Sara Pardej

All Publications

• Effects of neighborhood level health and environment quality on academic and executive abilities in youth with Noonan syndrome spectrum disorder. Journal of the International Neuropsychological Society : JINS Pardej, S. K., Russo, O., Green, T. 2026: 1-9

  Abstract

  OBJECTIVE: The goal of the present study is to understand whether youth with Noonan Syndrome Spectrum Disorder (NSSD) are at increased risk of neurocognitive difficulties when living in resource depleted communities.METHOD: Youth (5-17 years; Mage = 9.48 years) with NSSD (n = 140) and unaffected youth (4-15 years; Mage = 9.63 years; n = 85) were included. We ascertained the Child Opportunity Index Health and Environment Index (COI H/E) national-level Z-scores and assessed academic achievement and executive function. Multiple regressions were run to analyze the effects of diagnosis (whether the child had NSSD), COI H/E Z-scores, and diagnosis * COI H/E Z-score interaction on academic achievement (i.e., word reading, math, spelling, and sentence comprehension) and executive skills (i.e., performance-based working memory and processing speed and parent-rated measure of daily executive skills).RESULTS: Diagnosis was a significant predictor in each model. COI H/E Z-score was a significant predictor of spelling and a marginally significant predictor of sentence comprehension scores. There was a significant diagnosis * COI H/E Z-score interaction for working memory, and marginally significant interactions for spelling and sentence comprehension scores. Higher H/E Z-scores were associated with better working memory in the NSSD group and better academic achievement in the unaffected group.CONCLUSIONS: While the effects of NSSD are large on all assessed domains, there is an additional burden of resource depletion on working memory abilities of youth with NSSD. Academic achievement in the NSSD group was lower than the unaffected group across resource-depleted/enriched environments, demonstrating the profound effects of NSSD on academic functioning.

  View details for DOI 10.1017/S1355617726101969

  View details for PubMedID 42089274

• T1w/T2w ratio as an in vivo proxy for reduced intracortical myelin content in youth with RASopathies: a cross-sectional study. Biological psychiatry. Cognitive neuroscience and neuroimaging Plank, J. R., Pardej, S. K., Raman, M. M., McNab, J., Green, T. 2026

  Abstract

  Myelin may represent a modifiable treatment target in neurodevelopmental disorders, yet accessible in vivo tools for assessing myelin alterations in clinical settings are limited. The T1-weighted/T2-weighted (T1w/T2w) ratio, derived from standard MRI, offers a proxy for cortical myelin and may aid in detecting abnormalities. Leveraging a genetics-first approach, we tested whether youth with RASopathies - neurodevelopmental disorders caused by RAS-MAPK variants - show differences in cortical myelin, measured using T1w/T2w ratios, compared with typically developing (TD) peers.In this prospective study, 112 youth (86 RASopathies, 26 TD, ages 6-17 years) completed T1w and T2w MRI scans, parent-rated mobility and strength impact scores, and NIH Toolbox cognitive assessments. T1w/T2w ratios were calculated at cortical depths in FreeSurfer, and average values were extracted from 68 regions-of-interest (ROIs). Group differences were assessed using ANCOVA with false discovery rate correction. Correlations between regional T1w/T2w ratios with mobility, strength, and cognitive scores were examined.Widespread decreases in T1w/T2w ratios were found in RASopathies compared to TD. Of ratios sampled at mid-depth, 63 of 68 cortical ROIs were reduced in RASopathies (pFDR<.050). Analysis controlling for global mean T1w/T2w identified six ROIs with reductions beyond the global cortical effect (pFDR<.050). Higher ratios were associated with better strength impact (p's=.001 - .005) and mobility (p's=.023 - .045), but not cognitive scores (p's=.059 - .716).T1w/T2w may serve as a sensitive tool for detecting microstructural alterations in genetically defined neurodevelopmental disorders. Future work is needed to clarify biological underpinnings and clinical relevance of T1w/T2w ratios for cognitive and functional outcomes.

  View details for DOI 10.1016/j.bpsc.2026.03.009

  View details for PubMedID 41905474

• The 9th International RASopathies Symposium. American journal of medical genetics. Part A Castel, P., Schoyer, L., Stronach, B., Bogdanova, R., Bennett, A. M., Blakeley, J., Bornhorst, M., Bowers, T., Brachmann, S. M., Burkitt-Wright, E., Chatfield, K., De Luca, A., El-Chammas, K., Elkadri, A., Fortunato, J. E., Gelb, B. D., Goriely, A., Gripp, K., Grover, K., Homan, L., Kern, K. A., Kiuru, M., Lawson, C. C., Lee, Y. S., McCormick, F., Ney, G., Nuevo-Tapioles, C., Pardej, S., Pierpont, E. I., Plank, J., Ratner, N., Rauen, K. A., Robinson, J. E., Rogers, L., Sheppard, S. E., Shiels, K., Stevenson, D., Tiemens, D., Traylor, M., Weaver, K. N., Yohe, M., Green, T. 2026

  Abstract

  The RASopathies are a group of congenital disorders with overlapping clinical manifestations that are caused by pathogenic germline or early somatic variants that result in the hyperactivation of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway. Given the heterogeneous clinical presentations of these disorders that involve abnormalities across multiple organ systems, multidisciplinary clinical management and progress in scientific research are essential for optimal patient diagnosis and care. The 9th International RASopathies Symposium, a biennial meeting, was organized by the patient advocacy group RASopathies Network and showcased recent discoveries, case studies, and advances in preclinical research. Participants, who included scientists, clinicians, industry representatives, patients, and family advocates, explored knowledge gaps, innovative clinical approaches, and lived experiences of individuals with a RASopathy. Sessions centered around organ systems were introduced with a patient perspective to highlight the burden of disease, continued with presentations from established and early-career investigators. Overall, the RASopathies Symposia serve as a catalyst for sustained community collaboration focused on enhancing patient health and accelerating the translation of discoveries into effective treatments.

  View details for DOI 10.1002/ajmg.a.70121

  View details for PubMedID 41834696

• A Multi-parametric MRI and Machine Learning Study of Cerebellar Structure in Youth with Neurofibromatosis Type 1. Cerebellum (London, England) Pardej, S. K., Plank, J. R., Raman, M. M., Green, T. 2026; 25 (1): 17

  Abstract

  Neurofibromatosis type 1 (NF1) is a genetic condition caused by pathogenic variants of the NF1 gene. While alterations in cerebral structural and microstructural differences have been reported in NF1, the cerebellum remains largely unexplored. Since individuals with NF1 are at risk for cognitive difficulties, which are in turn associated with cerebellar processes, understanding the underlying neural mechanisms is critical for intervention development.Youth (5-16 years) with NF1 (n = 30) and unaffected youth (n = 40) participated in neuropsychological (i.e., neurocognitive, parent report of motor abilities) testing and MRI to ascertain structural cerebellar metrics, including volume and white matter mean diffusivity (MD), fractional anisotropy (FA), neurite density (NDI), and orientation dispersion (ODI). We used ANCOVAs to compare between-groups and support vector modeling to investigate which variables (imaging, neurocognitive, motor) contribute the most to NF1 and unaffected participants distinction.After controlling for total brain volume, white matter volume was larger in the NF1 versus unaffected group with a large effect (partial η²=0.57). Cerebellar MD was higher in the NF1 group, while FA, NDI and ODI were lower in the NF1 group (p's < 0.05). Support vector modeling correctly classified 90.20% of participants as being in the NF1 or unaffected group. Top three weights were white matter volume, mobility ratings, and NDI.Differences in cerebellar white matter microstructure (compared to unaffected youth) were identified in NF1. Cerebellar white matter volume, NDI, and MD were particularly useful differentiators between NF1 and unaffected youth and may be underlying mechanisms of cerebellum-mediated neurocognitive deficits in NF1.

  View details for DOI 10.1007/s12311-026-01961-z

  View details for PubMedID 41667872

  View details for PubMedCentralID 10500831

• T1w/T2w ratio suggests reduced intracortical myelin content in youth with RASopathies. medRxiv : the preprint server for health sciences Plank, J. R., Pardej, S. K., Raman, M. M., McNab, J., Green, T. 2025

  Abstract

  Background Myelin may represent a modifiable treatment target in neurodevelopmental disorders, however, a reliable tool for in vivo assessment of myelin alterations in clinical settings is needed. Prior work shows commonly acquired T1-weighted (T1w) and T2-weighted (T2w) scans can be transformed into ratio maps and subsequently provide a reasonable estimate of cortical myelin content. We investigated T1w/T2w ratios for measuring cortical myelin in children with neurodevelopmental disorders of the RAS-MAPK signaling pathway. Methods In this prospective study, 112 children (86 RASopathies, 26 typical developing (TD), aged 6-17 years) completed T1w and T2w MRI scans and NIH Toolbox cognitive assessments. Parent-rated mobility and strength impact scores were also acquired. T1w/T2w ratio maps were calculated at three levels of the cortex in FreeSurfer, and average values were extracted from 68 regions-of-interest (ROIs) at each level across the brain and from eight subcortical ROIs. Group differences were assessed using analyses of covariance, including a false discovery rate adjustment for multiple comparisons. As an exploratory analysis, differences in cognitive scores and parent-rated health were assessed across quartiles of whole-brain T1w/T2w ratios. Results Widespread decreases in T1w/T2w ratios were found in the RASopathies group, suggesting decreased cortical myelin content. Of the T1w/T2w ratios sampled along the midline, 63 of 68 cortical ROIs were significantly reduced in RASopathies (pFDR<.050). Of the subcortical ROIs, only the T1w/T2w ratio in the accumbens was significantly reduced in RASopathies compared to TD (Cohens d=0.520, pFDR=.024). Exploratory quartile analyses across the whole sample indicated significant effects of T1w/T2w ratio quartile on mobility (p=.002) and strength impact ratings (p<.001), such that subjects in higher T1w/T2w ratio quartiles had better physical health ratings. Conclusions These results support the utility of T1w/T2w ratio mapping as a sensitive tool for detecting cortical myelin alterations in genetically defined neurodevelopmental disorders. Exploratory analyses suggest a relationship between cortical myelin content and physical mobility and stamina. Future work should explore the clinical relevance of these findings for cognitive and functional outcomes and assess their potential as biomarkers for targeted therapeutic interventions.

  View details for DOI 10.1101/2025.09.16.25335916

  View details for PubMedID 41001496

• Somatic Symptoms in a Population-Based Sample from Childhood to Adolescence: Stability and Concurrent and Longitudinal Predictors. Child psychiatry and human development Pardej, S. K., Waschbusch, D. A., Calhoun, S. L., Mayes, S. D. 2024

  Abstract

  The present study investigated group and individual stability and predictors of somatic symptoms from childhood to adolescence in a population-based sample. 259 youth were evaluated at 6-12 years (M 8.1) and 8 years later (M 15.2). Sixteen somatic symptoms from the parent-rated Pediatric Behavior Scale were used for analyses, in addition to psychopathology subscales. Most somatic symptom prevalence rates decreased from childhood to adolescence. Group mean scores were relatively stable over time. Individual stability for the absence of somatic symptoms in childhood and adolescence was high, yet individual stability for the presence of somatic symptoms at both time points was low. Most symptoms remitted for the majority of youth. New cases in adolescence were common. Significant correlates of childhood and adolescent somatic symptoms varied. Longitudinal predictors were childhood somatic symptoms and adolescent medication status. Childhood psychopathology scores did not predict the total adolescent somatic symptom score.

  View details for DOI 10.1007/s10578-024-01794-z

  View details for PubMedID 39613979

  View details for PubMedCentralID 3020286

• Oppositional Defiant Disorder in Autism and ADHD JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS Mayes, S. D., Pardej, S. K., Waschbusch, D. A. 2024

  Abstract

  Our study compared oppositional defiant disorder (ODD) in children with autism to ADHD-Combined presentation and ADHD-Inattentive presentation. Mothers of 2,400 children 3-17 years old with autism and/or ADHD completed the Pediatric Behavior Scale. ADHD-Combined was most strongly associated with ODD, with an ODD prevalence of 53% in children with ADHD-Combined only. When autism was added to ADHD-Combined, prevalence increased to 62% and the ODD score increased significantly. Autism+ADHD-Inattentive, Autism Only, and ADHD-Inattentive Only had ODD prevalences of 28%, 24% and 14%. In each diagnostic group, ODD had the same two factors (irritable/angry and oppositional/defiant); demographic differences between children with and without ODD were few; and correlations between ODD and conduct problems were large, correlations with depression were medium, and correlations with anxiety were small. However, ODD scores differed significantly between groups (Autism+ADHD-Combined > ADHD-Combined Only > Autism+ADHD-Inattentive and Autism Only > ADHD-Inattentive Only). The irritable/angry ODD component was greater in Autism+ADHD-Combined than in ADHD-Combined Only, whereas the oppositional/defiant component did not differ between the two groups. Autism was a significant independent risk factor for ODD, particularly the irritable/angry ODD component, but ADHD-Combined was the strongest risk factor. Therefore, the high co-occurrence of ADHD-Combined in autism (80% in our study) largely explains the high prevalence of ODD in autism. ADHD-Combined, autism, and ODD are highly comorbid (55-90%). Clinicians should assess all three disorders in referred children and provide evidence-based interventions to improve current functioning and outcomes for children with these disorders and reduce family and caretaker stress.

  View details for DOI 10.1007/s10803-024-06437-9

  View details for Web of Science ID 001279127400003

  View details for PubMedID 39066970

  View details for PubMedCentralID 7090378

• Prevalence and Correlates of Poor Safety Awareness and Accidental Injury in ASD, ADHD, ASD + ADHD, and Neurotypical Youth Samples (Jun, 10.1007/s10803-024-06417-z, 2024) JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS Pardej, S. K., Mayes, S. D. 2024; 54 (8): 3193

  View details for DOI 10.1007/s10803-024-06442-y

  View details for Web of Science ID 001260370200001

  View details for PubMedID 38949759

• Feasibility and acceptability of a telehealth intervention for improving peer relationships for adolescents with neurofibromatosis type 1: a single-arm pilot study JOURNAL OF PEDIATRIC PSYCHOLOGY Glad, D. M., Pardej, S. K., Olszewski, E., Klein-Tasman, B. P. 2024; 49 (9): 647-655

  Abstract

  Elevated rates of social difficulties are evident for children and adolescents with neurofibromatosis type 1 (NF1) but the effects of social skills interventions have not been investigated for this population. The Program for the Education and Enrichment of Relational Skills (PEERS®), a widely established social skills intervention in autism spectrum disorders with expansion to other conditions, was recently modified to be offered virtually. This study examined the feasibility and acceptability of this telehealth intervention.27 adolescents with NF1 with social skills difficulties and at least 1 caregiver enrolled in the study. 19 of those participants (Mage = 14.21 years, SD = 1.63; 7 females; 79% White) completed PEERS® via telehealth in a single-arm pilot study. Dropout rates, attendance records, helpfulness of the curriculum topics and caregiver-reported acceptability, including ratings on the Treatment Acceptability Questionnaire, were examined.Low study drop out (30% of enrolled participants; 14% of participants who began the intervention) and high attendance rates were observed. Caregivers found sessions related to common, everyday interactions most helpful. Adolescents indicated sessions related to having get-togethers and social nuances (e.g., humor) as most helpful. Caregiver ratings indicated acceptability of the intervention.This investigation supported the feasibility and acceptability of telehealth PEERS®, a social skills intervention program, among adolescents with NF1 and their caregivers based on attendance patterns as well as appraisal of the curriculum and telehealth modality.

  View details for DOI 10.1093/jpepsy/jsae050

  View details for Web of Science ID 001251773400001

  View details for PubMedID 38908005

• Prevalence and Correlates of Poor Safety Awareness and Accidental Injury in AASD, ADHD, ASD plus ADHD, and Neurotypical Youth Samples JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS Pardej, S. K., Mayes, S. D. 2025; 55 (9): 3040-3049

  Abstract

  The purpose of the present study is to compare risk and predictors of poor safety awareness and accidental injuries in ASD, ADHD, and neurotypical samples. Neurodivergent groups (ADHD-I n = 309; ADHD-C n = 747; ASD-only n = 328; ASD + ADHD n = 1,108) were 2-17 years old. The neurotypical group (n = 186) was 6-12 years of age. Maternal ratings on the Pediatric Behavior Scale examined safety awareness, accidental injury, and psychological problems. Children with ASD + ADHD had significantly poorer safety awareness and accidental injury ratings than all other groups. Predictors of poor safety awareness in the total ASD and/or ADHD sample were: impulsivity, younger age, lower IQ, and hyperactivity. Predictors of accidental injuries were: incoordination, hyperactivity, and conduct problems. Clinicians working with children who have ASD and ADHD are encouraged to screen for poor safety awareness, discuss child safety measures, and provide evidence-based intervention to improve safety awareness and mitigate the risk of injury.

  View details for DOI 10.1007/s10803-024-06417-z

  View details for Web of Science ID 001236520400001

  View details for PubMedID 38822900

  View details for PubMedCentralID 2690559

• A systematic review of the literature about the cognitive and behavioral phenotype of adolescents with NF1 CHILDRENS HEALTH CARE Pardej, S. K., Glad, D. M., Enderle, M. J., Salas, S. A., Young, B. N., Klein-Tasman, B. P. 2026; 55 (1): 94-127

  View details for DOI 10.1080/02739615.2024.2316100

  View details for Web of Science ID 001175146000001