Publications by authors named "Amy E Margolis"

23 Publications

  • Page 1 of 1

Prenatal environmental tobacco smoke exposure alters children's cognitive control circuitry: A preliminary study.

Environ Int 2021 May 6;155:106516. Epub 2021 May 6.

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.

Background And Objectives: Prenatal exposure to environmental tobacco smoke (ETS) is associated with increased attention problems in children, however, the effects of such exposure on children's brain structure and function have not been studied. Herein, we probed effects of prenatal ETS on children's cognitive control circuitry and behavior.

Methods: Forty-one children (7-9 years) recruited from a prospective longitudinal birth cohort of non-smoking mothers completed structural and task-functional magnetic resonance imaging to evaluate effects of maternal ETS exposure, measured by maternal prenatal urinary cotinine. Attention problems and externalizing behaviors were measured by parent report on the Child Behavior Checklist.

Results: Compared to non-exposed children, exposed children had smaller left and right thalamic and inferior frontal gyrus (IFG) volumes, with large effect sizes (p-FDR < .05, Cohen's D range from 0.79 to 1.07), and increased activation in IFG during the resolution of cognitive conflict measured with the Simon Spatial Incompatibility Task (38 voxels; peak t(25) = 5.25, p-FWE = .005). Reduced thalamic volume was associated with increased IFG activation and attention problems, reflecting poor cognitive control. Mediation analyses showed a trend toward left thalamic volume mediating the association between exposure and attention problems (p = .05).

Conclusions: Our findings suggest that maternal ETS exposure during pregnancy has deleterious effects on the structure and function of cognitive control circuitry which in turn affects attentional capacity in school-age children. These findings are consistent with prior findings documenting the effects of active maternal smoking on chidlren's neurodevleoment, pointing to the neurotixicity of nicotine regardless of exposure pathway.
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http://dx.doi.org/10.1016/j.envint.2021.106516DOI Listing
May 2021

Contributions of Cerebellar White Matter Microstructure to Social Difficulty in Nonverbal Learning Disability.

Cerebellum 2021 Apr 15. Epub 2021 Apr 15.

New York State Psychiatric Institute and Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Box 74 / Room 2403, New York, NY, 10032, USA.

Emerging evidence suggests that the cerebellum may contribute to variety of cognitive capacities, including social cognition. Nonverbal learning disability (NVLD) is characterized by visual-spatial and social impairment. Recent functional neuroimaging studies have shown that children with NVLD have altered cerebellar resting-state functional connectivity, which is associated with various symptom domains. However, little is known about cerebellar white matter microstructure in NVLD and whether it contributes to social deficits. Twenty-seven children (12 with NVLD, 15 typically developing (TD)) contributed useable diffusion tensor imaging data. Tract-based spatial statistics (TBSS) were used to quantify fractional anisotropy (FA) in the cerebellar peduncles. Parents completed the Child Behavior Checklist, providing a measure of social difficulty. Children with NVLD had greater fractional anisotropy in the left and right inferior cerebellar peduncle. Furthermore, right inferior cerebellar peduncle FA was associated with social impairment as measured by the Child Behavior Checklist Social Problems subscale. Finally, the association between NVLD diagnosis and greater social impairment was mediated by right inferior cerebellar peduncle FA. These findings provide additional evidence that the cerebellum contributes both to social cognition and to the pathophysiology of NVLD.
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http://dx.doi.org/10.1007/s12311-021-01265-4DOI Listing
April 2021

Frontoparietal and default mode network connectivity varies with age and intelligence.

Dev Cogn Neurosci 2021 Apr 27;48:100928. Epub 2021 Jan 27.

The Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, United States. Electronic address:

Background: Anticorrelated resting state connectivity between task-positive and task-negative networks in adults supports flexible shifting between externally focused attention and internal thought. Findings suggest that children show positive correlations between task-positive (frontoparietal; FP) and task-negative (default mode; DMN) networks. FP-DMN connectivity also associates with intellectual functioning across the lifespan. We investigated whether FP-DMN connectivity in healthy children varied with age and intelligence quotient (IQ).

Methods: We utilized network-based statistics (NBS) to examine resting state functional connectivity between FP and DMN seeds in N = 133 7-25-year-olds (M = 15.80). Linear regression evaluated FP-DMN associations with IQ.

Results: We detected NBS subnetworks containing both within- and between-network connections that were inversely associated with age. Four FP-DMN connections showed more negative connectivity between FP (inferior frontal gyrus and precentral gyrus) and DMN regions (frontal medial cortex, precuneus, and frontal pole) among older participants. Frontal pole-precentral gyrus connectivity inversely associated with IQ.

Conclusions: FP-DMN connectivity was more anticorrelated at older ages, potentially indicating dynamic network segregation of these circuits from childhood to early adulthood. Youth with more mature (i.e., anticorrelated) FP-DMN connectivity demonstrated higher IQ. Our findings add to the growing body of literature examining neural network development and its association with IQ.
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http://dx.doi.org/10.1016/j.dcn.2021.100928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848769PMC
April 2021

Associations between Amygdala-Prefrontal Functional Connectivity and Age Depend on Neighborhood Socioeconomic Status.

Cereb Cortex Commun 2020 23;1(1):tgaa033. Epub 2020 Jul 23.

New York State Psychiatric Institute and Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Although severe early life stress has been shown to accelerate the development of frontolimbic resting-state functional connectivity (RSFC), less is known about the effects of socioeconomic disadvantage, a prolonged and multifaceted stressor. In a cross-sectional study of 127 participants aged 5-25, we examined whether lower neighborhood socioeconomic status (SES; measured by Area Deprivation Index and neighborhood poverty and educational attainment) was associated with prematurely reduced amygdala-ventromedial prefrontal cortex (vmPFC) RSFC. We further tested whether neighborhood SES was more predictive than household SES and whether SES effects on connectivity were associated with anxiety symptoms. We found reduced basolateral amygdala-vmPFC RSFC at earlier ages in participants from more disadvantaged neighborhoods; this effect was unique to neighborhood SES and absent for household SES. Furthermore, this reduced connectivity in more disadvantaged youth and increased connectivity in more advantaged youth were associated with less anxiety; children who deviated from the connectivity pattern associated with their neighborhood SES had more anxiety. These results demonstrate that neighborhood socioeconomic disadvantage is associated with accelerated maturation of amygdala-vmPFC RSFC and suggest that the pathophysiology of pediatric anxiety depends on a child's neighborhood socioeconomic characteristics. Our findings also underscore the importance of examining SES effects in studies of brain development.
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http://dx.doi.org/10.1093/texcom/tgaa033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503474PMC
July 2020

Altered structure and functional connectivity of the hippocampus are associated with social and mathematical difficulties in nonverbal learning disability.

Hippocampus 2021 Jan 19;31(1):79-88. Epub 2020 Sep 19.

The Division of Child and Adolescent Psychiatry, Department of Psychiatry, The New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, New York, New York, USA.

The hippocampus is known to play a critical role in a variety of complex abilities, including visual-spatial reasoning, social functioning, and math. Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial reasoning that are accompanied by impairment in social function or mathematics, as well as motor or executive function skills. Despite the overlap between behaviors supported by the hippocampus and impairments in NVLD, the structure and function of the hippocampus in NVLD has not been studied. To address this gap in the literature, we first compared hippocampal volume and resting-state functional connectivity in children with NVLD (n = 24) and typically developing (TD) children (n = 20). We then explored associations between hippocampal structure, connectivity, and performance on measures of spatial, social, and mathematical ability. Relative to TD children, those with NVLD showed significant reductions in left hippocampal volume and greater hippocampal-cerebellar connectivity. In children with NVLD, reduced hippocampal volume associated with worse mathematical problem solving. Although children with NVLD exhibited more social problems (social responsiveness scale [SRS]) and higher hippocampal-cerebellar connectivity relative to TD children, greater connectivity was associated with fewer social problems among children with NVLD but not TD children. Such an effect may suggest a compensatory mechanism. These structural and functional alterations of the hippocampus may disrupt its putative role in organizing conceptual frameworks through cognitive mapping, thus contributing to the cross-domain difficulties that characterize NVLD.
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http://dx.doi.org/10.1002/hipo.23264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749072PMC
January 2021

Estimated Prevalence of Nonverbal Learning Disability Among North American Children and Adolescents.

JAMA Netw Open 2020 04 1;3(4):e202551. Epub 2020 Apr 1.

Center for the Developing Brain, Child Mind Institute, New York, New York.

Importance: Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial processing but not in reading or verbal ability; in addition, problems in math calculation, visual executive functioning, fine-motor skills, and social skills are often present. To our knowledge, there are no population-based estimates of the prevalence of NVLD in community samples.

Objective: To estimate the prevalence of the NVLD cognitive profile in 3 independent samples of children and adolescents from studies centered around brain imaging in the US and Canada.

Design, Setting, And Participants: This cross-sectional study used data from 2 samples recruited from the community and overselected for children with psychiatric disorders (Healthy Brain Network [HBN], January 1, 2015, to December 31, 2019, and Nathan Kline Institute-Rockland Sample [NKI], January 1, 2011, to December 31, 2018) and 1 community-ascertained population sample (Saguenay Youth Study [SYS], January 1, 2003, to December 31, 2012) overselected for active maternal smoking during pregnancy.

Main Outcomes And Measures: Prevalence of NVLD. Criteria for NVLD were based on clinical records of deficits in visual-spatial reasoning and impairment in 2 of 4 domains of function (fine-motor skills, math calculation, visual executive functioning, and social skills). Sample weighting procedures adjusted for demographic differences in sample frequencies compared with underlying target populations. Inflation factor weights accounted for overrepresentation of psychiatric disorders (HBN and NKI samples).

Results: Across 3 independent samples, the prevalence of NVLD was estimated among 2596 children and adolescents aged 6 to 19 years (mean [SD] age, 12.5 [3.4] years; 1449 male [55.8%]). After sample and inflation weights were applied, the prevalence of NVLD was 2.78% (95% CI, 2.03%-3.52%) in the HBN sample and 3.9% (95% CI, 1.96%-5.78%) in the NKI sample. In the SYS sample, the prevalence of NVLD was 3.10% (95% CI, 1.93%-4.27%) after applying the sample weight. Across samples and estimation strategies, the population prevalence of NVLD was estimated to range from 3% to 4%. When applied to the US population younger than 18 years, 2.2 million to 2.9 million children and adolescents were estimated to have NVLD.

Conclusions And Relevance: The findings suggest that the prevalence of NVLD in children and adolescents may be 3% to 4%. Given that few youths are diagnosed with NVLD and receive treatment, increased awareness, identification of the underlying neurobiological mechanisms, and development and testing interventions for the disorder are needed.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.2551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148441PMC
April 2020

Spatial Network Connectivity and Spatial Reasoning Ability in Children with Nonverbal Learning Disability.

Sci Rep 2020 01 17;10(1):561. Epub 2020 Jan 17.

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, the New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, 1051 Riverside Drive, New York, NY, 10032, USA.

Nonverbal Learning Disability (NVLD) is characterized by deficits in visual-spatial, but not verbal, reasoning. Nevertheless, the functioning of the neural circuits supporting spatial processing have yet to be assessed in children with NVLD. We compared the resting state functional connectivity of a spatial brain network among children with NVLD, children with reading disorder (RD), and typically developing (TD) children. Seventy-five participants (7-15 years old) were included in the study (20 TD, 24 NVLD, and 31 RD). Group differences in global efficiency and functional connectivity among 12 regions comprising a previously defined spatial network were evaluated. Associations with behavior were explored. Global efficiency of the spatial network associated positively with spatial ability and inversely with socioemotional problems. Within the spatial network, associations between left posterior cingulate (PCC) and right retrosplenial cortical activity were reduced in children with NVLD relative to those without spatial deficits (RD and TD). Connectivity between left PCC and right posterior cerebellum (Crus I and II) was reduced in both groups of children with learning disabilities (NVLD and RD) relative to TD children. Functional connectivity of the spatial network was atypically associated with cognitive and socioemotional performance in children with NVLD. Identifying a neurobiological substrate for NVLD provides evidence that it is a discrete clinical entity and suggests targets for treatment.
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http://dx.doi.org/10.1038/s41598-019-56003-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969178PMC
January 2020

Prenatal exposure to polycyclic aromatic hydrocarbons modifies the effects of early life stress on attention and Thought Problems in late childhood.

J Child Psychol Psychiatry 2020 11 7;61(11):1253-1265. Epub 2020 Jan 7.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY, USA.

Background: Risk for childhood psychopathology is complex and multifactorial, implicating direct and interacting effects of familial and environmental factors. The role of environmental neurotoxicants in psychiatric risk is of growing concern, including polycyclic aromatic hydrocarbons (PAH), common in air pollution. Prenatal PAH exposure is linked to adverse physical, behavioral, and cognitive outcomes as well as increasing psychiatric risk. It is unclear whether environmental exposures, like PAH, magnify the effects of exposure to early life stress (ELS), a critical risk factor for psychopathology. The current work aimed to test potential interactions between prenatal PAH exposure and psychosocial/socioeconomic stress on psychiatric symptoms in school-age children.

Methods: Data were from the Columbia Center for Children's Environmental Health Mothers and Newborns longitudinal birth cohort study. Prenatal PAH exposure was ascertained though air monitoring during pregnancy and maternal PAH-DNA adducts at delivery. Mothers reported on ELS (child age 5) and on child psychiatric symptoms across childhood (child age 5, 7, 9, and 11) using the Child Behavior Checklist (CBCL).

Results: Significant prenatal airborne PAH × ELS interactions (FDR-corrected) predicted CBCL Attention (β = 0.22, t(307) = 3.47, p < .001, p = .003) and Thought Problems T-scores (β = 0.21, t(307) = 3.29, p = .001, p = .004) at age 11 (n = 319). Relative to those with lower exposure, children with higher prenatal PAH exposure exhibited stronger positive associations between ELS and CBCL Attention and Thought Problem T-scores. This interaction was also significant examining convergent ADHD measures (Conners, DuPaul) and examining maternal PAH-DNA adducts (β = 0.29, t(261) = 2.48, p = .01; n = 273). A three-way interaction with assessment wave indicated that the PAH × ELS interaction on Attention Problems was stronger later in development (β = 0.03, t(1,601) = 2.19, p = .03; n = 477).

Conclusions: Prenatal exposure to PAH, a common neurotoxicant in air pollution, may magnify or sustain the effects of early life psychosocial/socioeconomic stress on psychiatric outcomes later in child development. This work highlights the critical role of air pollution exposure on child mental health.
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http://dx.doi.org/10.1111/jcpp.13189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338249PMC
November 2020

Functional connectivity of the reading network is associated with prenatal polybrominated diphenyl ether concentrations in a community sample of 5 year-old children: A preliminary study.

Environ Int 2020 01 16;134:105212. Epub 2019 Nov 16.

Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Genetic factors explain 60 percent of variance in reading disorder. Exposure to neurotoxicants, including polybrominated diphenyl ethers (PBDEs), may be overlooked risk factors for reading problems. We used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between prenatal PBDE concentrations and functional connectivity of a reading-related network (RN) in a community sample of 5-year-old children (N = 33). Maternal serum PBDE concentrations (∑PBDE) were measured at 12.2 ± 2.8 weeks gestation (mean ± SD). The RN was defined by 12 regions identified in prior task-based fMRI meta-analyses; global efficiency (GE) was used to measure network integration. Linear regression evaluated associations between ∑PBDE, word reading, and GE of the RN and the default mode network (DMN); the latter to establish specificity of findings. Weighted quantile sum regression analyses evaluated the contributions of specific PBDE congeners to observed associations. Greater RN efficiency was associated with better word reading in these novice readers. Children with higher ∑PBDE showed reduced GE of the RN; ∑PBDE was not associated with DMN efficiency, demonstrating specificity of our results. Consistent with prior findings, ∑PBDE was not associated word reading at 5-years-old. Altered efficiency and integration of the RN may underlie associations between ∑PBDE concentrations and reading problems observed previously in older children.
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http://dx.doi.org/10.1016/j.envint.2019.105212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048018PMC
January 2020

Phonological memory problems are magnified in children from language minority homes when predicting reading disability.

J Child Lang 2020 05 5;47(3):680-694. Epub 2019 Nov 5.

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, the New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University Irving Medical Center, USA.

Children from language minority (LM) environments speak a language at home that differs from that at school, are often from socioeconomically disadvantaged backgrounds, and are at risk for reading impairment. We evaluated the main effects and interaction of language status and phonological memory and awareness on reading disorder in 352 children from socioeconomically disadvantaged backgrounds. A significant phonological memory by language status interaction indicated that phonological memory problems were magnified in predicting reading impairment in children from LM versus English dominant (ED) homes. Among children without reading disorder, language minority status was unrelated to phonological processing.
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http://dx.doi.org/10.1017/S0305000919000576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263306PMC
May 2020

Bilingualism May Be Protective Against Executive Function and Visual Processing Deficits Among Children With Attention Problems.

J Atten Disord 2021 04 22;25(6):865-873. Epub 2019 Jul 22.

New York State Psychiatric Institute and Columbia University Irving Medical Center, New York City, USA.

The current study examined how the opposing effects of bilingualism and attention problems operate on executive functioning, visual processing, and verbal fluency in children with clinically significant levels of attention problems. We tested whether bilingualism moderated associations between attention problems and visual processing, executive functioning, and verbal fluency. Bilingual children ( = 331) showed visual processing advantages relative to their monolingual peers ( = 165), but only at higher, and not lower, levels of attention problems. Bilingualism did not moderate the association between attention problems and interference control; however, across all children, those with higher levels of attention problems had more difficulty with interference control. Monolingual children demonstrated advantages in verbal fluency relative to bilingual children, but this did not vary with attention problems. Visual processing advantages in bilinguals are detected among children with heightened attention problems, but advantages in interference control are not; findings may have implications for classroom interventions.
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http://dx.doi.org/10.1177/1087054719861745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360367PMC
April 2021

Profiles of infant communicative behavior.

Dev Psychol 2019 Aug 6;55(8):1594-1604. Epub 2019 Jun 6.

Division of Child and Adolescent Psychiatry.

Prior studies of mother-infant interaction have generally used a variable-centered approach to associate face-to-face communication with psychosocial outcomes. Herein, we use a person-centered approach to identify clusters of infants who exhibit similar behavioral profiles during face-to-face communication with their mothers. Four infant communication channels were examined-gaze, facial affect, vocal affect, and head orientation-coded from videotape at a 1-s temporal resolution. We used -means clustering to classify community infants ( = 132) into 10 groups, based on variation in the intercept and the autocorrelation function at the first time lag, representing respectively the overall level of behavior and the predictability of the infant's moment-by-moment behavioral stream, in each of the 4 communication channels. In this exploratory study, 10 clusters were identified, some with unusual levels or predictability of behavior in varying channels, and clusters associated differentially with risk outcomes (infant 4-month temperament and 12-month attachment). Distinct forms of affective dysregulation were identified: sustained negative vocal affect associated with degree of disorganization; random vocal affect associated with attachment resistance; random facial affect and vocal affect, irrespective of positive/negative valence, associated with infant difficult temperament. Clustering multiple channels of infant communication generated unique behavioral profiles and predicted 4- and 12-month outcomes, suggesting that these clusters may indeed represent natural types of infant communicative behavior, not easily observed with the naked eye, that may be useful behavioral markers of clinical risk. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/dev0000745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646071PMC
August 2019

Neural correlates of cognitive control deficits in children with reading disorder.

Brain Imaging Behav 2020 Oct;14(5):1531-1542

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, the New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, Unit 74. 10032, 1051 Riverside Drive, New York, NY, USA.

Reading disorder (RD) is characterized by deficient phonological processing, but children with RD also have cognitive control deficits, the neural correlates of which are not fully understood. We used fMRI to assess neural activity during the resolution of cognitive conflict on the Simon Spatial Incompatibility task and patterns of resting-state functional connectivity (RSFC) from task control (TC) regions in 7-12-year-old children with RD compared to their typically developing (TD) peers. Relative to TD children (n = 17), those with RD (n = 16) over-engaged a right superior/medial frontal cluster during the resolution of conflict (p = .05). Relative to TD children (n = 18), those with RD (n = 17) also showed reduced RSFC (voxel-wise p < .001; cluster-size p < .05, FDR corrected) from cingulo-opercular seeds to left hemisphere fronto-parietal and temporo-parietal reading-related regions, perhaps reflecting reduced organization of TC circuits and reduced integration with reading-related regions. Children with RD additionally showed reduced RSFC between fronto-parietal and default mode network regions. Follow-up analyses in a subset of children with both useable task and resting state data (RD = 13; TD = 17) revealed that greater conflict-related activation of the right frontal Simon task ROI associated with better word-reading, perhaps suggesting a compensatory role for this over-engagement. Connectivity from fronto-parietal seeds significantly associated with Simon task performance and word-reading accuracy in RD children. These findings suggest that altered functioning and connectivity of control circuits may contribute to cognitive control deficits in children with RD. Future studies should assess the utility of adding cognitive control training to reading remediation programs.
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http://dx.doi.org/10.1007/s11682-019-00083-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765445PMC
October 2020

A preliminary study on prenatal polybrominated diphenyl ether serum concentrations and intrinsic functional network organization and executive functioning in childhood.

J Child Psychol Psychiatry 2019 09 18;60(9):1010-1020. Epub 2019 Mar 18.

Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: The prenatal period is a period of vulnerability during which neurotoxic exposures exert persistent changes in brain development and behavior. Polybrominated diphenyl ethers (PBDEs), used as flame retardants in commercial products, are known to be developmental neurotoxicants. PBDEs were phased out of use in the United States a decade ago, but exposure remains widespread due to their release from existing products and biopersistence. Despite consistent animal and epidemiological evidence of developmental neurotoxicity, the neural substrates linking prenatal PBDE serum concentrations to impaired neurodevelopment are poorly understood.

Methods: In the present study, we used resting state functional magnetic resonance imaging (fMRI) to examine associations between prenatal PBDE concentrations measured in maternal serum and intrinsic functional network organization (i.e., global and local efficiency; estimated using a graph-theoretical approach) in 5-year-old children (n = 34). We explored whether PBDE serum concentrations were associated with executive functioning (EF) assessed using a parent-report questionnaire (BRIEF-P) (n = 106) and whether changes in intrinsic functional network organization linked the association between prenatal PBDE serum concentrations and EF problems.

Results: Children with higher prenatal PBDE serum concentrations showed: (a) increased global efficiency of brain areas involved in visual attention (e.g., inferior occipital gyrus) (β's = .01, FDR-corrected p's ≤ .05); (b) more reported EF problems (β's = .001, FDR-corrected p's ≤ .05). Higher global efficiency of brain areas involved in visual attention was associated with more EF problems (β's = .01, FDR-corrected p's < .05).

Conclusions: Intrinsic functional network organization of visual attention brain areas linked prenatal PBDE concentrations to EF problems in childhood. Visual attention may contribute to the development of higher-order cognitive functions, such as EF, which could be explored in future studies.
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http://dx.doi.org/10.1111/jcpp.13040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105394PMC
September 2019

Salience network connectivity and social processing in children with nonverbal learning disability or autism spectrum disorder.

Neuropsychology 2019 Jan 8;33(1):135-143. Epub 2018 Nov 8.

Division of Child and Adolescent Psychiatry, Department of Psychiatry, Columbia University Irving Medical Center.

Objective: Nonverbal learning disability (NVLD) is a putative neurodevelopmental disorder characterized by spatial processing deficits as well as social deficits similar to those characteristic of autism spectrum disorder (ASD). Nonetheless, NVLD may be a distinct disorder that is differentially associated with the functioning and connectivity of the salience (SN) and default mode (DMN) networks that support social processing. Thus, we sought to assess and compare connectivity across these networks in children with NVLD, ASD, and typically developing children.

Method: Resting-state fMRI data were examined in 17 children with NVLD, 17 children with ASD selected from the Autism Brain Imaging Data Exchange (ABIDE), and 40 TD children (20 from ABIDE). Average DMN and SN functional connectivity and pairwise region-to-region connectivity were compared across groups. Associations with social impairment and IQ were assessed.

Results: Children with NVLD showed reduced connectivity between SN regions (anterior insula to anterior cingulate and to rostral prefrontal cortex [rPFC]), whereas children with ASD showed greater connectivity between SN regions (supramarginal gyrus to rPFC) relative to the other groups. Both clinical groups showed higher levels of parent-reported social problems, which related to altered SN connectivity in the NVLD group. No differences were detected in overall average connectivity within or between networks.

Conclusions: The social deficits common across children with NVLD and ASD may derive from distinct alterations in connectivity within the SN. Such findings represent the first step toward identifying a neurobiological signature of NVLD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322976PMC
January 2019

Family nurture intervention for preterm infants facilitates positive mother-infant face-to-face engagement at 4 months.

Dev Psychol 2018 Nov 4;54(11):2016-2031. Epub 2018 Oct 4.

Department of Psychiatry, Columbia University Medical Center.

Although preterm infants are at risk for social deficits, interventions to improve mother-infant interaction in the neonatal intensive care unit (NICU) are not part of standard care (SC). Study participants were a subset from a randomized controlled trial of a new intervention for premature infants, the Family Nurture Intervention (FNI), designed to help mothers and infants establish an emotional connection. At infants' 4 months corrected age, mother-infant face-to-face interaction was filmed and coded on a 1-s time base for mother touch, infant vocal affect, mother gaze, and infant gaze. Time-series models assessed self- and interactive contingency. Comparing FNI to SC dyads, FNI mothers showed more touch and calmer touch patterns, and FNI infants showed more angry-protest but less cry. In maternal touch self-contingency, FNI mothers were more likely to sustain positive touch and to repair moments of negative touch by transitioning to positive touch. In maternal touch interactive contingency, when infants looked at mothers, FNI mothers were likely to respond with more positive touch. In infant vocal affect self-contingency, FNI infants were more likely to sustain positive vocal affect and to transition from negative to positive vocal affect. In maternal gaze interactive contingency, following infants' looking at mother, FNI mothers of male infants were more likely to look at their sons. In maternal gaze self-contingency, following mothers' looking away, FNI mothers of male infants were more likely to look at their sons. Documentation of positive effects of the FNI for 4-month mother-infant face-to-face communication is useful clinically and has important implications for an improved developmental trajectory of these infants. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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http://dx.doi.org/10.1037/dev0000557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202224PMC
November 2018

Amygdala sub-regional functional connectivity predicts anxiety in children with reading disorder.

Dev Sci 2018 09 15;21(5):e12631. Epub 2017 Nov 15.

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, the New York State Psychiatric Institute, New York.

Pediatric reading disorder (RD) is associated with an increased risk of anxiety symptoms, yet understudied are the neurobiological factors that might underlie anxiety in children with RD. Given the role of the amygdala in anxiety, we assessed resting state functional connectivity of amygdalar subregions in children with RD to identify functional correlates of anxiety and reading impairment. We collected resting state functional MRI data from 22 children with RD and 21 typically developing (TD) children, ages 7 to 13 years. We assessed group differences in resting state functional connectivity (RSFC) from amygdalar subregions. Associations of amygdalar RSFC and volume with reading impairment, reading fluency scores, and anxiety symptoms were explored. Relative to TD children, those with RD showed increased RSFC from amygdalar nuclei to medial prefrontal cortex. Across all subjects, RSFC from right centromedial amygdala to left medial prefrontal cortex positively predicted both reading impairment and self-reported anxiety, and anxiety mediated the relationship between RSFC and reading impairment. These findings are consistent with amygdalar functional abnormalities in pediatric anxiety disorders, suggesting a common neurobiological mechanism underlying anxiety and reading impairment in children. Thus, aberrant patterns of RSFC from amygdalar subregions may serve as potential targets for the treatment of anxiety symptoms that typically co-occur with RD. Our dimensional approach to studying anxiety in RD revealed how amygdalar connectivity underlies anxiety and reading impairment across a continuum from normal to abnormal.
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http://dx.doi.org/10.1111/desc.12631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042207PMC
September 2018

Combined effects of prenatal exposure to polycyclic aromatic hydrocarbons and material hardship on child ADHD behavior problems.

Environ Res 2018 01 4;160:506-513. Epub 2017 Oct 4.

Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722W. 168th Street, New York, NY 10032, USA; Columbia Center for Children's Environmental Health, Mailman School of Public Health, Columbia University, 722W. 168th Street, New York, NY 10032, USA. Electronic address:

Importance: Polycyclic aromatic hydrocarbons (PAH) are carcinogenic and neurotoxic combustion by-products commonly found in urban air. Exposure to PAH is disproportionately high in low income communities of color who also experience chronic economic stress.

Objective: In a prospective cohort study in New York City (NYC) we previously found a significant association between prenatal PAH exposure and Attention Deficit Hyperactivity Disorder (ADHD) behavior problems at age 9. Here, we have evaluated the joint effects of prenatal exposure to PAH and prenatal/childhood material hardship on ADHD behavior problems.

Materials And Methods: We enrolled nonsmoking African-American and Dominican pregnant women in New York City between 1998 and 2006 and followed their children through 9 years of age. As a biomarker of prenatal PAH exposure, PAH-DNA adducts were measured in maternal blood at delivery and were dichotomized at the limit of detection (to indicate high vs. low exposure). Maternal material hardship (lack of adequate food, housing, utilities, and clothing) was self-reported prenatally and at multiple time points through child age 9. Latent variable analysis identified four distinct patterns of hardship. ADHD behavior problems were assessed using the Conners Parent Rating Scale- Revised. Analyses adjusted for relevant covariates.

Results: Among 351 children in our sample, across all hardship groups, children with high prenatal PAH exposure (high adducts) generally had more symptoms of ADHD (higher scores) compared to those with low PAH exposure. The greatest difference was seen among the children with hardship persisting from pregnancy through childhood. Although the interactions between high PAH exposure and hardship experienced at either period ("persistent" hardship or "any" hardship) were not significant, we observed significant differences in the number of ADHD symptoms between children with high prenatal PAH exposure and either persistent hardship or any hardship compared to the others. These differences were most significant for combined high PAH and persistent hardship: ADHD Index (p < 0.008), DSM-IV Inattentive (p = 0.006), DSM-IV Hyperactive Impulsive problems (p = 0.033), and DSM-IV Index Total (p = 0.009).

Conclusion: The present findings add to existing evidence that co-exposure to socioeconomic disadvantage and air pollution in early life significantly increases the risk of adverse neurodevelopmental outcomes. They suggest the need for multifaceted interventions to protect pregnant mothers and their children.
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http://dx.doi.org/10.1016/j.envres.2017.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724364PMC
January 2018

Verbal-spatial IQ discrepancies impact brain activation associated with the resolution of cognitive conflict in children and adolescents.

Dev Sci 2018 03 15;21(2). Epub 2017 Feb 15.

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, the New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, New York, USA.

Verbal-spatial discrepancies are common in healthy individuals and in those with neurodevelopmental disorders associated with cognitive control deficits including: Autism Spectrum Disorder, Non-Verbal Learning Disability, Fragile X, 22q11 deletion, and Turner Syndrome. Previous data from healthy individuals suggest that the magnitude of the difference between verbal IQ (VIQ) and performance IQ (PIQ) scores (the VIQ>PIQ discrepancy) is associated with reduced thickness in frontal and parietal cortices (inferior frontal, anterior cingulate, inferior parietal lobule, and supramarginal gyrus) that support cognitive control. Unknown is whether the VIQ>PIQ discrepancy is associated with functional deficits in these areas in healthy or ill children and adolescents. We assessed the effects of the VIQ>PIQ discrepancy on fMRI BOLD response during the resolution of cognitive conflict in 55 healthy children and adolescents during performance of a Simon Spatial Incompatibility task. As the magnitude of the VIQ>PIQ discrepancy increased, activation of fronto-striatal, limbic, and temporal regions decreased during conflict resolution (p < .05, corrected). In exploratory analyses, the VIQ>PIQ discrepancy was associated with reduced functional connectivity from right inferior frontal gyrus to right thalamus and increased functional connectivity to right supramarginal gyrus (ps < .03, uncorrected). The VIQ>PIQ discrepancy may be an important aspect of an individual's cognitive profile and likely contributes to, or is associated with, deficient cognitive control processes characteristic of many childhood disorders.
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http://dx.doi.org/10.1111/desc.12550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557695PMC
March 2018

Bisphenol A exposure and symptoms of anxiety and depression among inner city children at 10-12 years of age.

Environ Res 2016 Nov 3;151:195-202. Epub 2016 Aug 3.

Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W. 168th St., New York, NY 10032, USA; Columbia Center for Children's Environmental Health, Columbia University, 722 W. 168th St., New York, NY 10032, USA.

Background: Experimental and epidemiological studies suggest that gestational exposure to Bisphenol A (BPA), an ubiquitous endocrine disrupting chemical, may lead to neurobehavioral problems in childhood; however, not all results have been consistent. We previously reported a positive association between prenatal BPA exposure and symptoms of anxiety/depression reported by the mother at child age 7-9 years in boys, but not girls.

Objectives: Here, in the same birth cohort, we investigated the association of prenatal BPA exposure with symptoms of depression and anxiety self-reported by the 10-12 year olds, hypothesizing that we would observe sex-specific differences in anxiety and depressive symptoms.

Methods: African-American and Dominican women living in Northern Manhattan and their children were followed from mother's pregnancy through children's age 10-12 years. BPA was quantified in maternal urine collected during the third trimester of pregnancy and in child urine collected at ages 3 and 5 years. Children were evaluated using the Revised Children's Manifest Anxiety Scale (RCMAS) and Children's Depression Rating Scale (CDRS). We compared the children in the highest tertile of BPA concentration to those in the lower two tertiles. Associations between behavior and prenatal (maternal) BPA concentration or postnatal (child) BPA concentration were assessed in regression models stratified by sex.

Results: Significant positive associations between prenatal BPA and symptoms of depression and anxiety were observed among boys. Postnatal BPA exposure was not significantly associated with outcomes. There was substantial co-occurrence of anxiety and depressive symptoms in this sample.

Conclusion: These results provide evidence that prenatal BPA exposure is associated with more symptoms of anxiety and depression in boys but not in girls at age 10-12 years.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5071142PMC
http://dx.doi.org/10.1016/j.envres.2016.07.028DOI Listing
November 2016

Longitudinal effects of prenatal exposure to air pollutants on self-regulatory capacities and social competence.

J Child Psychol Psychiatry 2016 07 17;57(7):851-60. Epub 2016 Mar 17.

Heilbrunn Department of Population and Family Health, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA.

Background: We evaluated the influence of prenatal exposure to widespread urban air pollutants on the development of self-regulation and social competence in a longitudinal prospective cohort of children born to nonsmoking minority women in New York City.

Methods: Air pollutant exposure was estimated categorically by level of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in maternal blood collected at delivery, providing a biomarker of maternal exposure to PAH over a 2- to 3-month period. Deficient emotional self-regulation (DESR) was defined as moderate elevations on three specific scales of the child behavior checklist (anxious/depressed, aggressive behavior, and attention problems). We used generalized estimating equations to assess the influence of prenatal exposure to PAH on DESR in children at 3-5, 7, 9, and 11 years of age, adjusted for gender and race/ethnicity. Next, we assessed the association of prenatal exposure to PAH with social competence, as measured by the social responsiveness scale (SRS), the association of impaired self-regulation with social competence, and whether impairment in self-regulation mediated the association of prenatal exposure to PAH with social competence.

Results: We detected a significant interaction (at p = .05) of exposure with time, in which the developmental trajectory of self-regulatory capacity was delayed in the exposed children. Multiple linear regression revealed a positive association between presence of PAH-DNA adducts and problems with social competence (p < .04), level of dysregulation and problems with social competence (p < .0001), and evidence that self-regulation mediates the association of prenatal exposure to PAH with social competence (p < .0007).

Conclusions: These data suggest that prenatal exposure to PAH produces long-lasting effects on self-regulatory capacities across early and middle childhood, and that these deficits point to emerging social problems with real-world consequences for high-risk adolescent behaviors in this minority urban cohort.
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http://dx.doi.org/10.1111/jcpp.12548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333974PMC
July 2016

Research Review: Environmental exposures, neurodevelopment, and child mental health - new paradigms for the study of brain and behavioral effects.

J Child Psychol Psychiatry 2016 07 14;57(7):775-93. Epub 2016 Mar 14.

Columbia Center for Children's Environmental Health, Mailman School of Public Health, Columbia University, New York, NY, USA.

Background: Environmental exposures play a critical role in the genesis of some child mental health problems.

Methods: We open with a discussion of children's vulnerability to neurotoxic substances, changes in the distribution of toxic exposures, and cooccurrence of social and physical exposures. We address trends in prevalence of mental health disorders, and approaches to the definition of disorders that are sensitive to the subtle effects of toxic exposures. We suggest broadening outcomes to include dimensional measures of autism spectrum disorders, attention-deficit hyperactivity disorder, and child learning capacity, as well as direct assessment of brain function.

Findings: We consider the impact of two important exposures on children's mental health: lead and pesticides. We argue that longitudinal research designs may capture the cascading effects of exposures across biological systems and the full-range of neuropsychological endpoints. Neuroimaging is a valuable tool for observing brain maturation under varying environmental conditions. A dimensional approach to measurement may be sensitive to subtle subclinical toxic effects, permitting the development of exposure-related profiles and testing of complex functional relationships between brain and behavior. Questions about the neurotoxic effects of chemicals become more pressing when viewed through the lens of environmental justice.

Conclusions: Reduction in the burden of child mental health disorders will require longitudinal study of neurotoxic exposures, incorporating dimensional approaches to outcome assessment, and measures of brain function. Research that seeks to identify links between toxic exposures and mental health outcomes has enormous public health and societal value.
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http://dx.doi.org/10.1111/jcpp.12537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914412PMC
July 2016

Neuroimaging is a novel tool to understand the impact of environmental chemicals on neurodevelopment.

Curr Opin Pediatr 2014 Apr;26(2):230-6

aDepartment of Preventive Medicine, Icahn School of Medicine at Mount Sinai bDivision of Child & Adolescent Psychiatry, Center for Developmental Neuropsychiatry, Department of Psychiatry, the New York State Psychiatric Institute and the College of Physicians and Surgeons, Columbia University, Columbia Center for Children's Environmental Health, Columbia University cDepartments of Radiology and Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Purpose Of Review: The prevalence of childhood neurodevelopmental disorders has been increasing over the last several decades. Prenatal and early childhood exposure to environmental toxicants is increasingly recognized as contributing to the growing rate of neurodevelopmental disorders. Very little information is known about the mechanistic processes by which environmental chemicals alter brain development. We review the recent advances in brain imaging modalities and discuss their application in epidemiologic studies of prenatal and early childhood exposure to environmental toxicants.

Recent Findings: Neuroimaging techniques (volumetric and functional MRI, diffusor tensor imaging, and magnetic resonance spectroscopy) have opened unprecedented access to study the developing human brain. These techniques are noninvasive and free of ionization radiation making them suitable for research applications in children. Using these techniques, we now understand much about structural and functional patterns in the typically developing brain. This knowledge allows us to investigate how prenatal exposure to environmental toxicants may alter the typical developmental trajectory.

Summary: MRI is a powerful tool that allows in-vivo visualization of brain structure and function. Used in epidemiologic studies of environmental exposure, it offers the promise to causally link exposure with behavioral and cognitive manifestations and ultimately to inform programs to reduce exposure and mitigate adverse effects of exposure.
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http://dx.doi.org/10.1097/MOP.0000000000000074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104673PMC
April 2014