Children exposed to early institutional rearing are at risk for developing psychopathology. The present investigation examines caregiving quality and the role of attachment security as they relate to ...symptoms of psychopathology in young children exposed to early institutionalization.
Participants were enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal intervention study of children abandoned and placed in institutions at or shortly after birth. Measures included observed caregiving when children were 30 months of age, observed attachment security at 42 months, and caregiver reports of children's psychopathology at 54 months. At 54 months, some children remained in institutions, others were in foster care, others had been adopted domestically, and still others had been returned to their biological families. Thus, the children had experienced varying amounts of institutional rearing.
After controlling for gender, quality of caregiving when children were 30 months old was associated with symptoms of multiple domains of psychopathology at 54 months of age. Ratings of security of attachment at 42 months mediated the associations between quality caregiving at 30 months and fewer symptoms of psychopathology at 54 months.
Among deprived young children, high-quality caregiving at 30 months predicted reduced psychopathology and functional impairment at 54 months. Security of attachment mediated this relationship. Interventions for young children who have experienced deprivation may benefit from explicitly targeting caregiver-child attachment relationships.
This study examined the validity of criteria for indiscriminately social/disinhibited and emotionally withdrawn/inhibited reactive attachment disorder (RAD).
As part of a longitudinal intervention ...trial of previously institutionalized children, caregiver interviews and direct observational measurements provided continuous and categorical data used to examine the internal consistency, criterion validity, construct validity, convergent and discriminant validity, association with functional impairment, and stability of these disorders over time.
As in other studies, the findings showed distinctions between the two types of RAD. Evidence-derived criteria for both types of RAD showed acceptable internal consistency and criterion validity. In this study, rates of indiscriminately social/disinhibited RAD at baseline and at 30, 42, and 54 months were 41/129 (31.8%), 22/122 (17.9%), 22/122 (18.0%), and 22/125 (17.6%), respectively. Signs of indiscriminately social/disinhibited RAD showed little association with caregiving quality. Nearly half of children with indiscriminately social/disinhibited RAD had organized attachment classifications. Signs of indiscriminately social/disinhibited RAD were associated with signs of activity/impulsivity and of attention-deficit/hyperactivity disorder and modestly with inhibitory control but were distinct from the diagnosis of attention-deficit/hyperactivity disorder. At baseline, 30, 42, and 54 months, 6/130 (4.6%), 4/123 (3.3%), 2/125 (1.6%), and 5/122 (4.1%) of children met criteria for emotionally withdrawn/inhibited RAD. Emotionally withdrawn/inhibited RAD was moderately associated with caregiving at the first three time points and strongly associated with attachment security. Signs of this type of RAD were associated with depressive symptoms, although two of the five children with this type of RAD at 54 months did not meet criteria for major depressive disorder. Signs of both types of RAD contributed independently to functional impairment and were stable over time.
Evidence-derived criteria for indiscriminately social/disinhibited and emotionally withdrawn/inhibited RAD define two statistically and clinically cohesive syndromes that are distinct from each other, shows stability over 2 years, have predictable associations with risk factors and attachment, can be distinguished from other psychiatric disorders, and cause functional impairment.
Objective We sought to describe placental findings in asphyxiated term newborns meeting therapeutic hypothermia criteria and to assess whether histopathologic correlation exists between these ...placental lesions and the severity of later brain injury. Study Design We conducted a prospective cohort study of the placentas of asphyxiated newborns, in whom later brain injury was defined by magnetic resonance imaging. Results A total of 23 newborns were enrolled. Eighty-seven percent of their placentas had an abnormality on the fetal side of the placenta, including umbilical cord lesions (39%), chorioamnionitis (35%) with fetal vasculitis (22%), chorionic plate meconium (30%), and fetal thrombotic vasculopathy (26%). A total of 48% displayed placental growth restriction. Chorioamnionitis with fetal vasculitis and chorionic plate meconium were significantly associated with brain injury ( P = .03). Placental growth restriction appears to significantly offer protection against the development of these injuries ( P = .03). Conclusion Therapeutic hypothermia may not be effective in asphyxiated newborns whose placentas show evidence of chorioamnionitis with fetal vasculitis and chorionic plate meconium.
Tuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome in which cognitive and social-behavioral outcomes for patients vary widely in an unpredictable manner. The cause of adverse ...neurologic outcome remains unclear. The aim of this study was to investigate the hypothesis that disordered white matter and abnormal neural connectivity are associated with adverse neurologic outcomes.
Structural and diffusion magnetic resonance imaging was carried out in 40 subjects with TSC (age range, 0.5-25 years; mean age, 7.2 years; median age, 5 years), 12 of whom had autism spectrum disorders (ASD), and in 29 age-matched controls. Tractography of the corpus callosum was used to define a three-dimensional volume of interest. Regional averages of four diffusion scalar parameters of the callosal projections were calculated for each subject. These were the average fractional anisotropy (AFA) and the average mean, radial, and axial diffusivity.
Subjects with TSC had significantly lower AFA and higher average mean, radial, and axial diffusivity values compared to controls. Subjects with TSC and ASD had significantly lower AFA values compared to those without ASD and compared to controls. Subjects with TSC without ASD had similar AFA values compared to controls.
Diffusion tensor scalar parameters provided measures of properties of the three-dimensional callosal projections. In TSC, changes in these parameters may reflect microstructural changes in myelination, axonal integrity, or extracellular environment. Alterations in white matter microstructural properties were associated with TSC, and larger changes were associated with TSC and ASD, thus establishing a relationship between altered white matter microstructural integrity and brain function.
The purpose of this study was to examine the relationship between language pathways and autism spectrum disorders (ASDs) in patients with tuberous sclerosis complex (TSC). An advanced ...diffusion-weighted magnetic resonance imaging (MRI) was performed on 42 patients with TSC and 42 age-matched controls. Using a validated automatic method, white matter language pathways were identified and microstructural characteristics were extracted, including fractional anisotropy (FA) and mean diffusivity (MD). Among 42 patients with TSC, 12 had ASD (29%). After controlling for age, TSC patients without ASD had a lower FA than controls in the arcuate fasciculus (AF); TSC patients with ASD had even a smaller FA, lower than the FA for those without ASD. Similarly, TSC patients without ASD had a greater MD than controls in the AF; TSC patients with ASD had even a higher MD, greater than the MD in those without ASD. It remains unclear why some patients with TSC develop ASD, while others have better language and socio-behavioral outcomes. Our results suggest that language pathway microstructure may serve as a marker of the risk of ASD in TSC patients. Impaired microstructure in language pathways of TSC patients may indicate the development of ASD, although prospective studies of language pathway development and ASD diagnosis in TSC remain essential.
Cerebral pressure passivity is common in sick premature infants and may predispose to germinal matrix/intraventricular hemorrhage (GM/IVH), a lesion with potentially serious consequences. We studied ...the association between the magnitude of cerebral pressure passivity and GM/IVH.
We enrolled infants <32 weeks' gestational age with indwelling mean arterial pressure (MAP) monitoring and excluded infants with known congenital syndromes or antenatal brain injury. We recorded continuous MAP and cerebral near-infrared spectroscopy hemoglobin difference (HbD) signals at 2 Hz for up to 12 hours/day and up to 5 days. Coherence and transfer function analysis between MAP and HbD signals was performed in 3 frequency bands (0.05-0.25, 0.25-0.5, and 0.5-1.0 Hz). Using MAP-HbD gain and clinical variables (including chorioamnionitis, Apgar scores, gestational age, birth weight, neonatal sepsis, and Score for Neonatal Acute Physiology II), we built a logistic regression model that best predicts cranial ultrasound abnormalities.
In 88 infants (median gestational age: 26 weeks range 23-30 weeks), early cranial ultrasound showed GM/IVH in 31 (37%) and parenchymal echodensities in 10 (12%) infants; late cranial ultrasound showed parenchymal abnormalities in 19 (30%) infants. Low-frequency MAP-HbD gain (highest quartile mean) was significantly associated with early GM/IVH but not other ultrasound findings. The most parsimonious model associated with early GM/IVH included only gestational age and MAP-HbD gain.
This novel cerebrovascular monitoring technique allows quantification of cerebral pressure passivity as MAP-HbD gain in premature infants. High MAP-HbD gain is significantly associated with GM/IVH. Precise temporal and causal relationship between MAP-HbD gain and GM/IVH awaits further study.
Normal-appearing white matter has been shown via diffusion tensor imaging to be affected in tuberous sclerosis complex. Under the hypothesis that some systems might be differentially affected, ...including the visual pathways and systems of social cognition, diffusion properties of various regions of white matter were compared. For 10 patients and 6 age-matched control subjects, 3 T magnetic resonance imaging was assessed using diffusion tensor imaging obtained in 35 directions. Three-dimensional volumes corresponding to the geniculocalcarine tracts were extracted via tractography, and two-dimensional regions of interest were used to sample other regions. Regression analysis indicated lower fractional anisotropy in the splenium of corpus callosum and geniculocalcarine tracts in tuberous sclerosis complex group, as well as lower axial diffusivity in the internal capsule, superior temporal gyrus, and geniculocalcarine tracts. Mean and radial diffusivity of the splenium of corpus callosum were higher in the tuberous sclerosis complex group. The differences in diffusion properties of white matter between tuberous sclerosis complex patients and control subjects suggest disorganized and structurally compromised axons with poor myelination. The visual and social cognition systems appear to be differentially involved, which might in part explain the behavioral and cognitive characteristics of the tuberous sclerosis complex population.
Early life lead exposure might be a risk factor for neurocognitive impairment in adulthood.
We sought to assess the relationship between early life environmental lead exposure and intellectual ...function in adulthood. We also attempted to identify which time period blood-lead concentrations are most predictive of adult outcome.
We recruited adults in the Boston area who had participated as newborns and young children in a prospective cohort study that examined the relationship between lead exposure and childhood intellectual function. IQ was measured using the Wechsler Abbreviated Scale of Intelligence (WASI). The association between lead concentrations and IQ scores was examined using linear regression.
Forty-three adults participated in neuropsychological testing. Childhood blood-lead concentration (mean of the blood-lead concentrations at ages 4 and 10 years) had the strongest relationship with Full-Scale IQ (β = -1.89 ± 0.70, p = 0.01). Full-scale IQ was also significantly related to blood-lead concentration at age 6 months (β = -1.66 ± 0.75, p = 0.03), 4 years (β = -0.90 ± 0.41, p = 0.03) and 10 years (β = -1.95 ± 0.80, p = 0.02). Adjusting for maternal IQ altered the significance of the regression coefficient.
Our study suggests that lead exposure in childhood predicts intellectual functioning in young adulthood. Our results also suggest that school-age lead exposure may represent a period of increased susceptibility. Given the small sample size, however, the potentially confounding effects of maternal IQ cannot be excluded and should be evaluated in a larger study.
Background: Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimer's disease (AD). Objectives: We attempted to assess the ...relationship between early-life lead exposure and potential biomarkers for AD among young men and women. We also attempted to assess whether early-life lead exposure was associated with changes in expression of AD-related genes. Methods: We used sandwich enzyme-linked immunosorbent assays (ELISA) to measure plasma concentrations of amyloid β proteins Aβ₄₀ and Aβ₄₂ among 55 adults who had participated as newborns and young children in a prospective cohort study of the effects of lead exposure on development. We used RNA microarray techniques to analyze gene expression. Results: Mean plasma Aβ₄₂ concentrations were lower among 13 participants with high umbilical cord blood lead concentrations (> 10 μg/dL) than in 42 participants with lower cord blood lead concentrations (p = 0.08). Among 10 participants with high prenatal lead exposure, we found evidence of an inverse relationship between umbilical cord lead concentration and expression of ADAM metallopeptidase domain 9 (ADAM9), reticulon 4 (RTN4), and low-density lipoprotein receptor-related protein associated protein 1 (LRPAP1) genes, whose products are believed to affect Aß production and deposition. Gene network analysis suggested enrichment in gene sets involved in nerve growth and general cell development. Conclusions: Data from our exploratory study suggest that prenatal lead exposure may influence Aβ-related biological pathways that have been implicated in AD onset. Gene network analysis identified further candidates to study the mechanisms of developmental lead neurotoxicity.
Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimer's disease (AD). We attempted to assess the relationship between ...early-life lead exposure and potential biomarkers for AD among young men and women. We also attempted to assess whether early-life lead exposure was associated with changes in expression of AD-related genes. We used sandwich enzyme-linked immunosorbent assays (ELISA) to measure plasma concentrations of amyloid β proteins Aβ40 and Aβ42 among 55 adults who had participated as newborns and young children in a prospective cohort study of the effects of lead exposure on development. We used RNA microarray techniques to analyze gene expression. Mean plasma Aβ42 concentrations were lower among 13 participants with high umbilical cord blood lead concentrations (≥ 10 μg/dL) than in 42 participants with lower cord blood lead concentrations (p = 0.08). Among 10 participants with high prenatal lead exposure, we found evidence of an inverse relationship between umbilical cord lead concentration and expression of ADAM metallopeptidase domain 9 (ADAM9), reticulon 4 (RTN4), and low-density lipoprotein receptor-related protein associated protein 1 (LRPAP1) genes, whose products are believed to affect Aβ production and deposition. Gene network analysis suggested enrichment in gene sets involved in nerve growth and general cell development. Data from our exploratory study suggest that prenatal lead exposure may influence Aβ-related biological pathways that have been implicated in AD onset. Gene network analysis identified further candidates to study the mechanisms of developmental lead neurotoxicity.
PDF
