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

  • 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 > 

  • Neuropsychiatric phenotypes in children with Noonan syndrome. Developmental medicine and child neurology Naylor, P. E., Bruno, J. L., Shrestha, S. B., Friedman, M., Jo, B., Reiss, A. L., Green, T. 2023

    Abstract

    AIM: We investigated neuropsychiatric outcomes in children with Noonan syndrome and addressed limitations in previous research with a focus on prepubertal children, comparison to typically developing children, comprehensive neuropsychiatric evaluation, and controlling for overall cognitive abilities.METHOD: Forty-five children with Noonan syndrome (mean=8years 6months, SD=2years 2months; 29 females) and 40 typically developing children (mean=8years 9months, SD=2years; 22 females) were evaluated with objective, parent-report, and psychiatric interview measures.RESULTS: Children with Noonan syndrome demonstrated elevated symptoms across attention-deficit/hyperactivity disorder (ADHD) (attention, hyperactivity, and inhibition), autism spectrum disorder (ASD) (maintaining social relationships, behavioral rigidity, and sensory sensitivity), and oppositional defiant disorder (ODD) (aggression) symptom clusters relative to typically developing children (all p<0.05). Group differences in nearly all parent-report measures were significant after accounting for variations in intellectual functioning, suggesting that increased neurodevelopmental symptoms are not simply driven by overall intelligence. Twenty out of 42 children with Noonan syndrome met criteria for ADHD, eight out of 42 for ODD, and 11 out of 43 demonstrated clinically significant symptoms seen in children with ASD.INTERPRETATION: Children with Noonan syndrome are at increased risk for a range of ADHD, ASD, and ODD associated symptoms. A dimensional approach reveals significant ASD symptoms in Noonan syndrome that do not emerge when using the currently accepted categorical diagnostic approach.

    View details for DOI 10.1111/dmcn.15627

    View details for PubMedID 37130201

  • Adolescent brain development in girls with Turner syndrome. Human brain mapping Lozano Wun, V., Foland-Ross, L. C., Jo, B., Green, T., Hong, D., Ross, J. L., Reiss, A. L. 2023

    Abstract

    Turner syndrome (TS) is a common sex chromosome aneuploidy in females associated with various physical, cognitive, and socio-emotional phenotypes. However, few studies have examined TS-associated alterations in the development of cortical gray matter volume and the two components that comprise this measure-surface area and thickness. Moreover, the longitudinal direct (i.e., genetic) and indirect (i.e., hormonal) effects of X-monosomy on the brain are unclear. Brain structure was assessed in 61 girls with TS (11.3 ± 2.8 years) and 55 typically developing girls (10.8 ± 2.3 years) for up to 4 timepoints. Surface-based analyses of cortical gray matter volume, thickness, and surface area were conducted to examine the direct effects of X-monosomy present before pubertal onset and indirect hormonal effects of estrogen deficiency/X-monosomy emerging after pubertal onset. Longitudinal analyses revealed that, whereas typically developing girls exhibited normative declines in gray matter structure during adolescence, this pattern was reduced or inverted in TS. Further, girls with TS demonstrated smaller total surface area and larger average cortical thickness overall. Regionally, the TS group exhibited decreased volume and surface area in the pericalcarine, postcentral, and parietal regions relative to typically developing girls, as well as larger volume in the caudate, amygdala, and temporal lobe regions and increased thickness in parietal and temporal regions. Surface area alterations were predominant by age 8, while maturational differences in thickness emerged by age 10 or later. Taken together, these results suggest the involvement of both direct and indirect effects of X-chromosome haploinsufficiency on brain development in TS.

    View details for DOI 10.1002/hbm.26327

    View details for PubMedID 37126641

  • Novel effects of Ras-MAPK pathogenic variants on the developing human brain and their link to gene expression and inhibition abilities. Research square Rai, B., Naylor, P., Sanchez, M. S., Wintermark, M., Raman, M., Jo, B., Reiss, A., Green, T. 2023

    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>