Bruce F. Pennington

Toward a Neuropsychological Model of Infantile Autism: Are the Social Deficits Primary?

Although infantile autism was first described as a disorder of “affective contact,” in the past 20 years it has been largely regarded as a cognitive disorder, with socially deviant behavior seen as a secondary manifestation. After a discussion of diagnostic issues, the nature of the socially deviant behavior is described, and a brief history of theories to account for this behavior is presented. It is then suggested that the social symptoms may more fruitfully be viewed as primary because of (1) the dissociability of social and cognitive impairments both within and across developmentally disabled populations, (2) the special difficulty autistic children may have with social or affective stimuli, and (3) the rarity of social isolation even in severely damaged babies, and its resistance to modification in autistic children. In addition, the specific cognitive deficits suggested to be central to autism (4) can be found in at least as severe a form in sociable retarded children, (5) are theoretically inadequate to explain autistic aloofness, (6) cannot be found in all autistic children, and (7) may be the very cognitive abilities which rest most heavily on social functioning. Some implications are drawn for neuropsychological models of autism.

Molecular/clinical correlations in females with fragile X

Females who are affected by fragile X syndrome (FXS) can have significant physical, neuropsychological and emotional involvement. This study was designed to explore the relationships between these three domains and to learn how the degree of involvement in each of these phenotypic areas relates to molecular parameters including CGG repeat length and activation ratio (the proportion of normal FMR1 alleles on the active X chromosome). Three groups of females were studied: 35 women who grew up in a fragile X family but do not carry an FMR1 mutation, 92 women with a premutation, and 29 women with a full mutation. Correlations between neurocognitive, physical and emotional traits were calculated for each of the three groups. Within the full mutation group significant correlations were seen between schizotypal traits and full scale IQ. The Lie scale was significantly correlated with the physical findings index. The activation ratio correlated significantly with the measure of executive function (r = .50, P = .01). There was a trend toward correlations of activation ratio with the physical index score, outer ear prominence and IQ. CGG repeat number significantly correlated only with the physical index (r = .44, P = .01). Thus, activation ratio may be the more pertinent molecular parameter in full mutation women in determining the degree of cognitive and physical phenotypic involvement.

The neuropsychological phenotype in turner syndrome

Numerous studies have demonstrated a significant depression in performance IQ (PIQ) in Turner Syndrome (TS) females, but the neuropsychological interpretation of this finding remains unclear. The present study addressed the following questions regarding the neuropsychological phenotype in TS: Are TS women neuropsychologically impaired? Is the impairment lateralized and How consistent is the neuropsychological phenotype across TS individuals? Unlike previous studies, the present study utilized both normal and brain damaged female controls. All subjects were given an extended Halstead-Reitan neuropsychological battery. The TS females were significantly worse than normals but not significantly different from brain damaged females in their overall level of neuropsychological functioning. However, their impairment was not lateralized. Their pattern of lateralizing findings was similar to that found in the Diffuse and Normal groups, but significantly different from either the right or left unilateral lesion groups. Fairly consistent deficits were found on tests of visuospatial skills and long term memory, but there was considerable variability in all the other test findings among TS individuals. The results are discussed in relation to the recent findings (Inglis and Lawson, 1981) that verbal-performance IQ discrepancies may be unreliable indicators of lateralized cerebral dysfunction in females. Hence the depressed PIQ in TS appears not to indicate predominantly right hemisphere dysfunction and may not even indicate a consistent underlying neuropsychological phenotype.

Specific frontal lobe deficits among women with the fragile X gene

The neurocognitive phenotype of fragile X and its relation to cytogenetic expression were examined among 10 fragile X women with > or = 2% expression, 10 0% obligate carriers, and 10 controls. Measures were obtained for intellectual ability, achievement, and verbal, nonverbal, memory, and frontal lobe functions. Results show that no group demonstrated deficits on verbal, nonverbal, or memory measures. In contrast, when controlling for effects of IQ, the expressing fragile X women exhibited (1) deficits on measures of frontal lobe functioning, and (2) enhanced performance on verbal, but not figural, memory. Frontal lobe deficits may account for behavioral and cognitive manifestations of fragile X.

Social cognition skills among females with fragile X

Emotion perception and perspective-taking skills were examined among women with or without the fragile X gene. The performance of 56 control women was compared to the performance of 46 women who were carriers of the fragile X gene. Twenty-seven of the carrier women had 0–1% cytogenetic expression and did not appear affected by the gene, whereas the remaining 19 women had ≥2% cytogenetic expression and did appear affected by the gene. The emotion perception task employed was one for which deficits have been reported among individuals with autism. The results show that performance on this emotion-perception test and the perspective-taking measure was significantly related to full-scale IQ scores, but not to fragile X group status when effects of IQ were removed. Thus the results do not support the hypothesis that perspective-taking or emotion perception deficits are a component of the fragile X phenotype in females and represent an important differentiation between fragile X and autism.

Unexpected reading precocity in a normal preschooler: Implications for hyperlexia ☆

This is a case study of a left-handed, preschool boy of superior intelligence who read very early and at a level well beyond what his IQ would predict. He is developmentally normal with no signs of autism or related disorders. His reading age was 9.3 at age 2-11 and 11.2 at 4-2; these levels are considerably beyond what would be predicted by his IQ or language age. He was able to read nonwords and both regular and irregular words equally well, indicating his mechanisms of lexical access in reading are similar to those of normal readers. Unlike classical hyperlexics, his reading comprehension for both single words and sentences was well above age level. When his precocious reading first appeared, he was also advanced in reading-related linguistic skills, such as phoneme awareness, auditory verbal short-term memory, and word retrieval, but not in visuospatial skills. These results imply that neither pathological language and/or social development, nor pathological variation in the normal mechanisms of lexical access in reading are necessary causes for reading precocity in early childhood. A model for integrating subtypes of precocious readers with subtypes of normal and dyslexic readers is proposed.

Fragile X Syndrome in a Normal IQ Male with Learning and Emotional Problems

The present case study features an adult male who was diagnosed with fragile X syndrome after the identification of this syndrome in his more affected brother. The patient presented with a Full Scale IQ within the broad range of normal and has been diagnosed with a schizotypal personality disorder. He shows significant deficits in the social and emotional aspects of daily life, but has striking cognitive strengths relating to reading and vocabulary as compared to most males affected with fragile X syndrome. DNA testing of blood leukocytes revealed that he has a fully expanded FMR1 CGG repeat mutation associated with almost complete lack of methylation. Protein studies demonstrate a limited production of FMRP, the protein produced by the FMR1 gene. It is believed that the near absence of methylation of the fully expanded mutation and the resultant expression of the FMR1 protein is responsible for the strong cognitive abilities of this fragile X patient.

Implications of Social Deficits in Autism for Neurological Dysfunction

In this chapter, we will consider some of the implications of the social deficits in autism for neurological dysfunction. In the first section, we will consider the nature of the social deficit, and the arguments for considering it a primary and not a secondary manifestation of neurological disorder. In the second section, we will review some of the evidence for specific neurological systems involved in social and attachment behavior, and in the third section, we will consider whether any clinical evidence supports the involvement of these systems in autism. Finally, we will suggest some implications for future research.