harmful effect of early postnatal exposure to indoor molds on children's cognitive development and provide additional evidence on the role of environmental determinants in human cognitive development.     

Profile of cognitive functioning in women with the fragile X mutation

Two studies tested the specificity of the neurocognitive profile of women with fragile X syndrome (FXS). First, women with an FXS full mutation were compared with women with a premutation and women without FXS who grew up in FXS families. Women with FXS had a significantly lower IQ than the other groups, and analyses of subtest profiles showed they had a relative weakness on Arithmetic and strength on Picture Completion. Women with FXS performed worse than the other groups on executive function, spatial ability, and visual memory. Next, women with FXS were compared with women without FXS matched on age and IQ. A similar IQ profile was found, but women with FXS were worse than controls only on executive function. The authors also examined which neurocognitive indices were related to the underlying biology of the disorder. Overall, the results indicated that executive rather than visuospatial deficits were primary in the neurocognitive profile of FXS.     

Acute effects of exercise posture on executive function in transient ischemic attack patients

In patients with stroke or transient ischemic attacks (TIA), a decline in executive function may limit an individual's ability to process motor tasks and relearn motor skills. The purpose of this study was to assess the acute effect of exercise posture (seated vs. supine cycle ergometry) on executive function and prefrontal cortex perfusion in patients with TIA. Eleven TIA patients (65 ± 10 years) and 15 age‐matched, healthy controls (HC; 62 ± 7 years) completed two exercise tests to maximal capacity (one seated, one supine) and two 30‐min submaximal exercise tests (one seated, one supine). Executive function was assessed prior to and following (1.5 min post, 15 min post) the submaximal exercise tests using a Stroop task. Prefrontal cortex perfusion (total hemoglobin) was continuously recorded using near‐infrared spectroscopy. There was no Posture (seated, supine) × Group (TIA, HC) interaction for the Stroop task (p > .05). HC completed Stroop tasks significantly faster than TIA (51.9[SD = 10.3] vs. 64.2[8.5] s, respectively), while Stroop completion time significantly improved between baseline and 1.5 min post (61.3[10] vs. 58.1[9.4] s, respectively) and 1.5 min post and 15 min post (54.8[8.9] s). Posture and group had no significant influence on prefrontal cortex perfusion (p > .05). In summary, executive function improves to a similar extent in TIA and age‐matched, healthy controls following an acute bout of exercise, regardless of exercise posture. As acute improvements in executive function were maintained for 15 min, there could be an important window of opportunity for assigning executive tasks following exercise rehabilitation for patients with TIA.     

Association between childhood obesity,cognitive development,physical fitness and social-emotional wellbeing in a transitional economy

Background: It has been suggested that obese children have lower cognitive function, demonstrate poorer physical performance and are more susceptible to social-emotional problems.

Aims: To describe associations between human physical growth, cognitive development, physical fitness and social-emotional characteristics of obese and non-obese children and to verify the predictors of intellectual coefficient by socioeconomic status (SES).

Subjects and methods: A sample of 107 non-obese (N-Ob) children [?1?z-score body mass index (BMI) ≤1?z-score] and 108 obese (Ob) children [2 z-score ≤BMI ≤5?z-score] from a larger cohort was evaluated. Intellectual coefficient (IQ), social-emotional wellbeing (SEW), 6-minute walk test (6MWT) and SES (mid-low, low and very low) were assessed.

Results: Ob children were taller, heavier and present more height for age and BMI than N-Ob children (p?r?=?0.14), 6MWT and BMI z-score (r?=??0.18) and 6MWT and SEW (r?=?0.15) was found. Multiple regression analysis revealed that BMI z-score had a negative impact on IQ in the mid-low SES sub-group and that SEW had a positive effect on IQ in the very-low SES sub-group.

Conclusions: In Chilean pre-school children from low-income families cognitive ability varied according to SES.     

Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study

BACKGROUND: Studies of groups of individuals who have a genetically high risk of developing schizophrenia, have found neuropsychological impairments that highlight likely trait markers of the schizophrenic genotype. This paper describes the change in neuropsychological function and associations with psychiatric state of high risk participants during the first two assessments of the Edinburgh High Risk Study. METHODS: Seventy-eight high risk participants and 22 normal controls, age and sex matched completed two neuropsychological assessments 18 months to 2 years apart. The areas of function assessed include intellectual function, executive function, learning and memory, and verbal ability and language. RESULTS: The high risk participants performed significantly worse on particular tests of verbal memory and executive function over the two assessments than matched controls. Those high risk participants who experienced psychotic symptoms were found to exhibit a decline in IQ and perform worse on tests of verbal memory and executive function than those without symptoms. An increase in psychotic symptoms between the two assessments in the high risk group was found to be associated with an apparent decline in IQ and memory. CONCLUSIONS: The results suggest that the development of psychotic symptoms is preceded by a decline in IQ and memory. This may reflect a general and a more specific disease process respectively.     

行为问题儿童的智力水平配对研究

目的：探讨行为问题儿童的智力水平及特征。方法：采用Achenbach儿童行为问卷（CBCL）（父母问卷）和中国联合型瑞文测验第二版（CRT－C2）在小学1－5年级学龄儿童中筛选行为问题儿童。从同性别非行为问题儿童中选择与问题儿童年龄最接近的儿童组成对照组，配对比例为1：2。采用韦氏儿童智力量表（WISC－CR）测验儿童智力水平。结果：（1）行为问题儿童的IQ基本在正常范围，与对照组水平接近。译码是儿童行为问题的保护因素，智力不平衡是危险因素。（2）智力不平衡是内向行为问题的危险因素；CRT－C2IQ是外向行为问题的保护因素；译码是混合问题的保护因素。结论：行为问题儿童虽然智力发育在正常水平，但智力不平衡者较多，提示行为问题儿童半球功能不平衡，有脑功能损伤的可能。