DNA pooling identifies QTLs on chromosome 4 for general cognitive ability in children.
(1/986)
General cognitive ability (g), which is related to many aspects of brain functioning, is one of the most heritable traits in neuroscience. Similarly to other heritable quantitatively distributed traits, genetic influence on g is likely to be due to the combined action of many genes of small effect [quantitative trait loci (QTLs)], perhaps several on each chromosome. We used DNA pooling for the first time to search a chromosome systematically with a dense map of DNA markers for allelic associations with g. We screened 147 markers on chromosome 4 such that 85% of the chromosome were estimated to be within 1 cM of a marker. Comparing pooled DNA from 51 children of high g and from 51 controls of average g, 11 significant QTL associations emerged. The association with three of these 11 markers ( D4S2943, MSX1 and D4S1607 ) replicated using DNA pooling in independent samples of 50 children of extremely high g and 50 controls. Furthermore, all three associations were confirmed when each individual was genotyped separately ( D4S2943, P = 0. 00045; MSX1, P = 0.011; D4S1607, P = 0.019). Identifying specific genes responsible for such QTL associations will open new windows in cognitive neuroscience through which to observe pathways between genes and learning and memory. (+info)
Evaluating methods for estimating premorbid intellectual ability in closed head injury.
(2/986)
OBJECTIVES: The present study examines the utility of three measures of premorbid intellectual functioning in closed head injury, the National adult reading test (NART), the Cambridge contextual reading test (CCRT), and the spot the word test (STW). METHODS: In the first experiment, a group of 25 patients with closed head injury were compared with 50 healthy controls and 20 orthopaedic trauma controls. In the second experiment, the strength of correlation between the premorbid measures and current intellectual level were assessed in 114 healthy adults. RESULTS: The head injured group performed significantly more poorly than both control groups on measures of current intellectual ability. However, no significant differences emerged between the groups on any of the premorbid measures. In the large control sample, both the NART and the CCRT accounted for about 50% of the variance in current verbal intelligence. However, by contrast, the STW only accounted for 29% of the variability in verbal intelligence. Adding demographic variables to the prediction of current intellectual level increased the amount of variance explained to 60% for the NART, 62% for the CCRT, but only 41% for the STW. CONCLUSION: The results provide supportive evidence for the use of the CCRT and NART in estimating premorbid intellectual functioning in patients who have sustained closed head injuries, but suggest caution when employing the STW. (+info)
A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus.
(3/986)
OBJECTIVE: To prospectively analyze the association between changes in cognitive function and circulating anticardiolipin antibodies (aCL) over a period of 5 years in patients with systemic lupus erythematosus (SLE). METHODS: Cognitive function was assessed in 51 unselected female SLE patients at baseline and after a mean followup of 64.5 months (range 52-71 months), using standardized tests of cognitive function, i.e., the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, and the California Verbal Learning Test. Circulating IgG, IgA, and IgM aCL and anti-double-stranded DNA (anti-dsDNA) antibody levels were determined by enzyme-linked immunosorbent assay on 4-7 occasions over the same time period. Persistent antibody reactivity was defined as levels more than 2 standard deviations (moderately positive) and more than 5 standard deviations (highly positive) above the mean for normal controls over the duration of the study. Changes in overall cognitive performance and in raw scores on individual cognitive tests were compared in patients who were persistently positive or negative for aCL. RESULTS: At baseline 11 patients (22%) were cognitively impaired, compared with 7 (14%) at followup. Between 16% and 37% of patients had persistently elevated aCL levels of different isotypes. There was no significant difference in the prevalence of overall cognitive impairment in patients who were persistently positive for aCL compared with those who were not. In contrast, over the period of study, patients who had persistent IgG aCL positivity had a reduction in psychomotor speed, and patients who had persistent IgA aCL positivity had a reduction in conceptual reasoning and executive ability. Similar associations with anti-dsDNA antibodies were not found. CONCLUSION: These results suggest that IgG and IgA aCL may be responsible for long-term subtle deterioration in cognitive function in patients with SLE. (+info)
Neuropsychological sequelae of haemolytic uraemic syndrome. Investigators of the HUS Cognitive Study.
(4/986)
BACKGROUND: Severe haemolytic uraemic syndrome (HUS) in childhood can cause stroke, hemiplegia, cortical blindness, and psychomotor retardation. These outcomes are evident at the time of discharge immediately after the acute illness. Less is known about the neuropsychological outcomes of less severely affected children who recover from acute HUS. AIMS: This multicentre case control study investigated the hypothesis that children who survive an acute episode of HUS without recognizable neurological injuries have greater impairment of cognitive, academic, and behavioural functions than controls. DESIGN: Children with HUS were eligible if they had no evidence of severe neurological dysfunction when discharged from one of six Canadian hospitals. Controls had been admitted to hospital for a non-HUS illness and were matched by age, sex, first language, and socioeconomic status. All subjects underwent evaluation of behaviour, academic achievement, cognitive function, and verbal abilities using standardised tests administered by a psychometrist blinded to the case or control status. RESULTS: Ninety-one case control pairs were enrolled. No important differences between patients with HUS and paired controls were evident on tests of IQ, behaviour, verbal abilities, or academic achievement. There was no increased risk of attention deficit disorder among patients with HUS. There was no correlation between the severity of acute renal failure and neuropsychological measures, although scores on some verbal ability tests were lower in those with the highest serum creatinine concentrations during illness. CONCLUSIONS: Children discharged from hospital without apparent neurological injury after an episode of acute HUS do not have an increased risk of subclinical problems with learning, behaviour, or attention. (+info)
Outcome of very severe birth asphyxia.
(5/986)
The aim of this study was to establish the outcome of very severe birth asphyxia in a group of babies intensively resuscitated at birth. 48 infants, born between 1966 and 1971 inclusive, were selected; 15 were apparently stillborn and 33 had not established spontaneous respirations by 20 minutes after birth. One-half of them died, but 3 to 7 years later three-quarters of the survivors are apparently normal. Later handicap was associated with factors leading to prolonged partial intrapartum asphyxia, while acute periods of more complete asphyxia were not necessarily harmful. (+info)
Spatial attention deficits in patients with acquired or developmental cerebellar abnormality.
(6/986)
Recent imaging and clinical studies have challenged the concept that the functional role of the cerebellum is exclusively in the motor domain. We present evidence of slowed covert orienting of visuospatial attention in patients with developmental cerebellar abnormality (patients with autism, a disorder in which at least 90% of all postmortem cases reported to date have Purkinje neuron loss), and in patients with cerebellar damage acquired from tumor or stroke. In spatial cuing tasks, normal control subjects across a wide age range were able to orient attention within 100 msec of an attention-directing cue. Patients with cerebellar damage showed little evidence of having oriented attention after 100 msec but did show the effects of attention orienting after 800-1200 msec. These effects were demonstrated in a task in which results were independent of the motor response. In this task, smaller cerebellar vermal lobules VI-VII (from magnetic resonance imaging) were associated with greater attention-orienting deficits. Although eye movements may also be disrupted in patients with cerebellar damage, abnormal gaze shifting cannot explain the timing and nature of the attention-orienting deficits reported here. These data may be consistent with evidence from animal models that suggest damage to the cerebellum disrupts both the spatial encoding of a location for an attentional shift and the subsequent gaze shift. These data are also consistent with a model of cerebellar function in which the cerebellum supports a broad spectrum of brain systems involved in both nonmotor and motor function. (+info)
How can we boost IQs of "dull children"?: A late adoption study.
(7/986)
From 5,003 files of adopted children, 65 deprived children, defined as abused and/or neglected during infancy, were strictly selected with particular reference to two criteria: (i) They were adopted between 4 and 6 years of age, and (ii) they had an IQ <86 (mean = 77, SD = 6.3) before adoption. The average IQs of adopted children in lower and higher socioeconomic status (SES) families were 85 (SD = 17) and 98 (SD = 14.6), respectively, at adolescence (mean age = 13.5 years). The results show (i) a significant gain in IQ dependent on the SES of the adoptive families (mean = 7.7 and mean = 19.5 IQ points in low and high SES, respectively), (ii) IQs after adoption are significantly correlated with IQs before adoption, and (iii) during adolescence, verbal IQs are significantly lower than performance IQs. (+info)
A genomic screen of autism: evidence for a multilocus etiology.
(8/986)
We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps >/=15) and are less compatible with models specifying +info)