Systematic review of studies on exposure to arsenic in drinking water and cognitive and neurobehavioral effects.

An association between exposure to arsenic (As) and neurologic and behavioral effects has been reported in some studies, but no systematic review is available of the evidence linking As in drinking water and neurobehavioral effects after consideration of study quality and potential confounding, with focus on low-level circumstances of exposure. We conducted a systematic review and reported it in compliance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, through a search of the databases PubMed, Web of Science, Scopus, and Embase. We included in the review the studies reporting results based on exposure from drinking water in humans. Endpoints were heterogeneous across studies, so we classified them into eight broad domains and developed an ad-hoc system to evaluate their methodological quality, based on three tiers. It was not possible to conduct meta-analysis because of the heterogeneity in exposure assessment and in the definition and assessment of outcomes. The search identified 18,518 articles. After elimination of duplicates and irrelevant articles, we retained 106 articles which reported results on As exposure and neurobehavioral effects, of which 22 reported risk estimates from exposure in drinking water (six among adults and 16 among children). None of the studies was conducted blindly. Among the studies in adults, two, which were conducted in highly exposed populations, were classified as high quality. These two studies were broadly consistent in reporting an association between exposure to As and decline in cognitive function; however, they provide no evidence of an association for exposure below 75 µg/L. The four lower-quality studies were based on populations with low exposure; these studies reported associations with inconsistent outcomes, few of which remained statistically significant after adjustment for multiple comparisons. Among the five high-quality studies of children, one reported an association between As in drinking water and intellectual function, whereas none of the other studies reported an association with different neurobehavioral indicators, after adjusting for potential confounders and multiple comparisons. Out of seven intermediate-quality studies, three reported an association with cognitive function or other outcomes; but sources of bias were not adequately controlled. The remaining studies were negative. The four low-quality studies did not contribute to the overall evidence because of methodological limitations. Our assessment of the available literature showed a lack of evidence for a causal association between exposure to As in drinking water and neurobehavioral effects. To clarify whether such an association exists, further studies prospectively evaluating changes in both the concentration of As in drinking water during the life course, and neurobehavioral outcomes, as well as appropriately controlling for potential confounders, are needed.

Executive functioning and treatment outcome among adolescents undergoing cognitive-behavioral therapy for binge-eating disorder.

BACKGROUND: Cognitive-behavioral therapy (CBT) is an evidence-supported treatment for adolescents with binge-eating disorder (BED). Executive dysfunctions, which are associated with binge eating and elevated body weight in youth, may undermine CBT outcomes by making it difficult for youth to engage with or adhere to treatment, including recalling and/or implementing intervention strategies in real-world contexts. METHODS: We assessed 73 adolescents [82.2% female; Mage = 15.0 ± 2.5 year; M baseline standardized body mass index (zBMI) = 1.9 ± 1.0 kg/m2] with BED at baseline, posttreatment, 6-, 12-, and 24-month follow-up. Linear mixed models examined the effects of baseline executive functioning (EF) on loss of control (LOC) eating and weight change following CBT. Linear and logistic regressions probed associations between EF, attendance, and attrition. RESULTS: More impulsive decision-making, as reflected in higher baseline scores on the Iowa Gambling Task, predicted better attendance (ß = .07; p = .019) and more frequent LOC eating following treatment (ß = .12; p = .017). Lower cognitive flexibility, as reflected in lower baseline T-scores on the Comprehensive Trail Making Test complex sequencing index, predicted higher zBMI following treatment (ß = -.03; p = .003). Inhibition, concentration, attention, and parent-reported EF behavior symptoms were not associated with outcome, attendance, or attrition. CONCLUSIONS: More impulsive decision-making and lower cognitive flexibility were associated with suboptimal response to CBT for BED, although findings should be interpreted with caution in light of the sample size and waitlist control design. Future research should examine whether strengthening EF could improve eating and weight outcomes among adolescents with BED who have lower pre-treatment EF.

Clusters of resilience and vulnerability: executive functioning, coping and mental distress in patients with diffuse low-grade glioma.

PURPOSE: Diffuse low-grade gliomas (dLGG) often have a frontal location, which may negatively affect patients' executive functions (EF). Being diagnosed with dLGG and having to undergo intensive treatment can be emotionally stressful. The ability to cope with this stress in an adaptive, active and flexible way may be hampered by impaired EF. Consequently, patients may suffer from increased mental distress. The aim of the present study was to explore profiles of EF, coping and mental distress and identify characteristics of each profile. METHODS: 151 patients with dLGG were included. Latent profile analysis (LPA) was used to explore profiles. Additional demographical, tumor and radiological characteristics were included. RESULTS: Four clusters were found: 1) overall good functioning (25% of patients); 2) poor executive functioning, good psychosocial functioning (32%); 3) good executive functioning, poor psychosocial functioning (18%) and; 4) overall poor functioning (25%). Characteristics of the different clusters were lower educational level and more (micro)vascular brain damage (cluster 2), a younger age (cluster 3), and a larger tumor volume (cluster 4). EF was not a distinctive factor for coping, nor was it for mental distress. Maladaptive coping, however, did distinguish clusters with higher mental distress (cluster 3 and 4) from clusters with lower levels of mental distress (cluster 1 and 2). CONCLUSION: Four distinctive clusters with different levels of functioning and characteristics were identified. EF impairments did not hinder the use of active coping strategies. Moreover, maladaptive coping, but not EF impairment, was related to increased mental distress in patients with dLGG.

Adaptive functioning and academic achievement in pediatric survivors of acute lymphoblastic leukemia: Associations with executive functioning, socioeconomic status, and academic support.

OBJECTIVES: This study examines associations of functional outcomes (adaptive functioning and academic achievement) with executive functioning (EF), socioeconomic status (SES), and academic support in pediatric acute lymphoblastic leukemia (ALL) survivors. METHODS: Fifty survivors of B-lineage ALL treated with chemotherapy-only (42% female, 76% NHW, ages 6-19) were evaluated on performance-based EF and academic achievement, and parent-rated EF and adaptive functioning. Area deprivation and child opportunity (i.e., SES) were extracted using census blocks and tracts. Academic support data were extracted from chart review. RESULTS: Compared to population norms, pediatric ALL survivors demonstrated significantly lower overall adaptive skills and performance in word reading and math calculation (all p ≤ .011). Frequencies of impairment were significantly elevated on all adaptive scales and in math calculation compared to the population (all p ≤ .002). Parent-rated EF significantly predicted overall adaptive skills (p < .001), while performance-based EF significantly predicted word reading and math calculation (all p < .05). Adaptive functioning was not associated with neighborhood-specific variables or academic support. However, academic support predicted word reading (p < .001), while area deprivation and academic support predicted performance-based EF (all p ≤ .02). CONCLUSIONS: Screening of functional outcomes, targeted intervention, and neuropsychological monitoring are necessary to support pediatric ALL survivors' neurocognitive and psychosocial development.

The clinical relevance of novel biomarkers as outcome parameter in adults with phenylketonuria.

Recent studies in PKU patients identified alternative biomarkers in blood using untargeted metabolomics. To test the added clinical value of these novel biomarkers, targeted metabolomics of 11 PKU biomarkers (phenylalanine, glutamyl-phenylalanine, glutamyl-glutamyl-phenylalanine, N-lactoyl-phenylalanine, N-acetyl-phenylalanine, the dipeptides phenylalanyl-phenylalanine and phenylalanyl-leucine, phenylalanine-hexose conjugate, phenyllactate, phenylpyruvate, and phenylacetate) was performed in stored serum samples of the well-defined PKU patient-COBESO cohort and a healthy control group. Serum samples of 35 PKU adults and 20 healthy age- and sex-matched controls were analyzed using ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry. Group differences were tested using the Mann-Whitney U test. Multiple linear regression analyses were performed with these biomarkers as predictors of (neuro-)cognitive functions working memory, sustained attention, inhibitory control, and mental health. Compared to healthy controls, phenylalanine, glutamyl-phenylalanine, N-lactoyl-phenylalanine, N-acetyl-phenylalanine, phenylalanine-hexose conjugate, phenyllactate, phenylpyruvate, and phenylacetate were significant elevated in PKU adults (p < 0.001). The remaining three were below limit of detection in PKU and controls. Both phenylalanine and N-lactoyl-phenylalanine were associated with DSM-VI Attention deficit/hyperactivity (R2 = 0.195, p = 0.039 and R2 = 0.335, p = 0.002, respectively) of the ASR questionnaire. In addition, N-lactoyl-phenylalanine showed significant associations with ASR DSM-VI avoidant personality (R2 = 0.265, p = 0.010), internalizing (R2 = 0.192, p = 0.046) and externalizing problems (R2 = 0.217, p = 0.029) of the ASR questionnaire and multiple aspects of the MS2D and FI tests, reflecting working memory with R2 between 0.178 (p = 0.048) and 0.204 (p = 0.033). Even though the strength of the models was not considered strong, N-lactoyl-phenylalanine outperformed phenylalanine in its association with working memory and mental health outcomes.

On executive functioning and childcare: The moderating role of parent-child interactions.

Childcare services are widely used by families and thereby exert an important influence on many young children. Yet, little research has examined whether childcare may impact the development of child executive functioning (EF), one of the pillars of cognitive development in early childhood. Furthermore, despite persisting hypotheses that childcare may be particularly beneficial for children who have less access to optimal developmental resources at home, research has yet to address the possibility that putative associations between childcare and EF may vary as a function of family factors. Among a sample of 180 mostly White middle-class families (91 girls), we examined if childcare participation in infancy was related to two aspects of EF (Delay and Conflict) at 3 years, and whether two aspects of maternal parenting behavior (sensitivity and autonomy support) moderated these associations. The results showed positive associations between participation in group-based childcare and Delay EF specifically among children of relatively less autonomy-supportive mothers. These findings suggest that out-of-home childcare services may play a protective role for children exposed to parenting that is less conducive to their executive development. RESEARCH HIGHLIGHTS: Little research has considered effects of childcare in infancy on executive functioning (EF). Long-standing hypothesis that childcare is more beneficial for children exposed to less sensitive and supportive parenting. We test interactions between maternal parenting and childcare participation in infancy in relation to EF at age 3 years. We find positive associations between participation in group-based childcare and Delay EF specifically among children of relatively less autonomy-supportive mothers.

Conceptualizing avoidant/restrictive food intake disorder via an executive functioning lens.

Avoidant/restrictive food intake disorder (ARFID) is a heterogeneous disorder wherein restrictive eating is primarily attributed to non-shape/weight-based reasons (e.g., sensory sensitivity) that empirical research continues to explore. Mounting evidence suggests that ARFID often presents alongside neurodevelopmental diagnoses (NDs) or divergent neurodevelopment broadly. Executive functioning (EF) differences often characterize divergent neurodevelopmental trajectories. Additionally, restrictive eating in anorexia nervosa has been conceptualized as related to EF factors (e.g., set shifting). Given the neurodevelopmental phenotype that may be associated with ARFID and the role of EF in anorexia nervosa, this paper proposes EF as a potentially important, yet understudied factor in ARFID pathology. We posit that various observed ARFID behavioral/cognitive tendencies can be conceptualized in relation to EF differences. We contextualize commonly observed ARFID presentations within "core" EF components (i.e., cognitive flexibility, working memory, inhibitory control), leading to hypotheses about EF in ARFID. Finally, we offer additional considerations/directions for future research on EF in ARFID. Increased research on EF in ARFID is needed to consider this potential common factor in the etiology and maintenance of this heterogeneous disorder. We aim to promote further consideration of EF in ARFID etiology, maintenance, and treatment-outcome research. PUBLIC SIGNIFICANCE: This article proposes that aspects of executive functioning (EF) may play a role in the onset and maintenance of avoidant/restrictive food intake disorder (ARFID), although this notion is largely untested by existing research. Further research on the role of EF in ARFID may assist with refining models and treatments for this heterogeneous disorder.

The importance of improving cognitive flexibility in adolescents with anorexia nervosa: The case for cognitive remediation therapy.

OBJECTIVE: Inefficiencies in executive functioning (EF), more specifically cognitive flexibility and an overly detailed processing style, are frequently observed in individuals with Anorexia Nervosa (AN) and have been identified as potential targets in treatment. Cognitive Remediation Therapy (CRT) is an adjunctive treatment approach specifically designed to have a positive impact on EF. Mainly evaluated in adults, CRT has been criticized for its perceived ineffectiveness in promoting weight restoration or directly reducing eating disorder symptoms. METHOD: We argue that we need to refocus our conceptual framework for using CRT as an adjunctive treatment and specifically explore its potential benefit in adolescents. RESULTS: Adolescence is a critical window for EF development during which CRT has the potential to have the most impact. While it may not specifically ameliorate eating disorder symptoms and directly improve weight gain, CRT may mitigate the impact of malnutrition on adolescent brain development, reduce attrition rates in treatment, and improve cognitive flexibility and (indirectly) other maintaining factors, thereby improving global functioning. DISCUSSION: More research needs to be done to understand the development of EF in adolescents with AN and how best to employ CRT as an adjunctive treatment to support development and target maintaining factors. The current article broadly reviews findings on executive functioning inefficiencies in adolescents with AN and discusses the purpose and role of CRT in treating AN. Finally, we highlight key critiques of using CRT and pose questions for future research. PUBLIC SIGNIFICANCE: Treatments targeting executive functioning in adolescents with AN are limited. We need to better understand how CRT can benefit adolescents in treatment. Increasing treatment options, including adjunctive treatments, is necessary to reduce the long-term impact of AN.

State-level working memory and dysregulated eating in children and adolescents: An exploratory ecological momentary assessment study.

BACKGROUND: Children with loss of control (LOC) eating and overweight/obesity have relative deficiencies in trait-level working memory (WM), which may limit adaptive responding to intra- and extra-personal cues related to eating. Understanding of how WM performance relates to eating behavior in real-time is currently limited. METHODS: We studied 32 youth (ages 10-17 years) with LOC eating and overweight/obesity (LOC-OW; n = 9), overweight/obesity only (OW; n = 16), and non-overweight status (NW; n = 7). Youth completed spatial and numerical WM tasks requiring varying degrees of cognitive effort and reported on their eating behavior daily for 14 days via smartphone-based ecological momentary assessment. Linear mixed effects models estimated group-level differences in WM performance, as well as associations between contemporaneously completed measures of WM and dysregulated eating. RESULTS: LOC-OW were less accurate on numerical WM tasks compared to OW and NW (ps < .01); groups did not differ on spatial task accuracy (p = .41). Adjusting for between-subject effects (reflecting differences between individuals in their mean WM performance and its association with eating behavior), within-subject effects (reflecting variations in moment-to-moment associations) revealed that more accurate responding on the less demanding numerical WM task, compared to one's own average, was associated with greater overeating severity across the full sample (p = .013). There were no associations between WM performance and LOC eating severity (ps > .05). CONCLUSIONS: Youth with LOC eating and overweight/obesity demonstrated difficulties mentally retaining and manipulating numerical information in daily life, replicating prior laboratory-based research. Overeating may be related to improved WM, regardless of LOC status, but temporality and causality should be further explored. PUBLIC SIGNIFICANCE STATEMENT: Our findings suggest that youth with loss of control eating and overweight/obesity may experience difficulties mentally retaining and manipulating numerical information in daily life relative to their peers with overweight/obesity and normal-weight status, which may contribute to the maintenance of dysregulated eating and/or elevated body weight. However, it is unclear whether these individual differences are related to eating behavior on a moment-to-moment basis.

Early childhood trauma exposure and neurocognitive and emotional processes: Associations in young children in a partial hospital program.

Early childhood trauma has been linked to neurocognitive and emotional processing deficits in older children, yet much less is known about these associations in young children. Early childhood is an important developmental period in which to examine relations between trauma and executive functioning/emotion reactivity, given that these capacities are rapidly developing and are potential transdiagnostic factors implicated in the development of psychopathology. This cross-sectional study examined associations between cumulative trauma, interpersonal trauma, and components of executive functioning, episodic memory, and emotion reactivity, conceptualized using the RDoC framework and assessed with observational and performance-based measures, in a sample of 90 children (ages 4-7) admitted to a partial hospital program. Children who had experienced two or more categories of trauma had lower scores in episodic memory, global cognition, and inhibitory control as measured in a relational (but not computerized) task, when compared to children with less or no trauma. Interpersonal trauma was similarly associated with global cognition and relational inhibitory control. Family contextual factors did not moderate associations. Findings support examining inhibitory control in both relationally significant and decontextualized paradigms in early childhood, and underscore the importance of investigating multiple neurocognitive and emotional processes simultaneously to identify potential targets for early intervention.

A brief bout of moderate intensity physical activity improves preadolescent children's behavioral inhibition but does not change their energy intake.

Children in rural communities consume more energy-dense foods relative to their urban peers. Identifying effective interventions for improving energy intake patterns are needed to address these geographic disparities. The primary aim of this study was to harness the benefits of physical activity on children's executive functioning to see if these improvements lead to acute changes in eating behaviors. In a randomized crossover design, 91 preadolescent (8-10y; M age = 9.48 ± 0.85; 50.5% female; 85.7% White, 9.9% Multiracial, 9.9% Hispanic) children (86% rural) completed a 20-minute physical activity condition (moderate intensity walking) and time-matched sedentary condition (reading and/or coloring) ~ 14 days apart. Immediately following each condition, participants completed a behavioral inhibition task and then eating behaviors (total energy intake, relative energy intake, snack intake) were measured during a multi-array buffet test meal. After adjusting for period and order effects, body fat (measured via DXA), and depressive symptoms, participants experienced significant small improvements in their behavioral inhibition following the physical activity versus sedentary condition (p = 0.04, Hedge's g = 0.198). Eating behaviors did not vary by condition, nor did improvements in behavioral inhibition function as a mediator (ps > 0.09). Thus, in preadolescent children, small improvements in behavioral inhibition from physical activity do not produce acute improvements in energy intake. Additional research is needed to clarify whether the duration and/or intensity of physical activity sessions would produce different results in this age group, and whether intervention approaches and corresponding mechanisms of change vary by individual factors, like age and degree of food cue responsivity.

Increased frequency of light physical activity during midlife and old age buffers against cognitive declines.

Although it is well established that moderate-to-vigorous physical activity (MVPA) buffers against declines in cognitive health, less is known about the benefits of light physical activity (LPA). Research on the role of LPA is crucial to advancing behavioral interventions to improve late life health outcomes, including cognitive functioning, because this form of physical activity remains more feasible and amenable to change in old age. Our study examined the extent to which increases in LPA frequency protected against longitudinal declines in cognitive functioning and whether such a relationship becomes pronounced in old age when opportunities for MVPA are typically reduced. We analyzed 9-year data from the national Midlife in the United States Study (n = 2,229; Mage = 56 years, range = 33-83; 56% female) using autoregressive models that assessed whether change in LPA frequency predicted corresponding changes in episodic memory and executive functioning in middle and later adulthood. Increases in LPA frequency predicted less decline in episodic memory (ß = 0.06, p = .004) and executive functioning (ß = 0.14, p < .001) over the 9-year follow-up period, even when controlling for moderate and vigorous physical activity. Effect sizes for moderate and vigorous physical activity were less than half that observed for LPA. Moderation models showed that, for episodic memory, the benefits of increases in LPA frequency were more pronounced at older ages. Findings suggest that increases in LPA over extended periods of time may help slow age-related cognitive declines, particularly in later life when opportunities for MVPA are often diminished.

Perceived Executive Functioning Deficits After Diagnosis in Women with Non-Metastatic Breast Cancer Prior to Adjuvant Therapies.

BACKGROUND: Perceived deficits in executive functioning are among the many difficulties that women diagnosed with breast cancer experience. This study assessed the presence of perceived deficits in executive functioning among women with breast cancer prior to systemic treatment and radiation and associations between perceived deficits in executive function and comorbid fatigue, sleep, and mood disturbance. METHOD: Participants were recruited following their breast cancer diagnosis and assessed using the Behavior Rating Inventory of Executive Function for Adults (BRIEF-A), subjective and objective measures of sleep duration and efficiency, and self-report measures of insomnia severity, sleep quality, fatigue, and mood disturbance. Hierarchical regression was used to examine associations between symptoms, adjusting for age and education. RESULTS: The final sample included 92 women with a mean age of 60.7 years and 13.5 years of education. Thirteen percent of participants reported global executive dysfunction. After partitioning out variability from other independent variables, fatigue (p = < .001), perceived sleep quality (p = .030), and symptoms of insomnia (p = .008) accounted for 13.3%, 5.7%, and 8.5% of unique variance in perceived executive functioning, respectively. Emotional fatigue was most strongly associated with perceived deficits in executive functioning. Neither subjective or objective sleep duration or efficiency was associated with perceived deficits in executive functioning. CONCLUSION: Fatigue, particularly emotional fatigue, insomnia, and poor sleep quality had the strongest associations with perceived deficits in executive functioning. Sleep interventions and fatigue management strategies may prove useful for women who seek to improve their perceived executive functioning.

Identifying neurofunctional domains across substance use disorders.

Background: Substance use disorders (SUDs) are heterogeneous across multiple functional domains. Various frameworks posit that domains (e.g., executive function) contribute to the persistence of SUDs; however, the domains identified in different studies vary.Objectives: We used factor analysis to identify the underlying latent domains present in a large sample (N = 5,244, 55.8% male) with a variety of SUDs to yield findings more generalizable than studies with a narrower focus.Method: Participants (1,384 controls and 3,860 participants with one or more SUDs including alcohol, cocaine, cannabis, and/or opioid use disorders) completed the Semi-Structured Assessment for Drug Dependence and Alcoholism, the NEO Personality Inventory, and the Wisconsin Card Sorting Test. Exploratory factor analysis (EFA) and fit indices (root mean-squared error of approximation (RMSEA), Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI)) were used to examine different latent variable models. A multiple indicators, multiple causes (MIMIC) approach-tested associations of the latent variables with sociodemographics, substance use, and a history of abuse/neglect.Results: A six-factor model (predominant alcohol, predominant cocaine, predominant opioid, externalizing, personality, and executive function) provided the best fit [RMSEA = 0.063 (90% CI 0.060, 0.066), CFI = 0.98, TLI = 0.96]. All factors were moderately correlated (coefficient = 0.25-0.55, p < .05) with the exception of executive function. MIMIC analysis revealed different patterns of associations (all p < .0001) with sociodemographics, substance use, and a history of abuse/neglect among the factors.Conclusions: The domains identified, particularly executive function, were parallel to those observed previously. These factors underscore the heterogeneous nature of SUDs and may be useful in developing more targeted clinical interventions.

Processing speed and executive functioning in relation to off-topic verbosity among young adults and older adults.

PURPOSE: Off-topic verbosity (OTV) is a tendency towards excessive, off-topic speech and has been linked with age-related deficits in executive functioning, particularly inhibition. However, there are numerous disagreements within the literature on what constitutes OTV, and there is a further lack of investigation into alternative cognitive explanations for the link between inhibition and OTV. The purpose of this study was to investigate the speech characteristics of OTV in young and older adults as well as to examine whether variations in OTV are better explained by diminished executive functioning or processing speed, as measured by the D-KEFS Stroop test. METHODS: Young adults (n = 65; age 18-28) and older adults (n = 85; age 60-98) completed the D-KEFS Color-Word Interference Test and provided verbal samples of autobiographical episodic and procedural speech. These speech samples were rated on three facets of OTV: tangentiality, egocentrism and quantity of speech. RESULTS: Procedural autobiographical speech was found to best measure age cohort variations in OTV, and higher OTV was associated with poorer Stroop test performance in older adults but not in young adults. In fact, young adults only displayed associations between poorer Stroop performance and a reduction in speech quantity. Finally, processing speed deficits were more associated with increased OTV in older adults than executive functioning. CONCLUSION: These results provide support for links between age-related cognitive decline and OTV, but the results suggest that processing speed may be more implicated than executive functioning.

Prenatal iron supplementation adjusted to maternal iron stores reduces behavioural problems in 4-year-old children.

Prenatal iron supplementation improves children's health and cognitive performance, but few studies explore behavioural development. This study assessed the effects of adjusting prenatal iron supplementation to maternal iron stores during early pregnancy on children's behavioural problems. Randomized controlled trial conducted in Tarragona (Spain) involving 230 nonanaemic pregnant women and their children after a 4-year follow-up. Based on haemoglobin (Hb) levels before gestational week (GW) 12, women receive different iron doses: those with Hb = 110-130 g/L were randomized to receive 80 or 40 mg/day and those with Hb > 130 g/L were randomized to receive 20 or 40 mg/day. Maternal iron stores at GW12 were classified using serum ferritin (SF) as low (SF < 15 µg/L), normal (SF = 15-65 µg/L), and normal-high (SF > 65 µg/L). Children's behaviour was assessed by parents using the Child Behaviour Checklist for ages 1.5-5 years and the Behaviour Rating Inventory of Executive Function-Preschool Version, and by teachers using the Teacher's Report Form for ages 1.5-5 years. Multivariable regression models were performed. Taking 80 mg/day of iron improved child behaviour when women had low iron stores but worsened it when mothers had normal-high iron stores, except for depressive and attention/hyperactivity problems. Taking 20 mg/day of iron improved behaviour only in those children whose mothers had SF > 65 µg/L in early pregnancy. Additionally, executive functioning improved at high doses of prenatal iron when maternal baseline SF < 15 µg/L. Adjusting prenatal iron supplementation to both maternal baseline Hb levels and iron stores reduces behavioural problems in 4-year-old children.

Maternal major depression during early pregnancy is associated with impaired child executive functioning at 4.5 years of age.

BACKGROUND: Maternal depression is a serious condition that affects up to 1 in 7 pregnancies. Despite evidence linking maternal depression to pregnancy complications and adverse fetal outcomes, there remain large gaps in its identification and treatment. More work is needed to define the specific timing and severity of depression that most urgently requires intervention, where feasible, to protect maternal health and the developing fetus. OBJECTIVE: This study aimed to examine whether the timing and severity of maternal depression and/or anxiety during pregnancy affect child executive functioning at age 4.5 years. Executive functioning in the preschool years is a strong predictor of both school readiness and long-term quality of life. STUDY DESIGN: This longitudinal observational pregnancy cohort study included a sample of 323 mother-child dyads taking part in the Ontario Birth Study, an open pregnancy cohort in Toronto, Ontario, Canada. Maternal symptoms of depression and anxiety were assessed at 12 to 16 and 28 to 32 weeks of gestation and at the time of child testing at age 4.5 years using the 4-item Patient Health Questionnaire. Child executive functioning was measured during a home visit using standardized computerized administration of the Flanker test (a measure of attention) and the Dimensional Change Card Sort (a measure of cognitive flexibility). Stepwise linear regressions, controlling for possible confounding variables, were used to assess the predictive value of continuous measures of maternal depression and/or anxiety symptoms at each assessment time on the Flanker test and Dimensional Change Card Sort. Posthoc general linear models were used to assess whether maternal depression severity categories (no symptom, mild symptoms, or probable major depressive disorder) were helpful in identifying children at risk. RESULTS: Across all children, after controlling for potential confounds, greater maternal depressive symptoms at weeks 12 to 16 weeks of gestation predicted worse performance on both the Flanker test (ΔR2=0.058; P<.001) and the Dimensional Change Card Sort (ΔR2=0.017; P=.018). Posthoc general linear modeling further demonstrated that the children of mothers meeting the screening criteria for major depression in early pregnancy scored 11.3% lower on the Flanker test and 9.8% lower on the Dimensional Change Card Sort than the children of mothers without maternal depressive symptoms in early pregnancy. Mild depressive symptoms had no significant effect on executive function scores. There was no significant effect of anxiety symptoms or maternal antidepressant use in early pregnancy or pandemic conditions or maternal symptoms in later pregnancy or at the time of child testing on either the Flanker or Dimensional Change Card Sort results. CONCLUSION: This study demonstrated that fetal exposure to maternal major depression, but not milder forms of depression, at 12 to 16 weeks of gestation is associated with impaired executive functioning in the preschool years. Child executive functioning is crucial for school readiness and predicts long-term quality of life. This emphasizes an urgent need to improve the recognition and treatment of maternal major depression, particularly in early pregnancy, to limit its negative effects on the patient and on child cognitive development.

Effects of daily full-term infant skin-to-skin contact on behavior and cognition at age three - secondary outcomes of a randomized controlled trial.

BACKGROUND: Daily skin-to-skin contact (SSC) during early infancy fosters the long-term development of children born preterm. This is the first randomized controlled trial assessing the potential beneficial effects of daily SSC on executive functioning and socio-emotional behavior of children born full-term. Whether children of mothers who experienced prenatal stress and anxiety benefitted more from SSC was also explored. METHODS: Pregnant women (N = 116) were randomly assigned to a SSC or care-as-usual (CAU) condition. Women in the SSC condition were instructed to perform one hour of SSC daily from birth until postnatal week five. Prenatal stress was measured with questionnaires on general and pregnancy-specific stress and anxiety completed by the mothers in gestational week 37. At child age three, mothers filled in questionnaires on children's executive functioning, and externalizing and internalizing behavior. Analyses were performed in an intention-to-treat (ITT), per-protocol, and dose-response approach. Netherlands Trial Register: NL5591. RESULTS: In the ITT approach, fewer internalizing (95% CI = 0.11-1.00, U = 2148.50, r = .24, p = .001) and externalizing (95% CI = 0.04-2.62, t = 2.04, d = 0.38, p = .04) problems were reported in the SSC condition compared to the CAU condition. Multivariate analyses of variance did not show group differences on executive functioning. Additional analyses of covariance showed no moderations by maternal prenatal stress. CONCLUSIONS: Current findings indicate that early daily SSC in full-term infants may foster children's behavioral development. Future replications, including behavioral observations of child behavior to complement maternal reports, are warranted.

Executive Functioning, Daily Self-Regulation, and Diabetes Management while Transitioning into Emerging Adulthood.

BACKGROUND: Executive functioning (EF) predicts better Type 1 diabetes (T1D) management in the high-risk years after high school, but the daily self-regulation processes involved are unclear. PURPOSE: To examine whether EF is associated with daily self-regulation that minimizes one's exposure or buffers adverse reactions to daily diabetes problems, and to determine whether these patterns become stronger during the transition out of high school. METHODS: A measurement burst design with convenience sampling was used. Seniors in high school with T1D (N = 207; 66% female) completed self-report (i.e., Behavioral Rating Inventory of Executive Functioning) and performance measures of EF (i.e., Delis-Kaplan Executive Function System). A 14-day daily diary assessing self-regulation failures, diabetes problems, affect, and indicators of diabetes management was completed at baseline and 1 year later. RESULTS: Correlations and multilevel modeling were conducted. Lower self-reported EF problems were associated with lower average levels of daily self-regulation failures, and these variables were associated with fewer daily diabetes problems. In contrast, better EF performance was unrelated to average daily self-regulation failures, and was unexpectedly associated with more frequent diabetes problems in year 2. Equally across years, on days participants reported lower than their average levels of daily self-regulation failures, they had fewer diabetes problems, regardless of EF. On days with lower than average diabetes problems, participants reported better diabetes management indicators. EF generally did not buffer daily associations in either year. CONCLUSIONS: Regardless of EF, promoting daily self-regulation may prevent diabetes problems and promote T1D management in daily life at this high-risk transitional time.

Type 1 diabetes (T1D) requires daily self-regulation (e.g., remembering to check blood glucose; regulating emotions, thoughts, and behaviors when diabetes problems arise). These processes draw on executive function (EF) abilities, which may be challenged after high school, when youth experience many life transitions while managing diabetes more independently from parents. The study examined how EF is associated with daily diabetes management as youth transition out of high school. Seniors in high school with T1D completed measures of EF and two 14-day daily diaries, one in the senior year and one the following year. Each evening, participants completed an online survey reporting on self-regulation failures (e.g., forgetting to test blood glucose), diabetes problems, and diabetes management over the past 24 hr. Those with better self-reported EF had lower self-regulation failures and fewer diabetes problems on average. On days with lower self-regulation failures, participants had fewer diabetes problems. On days with fewer diabetes problems, participants reported lower negative emotions, higher confidence in diabetes management, and better self-care behaviors and blood glucose levels. These daily associations occurred regardless of EF. Providing youth with training in self-regulation to prevent daily diabetes problems may promote T1D management during this high-risk transition.

APOE Effects on Late Life Cognitive Trajectories in Diverse Racial/Ethnic Groups.

OBJECTIVE: This study evaluated: (1) apolipoprotein E (APOE) ϵ4 prevalence among Black, Latino, and White older adults, (2) associations of APOE ϵ4 status with baseline level and change over time of cognitive outcomes across groups, and (3) combined impact of APOE ϵ4 prevalence and magnitude of effect on cognitive decline within each racial/ethnic group. METHOD: Participants included 297 White, 138 Latino, and 149 Black individuals from the longitudinal UC Davis Diversity Cohort who had APOE genotyping and ≥2 cognitive assessments. Magnitude of associations of ϵ4 with cognitive baseline and change across racial/ethnic groups was tested with multilevel parallel process longitudinal analyses and multiple group models. RESULTS: ϵ4 prevalence in Black (46%) and White participants (46%) was almost double that of Latino participants (24%). ϵ4 was associated with poorer baseline episodic memory only in White participants (p = .001), but had a moderately strong association with episodic memory change across all racial/ethnic groups (Blacks= -.061 SD/year, Latinos = -.055,Whites= -.055). ϵ4 association with semantic memory change was strongest in White participants (-.071), intermediate in Latino participants (-.041), and weakest in Black participants (-.022). CONCLUSION: Calculated cognitive trajectories across racial/ethnic groups were influenced in an additive manner by ϵ4 prevalence and strength of association with cognitive decline within the group. Group differences in ϵ4 prevalences and associations of ϵ4 with cognition may suggest different pathways from APOE to cognitive decline, and, AD possibly having less salient impact on cognitive decline in non-White participants. Differential effects of APOE on episodic memory and non-memory cognition have important implications for understanding how APOE influences late life cognitive decline.