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Bibliography Tag: developmental impacts

Smith et al., 2020

Smith, Dylan B., Arce, Andres N., Ramos Rodrigues, Ana, Bischoff, Philipp H., Burris, Daisy, Ahmed, Farah, & Gill, Richard J.; “Insecticide exposure during brood or early-adult development reduces brain growth and impairs adult learning in bumblebees;” Proceedings of the Royal Society B: Biological Sciences, 2020, 287(1922); DOI: 10.1098/rspb.2019.2442.


For social bees, an understudied step in evaluating pesticide risk is how contaminated food entering colonies affects residing offspring development and maturation. For instance, neurotoxic insecticide compounds in food could affect central nervous system development predisposing individuals to become poorer task performers later-in-life. Studying bumblebee colonies provisioned with neonicotinoid spiked nectar substitute, we measured brain volume and learning behaviour of 3 or 12-day old adults that had experienced in-hive exposure during brood and/or early-stage adult development. Micro-computed tomography scanning and segmentation of multiple brain neuropils showed exposure during either of the developmental stages caused reduced mushroom body calycal growth relative to unexposed workers. Associated with this was a lower probability of responding to a sucrose reward and lower learning performance in an olfactory conditioning test. While calycal volume of control workers positively correlated with learning score, this relationship was absent for exposed workers indicating neuropil functional impairment. Comparison of 3- and 12-day adults exposed during brood development showed a similar degree of reduced calycal volume and impaired behaviour highlighting lasting and irrecoverable effects from exposure despite no adult exposure. Our findings help explain how the onset of pesticide exposure to whole colonies can lead to lag-effects on growth and resultant dysfunction. FULL TEXT

Ait-Bali et al., 2020

Ait-Bali, Y., Ba-M’hamed, S., Gambarotta, G., Sassoe-Pognetto, M., Giustetto, M., & Bennis, M.; “Pre- and postnatal exposure to glyphosate-based herbicide causes behavioral and cognitive impairments in adult mice: evidence of cortical ad hippocampal dysfunction;” Archives of Toxicology, 2020; DOI: 10.1007/s00204-020-02677-7.


Glyphosate-based herbicides (GBH) are the most widely used pesticides worldwide. Despite considerable progress in describing the neurotoxic potential of GBH, the harmful effects on brain cytoarchitecture and behavior are still unclear. Here, we addressed the developmental impact of GBH by exposing female mice to 250 or 500 mg/kg doses of GBH during both pregnancy and lactation and then examined the downstream effects at the behavioral, neurochemical and molecular levels. We show that pre- and neonatal exposure to GBH impairs fertility and reproduction parameters as well as maternal behavior of exposed mothers. In offspring, GBH was responsible for a global delay in innate reflexes and a deficit in motor development. At the adult age, exposed animals showed a decrease of locomotor activity, sociability, learning and short- and long-term memory associated with alterations of cholinergic and dopaminergic systems. Furthermore, GBH-activated microglia and astrocytes, sign of neuroinflammation event in the medial prefrontal cortex and hippocampus. At the molecular level, a down-regulation of brain-derived neurotrophic factor (BDNF) expression and an up-regulation of tyrosine-related kinase receptor (TrkB), NR1 subunit of NMDA receptor as well as tumor necrosis factor alpha (TNFalpha) were found in the brain of GBH-exposed mice. The present work demonstrates that GBH induces numerous behavioral and cognitive abnormalities closely associated with significant histological, neurochemical and molecular impairments. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during developmental periods of central nervous system. FULL TEXT

Marks et al., 2010

Marks, A. R., Harley, K., Bradman, A., Kogut, K., Barr, D. B., Johnson, C., Calderon, N., & Eskenazi, B.; “Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study;” Environmental Health Perspectives, 2010, 118(12), 1768-1774; DOI: 10.1289/ehp.1002056.



Exposure to organophosphate (OP) pesticides, well-known neurotoxicants, has been associated with neurobehavioral deficits in children.


We investigated whether OP exposure, as measured by urinary dialkyl phosphate (DAP) metabolites in pregnant women and their children, was associated with attention-related outcomes among Mexican-American children living in an agricultural region of California.


Children were assessed at ages 3.5 years (n = 331) and 5 years (n = 323). Mothers completed the Child Behavior Checklist (CBCL). We administered the NEPSY-II visual attention subtest to children at 3.5 years and Conners’ Kiddie Continuous Performance Test (K-CPT) at 5 years. The K-CPT yielded a standardized attention deficit/hyperactivity disorder (ADHD) Confidence Index score. Psychometricians scored behavior of the 5-year-olds during testing using the Hillside Behavior Rating Scale.


Prenatal DAPs (nanomoles per liter) were nonsignificantly associated with maternal report of attention problems and ADHD at age 3.5 years but were significantly related at age 5 years [CBCL attention problems: beta = 0.7 points; 95% confidence interval (CI), 0.2-1.2; ADHD: beta = 1.3; 95% CI, 0.4-2.1]. Prenatal DAPs were associated with scores on the K-CPT ADHD Confidence Index > 70th percentile [odds ratio (OR) = 5.1; 95% CI, 1.7-15.7] and with a composite ADHD indicator of the various measures (OR = 3.5; 95% CI, 1.1-10.7). Some outcomes exhibited evidence of effect modification by sex, with associations found only among boys. There was also limited evidence of associations between child DAPs and attention.


In utero DAPs and, to a lesser extent, postnatal DAPs were associated adversely with attention as assessed by maternal report, psychometrician observation, and direct assessment. These associations were somewhat stronger at 5 years than at 3.5 years and were stronger in boys. FULL TEXT

Tremlett et al, 2017

Tremlett, H., Bauer, K. C., Appel-Cresswell, S., Finlay, B. B., & Waubant, E.; “The gut microbiome in human neurological disease: A review;” Annals of Neurology, 2017, 81(3), 369-382; DOI: 10.1002/ana.24901.


Almost half the cells and 1% of the unique genes found in our bodies are human, the rest are from microbes, predominantly bacteria, archaea, fungi, and viruses. These microorganisms collectively form the human microbiota, with most colonizing the gut. Recent technological advances, open access data libraries, and application of high-throughput sequencing have allowed these microbes to be identified and their contribution to neurological health to be examined. Emerging evidence links perturbations in the gut microbiota to neurological disease, including disease risk, activity, and progression. This review provides an overview of the recent advances in microbiome research in relation to neuro(auto)immune and neurodegenerative conditions affecting humans, such as multiple sclerosis, neuromyelitis optica spectrum disorders, Parkinson disease, Alzheimer disease, Huntington disease, and amyotrophic lateral sclerosis. Study design and terminology used in this rapidly evolving, highly multidisciplinary field are summarized to empower and engage the neurology community in this “newly discovered organ.” FULL TEXT

Rodgaard et al., 2019

Rodgaard, E. M., Jensen, K., Vergnes, J. N., Soulieres, I., & Mottron, L.; “Temporal Changes in Effect Sizes of Studies Comparing Individuals With and Without Autism: A Meta-analysis;” JAMA Psychiatry, 2019; DOI: 10.1001/jamapsychiatry.2019.1956.



The definition and nature of autism have been highly debated, as exemplified by several revisions of the DSM (DSM-III, DSM-IIIR, DSM-IV, and DSM-5) criteria. There has recently been a move from a categorical view toward a spectrum-based view. These changes have been accompanied by a steady increase in the prevalence of the condition. Changes in the definition of autism that may increase heterogeneity could affect the results of autism research; specifically, a broadening of the population with autism could result in decreasing effect sizes of group comparison studies.


To examine the correlation between publication year and effect size of autism-control group comparisons across several domains of published autism neurocognitive research.


This meta-analysis investigated 11 meta-analyses obtained through a systematic search of PubMed for meta-analyses published from January 1, 1966, through January 27, 2019, using the search string autism AND (meta-analysis OR meta-analytic). The last search was conducted on January 27, 2019.


Meta-analyses were included if they tested the significance of group differences between individuals with autism and control individuals on a neurocognitive construct. Meta-analyses were only included if the tested group difference was significant and included data with a span of at least 15 years.

DATA EXTRACTION AND SYNTHESIS: Data were extracted and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline using fixed-effects models.


Estimated slope of the correlation between publication year and effect size, controlling for differences in methods, sample size, and study quality.


The 11 meta-analyses included data from a total of 27723 individuals. Demographic data such as sex and age were not available for the entire data set. Seven different psychological and neurologic constructs were analyzed based on data from these meta-analyses. Downward temporal trends for effect size were found for all constructs (slopes: -0.067 to -0.003), with the trend being significant in 5 of 7 cases: emotion recognition (slope: -0.028 [95% CI, -0.048 to -0.007]), theory of mind (-0.045 [95% CI, -0.066 to -0.024]), planning (-0.067 [95% CI, -0.125 to -0.009]), P3b amplitude (-0.048 [95% CI, -0.093 to -0.004]), and brain size (-0.047 [95% CI, -0.077 to -0.016]). In contrast, 3 analogous constructs in schizophrenia, a condition that is also heterogeneous but with no reported increase in prevalence, did not show a similar trend.


The findings suggest that differences between individuals with autism and those without the diagnosis have decreased over time and that possible changes in the definition of autism from a narrowly defined and homogenous population toward an inclusive and heterogeneous population may reduce our capacity to build mechanistic models of the condition. FULL TEXT

Sagiv et al., 2019

Sagiv, S. K., Bruno, J. L., Baker, J. M., Palzes, V., Kogut, K., Rauch, S., Gunier, R., Mora, A. M., Reiss, A. L., & Eskenazi, B.; “Prenatal exposure to organophosphate pesticides and functional neuroimaging in adolescents living in proximity to pesticide application;” Proceedings of the National Academy of Sciences of the United States of America, 2019; DOI: 10.1073/pnas.1903940116.


We have reported consistent associations of prenatal organophosphate pesticide (OP) exposure with poorer cognitive function and behavior problems in our Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a birth cohort of Mexican American youth in California’s agricultural Salinas Valley. However, there is little evidence on how OPs affect neural dynamics underlying associations. We used functional near-infrared spectroscopy (fNIRS) to measure cortical activation during tasks of executive function, attention, social cognition, and language comprehension in 95 adolescent CHAMACOS participants. We estimated associations of residential proximity to OP use during pregnancy with cortical activation in frontal, temporal, and parietal regions using multiple regression models, adjusting for sociodemographic characteristics. OP exposure was associated with altered brain activation during tasks of executive function. For example, with a 10-fold increase in total OP pesticide use within 1 km of maternal residence during pregnancy, there was a bilateral decrease in brain activation in the prefrontal cortex during a cognitive flexibility task (β = -4.74; 95% CI: -8.18, -1.31 and β = -4.40; 95% CI: -7.96, -0.84 for the left and right hemispheres, respectively). We also found that prenatal OP exposure was associated with sex differences in brain activation during a language comprehension task. This first functional neuroimaging study of prenatal OP exposure suggests that pesticides may impact cortical brain activation, which could underlie previously reported OP-related associations with cognitive and behavioral function. Use of fNIRS in environmental epidemiology offers a practical alternative to neuroimaging technologies and enhances our efforts to assess the impact of chemical exposures on neurodevelopment. FULL TEXT

Jusko et al., 2012

Jusko, T. A., Klebanoff, M. A., Brock, J. W., & Longnecker, M. P.; “In-utero exposure to dichlorodiphenyltrichloroethane and cognitive development among infants and school-aged children;” Epidemiology, 2012, 23(5), 689-698; DOI: 10.1097/EDE.0b013e31825fb61d.


BACKGROUND: Dichlorodiphenyltrichloroethane (DDT) continues to be used for control of infectious diseases in several countries. In-utero exposure to DDT and dichlorodiphenyldichloroethylene (DDE) has been associated with developmental and cognitive impairment among children. We examined this association in an historical cohort in which the level of exposure was greater than in previous studies.

METHODS: The association of in-utero DDT and DDE exposure with infant and child neurodevelopment was examined in 1100 subjects in the Collaborative Perinatal Project, a prospective birth cohort enrolling pregnant women from 12 study centers in the United States from 1959 to 1965. Maternal DDT and DDE concentrations were measured in archived serum specimens. Infant mental and motor development was assessed at age 8 months using the Bayley Scales of Infant Development, and child cognitive development was assessed at age 7 years, using the Wechsler Intelligence Scale for Children.

RESULTS: Although levels of DDT and DDE were relatively high in this population (median DDT concentration, 8.9 mug/L; DDE, 24.5 mug/L), neither were related to Mental or Psychomotor Development scores on the Bayley Scales nor to Full-Scale Intelligence Quotient at 7 years of age. Categorical analyses showed no evidence of dose- response for either maternal DDT or DDE, and estimates of the association between continuous measures of exposure and neurodevelopment were indistinguishable from 0.

CONCLUSIONS: Adverse associations were not observed between maternal serum DDT and DDE concentrations and offspring neurodevelopment at 8 months or 7 years in this cohort. FULL TEXT

Gallegos et al., 2016

Gallegos, Cristina E., Bartos, Mariana, Bras, Cristina, Gumilar, Fernanda, Antonelli, Marta C., & Minetti, Alejandra; “Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring;” NeuroToxicology, 2016, 53, 20-28; DOI: 10.1016/j.neuro.2015.11.015.


The impact of sub-lethal doses of herbicides on human health and the environment is a matter of controversy. Due to the fact that evidence particularly of the effects of glyphosate on the central nervous system of rat offspring by in utero exposure is scarce, the purpose of the present study was to assess the neurobehavioral effects of chronic exposure to a glyphosate-containing herbicide during pregnancy and lactation. To this end, pregnant Wistar rats were exposed through drinking water to 0.2% or 0.4% of a commercial formulation of glyphosate (corresponding to a concentration of 0.65 or 1.30g/L of glyphosate, respectively) during pregnancy and lactation and neurobehavioral alterations in offspring were analyzed. The postnatal day on which each pup acquired neonatal reflexes (righting, cliff aversion and negative geotaxis) and that on which eyes and auditory canals were fully opened were recorded for the assessment of sensorimotor development. Locomotor activity and anxiety levels were monitored via open field test and plus maze test, respectively, in 45- and 90-day-old offspring. Pups exposed to a glyphosate-based herbicide showed early onset of cliff aversion reflex and early auditory canal opening. A decrease in locomotor activity and in anxiety levels was also observed in the groups exposed to a glyphosate-containing herbicide. Findings from the present study reveal that early exposure to a glyphosate-based herbicide affects the central nervous system in rat offspring probably by altering mechanisms or neurotransmitter systems that regulate locomotor activity and anxiety.

Landrigan and Goldman, 2011

Landrigan, Philip J, & Goldman, Lynn R; “Children’s vulnerability to toxic chemicals: a challenge and opportunity to strengthen health and environmental policy;” Health Affairs, 2011, 30(5), 842-850; DOI: 10.1377/hlthaff.2011.0151.


A key policy breakthrough occurred nearly twenty years ago with the discovery that children are far more sensitive than adults to toxic chemicals in the environment. This finding led to the recognition that chemical exposures early in life are significant and preventable causes of disease in children and adults. We review this knowledge and recommend a new policy to regulate industrial and consumer chemicals that will protect the health of children and all Americans, prevent disease, and reduce health care costs. The linchpins of a new US chemical policy will be: first, a legally mandated requirement to test the toxicity of chemicals already in commerce, prioritizing chemicals in the widest use, and incorporating new assessment technologies; second, a tiered approach to premarket evaluation of new chemicals; and third, epidemiologic monitoring and focused health studies of exposed populations.  FULL TEXT

Bakian et al., 2019

Bakian, Amanda V., & VanDerslice, James A.; “Pesticides and autism;” BMJ, 2019, 364, l1149; DOI: 10.1136/bmj.l1149.


Editorial in response to von Ehrenstein et al., 2019.


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