Sarah Raz

Neonatal hypoxic risk in preterm birth infants: the influence of sex and severity of respiratory distress on cognitive recovery.

The authors examined the differential effects of neonatal respiratory distress syndrome (RDS)--a condition associated with elevated risk for neonatal hypoxia-ischemia--on the cognitive development of the two sexes. The authors also attempted to establish whether the severity of respiratory distress is linked to cognitive outcome. Findings revealed an appreciable female advantage in cognitive recovery from RDS, yet the association between severity of RDS and outcome did not reach conventional statistical significance level. The sex effect on intelligence test performance was significantly greater for nonverbal subtests than for verbal ones. These results augment earlier findings of sex differences in cognitive recovery from perinatal intracranial hemorrhage. The current investigation also extends these results to a population of children at neonatal hypoxic risk for whom early brain injury was excluded on the basis of neonatal cranial ultrasound findings.

A female advantage in cognitive recovery from early cerebral insult

Gender differences in cognitive outcome were examined in children born prematurely who had incurred early cerebral lesions and in a high-risk comparison group. The boys and girls, who had suffered perinatal intracranial hemorrhage-the most common neurological insult in the preterm infant-were similar in their antenatal, perinatal, and postnatal course, as well as in their socio-familial attributes. After statistical adjustment to account for the extent of the insult, a significant gender difference in cognitive recovery was observed in the lesion group. Girls outperformed boys by about half a standard deviation on standardized intelligence tests. No gender differences were observed in the comparison group. The implications of the results for theories and empirical findings on gender differences in vulnerability to deviation from normal development are discussed.

Influence of slight to moderate risk for birth hypoxia on acquisition of cognitive and language function in the preterm infant: a cross-sectional comparison with preterm-birth controls.

The cognitive and language performance of a group of 26 preterm-birth preschool and early school-age children with slight to moderate risk for perinatal hypoxia was compared with the performance of a preterm-birth comparison group of 26 children. Despite the relatively small discrepancy in degree of risk, the cognitive performance of the 2 groups diverged significantly. When data for children with known perinatal arterial pH were combined, a curvilinear (quadratic) regression model provided the best fit. Increasing acidosis was linearly related to decreases in cognitive skills, with the bend in the curve occurring well within the normal range of pH values. Hence, in the preterm infant, even minor risk for birth hypoxia may result in discernible deviation from the expected developmental trajectory.

Morphological brain abnormalities in schizophrenia determined by computed tomography: A problem of measurement?

The size of the cerebral ventricles was estimated from computed tomographic (CT) scans of 14 young patients with schizophrenia and 12 medical controls. The subjects were a representative subsample from a larger sample studied by Boronow et al. (1985). Although no CT abnormalities were detected in the psychiatric patients using traditional measures (mechanical planimetry for the lateral ventricles and a linear measure for the third ventricle), a volumetric analysis of the same 26 scans revealed enlargement of the lateral and third ventricles in the schizophrenics. The effect revealed by volumetric measures of the lateral ventricles was 58% greater than that obtained with digital planimetry and 96% greater than the effect found using mechanical planimetry. No differences were found between volumetric and digital planimetric measures of the third ventricle, but the effect revealed by the latter measure was 114% greater than that obtained by a linear index. It is suggested that volumetric measures of lateral ventricles based on information from several CT slices may be more sensitive to group differences in ventricular size than planimetry. Likewise, area measures of the third ventricle may be more sensitive to group differences than linear measures.

Sex differences in early vulnerability to cerebral injury and their neurodevelopmental implications

Sex differences in early vulnerability to cerebral injury were examined in a 10-year cohort of preterm infants. The 173 infants, whose gestational age was 32 weeks or less, were diagnosed with intracranial hemorrhage (ICH), the most common cerebral insult in the premature neonate. Determination of ICH severity was based on neuroimaging evidence obtained during the neonatal period. Because the females in the sample exhibited greater dysmaturity coupled with lower birthweight, as compared with their male counterparts, analysis of covariance was applied to the data. After statistically controlling for the influence of potentially confounding perinatal variables, gender was found to provide a unique contribution to extent of ventricular dilation, an index of ICH severity. Male sex was associated not only with greater ventriculomegaly, but also with a higher grade of ICH. The latter effect was demonstrable in a large subsample of 72 males and 77 females whose birthweights were 1,750 g or below, and who did not differ significantly in gestational age. The implications of these results for theories about the neurobiological origins of sex differences in susceptibility to deviation from normal development are addressed.

Ventriculomegaly in schizophrenia: Is the choice of controls important?

The issue of adequate controls for the study of ventriculomegaly in schizophrenia has been explored initially by Andreasen et al. (1982), who proposed that healthy volunteers, a group with presumably smaller ventricles than medical controls, be considered the optimal comparison group in this area of research. Recently, Smith and Iacono (1986) suggested that group differences may appear to be greater when controls who are patients are used, as a result of the systematic exclusion of medical patients with large though normal ventricles. We conducted a meta-analysis of 37 studies of lateral ventriculomegaly in schizophrenia to clarify this issue. The results indicate that the average effect size in studies with healthy controls does not differ significantly from that obtained in studies employing medical, neurological, or psychiatric (nonpsychotic) controls. Thus, any group without gross neurological damage or severe psychopathology may be used for establishing ventriculomegaly in schizophrenia.

Neonatal respiratory dysfunction and neuropsychological performance at the preschool age: a study of very preterm infants with bronchopulmonary dysplasia.

OBJECTIVE The neuropsychological outcome of chronic lung disease (CLD) in the very preterm (VP) infant may be determined by a process involving chronic hypoxia, with superimposed acute hypoxic episodes, in the developing brain. We wished to study the differences in quality of outcome between VP preschoolers with and without history of the most common form of CLD in the preterm infant, bronchopulmonary dysplasia (BPD). We also examined the strength of association between BPD severity and neuropsychological outcome, with degree of severity defined according to the National Institute of Child Health and Human Development (NICHD) National Heart, Lung and Blood Institute (NHLBI) Workshop categorical ranking scheme (Jobe & Bancalari, 2001) or in accord with dimensional views of severity of respiratory illness. METHOD We evaluated the intellectual, language, and motor outcomes of 156, predominantly middle-class preschoolers with history of VP birth, with (n = 80) or without (n = 76) BPD. We used supplemental oxygen requirement or need for mechanical ventilation as indirect indexes of respiratory dysfunction. RESULTS Following adjustment for potentially confounding sociodemographic variables and perinatal medical risk factors, we found no group differences in neuropsychological outcome based on categorical ranking of BPD severity. However, continuous measures of BPD severity accounted for a unique portion of the variance in fine motor performance (η²p = .05), while patent ductus arteriosus, a risk marker or antecedent of BPD, explained a unique portion of the variance in both receptive language (η²p = .048), and gross motor (η²p = .061) function. CONCLUSION A significant, yet circumscribed, association was demonstrated between neonatal hypoxic risk, in the VP infant, and neuropsychological outcome assessed in the preschool years.

Structural Brain Abnormalities in the Major Psychoses

Since Kraepelin first described the symptoms associated with schizophrenia or “dementia praecox,” numerous studies have attempted to elucidate its etiology. Explanatory efforts ranged from incorporating schizophrenia into a diversity of normal human experiences (Laing, 1960) to describing it as an organic brain disease (e.g., Crow, 1983, 1984). It is this latter approach that generated great interest in structural parameters of schizophrenic brains.

Relationship Between Cognitive and Morphological Asymmetry in Dementia of the Alzheimer Type: A CT Scan Study

In this study we investigated the association between morphological asymmetry and patterns of cognitive ability in dementia of Alzheimers type (DAT). Digitized CT scans were used to estimate volumetric parameters of the brain. The volume of the cranium, brain parenchyma, the subarachnoid space, and lateral ventricles was computed. The volume of the subarachnoid space was used as an index of cortical atrophy, while the ventricular volume served as an estimate of subcortical atrophy. Asymmetry indices were computed for all structures as the difference between left and right volume divided by their average and multiplied by 100. Cognitive asymmetry index was computed by dividing the difference between VIQ and PIQ of the Wechsler Adult Intelligence Scale (WAIS) by their average and multiplying by 100. After statistically controlling for cranial asymmetry, hemispheric asymmetry was found to correlate positively with cognitive asymmetry. The correlation was somewhat greater for male than for female patients. Asymmetry of both cortical and subcortical atrophy correlated negatively with cognitive asymmetry.

Postnatal growth and neuropsychological performance in preterm-birth preschoolers.

OBJECTIVE Compromised postnatal growth is an important risk factor accounting for poorer neuropsychological performance of preterm children during the preschool years, yet its unique contribution to explaining outcome variance within this high risk group has yet to be determined. Therefore, we examined within a large preterm sample (1) the relationships between head growth, measured either at birth or preschool age, and outcome; (2) the relationships of binary versus dimensional head growth measures and performance; and (3) the unique contribution of preschool-age head growth, after adjustment for general physical development (indexed by stature), to variance in neuropsychological functioning. METHOD We evaluated 264 preterm (<36 weeks) preschoolers, without severe handicaps, using cognitive, language, and motor skill measures. Multiple regression analyses, adjusting for sociodemographic factors and pre-, peri-, and postnatal confounds, were used to study associations between growth indices and performance. RESULTS While suboptimal head growth classification at birth was significantly associated only with motor performance, suboptimal head growth at preschool age explained a significant portion of variance in intellectual and language measures (g = .46 to .60). Treating preschool head size as a continuous dimension yielded null results, however, with body-height explaining a significant portion of the variance across several domains. CONCLUSION Among postnatal anthropometric indices, preschool stature, rather than head circumference, remains a consistent correlate of preschool outcome in preterm children, highlighting the contribution of general physical development to neuropsychological performance. Further investigation of the underlying mechanisms likely involves exploration of complex relationships between postnatal nutrition, growth hormone levels, body and brain development, and neuropsychological functioning.