Search

High-stakes achievement testing is a centerpiece of education reform. Children from socially disadvantaged backgrounds typically perform more poorly than their more advantaged peers. The authors evaluated 91 fifth-grade children from low-income urban schools using clinical neuropsychological tests and behavioral questionnaires and obtained fourth-grade scores on state mandated standards-based testing. Goals were to determine whether executive functions are selectively diminished in children from poor urban environments and to evaluate to what extent integrity of executive functions is associated with test scores. Neuropsychological variables (particularly executive functions) accounted for 40% of the variance in English scores and 30% in mathematics. Efforts to improve children's academic achievement should consider developmental factors as well as curricular content. [ABSTRACT FROM AUTHOR]

Children referred for evaluation of learning impairment (LI, N =100) and a comparison group of nonreferred (NLI, N = 243) children were evaluated on a visual filtering task. The task was designed hierarchically to provide for evaluation of component operations-serial search, parallel search, decision, and response. With each additional processing demand, response times increased disproportionately for the LI group relative to the NLI group. Overall response time reliably predicted academic skills and cognitive ability, but was more strongly related to group membership. Thus, this nonverbal visual task is sensitive to a characteristic of children with learning problems over and above discrete academic and cognitive skills. Children with problems adapting to the demands of schooling may be distinguished by a disproportionate vulnerability to processing load. [ABSTRACT FROM AUTHOR]

Maternal trauma has intergenerational implications, including worse birth outcomes, altered brain morphology, and poorer mental health. Research investigating intergenerational effects of maternal trauma on infant stress reactivity and regulation is limited. Maternal mental health during pregnancy may be a contributor: psychopathology is a sequela of trauma exposure and predictor of altered self-regulatory capacity in offspring of affected mothers. We assessed associations among maternal lifetime trauma and infant stress responsivity, mediated by psychological symptoms in pregnancy. Mothers reported lifetime trauma history and anxiety, depressive, and posttraumatic stress symptoms during pregnancy. At infant age 6 months, stress reactivity and regulation were assessed via maternal behavior ratings (Infant Behavior Questionnaire-Revised, IBQ-R) and behavioral (negative mood) and physiological (respiratory sinus arrhythmia, RSA) markers during a laboratory stressor (Still-Face Paradigm). Maternal trauma was directly associated with lower infant physiological regulation and indirectly associated with lower levels of both infant behavioral and physiological regulation via higher maternal anxiety during pregnancy. Maternal trauma was also indirectly associated with higher infant reactivity via higher maternal anxiety during pregnancy. Post hoc analyses indicated differential contributions of maternal prenatal versus postnatal anxiety to infant outcomes. Findings highlight potential contributory mechanisms toward maladaptive child stress response, which has been associated with poor behavioral, cognitive, and academic outcomes.

We examined effects of maternal and child lifetime traumatic stress exposures, infant temperament, and caregiving quality on parent ratings of preschoolers' executive functioning (EF). Maternal lifetime trauma was associated with preschoolers' EF problems; this association was mediated by greater child trauma exposure. Infant temperament was associated with EF abilities, particularly among females. Among males, infant extraversion/surgency mediated the association of maternal lifetime trauma with poorer child EF. Caregiving quality was negatively associated with maternal and child trauma exposures but did not predict child EF. Findings have implications for interventions to identify children at risk for poor EF and optimize outcomes.

Learning disorders can have adverse impacts on children and families extending beyond the academic skills deficits. The goal of the present study was to assess the impact of the school's response, following an independent evaluation, for child and family school-related quality of life (QOL). We hypothesized that a positive school response would be associated with improved QOL. Parents completed the LDQOL/15, a brief measure of school-related QOL, at the time that their child received an independent evaluation and again a year later ( N = 155). At follow-up, parents reported the tenor of the school's response to the evaluation and whether special education services had changed. QOL problems were very high in this referred population, with 66% of respondents rating a level of problems in the clinical range at baseline. Predicted interactions between time of assessment (baseline/follow-up) and the school's response to the evaluation were confirmed for all outcome variables; a positive school response was associated with improved QOL. Nevertheless, the overall prevalence of school-related QOL problems remained high a year after the evaluation. These findings indicate that special education interventions can mitigate learning disabilities' impacts, but even with these services, many children with learning disorders and their families continue to be significantly affected.

Functional abdominal pain (FAP) is a common physical complaint in children and adolescents. Prior research has documented associations between FAP symptoms and mood, especially internalizing behaviors. Limited research is available examining the association between symptom burden and cognitive function in this pediatric population. This study explored associations between FAP symptoms, internalizing behaviors, and cognitive and school function in children and adolescents. Twenty-seven participants (mean age = 12.6 years, range 8.8-16.5; 33% male) diagnosed with FAP completed assessments of cognitive, emotional, and behavioral function, as well as FAP symptom severity. Mean performances on cognitive tests were within age-expected ranges. Within this context, however, higher overall burden of FAP symptoms was associated with slower processing speed, more self-reported metacognitive problems and internalizing behaviors, and more school absences. Cognitive function was systematically associated with internalizing behaviors but not physical symptoms. Overall, findings revealed that FAP may be associated with cognitive inefficiencies in addition to internalizing problems. Cognitive symptoms may be linked to internalizing behaviors associated with FAP.

Objective: This study examined longitudinal associations between performance on the Rey-Osterrieth Complex Figure-Developmental Scoring System (ROCF-DSS) at 8 years of age and academic outcomes at 16 years of age in 133 children with dextro-transposition of the great arteries (d-TGA)., Method: The ROCF-DSS was administered at the age of 8 and the Wechsler Individual Achievement Test, First and Second Edition (WIAT/WIAT-II) at the ages of 8 and 16, respectively. ROCF-DSS protocols were classified by Organization (Organized/Disorganized) and Style (Part-oriented/Holistic). Two-way univariate (ROCF-DSS Organization × Style) ANCOVAs were computed with 16-year academic outcomes as the dependent variables and socioeconomic status (SES) as the covariate., Results: The Organization × Style interaction was not statistically significant. However, ROCF-DSS Organization at 8 years was significantly associated with Reading, Math, Associative, and Assembled academic skills at 16 years, with better organization predicting better academic performance., Conclusions: Performance on the ROCF-DSS, a complex visual-spatial problem-solving task, in children with d-TGA can forecast academic performance in both reading and mathematics nearly a decade later. These findings may have implications for identifying risk in children with other medical and neurodevelopmental disorders affecting brain development.

Objective: The term apraxia is clearly understood in adult behavioral neurology, with assessment of gesture central to the diagnosis. In contrast, the concept of "developmental dyspraxia" has been more problematic. In an effort to better specify its potential significance, we describe preliminary practice-based evidence for understanding developmental dyspraxia acquired within a theoretical framework informed by both adult behavioral neurology and a neuroconstructivist appreciation of neurodevelopmental disorders. Specifically, we describe the experience of a diagnostic clinic for children with learning disorders that adopted this framework and compare clinical characteristics of children diagnosed with dyspraxia with those of children diagnosed with dyslexia during the same time period., Method: The dyspraxia diagnosis was based on the presence of impaired gesture and/or cognitive problems with planning. Over the target period, 71 children were diagnosed with dyspraxia and 114 children were diagnosed with dyslexia. Twenty-nine of the 71 children with dyspraxia were also diagnosed with dyslexia. Domains assessed included early developmental milestones, neurologic findings, cognition, speech and language, academic skills, and psychosocial functioning., Results: Compared to the dyslexia group, children with dyspraxia (with or without dyslexia) had more problems with speech and language planning and planning in everyday life. Children with dyspraxia without dyslexia had more frequent early motor delays and deficits in visuospatial production than the other groups. The dyslexia groups predictably demonstrated poorer single word reading and phonologic processing compared to the dyspraxia only group (all P < .01)., Conclusions: A neurologic finding of impaired gesture in children with learning disorders may signal a broader neurodevelopmental profile of developmental dyspraxia with both theoretical relevance and meaningful implications for evaluation and treatment. Cognitive problems with planning are particularly relevant.

Purpose: Pubertal suppression is standard of care for early pubertal transgender youth to prevent the development of undesired and distressing secondary sex characteristics incongruent with gender identity. Preliminary evidence suggests pubertal suppression improves mental health functioning. Given the widespread changes in brain and cognition that occur during puberty, a critical question is whether this treatment impacts neurodevelopment. Methods: A Delphi consensus procedure engaged 24 international experts in neurodevelopment, gender development, puberty/adolescence, neuroendocrinology, and statistics/psychometrics to identify priority research methodologies to address the empirical question: is pubertal suppression treatment associated with real-world neurocognitive sequelae? Recommended study approaches reaching 80% consensus were included in the consensus parameter. Results: The Delphi procedure identified 160 initial expert recommendations, 44 of which ultimately achieved consensus. Consensus study design elements include the following: a minimum of three measurement time points, pubertal staging at baseline, statistical modeling of sex in analyses, use of analytic approaches that account for heterogeneity, and use of multiple comparison groups to minimize the limitations of any one group. Consensus study comparison groups include untreated transgender youth matched on pubertal stage, cisgender (i.e., gender congruent) youth matched on pubertal stage, and an independent sample from a large-scale youth development database. The consensus domains for assessment includes: mental health, executive function/cognitive control, and social awareness/functioning. Conclusion: An international interdisciplinary team of experts achieved consensus around primary methods and domains for assessing neurodevelopmental effects (i.e., benefits and/or difficulties) of pubertal suppression treatment in transgender youth., Competing Interests: No competing financial interests exist., (© Diane Chen et al. 2020: Published by Mary Ann Liebert, Inc.)

Studies using diffusion tensor imaging (DTI) have documented alterations in the attention and executive system in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). While abnormalities in the frontal lobe have also been reported, the associated white matter fiber bundles have not been investigated comprehensively due to the complexity in tracing them through fiber crossings. Furthermore, most studies have used a non-specific DTI model to understand white matter abnormalities. We present results from a first study that uses a multi-shell diffusion MRI (dMRI) data set coupled with an advanced multi-fiber tractography algorithm to probe microstructural measures related to axonal/cellular density and volume of fronto-striato-thalamic pathways in children with ADHD (N = 30) and healthy controls (N = 28). Head motion was firstly examined as a priority in order to assure that no group difference existed. We investigated 45 different white matter fiber bundles in the brain. After correcting for multiple comparisons, we found lower axonal/cellular packing density and volume in ADHD children in 8 of the 45 fiber bundles, primarily in the right hemisphere as follows: 1) Superior longitudinal fasciculus-II (SLF-II) (right), 2) Thalamus to precentral gyrus (right), 3) Thalamus to superior-frontal gyrus (right), 4) Caudate to medial orbitofrontal gyrus (right), 5) Caudate to precentral gyrus (right), 6) Thalamus to paracentral gyrus (left), 7) Caudate to caudal middlefrontal gyrus (left), and 8) Cingulum (bilateral). Our results demonstrate reduced axonal/cellular density and volume in certain frontal lobe white matter fiber tracts, which sub-serve the attention function and executive control systems. Further, our work shows specific microstructural abnormalities in the striato-thalamo-cortical connections, which have not been previously reported in children with ADHD.

Learning problems (LP) can have wider implications than the academic deficits per se. The goal of the present series of studies was to develop a reliable and valid quality-of-life measure targeted to children and adolescents with LP. In Study 1, using a 35-item questionnaire, we surveyed 151 parents/guardians of children referred for assessment of learning disorders. Exploratory factor analysis identified a three-factor model: Academic Performance, School Understanding, and Child/Family Psychological. These factors were validated against standardized measures of academic achievement and psychosocial functioning. The questionnaire was then reduced to 15 items-the LD/QOL15 -and administered to a community sample of 325 parents/guardians of children in Grades 1 to 8 (Study 2). The three-factor model was verified with confirmatory factor analysis. Comparison of general education ( n = 232) and LP ( n = 93) groups within the community sample documented substantial group differences ( p < .0001), with the LP group having higher mean scores. These differences were larger for older students (Grades 5-8) than younger students (Grades 1-4; p < .01). The LD/QOL15 is a brief and reliable measure that is valid to assess quality of life and, potentially, outcomes in children and adolescents with LP.

Although there are many anecdotal reports of children with developmental dyslexia complaining of vision symptoms when reading, empirical studies are lacking. The primary aim of the present study was to document self-reported vision-related symptoms in children with developmental dyslexia and typically reading peers. We also explored whether vision symptoms were correlated with sensorimotor measures of vergence, accommodation and ocular motor tracking skills. Using a prospective group comparison observational design, we assessed 28 children with developmental dyslexia (DD) and 33 typically reading children (TR) 7-11 years of age. Participants completed psychoeducational testing, a comprehensive sensorimotor eye examination, and the Convergence Insufficiency Symptom Survey (CISS), which includes 9 items pertaining to vision-related symptoms (CISS-V) and 6 that could have cognitive influence (CISS-C). CISS-V were significantly greater in DD than TR children. Ocular motor tracking, assessed by an infra-red limbal eye tracker while reading text, was most clearly associated with the visual symptoms, but only within the DD group. Vision-related symptom surveys followed by a comprehensive eye examination with detailed evaluation of sensorimotor functioning for those who report a high prevalence of symptoms may be clinically relevant for children with DD., (Published by Elsevier Ltd.)

Importance: Developmental dyslexia (DD) is a specific learning disability of neurobiological origin whose core cognitive deficit is widely believed to involve language (phonological) processing. Although reading is also a visual task, the potential role of vision in DD has been controversial, and little is known about the integrity of visual function in individuals with DD., Objective: To assess the frequency of visual deficits (specifically vergence, accommodation, and ocular motor tracking) in children with DD compared with a control group of typically developing readers., Design, Setting, and Participants: A prospective, uncontrolled observational study was conducted from May 28 to October 17, 2016, in an outpatient ophthalmology ambulatory clinic among 29 children with DD and 33 typically developing (TD) children., Main Outcomes and Measures: Primary outcomes were frequencies of deficits in vergence (amplitude, fusional ranges, and facility), accommodation (amplitude, facility, and accuracy), and ocular motor tracking (Developmental Eye Movement test and Visagraph eye tracker)., Results: Among the children with DD (10 girls and 19 boys; mean [SD] age, 10.3 [1.2] years) and the TD group (21 girls and 12 boys; mean [SD] age, 9.4 [1.4] years), accommodation deficits were more frequent in the DD group than the TD group (16 [55%] vs 3 [9%]; difference = 46%; 95% CI, 25%-67%; P < .001). For ocular motor tracking, 18 children in the DD group (62%) had scores in the impaired range (in the Developmental Eye Movement test, Visagraph, or both) vs 5 children in the TD group (15%) (difference, 47%; 95% CI, 25%-69%; P < .001). Vergence deficits occurred in 10 children in the DD group (34%) and 5 children in the TD group (15%) (difference, 19%; 95% CI, -2.2% to 41%; P = .08). In all, 23 children in the DD group (79%) and 11 children in the TD group (33%) had deficits in 1 or more domain of visual function (difference, 46%; 95% CI, 23%-69%; P < .001)., Conclusions and Relevance: These findings suggest that deficits in visual function are far more prevalent in school-aged children with DD than in TD readers, but the possible cause and clinical relevance of these deficits are uncertain. Further study is needed to determine the extent to which treating these deficits can improve visual symptoms and/or reading parameters.

Objectives: We compared the IQ and academic achievement of the young adult offspring of parents malnourished in infancy and those of a healthy control group in order to test the hypothesis that the offspring of previously malnourished individuals would show IQ and academic deficits that could be related to reduced parental socioeconomic status., Methods: We conducted a group comparison study based on a community sample in Barbados (Barbados Nutrition Study). Participants were adult children ≥16 years of age whose parents had been malnourished during the first year of life (n = 64; Mean age 19.3 years; 42% male) or whose parents were healthy community controls (n = 50; Mean age 19.7 years; 48% male). The primary outcome was estimated IQ (Wechsler Abbreviated Scale of Intelligence); a secondary outcome was academic achievement (Wide Range Achievement Test - Third Edition). Data were analyzed using PROC MIXED with and without adjusting for parental socioeconomic status (Hollingshead Index of Social Position)., Results: IQ was reduced in the offspring of previously malnourished parents relative to the offspring of controls (9.8 point deficit; P < 0.01), but this difference was not explained by parental socioeconomic status or parental IQ. The magnitude of the group difference was smaller for basic academic skills and did not meet criteria for statistical significance., Discussion: The deleterious impact of infant malnutrition on cognitive function may be transmitted to the next generation; however, this intergenerational effect does not appear to be explained by the reduced socioeconomic status or IQ of the parent generation.

Objective: To survey educational outcomes after an interdisciplinary, neuropsychologically based team assessment for learning disorders., Method: Parents of 137 children who underwent a comprehensive interdisciplinary neuropsychologically based assessment for learning problems completed an online survey one to four years later. Questions pertained broadly to school outcomes: positive or negative school responses, changes in special education services, and parental perceptions about the helpfulness of those services. These outcomes were examined in relation to demographic characteristics and parent satisfaction with the evaluation. We also obtained recent performance on state-based academic testing for descriptive purposes., Results: Parents reported that schools generally responded positively (78%), and 70% reported that their children had access to more or different special education services after the evaluation. Parents nearly uniformly (98%) viewed these services as helpful. Positive changes in education services were related to income (lower income received more services, p < .05) and parent satisfaction with the evaluation (p < .05). The intensity of special education services was strongly related to performance on state-based testing (p < .0001-p < .01)., Conclusions: School response is a relatively objective and meaningful metric of educational outcome after neuropsychologically based evaluation for children with learning problems.

Childhood malnutrition and maltreatment (abuse, neglect) are both prevalent, particularly in resource-limited settings. Despite their known negative impact on child development, there is surprisingly little research documenting their interrelationships. To address this gap, we administered the Childhood Trauma Questionnaire-Short Form (CTQ-SF), a retrospective structured self-report of childhood abuse and neglect, in a Barbadian cohort of 77 adult survivors of infant malnutrition, limited to the first year of life, and 62 healthy controls from the same classrooms and neighborhoods (mean age ± SD = 43.8±2.3 years). This cohort has been followed since birth. Using factor analysis and comparison with archival data addressing similar constructs, we found evidence for reliability and validity of the CTQ-SF in this population. Linear regression analyses, with and without adjusting for childhood household standard of living at three childhood ages, revealed that a history of infant malnutrition was significantly associated with increased levels of self-reported physical neglect in childhood, and, to a somewhat lesser degree, emotional neglect. This study highlights the co-occurrence of infant malnutrition and self-reported maltreatment in childhood in Barbados, with potential public health implications., Competing Interests: Disclosure statement The authors declare that they have no conflict of interest.

Background: Early childhood malnutrition affects 113 million children worldwide, impacting health and increasing vulnerability for cognitive and behavioral disorders later in life. Molecular signatures after childhood malnutrition, including the potential for intergenerational transmission, remain unexplored., Methods: We surveyed blood DNA methylomes (~483,000 individual CpG sites) in 168 subjects across two generations, including 50 generation 1 individuals hospitalized during the first year of life for moderate to severe protein-energy malnutrition, then followed up to 48 years in the Barbados Nutrition Study. Attention deficits and cognitive performance were evaluated with the Connors Adult Attention Rating Scale and Wechsler Abbreviated Scale of Intelligence. Expression of nutrition-sensitive genes was explored by quantitative reverse transcriptase polymerase chain reaction in rat prefrontal cortex., Results: We identified 134 nutrition-sensitive, differentially methylated genomic regions, with most (87%) specific for generation 1. Multiple neuropsychiatric risk genes, including COMT, IFNG, MIR200B, SYNGAP1, and VIPR2 showed associations of specific methyl-CpGs with attention and IQ. IFNG expression was decreased in prefrontal cortex of rats showing attention deficits after developmental malnutrition., Conclusions: Early childhood malnutrition entails long-lasting epigenetic signatures associated with liability for attention and cognition, and limited potential for intergenerational transmission., Competing Interests: Competing Financial Interests: The authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Purpose: Survivors of childhood acute lymphoblastic leukemia (ALL) exhibit increased rates of neurocognitive deficits. This study was conducted to test whether interpatient variability in neurocognitive outcomes can be explained by polymorphisms in candidate genes conferring susceptibility to neurocognitive decline., Methods: Neurocognitive testing was conducted in 350 pediatric leukemia survivors, treated on Dana-Farber Cancer Institute ALL Consortium Protocols 95-01 or 00-01. Genomic DNA was isolated from bone marrow collected at remission. Candidate polymorphisms were selected on the basis of prior literature, targeting genes related to drug metabolism, oxidative damage, altered neurotransmission, neuroinflammation, and folate physiology. Single nucleotide polymorphisms were detected using either a customized multiplexed Sequenom MassARRAY assay or polymerase chain reaction-based allelic discrimination assays. Multivariable logistic regression models were used to estimate the effects of genotype on neurocognitive outcomes, adjusted for the effects of demographic and treatment variables. False-discovery rate correction was made for multiple hypothesis testing, indicated as a Q value., Results: Inferior cognitive or behavioral outcomes were associated with polymorphisms in three genes related to oxidative stress and/or neuroinflammation: NOS3 (IQ, Q = 0.008; Vocabulary Q = 0.011; Matrix Reasoning Q = 0.008), SLCO2A1 (IQ Q = 0.043; Digit Span Q = 0.006; Block Design Q = 0.076), and COMT (Behavioral Assessment System for Children-2 Attention Q = 0.080; and Hyperactivity Q = 0.084). Survivors homozygous for NOS3 894T, with at least one SLCO2A1 variant G allele or with at least one GSTP1 variant allele, had lower mean estimated IQ scores than those without these genotypes., Conclusion: These data are consistent with the hypothesis that oxidative damage contributes to chemotherapy-associated neurocognitive decline among children with leukemia., (© 2015 by American Society of Clinical Oncology.)

Objective: The frequent lack of correspondence between performance and observational measures of executive functioning, including working memory, has raised questions about the validity of the observational measures. This study was conducted to investigate sources of this discrepancy through correlation of volumetric and cortical thickness (CT) neuroimaging values with performance and questionnaire measures of working memory (WM)., Methods: Using longitudinal data from the NIH MRI Study of Normal Brain Development (Volumes, N= 347, 54.3% female; CT, N= 350, 54.6% female; age range: 6 to 16.9 years), scores on the Behavioral Rating Inventory of Executive Function (BRIEF) WM, Emotional Control (EC) and Inhibition (INH) scales; Wechsler Scale of Intelligence for Children-III Digit Span; and Cambridge Neuropsychological Test Battery Spatial Working Memory (CANTAB SWM) were correlated with each other and with morphometric measurements using mixed effects linear regression models., Results: BRIEF WM was correlated with CANTAB SWM (p < .001). With whole brain correction, BRIEF WM and EC were both correlated with CT of the posterior parahippocampal gyrus (PHG), EC on the right side only. Performance measures of WM were unrelated to lobar volumes or CT, but were associated with volumes of hippocampus and amygdala., Conclusions: The known role of PHG in contextual learning suggests that the BRIEF WM assesses contextualized learning/memory, potentially explaining its loose correspondence to the decontextualized performance measures. Observational measures can be useful and valid functional metrics, complementing performance measures. Labels used to characterize scales should be interpreted with caution, however., (PsycINFO Database Record (c) 2015 APA, all rights reserved.)

Purpose: This study aimed to evaluate lexical retrieval, presurgery and postsurgery, among children and adolescents who had undergone temporal lobe resection for intractable epilepsy and to compare outcomes in patients whose surgery involved the left temporal lobe or the right temporal lobe., Materials and Methods: A retrospective chart review identified 36 patients from a major pediatric epilepsy treatment center who had undergone temporal lobe resection (21 underwent left temporal lobe resection; 15 underwent right temporal lobe resection) for intractable epilepsy and who had completed neuropsychological testing that included a measure of confrontation naming (Boston Naming Test, BNT) and verbal fluency (Delis-Kaplan Executive Function System (D-KEFS) Fluency) prior to and after surgery. Linear mixed effects regression models were used to evaluate presurgery and postsurgery changes and to compare the left temporal lobe resection group with the right temporal lobe resection group., Principal Results: Confrontation naming performance declined after left, but not right, temporal lobe resection (p<0.05). This effect was not documented for verbal fluency., Major Conclusions: Left temporal lobe resection for intractable epilepsy is associated with a decline in lexical retrieval. The risk of decline in specific language functions following surgery involving the left temporal lobe should be incorporated in the counseling of patients and families in decision-making with regard to surgery., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To compare neuropsychological profiles of adults who had experienced an episode of moderate to severe protein-energy malnutrition confined to the first year of life with that of a healthy community comparison group., Method: We assessed neuropsychological functioning in a cohort of Barbadian adults, all of whom had birth weight >2268 g. The previously malnourished group (N = 77, mean age = 38 years, 53% male) had been hospitalized during the first year of life for moderate to severe protein energy malnutrition and subsequently enrolled in a program providing nutrition education, home visits and subsidized foods to 12 years of age. They also had documented, adequate nutrition throughout childhood and complete catch-up in growth by the end of adolescence. The healthy comparison group (N = 59, mean age = 38 years, 54% male) were recruited as children from the same classrooms and neighborhoods., Results: Adjusted for effects of standard of living during childhood and adolescence and current intellectual ability level, there were nutrition group differences on measures of cognitive flexibility and concept formation, as well as initiation, verbal fluency, working memory, processing speed, and visuospatial integration. Behavioral and cognitive regulation were not affected., Conclusions: Postnatal malnutrition confined to the first year of life is associated with neurocognitive compromise persisting into midlife. Early malnutrition may have a specific neuropsychological signature, affecting response initiation to a somewhat greater extent than response inhibition.

Objectives: To evaluate IQ and academic skills in adults who experienced an episode of moderate-to-severe infantile malnutrition and a healthy control group, all followed since childhood in the Barbados Nutrition Study., Methods: IQ and academic skills were assessed in 77 previously malnourished adults (mean age = 38.4 years; 53% male) and 59 controls (mean age = 38.1 years; 54% male). Group comparisons were carried out by multiple regression and logistic regression, adjusted for childhood socioeconomic factors., Results: The previously malnourished group showed substantial deficits on all outcomes relative to healthy controls (P < 0.0001). IQ scores in the intellectual disability range (< 70) were nine times more prevalent in the previously malnourished group (odds ratio = 9.18; 95% confidence interval = 3.50-24.13). Group differences in IQ of approximately one standard deviation were stable from adolescence through mid-life., Discussion: Moderate-to-severe malnutrition during infancy is associated with a significantly elevated incidence of impaired IQ in adulthood, even when physical growth is completely rehabilitated. An episode of malnutrition during the first year of life carries risk for significant lifelong functional morbidity.

Intelligence quotient (IQ) scores tend to remain stable across the lifespan. Nevertheless, in some healthy individuals, significant decreases or increases in IQ have been observed over time. It is unclear whether such changes reflect true functional change or merely measurement error. Here, we applied surface-based corticometry to investigate vertex-wise cortical surface area and thickness correlates of changes in Full Scale IQ (FSIQ), Performance IQ (PIQ) and Verbal IQ (VIQ) in a representative sample of children and adolescents (n=188, mean age=11.59years) assessed two years apart as part of the NIH Study of Normal Brain Development. No significant associations between changes in IQ measures and changes in cortical surface area were observed, whereas changes in FSIQ, PIQ, and VIQ were related to rates of cortical thinning, mainly in left frontal areas. Participants who showed reliable gains in FSIQ showed no significant changes in cortical thickness on average, whereas those who exhibited no significant FSIQ change showed moderate declines in cortical thickness. Importantly, individuals who showed large decreases in FSIQ displayed the steepest and most significant reductions in cortical thickness. Results support the view that there can be meaningful cognitive ability changes that impact IQ within relatively short developmental periods and show that such changes are associated with the dynamics of cortical thickness development., (© 2013.)

Background: Dexamethasone is more efficacious than prednisone in the treatment of acute lymphoblastic leukemia (ALL), but has also been associated with greater toxicity. We compared neuropsychological outcomes for patients treated on DFCI ALL Consortium Protocol 00-01, which included a randomized comparison of the two steroid preparations during post-induction therapy in children and adolescents with ALL., Procedure: Between 2000 and 2005, 408 children with standard-risk or high-risk ALL treated on Dana-Farber Cancer Institute Consortium Protocol 00-01 were randomly assigned to prednisone or dexamethasone administered as 5-day pulses every 3 weeks for 2 years, beginning at week 7 of treatment. Blinded neuropsychological testing was completed for 170 randomized patients (prednisone, N = 76; dexamethasone, N = 94), all of whom were in continuous complete remission after completion of therapy., Results: Outcomes were comparable for most variables, although patients on the dexamethasone arm performed more poorly on a measure of fluid reasoning (P = 0.02). They also tended to be more likely to be enrolled in special education (dexamethasone, 33% vs. prednisone, 20%, P = 0.09)., Conclusions: Dexamethasone has well documented benefit in treatment of ALL. Although formal testing provided little indication of increased risk for neurotoxicity relative to prednisone, the somewhat greater utilization of special education services by patients treated with dexamethasone merits further investigation., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Early childhood malnutrition is associated with cognitive and behavioral impairment during childhood and adolescence, but studies in adulthood are limited., Methods: Using the NEO-PI-R personality inventory, we compared personality profiles at 37-43 years of age (M 40.3 years, SD 1.9) of Barbadian adults who had experienced moderate-to-severe protein-energy malnutrition (PEM) in the first year of life (n = 77) with healthy controls, who were former classmates of the index cases and were matched for age, gender, and handedness in childhood (n = 57). The previously malnourished participants had been rehabilitated, with good health and nutrition documented up to 12 years of age, and study participants were followed longitudinally from childhood to 40 years. Group comparisons were adjusted for childhood and adolescent standard of living, with and without correcting for IQ., Results: At the broad domain or factor level, previously malnourished participants had higher scores on Neuroticism and lower scores on Extraversion, Openness, Agreeableness, and Conscientiousness than did the healthy controls. At the subdomain or facet level, previously malnourished participants reported more anxiety, vulnerability, shyness and lowered sociability, less intellectual curiosity, greater suspiciousness of others, a more egocentric than altruistic orientation, and a lowered sense of efficacy or competence., Conclusions: Malnutrition limited to the first year of life with good health and nutrition documented up to 12 years of age is associated with a significant overrepresentation of adult personality trait scores outside of the average range. This outcome has important implications for a variety of important life and mental health outcomes., (© 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.)

Background: Radiation and chemotherapy targeted to the central nervous system (CNS) can cause cognitive impairment, including impaired memory. These memory impairments may be referable to damage to hippocampal structures resulting from CNS treatment., Procedure: In the present study, we explored episodic memory and its neuroimaging correlates in 10 adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation therapy and both systemic and intrathecal chemotherapy and 10 controls matched for age and sex, using a subsequent memory paradigm after episodic encoding of visual scenes., Results: We report behavioral, structural, and functional changes in the brains of the adult survivors. They demonstrated poorer recognition memory, hippocampal atrophy, and altered blood oxygenation level-dependent (BOLD) signal in the hippocampus. Whole brain statistical map analysis revealed increased BOLD signal/activation in several brain regions during unsuccessful encoding in ALL survivors, potentially reflecting ineffective neural recruitment. Individual differences in memory performance in ALL participants were related to magnitude of BOLD response in regions associated with successful encoding., Conclusions: Taken together, these findings describe long term neuroimaging correlates of cognitive dysfunction after childhood exposure to CNS-targeted cancer therapies, suggesting enduring damage to episodic memory systems., (Copyright © 2012 Wiley Periodicals, Inc.)

Systemic corticosteroids are a mainstay of treatment for many pediatric medical conditions. Although their impact on the central nervous system has been well-studied in animal models and adults, less is known about such effects in pediatric populations. The current study investigated acute effects of corticosteroids on memory, executive functions, emotion, and behavior in children and adolescents with inflammatory bowel disease (IBD). Patients 8-17 years with IBD (Crohn's disease, CD; ulcerative colitis, UC) on high-dose prednisone (n = 33) and IBD patients in remission off steroids (n = 33) completed standardized neuropsychological tests and behavior rating scales. In the IBD sample as a whole, few steroid effects were found for laboratory cognitive measures, but steroid-treated patients were rated as exhibiting more problems with emotional, and to a lesser extent with cognitive function in daily life. Steroid effects, assessed by laboratory measures and questionnaires, were more prevalent in CD than UC patients; UC patients on steroids sometimes performed better than controls. Sleep disruption also predicted some outcomes, diminishing somewhat the magnitude of the steroid effects. Corticosteroid therapy can have acute effects on cognition, emotion, and behavior in chronically ill children; the clinical and long-term significance of these effects require further investigation.

We examined the role of maternal depressive symptoms reported during childhood as a predictor of an important personality trait, Openness to Experience (O), in middle adulthood. Participants were 95 adults (38 previously malnourished, 57 control, mean age 42.1 years) who had been followed longitudinally since childhood by the Barbados Nutrition Study. Maternal depressive symptoms had been measured when the participants were 5-11 years of age by the General Adjustment and Morale Scale; O was measured in adulthood by the Revised NEO-Personality Inventory (NEO-PI-R). Multiple regression analyses, adjusted for childhood household standard of living, showed a significant main effect on O of maternal depressive symptoms ( p < 0.01). Maternal depression also attenuated the significant effect of childhood malnutrition by 14%. Maternal depressive symptoms in childhood may therefore play a causal role in adult personality, in particular Openness to Experience, with implications for creativity.

Objectives: The purpose of this study was to compare the prevalence of conduct problems in a well-documented sample of Barbadian adolescents malnourished as infants and a demographic comparison group and to determine the extent to which cognitive impairment and environmental factors account for this association., Methods: Behavioral symptoms were assessed using a 76-item self-report scale in 56 Barbadian youth (11-17 years of age) with histories of protein-energy malnutrition (PEM) limited to the first year of life and 60 healthy classmates. Group comparisons were carried out by longitudinal and cross-sectional multiple regression analyses at 3 time points in childhood and adolescence., Results: Self-reported conduct problems were more prevalent among previously malnourished youth (P < 0.01). Childhood IQ and home environmental circumstances partially mediated the association with malnutrition. Teacher-reported classroom behaviors at earlier ages were significantly correlated with youth conduct problems, confirming the continuity of conduct problems through childhood and adolescence., Discussion: Self-reported conduct problems are elevated in children and adolescents with histories of early childhood malnutrition. Later vulnerability to increased conduct problems appears to be mediated by the more proximal neurobehavioral effects of the malnutrition on cognitive function and by adverse conditions in the early home environment.

Objective: Lifelong functional, adaptive, and economic outcomes of moderate to severe infantile malnutrition are not well known. We assessed social status and income at midlife in a cohort of Barbadian adults, hospitalized for protein-energy malnutrition (PEM) during the first year of life, with good nutrition and health thereafter, in the context of a 40-year longitudinal case-control study. We also examined to what extent childhood IQ mediated any group differences., Methods: Educational achievement, occupational status, and standard of living were assessed by the Hollingshead scales and a site-specific Ecology Questionnaire in Barbadian adults (aged 37-43 years) with a history of malnutrition (n = 80) and a matched healthy control group (n = 63), classmates of the index cases. Malnutrition effects, adjusted for childhood standard of living, were estimated by longitudinal multiple regression analyses, with and without childhood IQ, in the models., Results: PEM predicted poorer socioeconomic outcomes with medium to large effect sizes (0.50-0.94), but childhood IQ substantially attenuated the magnitude of these effects (adjusted effect sizes: 0.17-0.34). The gap in weekly household income between the PEM and control groups increased substantially over the life span (P < .001)., Conclusions: Moderate to severe PEM during the first year of life with adequate nutrition and health care thereafter is associated with significant depression of socioeconomic outcomes in adulthood, mediated in part by cognitive compromise in affected individuals. This finding underscores the potential long-term economic burden of infant malnutrition, which is of major concern given the continued high prevalence of malnutrition worldwide.

Background: Children treated for acute lymphoblastic leukemia (ALL) as High Risk (HR) patients may be more vulnerable to neurocognitive late effects because of the greater intensity of their therapy. We compared neuropsychological outcomes in children treated for Standard Risk (SR) or HR ALL on Dana-Farber Cancer Institute (DFCI) Consortium ALL Protocol 95-01. We also evaluated their performance relative to normative expectations., Procedure: Between 1996 and 2000, 498 children with newly diagnosed ALL were treated on Protocol 95-01, 298 of whom were eligible for neuropsychological follow-up. A feature of this protocol was modification of risk group criteria to treat more children as SR rather than HR patients, intended to minimize toxicities. Testing was completed at a median of 5.3 years post-diagnosis for 211 patients (70.8%; ages 6-25 years; 45.5% male; 40% HR), all of whom were in continuous complete remission., Results: Test scores for both groups were generally at or above normative expectation, with the exception of verbal working memory, processing complex visual information, and parent ratings of metacognitive skills. After adjusting for covariates, the SR group performed better on measures of IQ and academic achievement, working memory and visual learning. Effect sizes, however, were only in the small to moderate range., Conclusions: HR patients exhibited neuropsychological deficits relative to SR patients, though the differences were modest in degree. Modification of the risk group criteria to treat more children on the SR protocol therefore likely afforded some benefit in terms of neurocognitive late effects., (Copyright © 2011 Wiley Periodicals, Inc.)

Infantile malnutrition is known to be associated with cognitive and behavioral impairment during childhood and adolescence. Data pertaining to longer-term effects on behavioral outcomes in adulthood are limited. In this study, we report associations between infantile malnutrition and attention problems in adults at midlife. Attention problems were assessed by the Conners Adult ADHD Rating Scales (CAARS) and the Conners Continuous Performance Test (CPT) in 145 Barbadian adults (aged 37-43 y) who had been followed longitudinally since childhood. Previously malnourished participants (n = 80) had experienced moderate to severe protein-energy malnutrition in the first year of life and were successfully rehabilitated thereafter. They were compared with healthy adults (n = 65) who were former classmates of the index cases and who had been matched for age, sex, and handedness in childhood. Multiple regression analyses showed persisting effects of childhood malnutrition on both the CAARS and the CPT, independent of effects of household standard of living assessed in childhood. The malnutrition effect on the CAARS ratings was independent of IQ, whereas this effect was attenuated for the CPT after adjustment for IQ. Teacher-reported attention problems in childhood predicted attention problems in adulthood, indicating continuity over the life span. Infantile malnutrition may have long-term effects on attentional processes nearly 40 y after the episode, even with excellent long-term nutritional rehabilitation and independent of socioeconomic conditions in childhood and adolescence. This finding has major public health implications for populations exposed to early childhood malnutrition.

The National Institutes of Health (NIH) Magnetic Resonance Imaging (MRI) Study of Normal Brain Development is a landmark study in which structural and metabolic brain development and behavior are followed longitudinally from birth to young adulthood in a population-based sample of healthy children. Cross-sectional findings from the neuropsychological test battery have been previously described (Waber et al., 2007). The present report details 4-year longitudinal neuropsychological outcomes for those children who were aged 6 to 18 years at baseline (N = 383), of whom 219 (57.2%) completed all 3 visits. Primary observations were (1) individual children displayed considerable variation in scores across visits on the same measures; (2) income-related differences were more prominent in the longitudinal than in the cross-sectional data; (3) no association between cognitive and behavioral measures and body mass index; and (4) several measures showed practice effects, despite the 2-year interval between visits. These data offer an unparalleled opportunity to observe normative performance and change over time on a set of standard and commonly used neuropsychological measures in a population-based sample of healthy children. They thus provide important background for the use and interpretation of these instruments in both research settings and clinical practice.

Children with benign rolandic epilepsy (BRE) experience elevated rates of cognitive, behavioral, and affective problems. Frequent epileptiform spike discharges may impair behavioral functioning. To elucidate this relationship, we evaluated associations between the EEG spike frequency index (SI) and parental ratings of psychosocial adjustment and executive functioning in school-aged children with EEGs typical of BRE. Twenty-one children (6-12 years) participated. Parents completed validated questionnaires at a median of 5 months (range: 1-8) after a routine outpatient EEG. The EEG SI was calculated for wakefulness and sleep. The strength of association between the SI and behavioral variables was evaluated by simple and multivariate correlation. Higher awake and sleep SIs were associated with more symptoms of depression (P<0.001), aggression and conduct problems (P<0.01). Higher sleep SI was associated with executive dysfunction and anxiety (P<0.05). Symptoms of hyperactivity and inattention had no correlation. Increased epileptiform activity in children with BRE may predict higher rates of mood and behavioral problems., Competing Interests: statement None of the authors has any conflict of interests to disclose., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Although corticosteroids remain a mainstay of treatment for acute lymphoblastic leukemia (ALL), they can cause troublesome neurobehavioral changes during active treatment, especially in young children. We evaluated acute neurobehavioral side effects of corticosteroid therapy in preschool versus school-age children by obtaining structured reports weekly for 1 month., Procedure: Parents of 62 children (2-17 years) treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 00-01 participated during the continuation phase of treatment. Patients received cyclical twice-daily 5-day courses of prednisone (PRED; 40 mg/m(2) /day) or dexamethasone (DEX; 6 mg/m(2) /day). Parents completed behavior rating scales about their child weekly during one steroid cycle [baseline (Day 0), active steroid (Day 7), post-steroid (Days 14 and 21)]., Results: Behavioral side effects increased significantly (P < 0.001) during the steroid week for preschool children (<6 years) on measures of emotional control, mood, behavior regulation, and executive functions, returning to baseline during the two "off-steroid" weeks. In contrast, school-age children (≥ 6 years) did not demonstrate an increase in side effects during the steroid week. Steroid type (PRED vs. DEX) was not a significant predictor of neurobehavioral side effects., Conclusions: Preschool children are at greater risk for neurobehavioral side effects during active steroid treatment for ALL than school-age children and adolescents. DEX was not associated with more neurobehavioral side effects than PRED. Counseling of families about side-effects should be adapted according to age. The observed effects, moreover, were transient, reducing concerns about longer-term neurobehavioral toxicities., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: To determine whether externalizing behaviors are more prevalent in youth who have experienced an episode of malnutrition in the first year of life than in healthy comparison youth., Method: Parents of previously malnourished youth and a matched healthy comparison group completed a behavior rating scale when the youth were 9-15 years of age and again, 2 years later, when they were 11-17 years of age. Longitudinal multiple regression analysis was applied to evaluate group differences adjusted for baseline age, sex, household standard of living, and maternal depressive symptoms., Results: Early childhood malnutrition was associated with problems in executive functioning at both occasions. Malnutrition also predicted discernibly higher parent-reported levels of aggression toward peers at 9-15 years than at 11-17 years. These findings were independent of baseline age, sex, household standard of living, and maternal depressive symptoms. Problem behaviors in general decreased during follow-up., Conclusion: Parents report persisting problems with executive functioning through adolescence in youth who suffered an episode of moderate-to-severe protein-energy malnutrition in the first year of life, while reports of aggression, although more common when this cohort were younger, did not persist at follow-up.

Prevailing psychometric theories of intelligence posit that individual differences in cognitive performance are attributable to three main sources of variance: the general factor of intelligence (g), cognitive ability domains, and specific test requirements and idiosyncrasies. Cortical thickness has been previously associated with g. In the present study, we systematically analyzed associations between cortical thickness and cognitive performance with and without adjusting for the effects of g in a representative sample of children and adolescents (N=207, Mean age=11.8; SD=3.5; Range=6 to 18.3 years). Seven cognitive tests were included in a measurement model that identified three first-order factors (representing cognitive ability domains) and one second-order factor representing g. Residuals of the cognitive ability domain scores were computed to represent g-independent variance for the three domains and seven tests. Cognitive domain and individual test scores as well as residualized scores were regressed against cortical thickness, adjusting for age, gender and a proxy measure of brain volume. g and cognitive domain scores were positively correlated with cortical thickness in very similar areas across the brain. Adjusting for the effects of g eliminated associations of domain and test scores with cortical thickness. Within a psychometric framework, cortical thickness correlates of cognitive performance on complex tasks are well captured by g in this demographically representative sample., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Documented associations between corpus callosum size and cognitive ability have heretofore been inconsistent potentially owing to differences in sample characteristics, differing methodologies in measuring CC size, or the use of absolute versus relative measures. We investigated the relationship between CC size and intelligence quotient (IQ) in the NIH MRI Study of Normal Brain Development sample, a large cohort of healthy children and adolescents (aged six to 18, n = 198) recruited to be representative of the US population. CC midsagittal area was measured using an automated system that partitioned the CC into 25 subregions. IQ was measured using the Wechsler Abbreviated Scale of Intelligence (WASI). After correcting for total brain volume and age, a significant negative correlation was found between total CC midsagittal area and IQ (r = -0.147; p = 0.040). Post hoc analyses revealed a significant negative correlation in children (age<12) (r = -0.279; p = 0.004) but not in adolescents (age≥12) (r = -0.005; p = 0.962). Partitioning the subjects by gender revealed a negative correlation in males (r = -0.231; p = 0.034) but not in females (r = 0.083; p = 0.389). Results suggest that the association between CC and intelligence is mostly driven by male children. In children, a significant gender difference was observed for FSIQ and PIQ, and in males, a significant age-group difference was observed for FSIQ and PIQ. These findings suggest that the correlation between CC midsagittal area and IQ may be related to age and gender.

This study examined the association between family functioning and the development of posttraumatic stress symptoms (PTSS) in youth and parents following an unintentional traumatic injury of a child. Fifty-one parent-child dyads completed questionnaires and a structured interview assessing PTSS and family functioning. Multiple regression analyses were applied to evaluate the contribution of family functioning to the development of PTSS after controlling for demographic characteristics and known predictors. Family functioning had both direct and moderating influences on the development of PTSS in parents. We were unable to demonstrate a systematic impact of family functioning on the development of PTSS in children from the same families.

The National Institutes of Health (NIH) Magnetic Resonance Imaging (MRI) Study of Normal Brain Development is a landmark study in which structural and metabolic brain development and behavior are followed longitudinally from birth to young adulthood in a population-based sample of healthy children. The neuropsychological assessment protocol for children aged 6 to 18 years is described and normative data are presented for participants in that age range (N = 385). For many measures, raw score performance improved steeply from 6 to 10 years, decelerating during adolescence. Sex differences were documented for Block Design (male advantage), CVLT, Pegboard and Coding (female advantage). Household income predicted IQ and achievement, as well as externalizing problems and social competence, but not the other cognitive or behavioral measures. Performance of this healthy sample was generally better than published norms. This linked imaging-clinical/behavioral database will be an invaluable public resource for researchers for many years to come.

Despite clinical impressions that cognitive complaints are prominent in patients with a history of craniopharyngioma, formal neuropsychologic documentation is inconsistent. This study assessed everyday cognitive complaints and neuropsychologic test performance to evaluate the prevalence of problems and the relationship of these domains to one another in patients treated for craniopharyngioma in childhood or adolescence. Ten patients treated for craniopharyngioma completed measures of everyday cognitive function (Cognitive Failures Questionnaire, Rivermead Behavioural Memory Test) and a battery of standard neuropsychologic tests. The prevalence of problems was ascertained for each measure. Most patients demonstrated significant deficits in everyday memory (Cognitive Failures Questionnaire, 9/10 patients; Rivermead Behavioural Memory Test, 7/10 patients). Scores were within normal limits, however, for intelligence quotient, achievement, attention, verbal memory, and spatial working memory. Processing speed was slow (5/10 patients). Spatial working memory predicted Cognitive Failures Questionnaire (P < 0.07), as did somatic symptoms from the Beck Depression Inventory (P < 0.01), but these associations appeared independent. Adolescents and young adults with treated craniopharyngioma experience deficits in everyday cognitive functions, many involving memory, that are not easily detected by standard neuropsychologic testing. The extent of self-rated cognitive problems is related to spatial working memory and somatic concerns.