RESUMEN
Pediatric post-traumatic stress disorder (pPTSD) is a prevalent and pervasive form of mental illness comprising a disparate constellation of psychiatric symptoms. Emerging evidence suggests that pPTSD may be characterized by alterations in functional networks traversing the brain. Yet, little is known about pathological changes in the structural tracts underlying functional connectivity. In adults, PTSD is linked to widespread change in white matter integrity throughout the brain, yet similar studies with youth populations have yet to be conducted. Current understanding of the nature and treatment of pPTSD may be enhanced by examining alterations in white matter, while further untangling effects of age and sex. Here, we assess the microstructure of 12 major white matter tracts in a sample of well-phenotyped youth with PTSD. Measures of fractional anisotropy were derived from diffusion tensor images acquired from 82 unmediated youth (ages 8-18), of whom 39 met criteria for pPTSD. Diagnosis of pPTSD was linked to remarkable age- and sex-linked differences in the microstructure of major white matter tracts including the uncinate fasciculus, cingulum bundle, and inferior longitudinal fasciculus. In each case, youth with PTSD show an absence of increased white matter integrity with age, suggesting an altered pattern of neurodevelopment that may contribute to persistence or worsening of illness. Broadly, our results suggest abnormal white matter development in pediatric PTSD, a finding which may contribute to illness persistence, comorbidity with other disorders, and poorer prognosis across time. Critically, these findings further speak to the nature of pPTSD as a 'whole-brain' disorder.
Asunto(s)
Trastornos por Estrés Postraumático , Sustancia Blanca , Adolescente , Adulto , Anisotropía , Encéfalo/diagnóstico por imagen , Niño , Imagen de Difusión Tensora , Humanos , Trastornos por Estrés Postraumático/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
OBJECTIVE: The objective of this feasibility study was to investigate whether myelin water fraction (MWF) patterns can differentiate children presenting with febrile seizures who will go on to develop nonfebrile epilepsy from those who will not. PATIENTS AND METHODS: As part of a prospective study of myelination patterns in pediatric epilepsy, seven subjects with febrile seizures underwent magnetic resonance imaging (MRI) including the following standard sequences-T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR)-and an additional experimental sequence, multicomponent-derived equilibrium single-pulse observation of T1 and T2 (mcDESPOT) to quantify MWF. For each of these subjects, MWF maps were derived and compared with an age-matched population-averaged MWF atlas. RESULTS: All seven subjects (<5 years old) initially presented with febrile seizures. Of the seven, four had complex seizures and three had simple seizures. All of the children with simple febrile seizures had higher MWF compared with model-derived controls and did not develop epilepsy. All of the children with complex febrile seizures had lower MWF than their model-derived control, and two of these subjects later developed epilepsy. CONCLUSION: This is the first study in which MWF maps were used to study children with febrile *seizures. This data suggests that relatively higher or stable MWF compared with normative data indicates a lower risk of nonfebrile epilepsy while relatively lower MWF may indicate a pathological condition that could lead to nonfebrile epilepsy.
Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Vaina de Mielina/metabolismo , Convulsiones Febriles/diagnóstico por imagen , Convulsiones Febriles/metabolismo , Agua/metabolismo , Preescolar , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Vaina de Mielina/patología , Estudios ProspectivosRESUMEN
Infancy and early childhood are periods of rapid brain development, during which brain structure and function mature alongside evolving cognitive ability. An important neurodevelopmental process during this postnatal period is the maturation of the myelinated white matter, which facilitates rapid communication across neural systems and networks. Though prior brain imaging studies in children (4 years of age and above), adolescents, and adults have consistently linked white matter development with cognitive maturation and intelligence, few studies have examined how these processes are related throughout early development (birth to 4 years of age). Here, we show that the profile of white matter myelination across the first 5 years of life is strongly and specifically related to cognitive ability. Using a longitudinal design, coupled with advanced magnetic resonance imaging, we demonstrate that children with above-average ability show differential trajectories of myelin development compared to average and below average ability children, even when controlling for socioeconomic status, gestation, and birth weight. Specifically, higher ability children exhibit slower but more prolonged early development, resulting in overall increased myelin measures by ~3 years of age. These results provide new insight into the early neuroanatomical correlates of cognitive ability, and suggest an early period of prolonged maturation with associated protracted white matter plasticity may result in strengthened neural networks that can better support later development. Further, these results reinforce the necessity of a longitudinal perspective in investigating typical or suspected atypical cognitive maturation.
Asunto(s)
Cognición/fisiología , Sustancia Blanca/crecimiento & desarrollo , Encéfalo/fisiología , Mapeo Encefálico , Estudios de Casos y Controles , Desarrollo Infantil/fisiología , Preescolar , Femenino , Predicción , Humanos , Lactante , Inteligencia/fisiología , Imagen por Resonancia Magnética , Masculino , Vaina de Mielina/patología , Fibras Nerviosas Mielínicas/fisiología , Sustancia Blanca/fisiologíaRESUMEN
Whether for basic research or biotechnology, DNA microarrays have become indispensable tools for studying the transcriptome. Normally, analyses begin with a set of known cDNA sequences to prepare microarray chips specific for a target organism with an extensively sequenced and annotated genome. For many organisms, however, genome programs are not complete or have not been initiated. The present study demonstrates that, whether using homologous or heterologous arrays, the chances of seeing interesting differences are similar. When a specific DNA microarray is not available, the results indicate that a reverse approach based on a heterologous array can be used to probe for interesting differences in gene expression. This may be sufficient in many studies but, if necessary, the genes exhibiting the most significant changes subsequently could be identified by traditional molecular approaches. Such a reverse strategy can provide a convenient and inexpensive approach to probe for significant genetic changes in many diverse studies, to monitor or mine critical biological information for basic or applied research, long before complete sequence data are available.