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Minor physical anomalies, dermatoglyphic asymmetries, and cortisol levels in adolescents with schizotypal personality disorder.

OBJECTIVE: A relationship between schizotypal personality disorder and schizophrenia has been documented in behavioral genetic studies, and there are similarities in the cognitive deficits and brain abnormalities associated with these disorders. Adolescents with schizotypal personality disorder are of particular interest because the postpubertal period is a critical one for the development of a DSM axis I disorder. It is likely that some schizotypal adolescents will remain stable over time, some will improve, and a subgroup will develop schizophrenia. This study tested the hypotheses that, like schizophrenic patients, schizotypal adolescents manifest an elevated rate of minor physical and dermatoglyphic anomalies, both of which suggest prenatal neurodevelopmental abnormalities. Cortisol release is also of interest because of evidence that the hypothalamic-pituitary-adrenal axis may influence the behavioral expression of vulnerability to schizophrenia. METHOD: Minor physical anomalies, dermatoglyphic asymmetries, and salivary cortisol levels were measured in three groups of adolescents: 20 with schizotypal personality disorder, 20 with other personality disorders, and 26 with no disorder. Assessments began at noon, and four saliva samples were obtained at hourly intervals. RESULTS: The schizotypal personality disorder group showed more minor physical anomalies and dermatoglyphic asymmetries than the normal comparison group and higher cortisol levels than both of the other groups. Group differences in cortisol level were most pronounced at the beginning of the evaluation. Cortisol level and age were positively correlated. CONCLUSIONS: The findings support the assumption that schizotypal personality disorder is associated with perturbations in fetal neurodevelopment and, under some circumstances, a heightened cortisol response.

Adolescent↗

Low GSK-3beta immunoreactivity in postmortem frontal cortex of schizophrenic patients.

OBJECTIVE: Glycogen synthase kinase-3 (GSK-3) is a protein kinase that is highly abundant in the brain. It is involved in signal transduction cascades of multiple cellular processes, particularly neurodevelopment. In an attempt to explore possible involvement of GSK-3beta in psychiatric disorders, the authors examined its levels in postmortem brain tissue. METHOD: Western blot analysis was performed to measure GSK-3beta in the frontal cortex of 14 schizophrenic patients, 15 patients with bipolar disorder, 15 patients with unipolar depression, and 14 normal comparison subjects. RESULTS: GSK-3beta levels were 41% lower in the schizophrenic patients than in the comparison subjects. Other diagnostic groups did not differ from the comparison subjects. CONCLUSIONS: These results are consistent with the notion that schizophrenia involves neurodevelopmental pathology. It remains to be investigated whether the active fraction of GSK-3beta, or its activity, is also low in frontal cortex of schizophrenic patients and if this is also reflected in other brain regions.

Adult↗

Growth and academic achievement in inner-city kindergarten children. The relationship of height, weight, cognitive ability, and neurodevelopmental level.

Measures of height, weight, nonverbal cognitive ability (Ravens progressive matrix), visual-motor-perceptual ability (Beery-Buktenica test of Visual Motor Integration [VMI]), the imitation-of-gestures technique, and academic achievement (Stanford Early Achievement) were obtained for a sample of 82 children from a poor inner-city community. In contrast to prior reports from the United States and about other developed countries, anthropometric measures were related both to academic achievement and to these measures of neurodevelopment. They were not consistently related to measures of nonverbal cognitive ability. Regression analyses revealed that general cognitive ability contributed more variance (39%) to predictions of achievement than all other variables, including weight for age (13%) and VMI (6%). Children with reduced somatic growth were likely to do poorly in school, but the data do not show that undernutrition causes learning failure. Rather, they suggest that environmental problems affecting the development of thought processes and nutrient intake precede both growth and learning failure.

Achievement↗

Very-low-birthweight infants at seven years: an assessment of the health and neurodevelopmental risk conveyed by chronic lung disease.

To determine whether history of chronic lung disease (CLD) in children born at very low birthweight (VLBW) confers additional risk for impaired health, growth, and neurodevelopment, 17 VLBW children born in 1984 who had CLD (requiring supplemental oxygen more than 30 days after birth) in infancy and 28 VLBW children who did not have CLD were assessed at age 7 years. Assessments included a medical history, standard physical and neurological examinations, pulmonary-function tests, and tests of neuropsychological and psychoeducational functioning. Health status did not differ between the groups. In contrast, children with CLD did not perform as well in neuropsychological and psychoeducational assessments. Although CLD confers little added risk to health, it seems to add significantly to risks for poor school performance that are known to be associated with very low birthweight.

Achievement↗

Resistance to thyroid hormone: implications for neurodevelopmental research on the effects of thyroid hormone disruptors.

Thyroid hormones are essential for normal behavioral, intellectual, and neurological development. Congenital hypothyroidism, if not treated, can result in irreversible mental retardation, whereas thyroid diseases with more moderate impairment of thyroid function, such as resistance to thyroid hormone, cause less severe intellectual and behavioral abnormalities, including attention deficit hyperactivity disorder. There is increasing evidence that exposure to certain synthetic compounds, including dioxins and polychlorinated biphenyls (PCBs), during the perinatal period can also impair learning, memory, and attentional processes in offspring. Animal and human studies suggest that exposure to these environmental toxicants impair normal thyroid function. Although the precise mechanisms of action of the adverse effects these toxicants have on neurodevelopment have not yet been elucidated, it is possible that they are partially or predominantly mediated by alterations in hormone binding to the thyroid hormone receptor. The convergence of studies that examine the neurodevelopmental consequences of moderate impairment of thyroid function, such as is found in resistance to thyroid hormone, with those studies that demonstrate the adverse behavioral and cognitive effects of perinatal exposure to dioxins and PCBs serves to generate new hypotheses to test in a research setting. Such studies may provide new insights into the basic pathogenesis of developmental neurotoxicity following exposure to thyroid-disrupting synthetic compounds.

Animals↗

Auditory brainstem evoked potentials in early-treated congenital hypothyroidism.

To evaluate the effect of early treatment of congenital hypothyroidism on central nervous system development, auditory brainstem evoked potentials were determined in 32 patients with hyperthyrotropinemia diagnosed during neonatal screening. The patients included 27 with congenital hypothyroidism and 5 with transient hypothyroidism. Abnormal auditory brainstem evoked potential tracings were found in 8 patients (congenital hypothyroidism in 7 and transient hypothyroidism in 1). Four of these patients had increased peripheral conduction time (wave I prolongation), and the other 4 had increased central conduction time (wave III or V prolongation). The patients with abnormal auditory brainstem evoked potentials did not show increased initial manifestations, yet 6 of them had lower initial thyroxine levels. Specific auditory brainstem evoked potential abnormalities were found in 25% of early-treated patients with congenital hypothyroidism. The possible causal relationship between deviant auditory brainstem evoked potential patterns and later neurodevelopment demands further clarification. This study suggests the usefulness of auditory brainstem evoked potential assessment to provide information about electrophysiologic deviation of the auditory pathway in patients with early-treated congenital hypothyroidism.

Child, Preschool↗

Speech and language deterioration in benign rolandic epilepsy.

A 5-year-old boy presented with typical clinical and electrophysiologic features of benign rolandic epilepsy. His neurodevelopment, language, and behavior prior to the onset of epilepsy were appropriately normal. He demonstrated marked deterioration of language and cognitive function during the course to a mild and then a moderate disability range. Serial sleep electroencephalographic recordings initially showed continuous and bilateral rolandic discharges with evolution to localized left rolandic spikes. Language and cognitive improvements were subsequently seen. Educational support and evolution of the electroencephalogram to a localized focus could have been contributory. It is anticipated, however, that he will have significant long-term problems in complex language.

Anomia↗

Antenatal diagnosis of central nervous system anomalies: can we predict prognosis?

Our technical ability to diagnose fetal anomalies of the central nervous system by ultrasonography and by fetal magnetic resonance imaging far exceeds our current knowledge of their possible neurodevelopmental implications later in life. This limitation often makes obstetric and clinical decisions very difficult. We retrospectively reviewed the ultrasonographic records of 6220 women who had been followed up at two large medical centers between 1994 and 1999. One hundred and sixty (2.6%) women had abnormal fetal central nervous system findings. The neurodevelopmental outcome of these children was assessed by a telephone interview with the parents. Small cerebellar size was the most frequent anomaly, followed by isolated mild ventriculomegaly and isolated choroid plexus pathology. Suboptimal neurodevelopmental outcome was found in 24% of children with isolated ventriculomegaly and in 9% with choroid plexus pathology. In the group of children with a "small cerebellum," suboptimal neurodevelopment was found in 19%. The measurement of transcerebellar diameter in respect to its developmental implication is, to our knowledge, described here for the first time. We believe that cerebellar measurements and their possible neurocognitive implications should be an integral part of future studies.

Abortion, Induced↗

Multiple cardiac rhabdomyomas as a sole symptom of tuberous sclerosis complex: case report with molecular confirmation.

We report a child in whom multiple cardiac rhabdomyomas were identified on routine fetal ultrasonography. Molecular genetic studies identified the TSC2 gene missense mutation (E36; 4672 G>A, 1558 E>K TSC2). Both general and neurodevelopment of the patient have been normal. When last examined at age 6 years, he had no skin manifestations of tuberous sclerosis complex. Computed tomography of the brain revealed two periventricular calcifications consistent with the molecular diagnosis. This is the first report of molecularly confirmed tuberous sclerosis complex in a child with multiple cardiac rhabdomyomas and no other clinical manifestations of the disease. We propose that all cases of multiple cardiac rhabdomyomas in an infant be given a tentative diagnosis of tuberous sclerosis complex.

Brain↗

Neurodevelopmental outcome of severe neonatal hemolytic hyperbilirubinemia.

We recruited 128 neonates with hyperbilirubinemia over a 5-year period (1995-2000) to study the short- and long-term effects of hemolytic hyperbilirubinemia on the auditory brainstem pathway and neurodevelopmental status. These children were divided into two groups: (1) a hemolytic group (n = 29; ABO incompatibility [n = 19], Rh incompatibility [n = 1], glucose-6-phosphate dehydrogenase deficiency [n = 8] and both ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency [n = 1]) and (2) a nonhemolytic group (n = 99). All received phototherapy. Exchange transfusions were performed for four (13.8%) in the hemolytic group and three (3%) in the nonhemolytic group. The brainstem auditory evoked potential was recorded at a mean age of 3.2 months in the hemolytic group and 3.1 months in the nonhemolytic group. Serial brainstem auditory evoked potential assessments were performed until 2 years of age (3 in the hemolytic group and 18 in the nonhemolytic group). All had regular physical, neurologic, visual, and auditory evaluation until 3 years of age. The rate of exchange transfusion was significantly higher in the hemolytic group than in the nonhemolytic group (P < .05). Brainstem auditory evoked potential abnormalities at the initial assessment occurred in three (10.4%) in the hemolytic group (all related to ABO incompatibility) and nine (9.1%) in the nonhemolytic group. At 2 years, the brainstem auditory evoked potential returned to normal except in three cases with a slightly increased hearing threshold (one [3.5%] in the hemolytic group at 60 dB nHL and two [2%] in the nonhemolytic group at 50 dB nHL]). There were no significant differences in the rate of brainstem auditory evoked potential abnormalities at the initial or subsequent assessments between both groups. All except five cases had a normal neurodevelopmental outcome at 3 years (three [two with ABO incompatibility and one with glucose-6-phosphate dehydrogenase deficiency] in the hemolytic group [10.4%] and two [2%] in the nonhemolytic group). All had mild motor delay and hypotonia, which returned to normal at 3 years. The rate of abnormal neurodevelopmental outcome was higher in the hemolytic group than in the nonhemolytic group, although with no significant difference between both groups (P = .08). All five cases in both groups with abnormal neurodevelopment had a normal brainstem auditory evoked potential at the initial assessment. There was no relationship between the abnormal initial brainstem auditory evoked potential and the final neurodevelopmental outcome. The toxic effect of hyperbilirubinemia on the auditory brainstem pathway and neurodevelopmental status in our cohort was transient. The prognosis of neonatal hemolytic hyperbilirubinemia in our Chinese cohort is excellent, possibly owing to an aggressive early-intervention approach.

Asian People↗

Role of instrumented fetal sheep preparations in defining the pathogenesis of human periventricular white-matter injury.

Periventricular white-matter injury is the major form of brain injury associated with prematurity and the leading cause of cerebral palsy in survivors of premature birth. Progress in understanding the pathogenesis of periventricular white-matter injury requires the development of animal models that are relevant to the unique physiology of the preterm human brain and that replicate the major neuropathologic features of human injury. The sheep is the most extensively studied true fetal preparation. The neurodevelopment of the preterm sheep fetus (0.65 gestation) is comparable to that of the preterm human between approximately 24 and 28 weeks. The size of the fetal sheep permits chronic instrumentation so that well-defined insults can be studied with reliable measurements of blood flow and metabolism in cerebral white-matter. We review here recent developments in the understanding of the role of cerebral hypoxia-ischemia and vulnerable oligodendrocyte progenitors in the pathogenesis of periventricular white-matter injury in the immature sheep fetus. We focus on recent developments in high-resolution spatially defined cerebral blood flow measurements in utero. We determined ovine white-matter maturation between 90 and 120 days' gestation, as defined by immunohistochemical localization of oligodendrocyte lineage-specific antibodies. There was considerable spatial and temporal heterogeneity in oligodendrocyte maturation in the immature periventricular white-matter. Oligodendrocyte maturation in the 90- to 105-day fetal sheep closely coincided with that of the preterm human during the high-risk period for white-matter injury. Hence, the immature state of the 90- to 105-day fetal periventricular white-matter is an optimal and dynamic developmental window to study the role of cellular-maturational factors in the pathogenesis of white-matter injury. We conclude with a review of the significant advantages of the instrumented fetal sheep to accelerate progress in the translation of preventive therapies for periventricular white-matter injury and cerebral palsy.

Animals↗

Treatment of children and adolescents with tics and Tourette syndrome.

Tics, patterned movements distinct from stereotypies, myoclonus, and other hyperkinetic movements, are quite common in children, particularly among those with developmental and psychiatric disorders. Thus, tics can indicate the presence of atypical neurodevelopment or broader difficulties with cognition or mood. Tics are also the cardinal feature of Tourette syndrome, a childhood-onset neurobehavioral disorder characterized by a chronic inability to suppress or an urge to perform patterned, repetitive movements. Patients with Tourette syndrome most commonly have, in addition to tics, symptoms of inattention, hyperactivity, obsessiveness, or anxiety. Achieving the most effective treatment of a child with tics is contingent on proper diagnosis of the movement disorder and thorough assessment for other problems, followed by consideration of both nonpharmacologic and pharmacologic interventions for any and all symptoms interfering with the child's function and quality of life. This review focuses primarily on the diagnosis and medical treatment of tics in children and adolescents with Tourette syndrome.

Adolescent↗

The introduction of breast milk donation in a Muslim country.

Breast milk donation (wet-nursing) for full-term babies is a well-known practice in Kuwait, but it has never been organized formally in a neonatal intensive care unit (NICU) for preterm babies. Donor milk banking as conducted in Western society is not considered to be ethical in Muslim society, where the milk donor and the recipient are required to know each other. Human milk is known to decrease the incidence of necrotizing enterocolitis; improve host defenses, digestion, absorption of nutrients, gastrointestinal function, and neurodevelopment of the child; and contribute to maternal physical and psychological well-being. A culturally accepted approach to donor milk banking is proposed as a means of overcoming the ethical issues surrounding milk donation in Muslim society. This report addresses the first step in raising awareness of the valuable contribution of donor milk to preterm babies and the organization of human milk donation for use in an NICU.

Adult↗

Erythropoietin in human milk: physiology and role in infant health.

Human milk contains substantial concentrations of erythropoietin, a hormone best known for its role in the regulation of erythropoiesis. Recent studies show that erythropoietin receptors are widely distributed in human tissues, including the gastrointestinal tract, endothelial cells, spinal cord, and brain, suggesting that erythropoietin plays a wider role in infant development. Mammary epithelial cells contribute to the production of erythropoietin in human milk, and erythropoietin concentrations appear to rise slowly in human milk during the first few months of lactation. Current data suggest that erythropoietin in human milk may play a pleiomorphic role in erythropoiesis, neurodevelopment, maturation of the gut, apoptosis, and immunity in the infant.

Adult↗

Reconsidering punitive and harsh discipline.

Corporal punishment and other harsh interventions continue to be widespread despite the fact that the leading theories or models of behavioral management do not support their effectiveness. There is overwhelming evidence that harsh interventions are damaging to children, both emotionally and physically. The effects of such trauma may be compounded when a child has preexisting learning difficulties. When schools respond to these challenges using harsh methods, children can be further traumatized. The authors review principles of childhood neurodevelopment, describe a model to understand children in context, and discuss how exposure to certain noxious sensory experiences can affect children's responses to threat or perceived threat. They also describe implications for school nurses.

Child↗

Body mass index in male and female children with infantile autism.

Morphometry, the measurement of forms, is an ancient practice. Recently, evidence has grown to support the notion that aberrant neurodevelopment may play a role in the pathophysiology of autism. Is the body, like the brain, affected by abnormal development in these patients? The aim of this study was to evaluate body mass index (BMI) of children with infantile autism, by comparing the BMI of 117 children with infantile autism with the corresponding BMI percentiles in an age- and sex-matched reference population. The BMI distribution of the male, but not female, children with infantile autism was significantly lower than that of the age-matched reference population. There was no evidence that BMI was associated with intelligence or socioeconomic status among children with infantile autism.

Autistic Disorder↗

Closer to the gold standard: an appraisal of formulae available in Italy for use in formula-fed infants.

Infant formulae are the only alternatives to breast milk for infants who are unable to continue breastfeeding through the first year of life. They aim to provide formula-fed infants with the same structural and functional benefits observed in breastfed infants. To achieve this, bioactive nutrients have been added to infant formulae in recent years: long-chain polyunsaturated fatty acids for neurodevelopment; probiotics and prebiotics for local gastrointestinal defence; and nucleotides for promoting the immune response. Changes in protein quantity and quality allow infant formulae to achieve a balance between providing the correct plasma amino acid profile and reducing the protein intake, which could prevent obesity in later life. Hydrolysed proteins may help prevent atopic disorders. Many short-term trials have been published but long-term follow-up data are needed in infants who have been fed the newer infant formulae, to fully understand the role of bioactive nutrients.

Carbohydrates↗

Effectiveness of intermittent diazepam prophylaxis in febrile seizures: long-term prospective controlled study.

The efficacy of intermittent rectal diazepam prophylaxis is assessed in the prevention of febrile seizures. In a prospective randomized cohort trial, 139 children (77 girls, 62 boys) who experienced a first febrile seizure were allocated to two groups: group A, which received intermittent diazepam (n = 68), and group B, which received no prophylaxis (n = 71). All children had a 3-year follow-up. The inclusion criteria were no personal history of afebrile seizures, normal neurodevelopment, no previous anticonvulsant therapy, and age between 6 months and 3 years. Each group was stratified to low, intermediate, and high risk according to the available clinical data. The 36-month recurrence rates in the no-prophylaxis group were 83% in high-risk patients, 55% in intermediate-risk patients, and 46% in low-risk patients. In the prophylaxis group, the recurrence rates were reduced in all risk groups: 38%, 35%, and 33%, respectively. Intermittent diazepam prophylaxis reduces the recurrence rate mainly in high-risk children provided that sufficient doses are given on time and adequately.

Age Factors↗