Predictors of cognitive test patterns in autism families

In a case-control study of cognitive performance, tests of intelligence, reading, spelling, and pragmatic language were administered to the parents and siblings of 90 community-ascertained probands with autism (AU group) and to the parents and siblings of 40 similarly ascertained probands with trisomy 21 Down syndrome (DS group). The two samples were comparable for age and parents' education; both groups were well-educated and had above-average intelligence. AU parents scored slightly but significantly lower on the WAIS-R Full Scale and Performance IQ, on two subtests (Picture Arrangement and Picture Completion), and on the Word Attack Test (reading nonsense words) from the Woodcock-Johnson battery. There were no differences between AU and DS siblings. As in earlier studies, AU parents, more often than DS parents, reported a history of early language-related cognitive difficulties; we were not able to replicate this in siblings. AU parents who reported such difficulties scored significantly lower on Verbal IQ, spelling, and the nonsense reading test. AU parents without a history of early language-related cognitive difficulties often had a Verbal IQ that exceeded Performance IQ by more than one standard deviation. AU siblings with early language-related difficulties had similar findings: lower Verbal IQ, poorer spelling, and poorer reading scores, compared to AU siblings without such a history. Parents with a positive history also scored worse on a measure of pragmatic language,the Pragmatic Rating Scale, but not on measures of social-related components of the broader autism phenotype. We propose that cognitive differences in a subset of autism family members are manifestations of the language-related component of the broader autism phenotype, and separate from the social-related component. This is consistent with the hypothesis that there are several genes that may interact to cause autism which segregate independently and have distinguishable manifestations in family members. The hypothesis would be further supported by finding different patterns of genetic loci linked to autism in families where one or both parents has language difficulties.     

Cognitive Deficits in Parents from Multiple-incidence Autism Families

This study compares parents of two autistic children with parents of a Down syndrome (DS) proband, on tests of intelligence, reading and spelling, and executive function. Autism parents performed significantly worse than DS parents on performance IQ, a test of executive function, and some reading measures (e.g. passage comprehension and rapid automatized naming). These results suggest that cognitive deficits may be an expression of the underlying genetic liability for autism and that these characteristics may contribute to a more broadly defined autism phenotype.     

Language abilities of siblings of children with autism

BACKGROUND: Language abilities of siblings of children with autism were examined to explore the possibility that language abilities are behavioral markers specific to the genetic liability for autism, as part of the broader phenotype. METHOD: Language abilities were compared among 27 siblings of children with autism, 23 siblings of children with mental retardation of unknown etiology (MR), and 22 siblings of children with developmental language disorders (DLD). Groups were matched by siblings' age, gender, birth order, family size, ethnicity, family income and by probands' gender and mental age. RESULTS: Siblings of children with autism achieved higher scores than siblings of children with DLD on receptive, expressive, and total language scales of the Children's Evaluation of Language Fundamentals and on verbal IQ. Moreover, within the DLD group, school problems in the domains of reading and arithmetic were more prevalent than within the other two groups. Only 2 siblings of children with autism received clinical diagnoses based on DSM-IV criteria compared to 3 siblings of children with MR and 7 siblings of children with DLD. CONCLUSIONS: After excluding data of the diagnosed siblings, no differences in language abilities could be discerned among the groups, except that more siblings in the DLD group were identified as having language difficulties. In summary, although language deficits characterize autism, siblings of children with autism were not found to demonstrate deficits in language skills assessed by formal language tests, IQ, or academic skills.     

Adult outcome for children with autism

BACKGROUND: Information on long-term prognosis in autism is limited. Outcome is known to be poor for those with an IQ below 50, but there have been few systematic studies of individuals with an IQ above this. METHOD: Sixty-eight individuals meeting criteria for autism and with a performance IQ of 50 or above in childhood were followed up as adults. Their mean age when first seen was 7 years (range 3-15 years); at follow-up the average age was 29 years (range 21-48 years). Outcome measures included standardised cognitive, language and attainment tests. Information on social, communication and behavioural problems was obtained from the Autism Diagnostic Interview (ADI). RESULTS: Although a minority of adults had achieved relatively high levels of independence, most remained very dependent on their families or other support services. Few lived alone, had close friends, or permanent employment. Communication generally was impaired, and reading and spelling abilities were poor. Stereotyped behaviours or interests frequently persisted into adulthood. Ten individuals had developed epilepsy. Overall, only 12% were rated as having a 'Very Good' outcome; 10% were rated as 'Good' and 19% as 'Fair'. The majority was rated as having a 'Poor' (46%) or 'Very Poor' (12%) outcome. Individuals with a childhood performance IQ of at least 70 had a significantly better outcome than those with an IQ below this. However, within the normal IQ range outcome was very variable and, on an individual level, neither verbal nor performance IQ proved to be consistent prognostic indicators. CONCLUSIONS: Although outcome for adults with autism has improved over recent years, many remain highly dependent on others for support. This study provides some information on prognostic indicators, but more fine-grained research is needed into the childhood variables that are associated with good or poor outcome.     

Eight-year-old very and extremely preterm children showed more difficulties in performance intelligence than verbal intelligence

Aim

This study determined possible discrepancies between verbal IQ and performance IQ in 8-year-old very preterm (VPT) and extremely preterm (EPT) children, and examined associations between verbal IQ and performance IQ, and sociodemographic factors, perinatal factors, early cognitive outcomes and also with school achievement scores.

Methods

This prospective cohort study included 120 eight-year-old VPT/EPT children. Cognitive development was assessed at the ages of 2, 5 and 8 years. Eight years’ school achievement results in arithmetic, reading and spelling were collected. Multiple regression analyses were performed to determine predictors of verbal IQ and performance IQ at the age of 8 years and to determine associations with school achievement scores.

Results

Mean performance IQ (89.8) was significantly lower than mean verbal IQ (99.4; Cohen's d = 0.59) at the age of 8 years. Gestational age (GA), small for GA status, and cognitive scores at the ages of 2 and 5 years significantly predicted verbal IQ and performance IQ at the age of 8 years. Performance IQ at age 8 years was an important predictor for arithmetic scores (β = 0.42).

Conclusion

Performance IQ was more strongly affected than verbal IQ in 8-year-old VPT/EPT children and was strongly related to mathematical difficulties.

     

Age at diagnosis and abilities in idiopathic hypercalcaemia.

Forty three children aged 6 to 16 years with a documented history of idiopathic infantile hypercalcaemia were assessed on a variety of cognitive and behavioural measures. No relation was found between the age at which hypercalcaemia was diagnosed and subsequent full scale intelligence quotients (IQ) and reading or spelling abilities. Verbal IQ was, however, significantly higher than performance IQ, which had an inverse relation with age at diagnosis. Furthermore, scores for deviant behaviour were found to correlate with age at diagnosis. Thus the characteristic psychological profile of this syndrome may be in part a function of hypercalcaemia during infancy.     

Oral and written language abilities of XXY boys: implications for anticipatory guidance

Previous studies of XXY boys suggest that they are at risk for certain communication disorders involving oral and written language. In this study, the language, reading, and spelling skills of a group of 14 XXY boys identified during neonatal cytogenetic screening were compared with those of a group of 15 control children. The two groups were matched for age, grade, race, parity, birth weight, parental age and education, and socioeconomic status. The mean age of the XXY group was 9 years 7 months and that of the control group was 9 years 3 months. The mean academic grade level for both groups was at the transition between third and fourth grade. There was selective reduction in verbal IQ scores for the XXY group and no significant differences apparent between groups for performance IQ scores. The decrease in verbal IQ was associated with a reduced full-scale IQ and also with significant problems in expressive language, auditory processing abilities, and auditory memory. Word-finding difficulties and problems in the production of syntax were major components of the specific expressive language deficit. Except for difficulties in the understanding of complex sentence structures, the receptive language skills of XXY boys did not differ significantly from those of the control group. These reductions in speech and language abilities correlated with decreased achievement by the XXY group on a variety of reading and spelling tasks. These results suggest that difficulty learning how to read and spell may be due to a preexistent language disability. Early attention to such expressive language problems may be essential to ameliorate secondary maladaptive behaviors due to chronic language-related learning disabilities.     

Towards a Cognitive Phenotype for Autism: Increased Prevalence of Executive Dysfunction and Superior Spatial Span amongst Siblings of Children with Autism

Two studies were conducted to examine executive function skills in siblings of children with autism. In Study 1, four computerised tasks (three executive tasks: the ID/ED set-shifting task; a spatial working memory task; and the Tower of London planning task; and a control spatial span task) from the CANTAB battery were used to compare 31 siblings of children with autism with 32 siblings of children with developmental delay and 32 children from unaffected families. In Study 2, the two sibling groups were compared on two manually administered executive tasks (verbal fluency and list recall). As a group, autism siblings showed superior spatial and verbal span, but a greater than expected number performed poorly on the set-shifting, planning, and verbal fluency tasks. There were no group differences in working memory performance. The implications of these findings for the broader phenotype of autism is discussed.     

Cognitive functioning in children on dialysis and post-transplantation

We studied 124 children, 62 patient-subjects who had end-stage renal disease (ESRD) and 62 sibling-controls who closely matched the patient-subjects in terms of their ethnicity and their socioeconomic status, to discern whether children with ESRD would perform less well than their siblings on standardized achievement and intelligence quotient (IQ) tests, and to determine whether ethnicity would influence such results. The subjects were recruited from nine pediatric transplant and dialysis centers across the United States. Thirty-one subjects were white (Euro-American), 17 were African-American, and 14 were categorized as 'other'. The average age of the patient-subjects was 13.7 +/- 0.44 yr; and of the sibling-controls 13.7 +/- 0.38 yr. Most patients (61%) and siblings (84%) were in regular school classes, and most (87% and 92%, respectively) attended school full-time. The average IQ percentile rank for the patients was significantly lower than their siblings (31 +/- 4 vs. 44 +/- 5, respectively, with normal = 50). Patients tended to score lower on achievement tests compared with their siblings (spelling: 88.7 +/- 4 vs. 94.6 +/- 2; arithmetic: 88.5 +/- 2 vs. 94.0 +/- 2; reading: 91.9 +/- 2 vs. 100 +/- 3, respectively). Patients scores on achievement tests were influenced by age at diagnosis and by the mother/caregiver's lower achievement. Also, increased time on dialysis predicted lower scores on achievement tests. Neither dialysis/transplant status nor ethnicity significantly affected outcome. Our data suggest that ESRD, but not ethnicity or dialysis/transplant status, is a risk factor for lower IQ and academic achievement, especially in younger children, in children who spend more time living with ESRD, and in children whose mother's/caregiver's have lower educational levels.     

Autism and developmental receptive language disorder--a comparative follow-up in early adult life. I: Cognitive and language outcomes

In this paper we compare adult outcome in a group of young men with autism and a group with developmental receptive language disorders. The two groups were first assessed in early childhood, when aged 7 to 8 years of age. Although matched at that time for nonverbal IQ (mean 92-93) and expressive language ability, the Autism group was significantly more impaired on most measures of social and communication skills and stereotyped behaviours. A later follow-up, in mid-childhood, suggested that although the groups were still quite distinct, social and behavioural problems had become more apparent in the Language group. The current study was completed when the participants were aged, on average, 23 to 24 years. The findings indicated that verbal IQ and receptive language scores had improved significantly more in the Autism group than in the Language group over time. Moreover, although the Language group were less severely impaired in their social use of language, many showed a number of abnormal features in this domain. There were no differences between the groups on tests of reading or spelling. Discriminant function analysis, which had clearly distinguished between the groups as children, now showed much greater overlap between them. Regression analysis indicated that although early language ability appeared to be related to outcome in the Autism group, in the Language group there was little association between measures of childhood functioning and later progress. The implications of these findings for understanding the nature of the underlying deficit in autism and the relationship between the two disorders are discussed.     

The effect of very low birth weight and social risk on neurocognitive abilities at school age.

We tested the hypothesis that very low birth weight (VLBW < 1.5 kg) children would have significantly poorer neurocognitive abilities at school age than would normal birth weight full-term age mates, that differences would persist after control for neurologic impairment and social risk, and that VLBW would interact with social risk. Two hundred forty-nine VLBW children and a randomly selected sample of 363 normal birth weight age mates born 1977 through 1979 were tested at 8 years. A neurologic examination and tests of intelligence, language, speech, reading, mathematics, spelling, visual and fine motor abilities, and behavior were performed. Twenty-four (10%) VLBW had a major neurologic abnormality compared with none of the controls. VLBW had significantly poorer scores on all tests, with the exception of speech and the total behavior score. These differences persisted among VLBW children without major neurologic abnormality, with the exception of social competence, reading, and spelling. Even normal IQ, neurologically normal VLBW had significantly poorer scores than did controls in expressive language, memory, visuomotor, and fine motor function, and measures of hyperactivity. When social risk was controlled in multiple regression analyses, VLBW still had an adverse effect on all outcome measures with the exception of speech. Social risk was, however, the major determinant of outcome. We found an interaction between VLBW and social risk only in verbal IQ and in the opposite direction than hypothesized.     

Verbal Memory and Performance IQ Predict Theory of Mind and Emotion Recognition Ability in Children with Autistic Spectrum Disorders and in Psychiatric Control Children

This study was designed to examine the developmental and cognitive correlates of theory of mind (ToM) and emotion recognition ability in children with autism (N = 20), with pervasive developmental disorder-not otherwise specified (PDD-NOS) (N = 20), and in psychiatric control children (N = 20). The diagnostic groups were person-to-person matched on age and verbal IQ. The age of the children was between 8 and 18 years; their Full Scale IQ was at least 65. The test battery included tasks for the matching and the context recognition of emotional expressions, and a set of first- and second-order ToM tasks. The relationships between composite domain scores and the subjects' age, Verbal IQ, Performance IQ, verbal memory, visual memory, and gender were examined in bivariate and multivariate analyses. Further, the subjects who reliably and consistently passed the tasks of a domain and those who could not were compared on developmental and cognitive characteristics. Overall, the results of the various analyses converged and indicated that verbal memory, Performance IQ, age and gender were the best predictors of social cognitive ability.     

Breast milk feeding and cognitive ability at 7-8 years

OBJECTIVE: To examine the association between duration of breast milk feeding and cognitive ability at 7-8 years in a birth cohort of very low birthweight infants. DESIGN: 280 survivors from a national birth cohort of 413 New Zealand very low birthweight infants born in 1986 were assessed at age 7-8 years on measures of verbal and performance intelligence quotient (IQ) using the WISC-R. At the same time mothers were questioned as to whether they had elected to provide expressed breast milk at birth and the total duration of breast milk feeding. RESULTS: Some 73% of mothers provided expressed breast milk and 37% breast fed for four months or longer. Increasing duration of breast milk feeding was associated with increases in both verbal IQ (p < 0.001) and performance IQ (p < 0.05): children breast fed for eight months or longer had mean (SD) verbal IQ scores that were 10.2 (0.56) points higher and performance IQ scores that were 6.2 (0.35) points higher than children who did not receive breast milk. These differences were substantially reduced after control for selection factors associated with receipt of breast milk. Nevertheless, even after control for confounding, there remained a significant (p < 0.05) association between duration of breast milk feeding and verbal IQ: children breast fed for eight months or longer had adjusted mean (SD) verbal IQ scores that were 6 (0.36) points higher than the scores of those who did not receive breast milk. CONCLUSIONS: These findings add to a growing body of evidence to suggest that breast milk feeding may have small long term benefits for child cognitive development.     

The development of siblings of children with autism at 4 and 14 months: social engagement, communication, and cognition

AIMS: To compare siblings of children with autism (SIBS-A) and siblings of children with typical development (SIBS-TD) at 4 and 14 months of age. METHODS: At 4 months, mother-infant interactional synchrony during free play, infant gaze and affect during the still-face paradigm, and infant responsiveness to a name-calling paradigm were examined (n = 21 in each group). At 14 months, verbal and nonverbal communication skills were examined as well as cognition (30 SIBS-A and 31 SIBS-TD). RESULTS: Most SIBS-A were functioning as well as the SIBS-TD at 4 and 14 months of age. However, some differences in early social engagement and later communicative and cognitive skills emerged. Synchrony was weaker in the SIBS-A dyads, but only for infant-led interactions. Infant SIBS-A revealed more neutral affect during the still-face procedure and were less upset by it than was true for the SIBS-TD. A surprising result was that significantly more SIBS-A responded to their name being called by their mothers compared to SIBS-TD. At 14 months, SIBS-A made fewer nonverbal requesting gestures and achieved lower language scores on the Bayley Scale. Six SIBS-A revealed a language delay of 5 months and were responsible for some of the significant differences between SIBS-A and SIBS-TD. Furthermore, infant SIBS-A who showed more neutral affect to the still face and were less able to respond to their name being called by their mothers initiated fewer nonverbal joint attention and requesting behaviors at 14 months, respectively. DISCUSSION: Focused on the genetic liability for the broad phenotype of autism as well as the possible influence of having a sibling with autism.     

Behavioural and cognitive phenotypes in idiopathic autism versus autism associated with fragile X syndrome

Background:  In order to better understand the underlying biological mechanism/s involved in autism, it is important to investigate the cognitive and behavioural phenotypes associated with idiopathic autism (autism without a known cause) and comorbid autism (autism associated with known genetic/biological disorders such as fragile X syndrome). Parental effects associated with each type of autism also serve to cast light on the biological underpinnings of autism.
Method:  Forty-nine participants with idiopathic autism (AD; Mean age: 11.16; SD: 6.08) and their parents (45 mothers; 34 fathers), and 48 participants with fragile X syndrome and co-morbid autism (FXS/AD; Mean age: 17.30; SD: 10.22) and their parents (32 mothers; 30 fathers) were administered the ADOS-G and the age-appropriate Wechsler test to ascertain autism and cognitive profiles respectively.
Results:  The AD and FXS/AD groups showed a similar profile on the ADOS domains, with slightly higher scores on the Communication domain in the FXS/AD group, after adjusting for full-scale IQ. Marked differences between the groups in their cognitive abilities were apparent, with the FXS/AD group showing significantly lower scores on all subtests except Comprehension. While no parental effects were found for the FXS/AD group, a paternal effect was apparent on the combined ADOS score for the AD group. Moreover, midparental effects were found in this group for full-scale IQ (FSIQ) and verbal IQ (VIQ). Analyses also revealed parental effects for the subtests of Similarities, Vocabulary, and Information with predominantly maternal effect, and Digit Span with predominantly paternal effect. Both parents contributed to the midparental effect for Processing Speed.
Conclusions:  The results, together with our previous findings, suggest that the postulated combination of susceptibility genes for autism may primarily involve cognitive rather than behavioural processes.     

Exploring the cognitive phenotype of autism: weak "central coherence" in parents and siblings of children with autism: I. Experimental tests

Previous twin and family studies have indicated that there are strong genetic influences in the etiology of autism, and provide support for the notion of a broader phenotype in first-degree relatives. The present study explored this phenotype in terms of one current cognitive theory of autism. Parents and brothers of boys with autism, boys with dyslexia, and normal boys were given tests of "central coherence", on which children with autism perform unusually well due to an information-processing bias favouring part/detail processing over processing of wholes/meaning. Results indicated that fathers of boys with autism, as a group, showed piecemeal processing across four tests of central coherence. This was not true for any other group. These findings raise the possibility that the broader autism phenotype may include a "cognitive style" (weak central coherence) that can confer information-processing advantages.     

Mind-reading difficulties in the siblings of people with Asperger's syndrome: evidence for a genetic influence in the abnormal development of a specific cognitive domain

BACKGROUND: Previous research suggests that the phenotype associated with Asperger's syndrome (AS) includes difficulties in understanding the mental states of others, leading to difficulties in social communication and social relationships. It has also been suggested that the first-degree relatives of those with AS can demonstrate similar difficulties, albeit to a lesser extent. This study examined 'theory of mind' (ToM) abilities in the siblings of children with AS relative to a matched control group. METHOD: 27 children who had a sibling with AS were administered the children's version of the 'Eyes Test' (Baron-Cohen, Wheelwright, Stone, & Rutherford, 1999). The control group consisted of 27 children matched for age, sex, and a measure of verbal comprehension, and who did not have a family history of AS/autism. RESULTS: A significant difference was found between the groups on the Eyes Test, the 'siblings' group showing a poorer performance on this measure of social cognition. The difference was more pronounced among female siblings. DISCUSSION: These results are discussed in terms of the familial distribution of a neuro-cognitive profile associated with AS, which confers varying degrees of social handicap amongst first-degree relatives. The implication of this finding with regard to the autism/AS phenotype is explored, with some discussion of why this neuro-cognitive profile (in combination with corresponding strengths) may have an evolutionary imperative.     

Abnormal cognitive function in treated congenital hypopituitarism.

AIMS: To assess cognitive function in school age children with congenital pituitary hormone deficiency (PHD). METHODS: Ten children with PHD (aged 6.0-15.6 years, mean 11.5 years) and sibling controls (aged 8.7-14.9 years, mean 12.1 years) were assessed using the Wechsler Intelligence Scale for Children (WISC-III UK). RESULTS: The patients' full scale IQ scores were all below average (mean 75, 95% CI 70-80), but were not significantly different to those of sibling controls (mean 82, 95% CI 75-89). There was no difference in verbal IQ between patients and siblings, but performance IQ was significantly reduced (mean 75, 95% CI 68-82 in patients; mean 88, 95% CI 80-96 in sibling controls). The reduced performance IQ reflected a poorer performance in tasks assessing perceptual organisational skills. CONCLUSIONS: Data suggest that children with PHD have an IQ that is below average when compared to the population norm and a reduced performance IQ when compared to sibling controls. This may reflect abnormal brain development or could be linked to the impact of hypoglycaemia or low thyroxine concentrations in early life. This information is of value when counselling parents and planning a child's care and education, although further, more extensive studies of patients and siblings are required.     

Developmental language disorders--a follow-up in later adult life. Cognitive, language and psychosocial outcomes

BACKGROUND: Little is known on the adult outcome and longitudinal trajectory of childhood developmental language disorders (DLD) and on the prognostic predictors. METHOD: Seventeen men with a severe receptive DLD in childhood, reassessed in middle childhood and early adult life, were studied again in their mid-thirties with tests of intelligence (IQ), language, literacy, theory of mind and memory together with assessments of psychosocial outcome. They were compared with the non language disordered siblings of the DLD cohort to control for shared family background, adults matched to the DLD cohort on age and performance IQ (IQM group) and a cohort from the National Child Development Study (NCDS) matched to the DLD cohort on childhood IQ and social class. RESULTS: The DLD men had normal intelligence with higher performance IQ than verbal IQ, a severe and persisting language disorder, severe literacy impairments and significant deficits in theory of mind and phonological processing. Within the DLD cohort higher childhood intelligence and language were associated with superior cognitive and language ability at final adult outcome. In their mid-thirties, the DLD cohort had significantly worse social adaptation (with prolonged unemployment and a paucity of close friendships and love relationships) compared with both their siblings and NCDS controls. Self-reports showed a higher rate of schizotypal features but not affective disorder. Four DLD adults had serious mental health problems (two had developed schizophrenia). CONCLUSION: A receptive developmental language disorder involves significant deficits in theory of mind, verbal short-term memory and phonological processing, together with substantial social adaptation difficulties and increased risk of psychiatric disorder in adult life. The theoretical and clinical implications of the findings are discussed.     

Cognitive abilities associated with the Silver-Russell syndrome.

There is no consensus opinion on whether or not cognitive impairments are found in the Silver-Russell syndrome. An investigation of a substantial sample was undertaken, using standardised assessments, in 20 boys and five girls aged 6.0 years to 11.8 years. Mean (SD) birth weights were -2.65 (0.95) SD scores, corrected for gestation. At evaluation the children had a mean (SD) age of 8.8 (1.8) years and a mean height of -2.26 (1.5) SD scores. Tests of cognitive abilities included assessments of general intelligence, reading and arithmetic attainments, and a cognitive processing task. Most had some degree of developmental delay: mean (SD) full scale IQ was 86 (24); 32% scored within the learning disability range (that is, IQ < 70); 40% were reading at least 24 months below their chronological age. Current head circumference correlated highly with full scale IQ. Assessments of special educational needs had been completed on 36%; 48% were receiving speech therapy. Approximately half of children with the Silver-Russell syndrome have significant impairment of their cognitive abilities.