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PubMedDate not supplied

Multimodal neuroimaging studies and neurodevelopment and neurodegeneration hypotheses of schizophrenia.

The interpretation of the huge number of results in schizophrenia research using neuroimaging is uncertain. However, the simultaneous use of complimentary data obtained with these techniques may yield more relevant information in this regard. In this paper we present a series of studies performed by our group in two schizophrenic samples with the use of structural (magnetic resonance imaging, MRI), functional [glucose positron emission tomography (PET) and N-acetyl-aspartate (NAA) magnetic resonance spectrocopy] and neurophysiological techniques (the P300 event-related potential). Transversal and longitudinal measurements were performed.The integrated vision of the results so obtained allows us to propose the hypothesis of a neurodevelopmentally determined state of prefrontal disinihibition, in which the degree of atrophy would directly relate to the metabolic rate. This state would already be present in the first stages of illness and could have neurotoxic consequences in the long term. This would explain the findings of an association between sulcal cerebrospinal fluid (CSF) and illness duration and decreased NAA levels in chronic but not in recent-onset cases. The prefrotnal disinhibition would overstimulate the limbic system and the hippocampus would become overactivated, the metabolic rate at this level being inversely related to P300 amplitude. Clozapine showed a more selective and intense action on that hyperactive metabolic tone than haloperidol.

Journal Article↗
PubMed1992

Neurodevelopment in infants and preschool children with congenital hypothyroidism: etiological and treatment factors affecting outcome.

Studied global intelligence and specific abilities of children from 1 to 5 years old, 108 with congenital hypothyroidism (CH) diagnosed by newborn screening and 71 sibling controls. Intelligence levels of the CH group were within the normal range but differed significantly from controls at age 5. CH demonstrated a language deficit at age 3, which diminished with age, as well as significantly poorer visuospatial and verbal skills at age 5. Children with absent thyroid glands or evidence of hypothyroidism in utero were outperformed by other CH children in most ability areas from 1 year on. Different components of ability were correlated with specific factors reflecting timing or duration of thyroid hormone deficiency, suggesting unique critical periods of thyroid hormone sensitivity for different specific cognitive abilities and their neural substrates. It is concluded that even though screened CH children are markedly improved by neonatal diagnosis, they are still at risk for subtle irreversible deficits, which depend on factors such as type, age at onset, and duration of disease.

Age Factors↗
PubMed1993

31P nuclear magnetic resonance spectroscopy: neurodevelopment and schizophrenia.

A number of studies have demonstrated alterations in the structure and function of the frontolimbic system in some schizophrenic patients. Recent in vivo phosphorus-31 nuclear magnetic resonance studies of the dorsal prefrontal cortex in neuroleptic-naive, first-episode schizophrenic patients and matched controls have shown evidence of alterations in membrane phospholipid and energy metabolism. The membrane alterations observed in the schizophrenic patients are compatible with either premature aging or altered timing and exaggeration of regressive events occurring during normal brain development. These molecular changes may precede onset of clinical symptoms and brain structural changes in schizophrenia and suggest fresh approaches to the pathogenesis and treatment of this illness.

Adult↗
PubMed1996

The effects of early and late preterm birth on brainstem and middle-latency auditory evoked responses in children with normal neurodevelopment.

In preterm and term infants, brainstem and middle latency auditory evoked responses (ABR and MLR) were obtained at 40 and 52 weeks conceptional age (CA) and at 5 years of age. A neurological and neuropsychological evaluation was performed at 5 years of age. To study the effect of preterm birth on the maturation of the ABR and MLR, the preterm infants were divided into early and late preterm groups. Only children with a normal neurodevelopmental outcome at 5 years of age were entered into the study. For ABR, the late preterm group showed significantly longer mean latencies IIc, III, V, and Vc when compared with the term group at 52 weeks CA. There was a trend to longer ABR latencies I in the early preterm group compared with the term group. At 52 weeks CA, the late preterm group showed longer mean interpeak latencies III-I and V-I when compared with the term as well as the early preterm group. At 5 years, the late preterm group showed significantly longer mean ABR latencies IIc and III when compared to the early preterm group. For MLR, the early preterm group showed significantly longer mean latencies of MLR component PO when compared with the term group at 40 weeks CA. At 52 weeks, the late preterm group also had longer mean MLR latencies P0 than the term group. At 5 years of age, the term group showed higher mean peak-to-peak amplitudes Na-P0 than the early as well as the late preterm group. To a large extent, the ABR results support the hypothesis that middle ear effusions in combination with retarded myelination of the central auditory pathway are responsible for the ABR differences found between term and preterm infants with a normal neurodevelopmental outcome at 5 years of age. The longer latencies and interpeak latencies found in late preterm infants when compared with early preterm infants might be explained by an augmented vulnerability of the auditory pathway between 30 and 34 weeks CA. The MLR differences found between term and preterm infants might be explained by a difference in the maturation of primary and nonprimary MLR components.

Auditory Cortex↗
PubMed1998

The clinical stigmata of aberrant neurodevelopment in schizophrenia.

The neurodevelopmental hypothesis of schizophrenia is currently a primary etiopathological model for schizophrenia. Its tenets derive from observations of epidemiological, postmortem, and brain imaging evidence of neurodevelopmental deviance. Clinical stigmata of neurodevelopmental arrest include the presence of obstetric complications, minor physical anomalies, abnormal dermatoglyphics, and childhood neuromotor precursors of adult schizophrenic illness. The relative importance of these stigmata and their relationship to brain imaging findings in schizophrenia are discussed.

Adult↗
PubMed2000

Timing of perinatal human immunodeficiency virus type 1 infection and rate of neurodevelopment. The Women and Infant Transmission Study Group.

BACKGROUND: Identifying HIV-1-infected children who are at greatest risk for disease-related morbidities is critical for optimal therapeutic as well as preventive care. Several factors have been implicated in HIV-1 disease onset and severity, including maternal and infant host characteristics, viral phenotype and timing of HIV-1 infection. Early HIV-1 culture positivity, i.e. intrauterine infection, has been associated with poor immunologic, virologic and clinical outcomes in children of HIV-infected women. However, a direct effect of timing of infection on neurodevelopmental outcome in infancy has not yet been identified. METHODS: Serial neurodevelopmental assessments were performed with 114 infants vertically infected with HIV-1 in a multicenter natural history, longitudinal study. Median mental and motor scores were compared at three time points. Longitudinal regression analyses were used to evaluate the neurodevelopmental functioning of children with early positive cultures and those with late positive cultures. RESULTS: Early infected infants scored significantly lower than late infected infants by 24 months of age and beyond on both mental (P = 0.05) and motor (P = 0.03) measures. Early HIV-1 infection was associated with a decline in estimated motor scores of 1 standard score point per month compared with 0.28 point in the late infected group (P < 0.02). Estimated mental scores of the early infected group declined 0.72 point/ month, whereas the average decline of the late infected group was 0.30 point/month (P < 0.13). CONCLUSION: Early HIV-1 infection increases a child's risk for poor neurodevelopmental functioning within the first 30 months of life.

Child Development↗
PubMed2001

Neurodevelopment in children with single-suture craniosynostosis and plagiocephaly without synostosis.

The objective of this study was to determine whether children with nonsyndromic craniosynostosis and plagiocephaly without synostosis demonstrated cognitive and psychomotor delays when compared with a standardized population sample. This was the initial assessment of a larger prospective study, which involved 21 subjects with nonsyndromic craniosynostosis (mean age, 10.9 months) and 42 subjects with plagiocephaly without synostosis (mean age, 8.4 months). Each child was assessed using the Bayley Scales of Infant Development-II (BSID-II) for cognitive and psychomotor development before therapeutic intervention (surgery for craniosynostosis and molding-helmet therapy for plagiocephaly without synostosis). The distribution of the scores was divided into four groups: accelerated, normal, mild delay, and significant delay. The distributions of the mental developmental index (MDI) and the psychomotor developmental index (PDI) were then compared with a standardized Bayley's age-matched population, using Fisher's exact chi-square test. Within the craniosynostosis group, the PDI scores were significantly different from the standardized distribution (p < 0.001). With regard to the PDI scores, 0 percent of the subjects in the craniosynostosis group were accelerated, 43 percent were normal, 48 percent had mild delay, and 9 percent had significant delay. In contrast, the MDI scores were not statistically different (p = 0.08). Within the group with plagiocephaly without synostosis, both the PDI and MDI scores were significantly different from the normal curve distribution (p < 0.001). With regard to the PDI scores, 0 percent of the subjects in the group with plagiocephaly without synostosis were accelerated, 67 percent were normal, 20 percent had mild delay, and 13 percent had significant delay. With regard to the MDI scores, 0 percent of the subjects in this group were accelerated, 83 percent were normal, 8 percent had mild delay and 9 percent had significant delay. This study indicates that before any intervention, subjects with single-suture syndromic craniosynostosis and plagiocephaly without synostosis demonstrate delays in cognitive and psychomotor development. Continued postintervention assessments are needed to determine whether these developmental delays can be ameliorated with treatment.

Child Development↗
PubMed1988

In utero exposure to organic solvents and human neurodevelopment.

Recent reports of growth and mental retardation in infants whose mothers abused solvent-containing substances, and of an association between central nervous system malformations and solvent exposure, have suggested that in utero exposure to organic solvents may have a profound effect on the development of the human brain. The present investigation compared the neurobehavioral development of 41 children whose mothers worked with organic solvents during pregnancy with a group of matched, unexposed children. The children were compared on a variety of measures, including the McCarthy Scales of General Abilities, growth (weight, height and head circumference) and mother's report of developmental milestones, behavior and personality. Potential confounders were controlled for in multiple regression analyses. Despite adequate power, no differences could be found between the two groups on any of the measures of neurobehavioral development or growth. This study suggests that in utero exposure to relatively low levels of organic solvent is not associated with adverse neurodevelopmental outcome.

Brain↗
PubMed1989

Cerebral blood-flow velocity during the first week of life of preterm infants and neurodevelopment at two years.

Disturbances in perinatal cerebral perfusion appear to be associated with unfavourable neurodevelopmental outcome. Using transcutaneous Doppler technique, the authors investigated cerebral blood-flow velocity patterns in the anterior cerebral artery (ACA) of an intensive care-unit population of preterm infants during the first week of life. The results were correlated with neurodevelopmental outcome at two years of age. Children with major disability at two years of age had significantly higher pulsatility index (PI) values, mainly increased peak systolic flow velocity (PSFV), compared with children with normal or more favourable outcome. End diastolic flow velocity and area under the velocity curve values of the ACA did not differ between the groups, indicating that cerebrovascular resistance and cerebral blood-flow were not different. It is thought that the higher PI and PSFV values were caused by increased compliance of the vascular bed supplied by the ACA, possibly induced by congestion and oedema of the periventricular white-matter due to ischaemic lesions, which also cause periventricular leukomalacia.

Blood Flow Velocity↗
PubMedDate not supplied

Community health nursing assessment of neurodevelopment in high-risk infants.

All infants discharged from designated perinatal center neonatal intensive care units in Illinois are referred for follow-up home visits by community health nurses. These visits provide parental support, teaching, and anticipatory guidance plus physical and developmental assessment of the infant. The maternal and child nursing consultants who coordinate this follow-up program are frequently called upon to assist the community health nurses in physical/developmental assessment techniques. The neurodevelopmental component of the assessment, including areas of alertness, tone, head circumference, vision and hearing screening, plus primitive reflexes, is described.

Attention↗
PubMed1996

Transient dystonia in non-handicapped low-birthweight infants and later neurodevelopment.

The aim of the present study was to evaluate the long-term prognostic significance of transient increase in muscle tone during infancy (dystonia) in very low-birthweight (VLBW) infants without cerebral palsy. Motor (Peabody Developmental Motor Scales), cognitive (Wechsler Preschool and Primary scale of Intelligence) and behavioural (Personality Inventory for Children, Yale Children's Inventory) development was assessed at 5 years of age. In a population-based sample of 50 VLBW children, transient dystonia was present in 14. In explorative analyses, transient dystonia was associated with low 1 min Apgar scores, neonatal bacterial infection, and lack of breast-milk in the neonatal period. Cognitive, neuromotor and behavioural development at 5 years of age was comparable in those with and without transient dystonia, although there was a statistically non-significant tendency towards more neuromotor problems in the dystonic children.

Apgar Score↗
PubMed1999

Babies, brains and culture: optimizing neurodevelopment on the savanna.

Cross-cultural child development research has demonstrated the influence of infant experience as well as constitutional, neurodevelopmental influences in infant outcomes. African infant precocity found in a number of studies is examined in the light of developmental models and in the context of the enriched child-rearing environment of pre-industrial societies. Examples are drawn from fieldwork in East Africa that demonstrate the different contributions of pregnancy, nutrition, early learning and cultural factors on developmental outcomes. The multiple enhancing infant rearing and nutritional factors are postulated to optimize the rate of neuro-development thereby contributing to psychomotor precocity.

Africa↗
PubMed1999

Visual function in term infants with hypoxic-ischaemic insults: correlation with neurodevelopment at 2 years of age.

AIMS: To determine if there is any association between the findings of visual assessment performed at the age of 5 months and neurodevelopmental outcome at the age of 2 years in children who have sustained hypoxic-ischaemic insults. METHODS: Twenty nine term infants with hypoxic-ischaemic encephalopathy and/or brain lesions on neonatal magnetic resonance imaging (MRI) were prospectively evaluated. At 5 months of age all the infants had their visual function assessed using the Atkinson Battery of Child Development for Examining Functional Vision, which includes the assessments of optokinetic nystagmus (OKN), acuity, visual fields, fixation shift and phase and orientation reversal visual evoked potentials. At 2 years of age the children had a structured neurological evaluation and a Griffiths developmental assessment. RESULTS: There was good correlation between the extent of the early detected visual impairment and both neuromotor and global development. Children with more than three out of five abnormal visual tests at 5 months of age tended to have abnormal neurological examination results and abnormal developmental quotients. Children with three or fewer abnormalities tended to have developmental quotients in the normal range; the level of their performance, however, was still related to the number of visual tests passed. CONCLUSIONS: Individual visual tests can provide important prognostic information. While abnormal OKN and acuity were always associated with abnormal outcome, normal results on visual evoked potentials and fixation shift tended to be associated with normal outcome.

Brain↗