Prior studies suggest that childhood maltreatment is associated with altered hippocampal volume. However, longitudinal studies are currently scarce, making it difficult to determine how alterations in hippocampal volume evolve over time. The current study examined the relationship between childhood maltreatment and hippocampal volumetric development across childhood and adolescence in a community sample.

In this longitudinal study, a community sample of 795 participants underwent brain magnetic resonance imaging (MRI) in three waves spanning ages 6–21 years. Childhood maltreatment was assessed using parent-report and children´s self-report at baseline (6–12 years old). Mixed models were used to examine the relationship between childhood maltreatment and hippocampal volume across time.

The quadratic term of age was significantly associated with both right and left hippocampal volume development. High exposure to childhood maltreatment was associated with reduced offset of right hippocampal volume and persistent reduced volume throughout adolescence.

Critically, the relationship between childhood maltreatment and reduced right hippocampal volume remained significant after adjusting for the presence of any depressive disorder during late childhood and adolescence and hippocampal volume polygenic risk scores. Time-by-CM and Sex-by-CM interactions were not statistically significant.

The present study showed that childhood maltreatment is associated with persistent reduction of hippocampal volume in children and adolescents, even after adjusting for the presence of major depressive disorder and genetic determinants of hippocampal structure.

Schizophrenia (SCZ) is a neuropsychiatric disorder with strong genetic heritability and predicted genetic heterogeneity, but limited knowledge regarding the underlying genetic risk variants. Classification into phenotype-driven subgroups or endophenotypes is expected to facilitate genetic analysis. Here, we report a teen boy with chronic psychosis and cerebellar hypoplasia (CBLH) and analyze data on 16 reported individuals with SCZ or chronic psychosis not otherwise specified associated with cerebellar hypoplasia to look for shared features.

We evaluated an 18-year-old boy with neurodevelopmental deficits from early childhood and onset of hallucinations and other features of SCZ at 10 years who had mild vermis-predominant CBLH on brain imaging. This prompted us to review prior reports of chronic psychosis or SCZ with cerebellar malformations using paired search terms including (1) cerebellar hypoplasia, Dandy-Walker malformation, Dandy-Walker variant, or mega-cisterna magna with (2) psychosis or SCZ. We found reports of 16 affected individuals from 13 reports. We reviewed clinical features focusing on demographic information, prenatal-perinatal history and neuropsychiatric and neurodevelopmental phenotypes, and independently reviewed brain imaging features.

All 17 individuals had classic psychiatric features of SCZ or chronic psychosis as well as shared neurodevelopmental features not previously highlighted including a downward shift in IQ of about 20 points, memory impairment, speech-language deficits, attention deficits and sleep disturbances. The brain imaging findings among these individuals consistently showed posterior vermis predominant CBLH with variable cerebellar hemisphere hypoplasia and enlarged posterior fossa (a.k.a. mega-cisterna magna). None had features of classic DWM.

In 17 individuals with chronic psychosis or SCZ and cerebellar malformation, we found a high frequency of neurodevelopmental disorders, a consistent brain malformation consisting of posterior vermis-predominant (and usually symmetric) CBLH, and no evidence of prenatal risk factors. The consistent phenotype and lack of prenatal risk factors for CBLH leads us to hypothesize that psychosis or schizophrenia associated with vermis predominant CBLH comprises a homogeneous subgroup of individuals with chronic psychosis/schizophrenia that is likely to have an underlying genetic basis. No comprehensive targeted gene panel for CBLH has yet been defined, leading us to recommend trio-based exome sequencing for individuals who present with this combination of features.

Concerns that exposure to more than one language in the home might negatively impact language development in young children with autism spectrum disorder (ASD) are common among caregivers. Although research directly examining the impact of a multilingual home environment in ASD is scarce, emerging evidence shows that language outcomes might be equivalent or better in children with ASD exposed to more than one language (Romero & Uddin, 2021). However, no evidence to date exists on whether exposure to more than one language affects early brain functional development in children with ASD. The current study aims to examine the (1) cross-sectional and (2) longitudinal associations between home language environment (exposure to one v. multiple languages at home, H1l vs. H>1l) and receptive and expressive language skills in young children with and without ASD, and (3) to investigate links between home language environment and brain functional network organization.

Participants included young children with ASD (n=67, mean age: 35±13 months, H>1l n=43) and typically developing (TD) children (n=39, mean age: 32±16 months, H>1l n=17) enrolled in a longitudinal study of early brain markers of autism. A subset of children with ASD for whom longitudinal behavioral data from two study visits were available (n=21, H>1l n=11) were used for exploratory analysis. Receptive language (RL) and expressive language (EL) skills were assessed by the Mullen Scales of Early Learning at each study visit. Data from 42 children with ASD (H>1l n=27) and 38 TD children (H>1l n= 15) for whom functional MRI data were acquired during natural sleep were included in functional connectivity (FC) analysis. ANCOVAs were employed to examine the effect of diagnosis, home language environment (H1l vs. H>1l) and its interaction on RL and EL skills while controlling for socioeconomic variables (i.e., maternal education level, income-to-needs ratio) and gestational age at birth. Linear mixed models were applied to explore the longitudinal effect of home language environment on RL and EL skills across two study visits in the ASD group. Lastly, FC analysis was conducted to compare functional connectivity across 7 canonical brain networks in children with and without ASD who were raised in H1l and H>1l.

We found significant diagnosis by home language environment interaction effect on EL skills, with children with ASD and H1l exhibiting the lowest EL skills. Longitudinal analysis identified a significant home language environment by study visit interaction effect on EL skills in children with ASD. Specifically, children with ASD and H1l showed lower EL skills at study visit 1 but equivalent EL skills at study visit 2 compared to children with ASD and H>1l. FC analysis revealed that children with ASD and H>1l displayed more typical brain network organization (similar to TD children) compared to those with H1l, specifically for FC between language, frontoparietal, and default mode networks.

These results suggest that early exposure to more than one language in the home may be linked with better expressive language skills in young children with ASD. Results of functional connectivity analysis also suggest that exposure to more than one language may be associated with more neurotypical functional network organization, particularly involving language and high-order networks.

Children born to mothers infected with human immunodeficiency virus (HIV) during pregnancy experience increased risk of neurocognitive impairment. In Botswana, HIV infection is common, but standardized cognitive testing is limited. The Penn Computerized Neurocognitive Battery (PennCNB) is a widely used cognitive test battery that streamlines evaluation of neurocognitive functioning. Our group translated and culturally adapted the PennCNB for use among children and adolescents in this high-burden, low-resource setting. The current study examined the construct validity and sensitivity to HIV infection and exposure of the culturally adapted PennCNB among a cohort of HIV-affected children and adolescents in Gaborone, Botswana.

628 school-aged children aged 7-17 years (n=223 children living with HIV [HIV+]; n=204 HIV exposed, uninfected [HEU]; and 201 HIV unexposed, uninfected [HUU]) completed the PennCNB. Participants were recruited from a clinic specializing in the care and treatment of HIV+ children and adolescents in Gaborone, Botswana, as well as from local schools. Confirmatory factor analyses were performed on efficiency measures for 13 PennCNB tests. Multiple regressions examined associations between HIV and neurocognitive functioning while controlling for age and sex. Multivariate normative comparisons were used to examine rates of overall cognitive impairment by comparing individual profiles of test scores to the multivariate distribution of test scores using age-normed data from the HUU group.

Confirmatory factor analysis supported four hypothesized neurocognitive domains: executive functioning, episodic memory, complex cognition, and sensorimotor/processing speed. As expected, there were main effects of age on cognitive performance across all domains (ps < .001), and there were small sex differences, with females performing better in executive functioning and males performing better on visuospatial processing. Children and adolescents living with HIV performed significantly worse than HUU across all domains (ps < .001), with the largest effect sizes on measures of abstraction, working memory, and processing speed. HEU also performed worse than HUU across several domains, with smaller effect sizes. Multivariate normative comparisons indicated that 27% of the HIV+ group evidenced global neurocognitive impairment.

Overall, results support the validity of a neurocognitive battery adapted for use in Botswana, a non-Western, resource-limited setting. Results indicated that the adapted battery applied to children and adolescents with limited computer familiarity had a similar factor structure as in Western settings, indicating that the PennCNB appeared to assess the hypothesized neurocognitive domains. Hypothesized associations with age and sex supported the battery’s construct validity. Moreover, the battery appears to be sensitive to cognitive impairments associated with perinatally-acquired HIV and in utero HIV-related exposures, as it discriminated between the HUU, HIV+, and HEU groups. Differences were found in specific domains and in detection of overall impairment, including approximately one quarter of children and adolescents living with HIV in this cohort evidencing global neurocognitive impairment. Together, these results provide evidence that the PennCNB could serve as a useful tool for the assessment of neurocognitive functioning in school-aged children and adolescents from Botswana and, potentially, other resource-limited settings.

Rapid neurodevelopment occurs during adolescence, which may increase the developing brain’s susceptibility to environmental risk and resilience factors. Adverse childhood experiences (ACEs) may confer additional risk to the developing brain, where ACEs have been linked with alterations in BOLD signaling in brain regions underlying inhibitory control. Potential resiliency factors, like a positive family environment, may attenuate the risk associated with ACEs, but limited research has examined potential buffers to adversity’s impact on the developing brain. The current study aimed to examine how ACEs relate to BOLD response during successful inhibition on the Stop Signal Task (SST) in regions underlying inhibitory control from late childhood to early adolescence and will assess whether aspects of the family environment moderate this relationship.

Participants (N= 9,080; Mage= 10.7, range= 9-13.8 years old; 48.5% female, 70.1% non-Hispanic White) were drawn from the larger Adolescent Brain Cognitive Development (ABCD) Study cohort. ACE risk scores were created (by EAS) using parent and child reports of youth’s exposure to adverse experiences collected at baseline to 2-year follow-up. For family environment, levels of family conflict were assessed based on youth reports on the Family Environment Scale at baseline and 2-year follow-up. The SST, a task-based fMRI paradigm, was used to measure inhibitory control (contrast: correct stop > correct go); the task was administered at baseline and 2-year follow-up. Participants were excluded if flagged for poor task performance. ROIs included left and right dorsolateral prefrontal cortex, anterior cingulate cortex, anterior insula, inferior frontal gyrus (IFG), and pre-supplementary motor area (pre-SMA). Separate linear mixed-effects models were conducted to assess the relationship between ACEs and BOLD signaling in ROIs while controlling for demographics (age, sex assigned at birth, race, ethnicity, household income, parental education), internalizing scores, and random effects of subject and MRI model.

Greater ACEs was associated with reduced BOLD response in the opercular region of the right IFG (b= -0.002, p= .02) and left (b= -0.002, p= .01) and right pre-SMA (b= -0.002, p= .01). Family conflict was related to altered activation patterns in the left pre-SMA, where youth with lower family conflict demonstrated a more robust negative relationship (b=.001, p= .04). ACEs were not a significant predictor in other ROIs, and the relationship between ACEs and BOLD response did not significantly differ across time. Follow-up brain-behavior correlations showed that in youth with lower ACEs, there was a negative correlation between increased activation in the pre-SMA and less impulsive behaviors.

Preadolescents with ACE history show blunted activation in regions underlying inhibitory control, which may increase the risk for future poorer inhibitory control with downstream implications for behavioral/health outcomes. Further, results demonstrate preliminary evidence for the family environment’s contributions to brain health. Future work is needed to examine other resiliency factors that may modulate the impact of ACE exposure during childhood and adolescence. Further, clinical scientists should continue to examine the relationship between ACEs and neural and behavioral correlates of inhibitory control across adolescent development, as risk-taking behaviors progress.

Exposure to toxic chemicals during early brain development increases the risk of neurodevelopmental problems in children. Parents' and prospective parents' understanding of the impact of toxic chemicals on brain development and the efficacy of translation tools for children's environmental health literacy are poorly understood. We developed and validated a questionnaire, PRevention of Toxic chemicals in the Environment for Children Tool (PRoTECT) to assess knowledge of toxic chemicals and neurodevelopment, intentions to reduce exposures to toxic chemicals, and preferences for actions by government and industry to prevent neurodevelopmental disorders. Using PRoTECT, we surveyed people of child-bearing age across five countries (Canada, United States (US), United Kingdom (UK), India, and Australia) to identify general patterns of responses on this questionnaire by demographic characteristics, including country, age, gender, parental status, pregnancy status, and education. We also employed a randomized control design to examine the efficacy of a knowledge translation video to instill knowledge and prompt behavioral changes to reduce exposures to toxic chemicals immediately following its presentation and after a six-week follow-up period.

We recruited 15,594 participants, ages 18 to 45, via CloudResearch's Prime Panels between October-December 2021. After completing the PRoTECT survey, participants were randomly assigned to watch the video Little Things Matter: Impact of Toxic Chemicals on Brain Development (i.e., the experimental group) or to serve as the control group. Next, both groups answered a series of questions to assess their knowledge of toxic chemicals, their intentions to reduce exposures to toxic chemicals, and barriers to changing their behaviours. After six-weeks, we recontacted a subset (N=4,842) of participants to repeat PRoTECT and answer the same series of behavioural questions assessing whether they modified any of their behaviours to reduce exposure and why or why not.

Most participants (i.e., 75-85%) agreed that toxic chemicals can impact brain development and endorsed preferences (∼85%) for allocating more resources to prevent neurodevelopmental disorders, especially people with higher education, parents and pregnant women, and people who lived in India. Despite this, a large proportion of participants (∼50%) trusted industry and believed that government effectively regulated toxic chemicals. After the six-week follow-up, experimental participants showed greater changes in scores on PRoTECT (i.e., between 5-15% change), indicating greater knowledge about harms posed by toxic chemicals, more intentions to reduce exposure, and stronger preferences for prevention as compared to the control group. Differences were larger among people from the US, those who were more highly educated, and people in their thirties. However, the differences between groups in making behavioural changes to reduce exposures were attenuated at the six-week follow up as compared to baseline. Significant barriers to reduce exposure to toxic chemicals were reported by both groups and included cost, inconvenience, and not knowing how to determine whether a product is non-toxic or where to purchase non-toxic products.

We observed greater knowledge and concerns about toxic chemicals among more affluent respondents, pregnant women and parents, and people living in India across both groups. While the video enhanced participants' knowledge about toxic chemicals and intentions to reduce exposure, they indicated that barriers hindered them from making behavioral changes.

In recent decades, a large body of evidence has linked prenatal exposure to environmental neurotoxins to adverse intellectual, neurodevelopmental, and psychiatric outcomes in offspring. This evidence has clearly highlighted the widespread impact of neurotoxin exposure on the developing brain; however, it is unclear how and why these exposures alter brain development in a way that appears to increase risk for multiple, seemingly disparate outcomes.

Shifting our focus from describing links between neurotoxin exposure and symptoms of offspring mental/cognitive problems considered categorically, to investigating how neurotoxins adversely affect domains of functioning known to cut across risk for multiple problems in offspring may be critical to answering these questions. This presentation will discuss how combining research in developmental neurotoxicology with novel systems that take dimensional approaches to understanding emotions, cognition, and behaviour (i.e., the NIHM Research Domain Criteria (RDoC)) may provide a fruitful future research direction for the field. The RDoC framework aims to understand neuropsychological outcomes (i.e., mental health, mental illness, IQ) across major domains of human emotion, cognition, behaviour, and social functioning, rather than within distinct diagnostic categories.

Using lead exposure as an example, this presentation will outline a framework for how researchers can use this dimensional approach to develop more specific hypotheses that can reveal how and why neurotoxin exposure increases risk for multiple adverse outcomes and elucidate the mechanisms that may underly these links.

Additionally, given that adverse development within domains of functioning can be detected prior to the onset of full-blown diagnoses, this research could enable us to develop more precise, targeted prevention and risk reduction campaigns. Adopting a dimensional framework will provide a more complete picture of the overall impact of prenatal exposure to neurotoxins - critical for informing public health policy.

No significant relationships.