Recent Publications & Updates

Quickly discover all publications on Dr. Tamar Green’s Google Scholar page.

Assistant Professor of Psychiatry and Behavioral Sciences (Interdisciplinary Brain Sciences)

Publications

  • RASopathies influences on neuroanatomical variation in children. Biological psychiatry. Cognitive neuroscience and neuroimaging McGhee, C. A., Honari, H., Siqueiros-Sanchez, M., Serur, Y., van Staalduinen, E. K., Stevenson, D., Bruno, J. L., Raman, M. M., Green, T. 2024

    Abstract

    RASopathies are a group of disorders characterized by pathogenic mutations in the Ras-mitogen-activated protein kinase (Ras/MAPK) signaling pathway. Distinct pathogenic variants in genes encoding proteins in the Ras/MAPK pathway cause Noonan syndrome (NS) and neurofibromatosis type 1 (NF1), which are associated with increased risk for autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD).This study examines the effect RASopathies (NS and NF1) has on human neuroanatomy, specifically on surface area (SA), cortical thickness (CT), and subcortical volumes. We compared structural T1-weighted images, using vertex-based analysis for cortical measures and Desikan ROI parcellation for subcortical volumes on children with RASopathies (n=91, mean age = 8.81, SD = 2.12) to sex- and age-matched TD (n=74, mean age=9.07, SD = 1.77).Compared to TD, RASopathies had convergent effects on SA and CT, exhibiting increased SA in the precentral gyrus, decreased SA in occipital regions, and thinner CT in the precentral gyrus. RASopathies exhibit divergent effects on subcortical volumes, with syndrome-specific influences from NS and NF1. Overall children with NS display decreased volumes in striatal and thalamic structures and children with NF1 display increased volumes in the hippocampus, amygdala, and thalamus.Our study reveals the converging and diverging neuroanatomical effects of RASopathies on human neurodevelopment. The convergence of cortical effects on SA and CT indicates a shared influence of Ras/MAPK hyperactivation on the human brain. Therefore, considering these measures as objective outcome indicators for targeted treatments is imperative.

    View details for DOI 10.1016/j.bpsc.2024.04.003

    View details for PubMedID 38621478

  • Comparing Irritability Across Childhood Psychiatric Disorders Using a Large-Scale Longitudinal Dataset Segal, H., Yang, G., Gothelf, D., Green, T. SPRINGERNATURE. 2023: 141-142
  • Polygenic Risk for ADHD and its Contributions to Brain and Behavioral Phenotypes in Noonan Syndrome Rai, B., Traglia, M., Green, T. SPRINGERNATURE. 2023: 155-156
  • The 8th International RASopathies Symposium: Expanding research and care practice through global collaboration and advocacy. American journal of medical genetics. Part A Pierpont, E. I., Bennett, A. M., Schoyer, L., Stronach, B., Anschutz, A., Borrie, S. C., Briggs, B., Burkitt-Wright, E., Castel, P., Cirstea, I. C., Draaisma, F., Ellis, M., Fear, V. S., Frone, M. N., Flex, E., Gelb, B. D., Green, T., Gripp, K. W., Khoshkhoo, S., Kieran, M. W., Kleemann, K., Klein-Tasman, B. P., Kontaridis, M. I., Kruszka, P., Leoni, C., Liu, C. Z., Merchant, N., Magoulas, P. L., Moertel, C., Prada, C. E., Rauen, K. A., Roelofs, R., Rossignol, R., Sevilla, C., Sevilla, G., Sheedy, R., Stieglitz, E., Sun, D., Tiemens, D., White, F., Wingbermühle, E., Wolf, C., Zenker, M., Andelfinger, G. 2023

    Abstract

    Germline pathogenic variants in the RAS/mitogen-activated protein kinase (MAPK) signaling pathway are the molecular cause of RASopathies, a group of clinically overlapping genetic syndromes. RASopathies constitute a wide clinical spectrum characterized by distinct facial features, short stature, predisposition to cancer, and variable anomalies in nearly all the major body systems. With increasing global recognition of these conditions, the 8th International RASopathies Symposium spotlighted global perspectives on clinical care and research, including strategies for building international collaborations and developing diverse patient cohorts in anticipation of interventional trials. This biannual meeting, organized by RASopathies Network, was held in a hybrid virtual/in-person format. The agenda featured emerging discoveries and case findings as well as progress in preclinical and therapeutic pipelines. Stakeholders including basic scientists, clinician-scientists, practitioners, industry representatives, patients, and family advocates gathered to discuss cutting edge science, recognize current gaps in knowledge, and hear from people with RASopathies about the experience of daily living. Presentations by RASopathy self-advocates and early-stage investigators were featured throughout the program to encourage a sustainable, diverse, long-term research and advocacy partnership focused on improving health and bringing treatments to people with RASopathies.

    View details for DOI 10.1002/ajmg.a.63477

    View details for PubMedID 37969032

  • THE RARE VARIANTS FRAMEWORK: INSIGHTS INTO NEUROPSYCHIATRIC PHENOTYPES PROVIDED BY STUDIES OF RARE GENETIC VARIANTS Green, T., Gur, R. ELSEVIER SCIENCE INC. 2023: S349-S350
  • THE INTERACTIVE EFFECTS OF POLYGENIC RISK SCORES AND SINGLE GENE DISORDERS ON THE SUBCORTICAL STRUCTURE Serur, Y., Rai, B., Raman, M., McGee, C., Green, T. ELSEVIER. 2023: S256-S257
  • INSIGHTS INTO THE RAS-MAPK EFFECT ON NEURODEVELOPMENT: MAPPING THE NEUROPSYCHIATRIC AND BRAIN PHENOTYPES IN CHILDREN WITH NOONAN SYNDROME Green, T. ELSEVIER SCIENCE INC. 2023: S351
  • Novel effects of Ras-MAPK pathogenic variants on the developing human brain and their link to gene expression and inhibition abilities. Translational psychiatry Rai, B., Naylor, P. E., Siqueiros-Sanchez, M., Wintermark, M., Raman, M. M., Jo, B., Reiss, A. L., Green, T. 2023; 13 (1): 245

    Abstract

    The RASopathies are genetic syndromes associated with pathogenic variants causing dysregulation of the Ras/mitogen-activated protein kinase (Ras-MAPK) pathway, essential for brain development, and increased risk for neurodevelopmental disorders. Yet, the effects of most pathogenic variants on the human brain are unknown. We examined: (1) How Ras-MAPK activating variants of PTPN11/SOS1 protein-coding genes affect brain anatomy. (2) The relationship between PTPN11 gene expression levels and brain anatomy, and (3) The relevance of subcortical anatomy to attention and memory skills affected in the RASopathies. We collected structural brain MRI and cognitive-behavioral data from 40 pre-pubertal children with Noonan syndrome (NS), caused by PTPN11 (n = 30) or SOS1 (n = 10) variants (age 8.53 ± 2.15, 25 females), and compared them to 40 age- and sex-matched typically developing controls (9.24 ± 1.62, 27 females). We identified widespread effects of NS on cortical and subcortical volumes and on determinants of cortical gray matter volume, surface area (SA), and cortical thickness (CT). In NS, we observed smaller volumes of bilateral striatum, precentral gyri, and primary visual area (d's < -0.8), and extensive effects on SA (d's >