Biology subjects

Overholtzer, L. N.

Publications and source records attributed to Overholtzer, L. N..

6 recordsLinked to original sources

bioRxiv2026

Air Pollution, Early Adversity, and Amygdala: Environmental Correlates of Psychopathology in Preadolescents

Early life adversity (ELA) and ambient fine particulate matter (PM2.5) are hypothesized to be environmental risk factors for altered brain structure and psychopathology, but their unique and interactive effects in childhood remain unclear. This study examines the interactive associations of ELA and annual average residential PM2.5 exposure (total mass and 15 components) on total amygdala and basolateral amygdala subregion volumes and psychopathology symptoms in a subset of children (N=3,601, 45% assigned female at birth, 9-10 years) from the Adolescent Brain Cognitive Development Study. Linear mixed-effects models, adjusting for sociodemographic factors, co-pollutants, and neuroimaging covariates, showed that ELA was associated with greater bifactor model-defined general, specific internalizing, and specific externalizing symptoms of psychopathology. PM2.5 moderated ELA associations with specific externalizing symptoms, with greater symptoms in those exposed to higher ELA and higher PM2.5 exposures. Among youth with higher ELA, smaller basolateral paralaminar volumes were linked to greater general and specific externalizing symptoms. These findings underscore the importance of considering psychosocial and physical environmental co-exposures when identifying children at risk for psychopathology.

neuroscience↗

bioRxiv2026

Structural brain alterations in autism: A large-scale voxel-based morphometry mega-analysis

BackgroundPrevious large-scale structural MRI analyses of the brain in autism have identified gray matter (GM) differences when using region-of-interest analyses based on gross anatomical regions. However, such analyses have limited spatial specificity and may obscure subtle focal differences. Whole brain voxel-based morphometry (VBM) analyses enable greater spatial precision to identify and localize previously undetected neuroanatomical alterations. PurposeTo rigorously identify voxel-wise GM and white matter (WM) volume differences in autism in the largest VBM mega-analysis to date. Materials and MethodsThis retrospective mega-analysis included structural 3D volumetric T1-weighted MRI brain scans from 3,051 participants (15.0 {+/-} 8.2 yrs; 76.8% male; 1,519 autism; 1,532 neurotypicals) collected across 51 sites/scanners. Voxel-wise GM and WM volumes were quantified using the ENIGMA CAT12 VBM pipeline. Linear mixed-effects regression was performed at each voxel to evaluate the association between diagnostic group and voxel-wise volume while adjusting for standard nuisance covariates ResultsAutism was associated with widespread lower GM volume involving cortical, subcortical, and cerebellar regions (peak t=7.39, peak {beta}=0.13); such GM differences were most notably detected in the bilateral orbitofrontal cortex, amygdala, thalamus, and posterior lobes of the cerebellum. WM volume was lower in autism across major projection, commissural, association, and cerebellar/brainstem tracts (peak t=6.74, peak {beta}=0.08), including the corona radiata, internal capsule, corpus callosum, and cerebellar peduncles. These findings remained consistent in sensitivity analyses, including covarying for full-scale IQ and the application of increasingly strict motion exclusion criteria. ConclusionAutism is associated with smaller voxel-wise GM and WM volume involving widespread cortical, subcortical, and cerebellar regions. This high-resolution identification and localization of structural brain differences support the involvement of distributed neural systems in autism that underlie reward processing, sensory integration, and motor functioning in autism. Summary statementIn the largest voxel-based morphometry study of autism to date, widespread smaller gray and white matter volumes were identified across distributed brain regions implicated in reward and sensorimotor function. Key ResultsO_LIOur largest voxel-based morphometry mega-analysis to date in autism (N=3,051), identified widespread gray and white matter alterations (peak t=7.39, peak {beta}=0.13). C_LIO_LIWe reveal novel associations within thalamic mediodorsal nuclei by leveraging finer voxel-wise volumetric analyses. C_LIO_LIAdditional associations in orbitofrontal cortex, amygdala, and cerebellum, along with extensive white matter alterations across projection, commissural, association fibers, reinforce reward-processing, sensory and motor development theories in autism. C_LI

neuroscience↗

bioRxiv2026

Developmental Differences in White Matter Microarchitecture in Youth with ADHD: Longitudinal Findings from the ABCD Study

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder and is a risk factor for later brain disorders. Here, we characterize the relationship between ADHD status and white matter cellularity across development and examine associations with medication, using a novel biophysical diffusion MRI model in youth aged 9 to 14 years. Methods: The ABCD Study(R) is a longitudinal cohort study with three biennial waves of brain MRI collection. Twenty-seven white matter tracts were delineated using multi-shell diffusion-weighted imaging (DWI) and tractography. Intracellular isotropic (RNI) and directional (RND) diffusion were quantified using the Restriction Spectrum Imaging (RSI) model. Longitudinal linear mixed-effect models characterize the effects of ADHD status and medication use on white matter cellularity across three waves. Results: By wave: 9,426 participants at baseline (mean [SD] age: 9.92 [0.63] years; 48.7% Female; 12.2% with ADHD), 6745 participants at 2-year (11.95 [0.65] years; 46.8% Female; 11.3% with ADHD), and 2,483 participants at 4-year (14.07 [0.69] years; 46.0% Female; 11.8% with ADHD). ADHD was associated with decreased RNI in 20 tracts at age 9, with evidence of developmental trajectory differences suggesting attenuation over early adolescence. We found enduring ADHD-associated decreases in RND of 16 tracts spanning ages 9 to 14 years, with methylphenidate effects on 2 tracts. Low-motion sensitivity analyses confirmed robust RNI findings, but not RND findings. ConclusionsADHD was associated with reductions in isotropic diffusion in white matter tracts, and possibly with complementary reductions in directional diffusion of select tracts. Isotropic diffusion findings suggest atypical glial cellularity in white matter during late childhood.

neuroscience↗

bioRxiv2025

ADHD Medications and Preadolescent Brain Structure: Patterns of Cortical Attenuation from the ABCD Study

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in the U.S., and the stimulant and nonstimulant medications used to treat ADHD are among the most widely prescribed treatments in youth. Stimulants--including amphetamine-based (AMP) and methylphenidate-based (MPH) medications--act primarily on dopaminergic and noradrenergic systems, while nonstimulants (NS) more selectively target noradrenergic pathways. Although pharmacotherapy is the most clinically effective treatment, its neurostructural effects remain poorly understood. Leveraging the Adolescent Brain Cognitive Development* Study (ABCD Study(R)), we used a machine learning approach to identify neuroanatomical targets of medications, followed by linear mixed-effects modeling to estimate the effects of ADHD status and medication class (AMP, MPH, NS) on cortical thickness, surface area, and cortical and subcortical volumes. ADHD was not associated with statistically significant differences; however, a consistent pattern emerged in which AMP and MPH effects attenuated ADHD effects, suggesting that stimulant medications may attenuate ADHD-related cortical patterns. NS medications showed a similar, albeit weaker, effect pattern. Notably, AMP and/or MPH use was associated with significant effects in the right entorhinal cortex and the right banks of the superior temporal sulcus, potentially reflecting overcompensatory effects, as well as in the left posterior cingulate, possibly indicating de novo medication-related differences.

neuroscience↗

bioRxiv2024

Outdoor Air Pollution Relates to Amygdala Subregion Volume and Apportionment in Early Adolescents

BackgroundOutdoor air pollution is associated with an increased risk for psychopathology. Although the neural mechanisms remain unclear, air pollutants may impact mental health by altering limbic brain regions, such as the amygdala. Here, we examine the association between ambient air pollution exposure and amygdala subregion volumes in 9-10-year-olds. MethodsCross-sectional Adolescent Brain Cognitive DevelopmentSM (ABCD) Study(R) data from 4,473 participants (55.4% male) were leveraged. Air pollution was estimated for each participants primary residential address. Using the probabilistic CIT168 atlas, we quantified total amygdala and 9 distinct subregion volumes from T1- and T2-weighted images. First, we examined how criteria pollutants (i.e., fine particulate matter [PM2.5], nitrogen dioxide, ground-level ozone) and 15 PM2.5 components related with total amygdala volumes using linear mixed-effect (LME) regression. Next, partial least squares correlation (PLSC) analyses were implemented to identify relationships between co-exposure to criteria pollutants as well as PM2.5 components and amygdala subregion volumes. We also conducted complementary analyses to assess subregion apportionment using amygdala relative volume fractions (RVFs). ResultsNo significant associations were detected between pollutants and total amygdala volumes. Using PLSC, one latent dimension (LD) (52% variance explained) captured a positive association between calcium and several basolateral subregions. LDs were also identified for amygdala RVFs (ranging from 30% to 82% variance explained), with PM2.5 and component co-exposure associated with increases in lateral, but decreases in medial and central, RVFs. ConclusionsFine particulate and its components are linked with distinct amygdala differences, potentially playing a role in risk for adolescent mental health problems. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/617429v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@e9f2ecorg.highwire.dtl.DTLVardef@14b677forg.highwire.dtl.DTLVardef@177f8daorg.highwire.dtl.DTLVardef@172dc0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Amygdala Subregion Volumes and Apportionment in Preadolescents -- Associations with Age, Sex, and Body Mass Index

The amygdala, a key limbic structure, is critical to emotional, social, and appetitive behaviors that develop throughout adolescence. Composed of a heterogeneous group of nuclei, questions remain about potential differences in the maturation of its subregions during development. In 3,953 9- and 10-year-olds from the Adolescent Brain Cognitive DevelopmentlZI Study, the CIT168 Amygdala Atlas was used to segment nine amygdala subregions. Linear mixed-effects models were used to examine the effects of age, sex, pubertal stage, and body mass index z-score (BMIz) on subregion volumes and their relative apportionment within the amygdala. Distinct associations were observed between age, sex, and BMIz and whole amygdala volume, subregion volumes, and subregion apportionment. Pubertal stage was not related to amygdala subregion volumes. Age was associated with near-global expansion of amygdala subregions during this developmental period. Female sex was linked to smaller volumes in most amygdala subregions, with larger relative apportionment in the dorsal subregions and smaller apportionment in the basolateral ventral paralaminar subregion. Higher BMIz was associated with smaller volumes in large basolateral subregions, with increased relative apportionment in smaller subregions. These findings provide a foundational context for understanding how developmental variables influence amygdala structure, with implications for understanding future risk for brain disorders. HighlightsO_LISegmentation of amygdala subregions in nearly 4,000 preadolescents. C_LIO_LIAge, but not puberty, was associated with a near-global expansion of the amygdala. C_LIO_LISex differences exist in preadolescent amygdala apportionment. C_LIO_LIChildhood obesity is linked to differences in the basolateral amygdala. C_LI

neuroscience↗