Publications

The ASPE team has abundantly contributed to ongoing conversations regarding the genetic and biological processes associated with autism. Check out some of our recent publications!

Distributed processing for value-based choice by prelimbic circuits targeting anterior-posterior dorsal striatal subregions in male mice

The Fuccillo lab published a paper in Q2 2023 in Nature Communications – findings from this paper will be used to inform project directions in ASPE 2.0. 

Choi K, Piasini E, Díaz-Hernández E, Cifuentes LV, Henderson NT, Holly EN, Subramaniyan M, Gerfen CR, Fuccillo MV. Distributed processing for value-based choice by prelimbic circuits targeting anterior-posterior dorsal striatal subregions in male mice. Nat Commun. 2023 Apr 6;14(1):1920. doi: 10.1038/s41467-023-36795-4. PMID: 37024449; PMCID: PMC10079960. https://pubmed.ncbi.nlm.nih.gov/37024449/

 

Allelic contribution of Nrxn1α to autism-relevant behavioral phenotypes in mice

The Zhou lab published a paper in Q1 2023 on systematic behavioral phenotyping from three mouse models of Nrxn1. This paper reports the importance of sex, genetic structure, and the amount of functional NRXN1 product in eliciting ASD-relevant behaviors, and the need for animal models carrying anomalies at multiple genes to elucidate the genetic underpinnings of autism. 

Xu B, Ho Y, Fasolino M, Medina J, O’Brien WT, Lamonica JM, Nugent E, Brodkin ES, Fuccillo MV, Bucan M, Zhou Z. Allelic contribution of Nrxn1α to autism-relevant behavioral phenotypes in mice. PLoS Genet. 2023 Feb 27;19(2):e1010659. doi: 10.1371/journal.pgen.1010659. PMID: 36848371; PMCID: PMC9997995. https://doi.org/10.1371/journal.pgen.1010659

Multivariate analysis of variegated expression in Neurons: A strategy for unbiased localization of gene function to candidate brain regions in larval zebrafish

The Granato lab published a paper in Q1 2023 in Genes, Brain, and Behavior. Techniques from this paper will be employed in zebrafish models in ASPE 2.0. 

Shoenhard H, Granato M. Multivariate analysis of variegated expression in Neurons: A strategy for unbiased localization of gene function to candidate brain regions in larval zebrafish. PLoS One. 2023 Feb 14;18(2):e0281609. doi: 10.1371/journal.pone.0281609. PMID: 36787331; PMCID: PMC9928119. https://doi.org/10.1371/journal.pone.0281609

Contrasting Views of Autism Spectrum Traits in Adults, Especially in Self-Reports vs. Informant-Reports for Women High in Autism Spectrum Traits

The Brodkin lab published a paper in Q4 of 2022 in the Journal of Autism and Development. This paper reports discrepancies between self-reports (by probands) and informant-reports of autism quantitative traits in probands, with especially strong discrepancies in autistic women.  This paper has important implications for how phenotyping should be done in genetic studies and clinical trials for adults on the autism spectrum.  The paper concludes that both informant-report and self-report data should be included in quantitative genetics studies and clinical trials for adults, as the two types of data provide distinct and important perspectives, especially for autistic women.  


Taylor SC, Gehringer BN, Dow HC, Langer A, Rawot E, Smernoff Z, Steeman S, Almasy L, Rader DJ, Bučan M, Brodkin ES. Contrasting Views of Autism Spectrum Traits in Adults, Especially in Self-Reports vs. Informant-Reports for Women High in Autism Spectrum Traits. J Autism Dev Disord. 2022 Dec 9:1–13. doi: 10.1007/s10803-022-05822-6. Epub ahead of print. PMID: 36484966; PMCID: PMC9734875. https://doi.org/10.1007/s10803-022-05822-6

Identification of a transcriptional signature found in multiple models of ASD and related disorders

The Korb lab published a paper in Q3 2022 in Genome Research. Approaches and concepts from this paper with guide experiments when testing ASPE candidate genes in the mouse neuronal culture system.

Thudium S, Palozola K, L’Her É, Korb E. Identification of a transcriptional signature found in multiple models of ASD and related disorders. Genome Res. 2022 Sep 14;32(9):1642–54. doi: 10.1101/gr.276591.122. Epub ahead of print. PMID: 36104286; PMCID: PMC9528985. https://pubmed.ncbi.nlm.nih.gov/36104286/

The Development and Validation of the First German Open Scale of Social Information Processing

Relevant to the proposed deep behavioral phenotyping that we are considering in ASPE 2.0, Ted Brodkin published a paper on social information processing in Q3 of 2022.

Niestroj SC, Steden S, Boecker M, Brodkin ES, Konrad K. The Development and Validation of the First German Open Scale of Social Information Processing. Psychopathology. 2022 Aug 31:1-12. doi: 10.1159/000525950. Epub ahead of print. PMID: 36044830. https://pubmed.ncbi.nlm.nih.gov/36044830/

Calculating genetic risk for dysfunction in pleiotropic biological processes using whole exome sequencing data

Ted Brodkin published a paper in Q3 of 2022 on autism genetics in the Journal of Neurodevelopmental Disorders which ASPE will take into consideration as we translate our genetic findings into the clinic.

Veatch OJ, Mazzotti DR, Schultz RT, Abel T, Michaelson JJ, Brodkin ES, Tunc B, Assouline SG, Nickl-Jockschat T, Malow BA, Sutcliffe JS, Pack AI. Calculating genetic risk for dysfunction in pleiotropic biological processes using whole exome sequencing data. J Neurodev Disord. 2022 Jun 24;14(1):39. doi: 10.1186/s11689-022-09448-8. PMID: 35751013. https://pubmed.ncbi.nlm.nih.gov/35751013/

Reconsidering animal models used to study autism spectrum disorder: Current state and optimizing future

Ted Brodkin published an autism-related paper in Q1 2022 in Genes, Brain, and Behavior. Concepts from this paper will be taken into consideration during the development and characterization of ASPE animal models. 

Silverman JL, Thurm A, Ethridge SB, Soller MM, Petkova SP, Abel T, Bauman MD, Brodkin ES, Harony-Nicolas H, Wöhr M, Halladay A. Reconsidering animal models used to study autism spectrum disorder: Current state and optimizing future. Genes Brain Behav. 2022 Jun;21(5): e12803. doi: 10.1111/gbb.12803. Epub 2022 Mar 14. PMID: 35285132. https://pubmed.ncbi.nlm.nih.gov/35285132/

Sufficient sleep duration in autistic children and the role of physical activity

In Q1 of 2022, Maja Bućan and ASPE collaborators published a paper that found that physical activity is a promising approach to help children obtain sufficient sleep duration in the journal Autism.

Elkhatib Smidt SD, Gooneratne N, Brodkin ES, Bucan M, Mitchell JA. Sufficient sleep duration in autistic children and the role of physical activity. Autism. 2022 May;26(4):814-826. https://pubmed.ncbi.nlm.nih.gov/34991371/

Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility

The Jongens lab published a paper in Q2 2022 that indicates a novel role for neurexin in the regulation of energy metabolism, as well as uncovers a clinically relevant seizure phenotype in flies lacking neurexin. This work depicts a novel role for neurexins in the regulation of energy metabolism by using a combination of metabolomic and physiological methodologies, thus establishing a foundation for future inquiries into the function of neurexins and the role of metabolic dysfunction in the etiology of autism.

Levy KA, Weisz ED, Jongens TA. Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility. Hum Mol Genet. 2022 May 25: ddac115. doi: 10.1093/hmg/ddac115. Epub ahead of print. PMID: 35617143. https://pubmed.ncbi.nlm.nih.gov/35617143/

Investigating the relationships between resilience, autism-related quantitative traits, and mental health outcomes among adults during the COVID-19 pandemic

In Q1 of 2022, Sara Taylor and the Brodkin lab published a paper in The Journal of Psychiatric Research. This paper reports the relationships among autism spectrum traits, mental health symptoms (depression and anxiety), and resilience during the COVID-19 pandemic.

Taylor SC, Smernoff ZL, Rajan M, Steeman S, Gehringer BN, Dow HC, Barzilay R, Rader DJ, Bucan M, Almasy L, Brodkin ES. Investigating the relationships between resilience, autism-related quantitative traits, and mental health outcomes among adults during the COVID-19 pandemic. J Psychiatr Res. 2022; 148:250-257. https://pubmed.ncbi.nlm.nih.gov/35151216/

Synaptic dysfunction connects autism spectrum disorder and sleep disturbances: A perspective from studies in model organisms

In Q1 of 2022, Ted Brodkin and Michael Hart published a paper that reviewed the connection between synaptic dysfunction, sleep disturbances, and autism in the journal Sleep Medicine Reviews

Doldur-Balli F, Imamura T, Veatch OJ, Gong NN, Lim DC, Hart MP, Abel T, Kayser MS, Brodkin ES, Pack AI. Synaptic dysfunction connects autism spectrum disorder and sleep disturbances: A perspective from studies in model organisms. Sleep Med Rev. 2022 Jan 25; 62:101595. https://pubmed.ncbi.nlm.nih.gov/35158305/

The relationship between autism spectrum and sleep-wake traits

In Q4 of 2021, Maja Bućan and ASPE collaborators published a paper in Autism Research. Using ASPE data, the paper presents actigraphy-derived sleep-wake rhythm data and looks at the relationship between those rhythms and social behaviors and executive functioning in high-functioning autism and family members. 

Elkhatib Smidt SD, Ghorai A, Taylor SC, Gehringer BN, Dow HC, Langer A, Rawot E, Zhang J, Mitchell JA, Rader DJ, Almasy L, Brodkin ES, Bućan M. The relationship between autism spectrum and sleep-wake traits. Autism Res. 2021: 1-12. https://pubmed.ncbi.nlm.nih.gov/34967137/

Heritability of quantitative autism spectrum traits in adults: A family-based study

Ted Brodkin and ASPE collaborators had a paper accepted for publication in Q3 of 2021 that was the first to demonstrate that a rich set of quantitative traits (phenotypes) that we are measuring in the ASPE study are significantly influenced by genes (are heritable), which demonstrates the feasibility of searching for specific genes that influence the traits. 

Sara C. Taylor, Samantha Steeman, Brielle Gehringer, Holly C. Dow, Allison Langer, Eric Rawot, Leat Perez, Matthew Goodman, Zoe Smernoff, Mahip Grewal, Oceania Eshraghi, Ashley A. Pallathra, Catherine Oksas, Melissa Mendez, Ruben C. Gur, Daniel Rader, Maja Bucan, Laura Almasy, Edward S. Brodkin.  Heritability of Quantitative Autism Spectrum Traits in Adults: A Family-Based Study. Autism Research. 2021 Aug;14(8):1543-1553. https://pubmed.ncbi.nlm.nih.gov/34245229/

The role of synaptic cell adhesion molecules and associated scaffolding proteins in social affiliative behaviors

Ted Brodkin published the following paper in Q3 of 2020 that discussed the role of NRXN1 and other synaptic cell adhesion molecules in autism-relevant social behaviors: 

Taylor SC, Ferri SL, Grewal M, Smernoff Z, Bucan M, Weiner JA, Abel T, Brodkin ES (2020) The role of synaptic cell adhesion molecules and associated scaffolding proteins in social affiliative behaviors.  Biological Psychiatry, 88(6):442-451. https://www.sciencedirect.com/science/article/pii/S0006322320301013?via%3Dihub

Stress-Induced Neuron Remodeling Reveals Differential Interplay Between Neurexin and Environmental Factors in Caenorhabditis elegans

Mike Hart published a paper in Q4 of 2019 on neurexin. This paper explored the interplay between genetic and environmental factors and demonstrated how underlying genetic defects (nrx-1 or nlg-1 mutation) can interact with environmental stressors to affect distinct neuronal and behavioral responses. These results provide a platform for understanding the combinatorial effect of genetics and environment on risk for pathogenesis of neuropsychiatric disorders.

Michael P. Hart: Stress-Induced Neuron Remodeling Reveals Differential Interplay Between Neurexin and Environmental Factors in Caenorhabditis elegans. Genetics 213(4): 1415-1430, Dec 2019. https://pubmed.ncbi.nlm.nih.gov/31558583/

Long genes linked to autism harbor broad enhancer-like chromatin domains

Zhao YT, Kwon DY, Johnson BS, Fasolino M, Lamonica JM, Kim YJ, Zhao BS, He C, Vahedi G, Kim TH  and Zhou Z* (2018). Long genes linked to autism harbor broad enhancer-like chromatin domains. Genome Research, 28:933-942. PMID: 29848492. https://genome.cshlp.org/content/28/7/933

Functional significance of rare neuroligin 1 variants found in autism

Maja Bućan published a paper in Q3 of 2017 that serves as the blueprint for ASPE’s analysis of different alleles and supports ASPE’s focus on synaptic proteins. This paper reports a novel mutation in NLGN1, a gene encoding a synaptic protein and binding partner of neurexin, in patients with ASD. Presented in this work is a mouse model that was developed with the patient-associated mutation in NLGN1m which exhibits atypical social behavior. These results suggest that a rare variant in NLGN1 is functionally significant and support that the NLGN1 synaptic pathway may be important in the etiology of neuropsychiatric disorders.

Moe Nakanishi, Jun Nomura, Xiao Ji, Kota Tamada, Takashi Arai, Eiki Takahashi, Maja Bućan, Toru Takumi. Functional significance of rare neuroligin 1 variants found in autism. PLOS Genetics 13(10): e1007035. https://pubmed.ncbi.nlm.nih.gov/28841651/

 

Elevating expression of MeCP2 T158M rescues DNA binding and Rett syndrome-like phenotypes

Lamonica JM, Kwon DY, Goffin D, Fenik P, Johnson BS, Cui Y, Guo H, Veasey S and Zhou Z* (2017). Elevating expression of MeCP2 T158M rescues DNA binding and Rett syndrome-like phenotypes. Journal of Clinical Investigation, 127 (5): 1889-1904. PMID28394263. https://www.ncbi.nlm.nih.gov/pubmed/28394263

 

Loss of CDKL5 in glutamatergic neurons disrupts hippocampal microcircuitry and leads to memory impairment in mice

Tang S, Wang I-T, Yue C, Takano H, Terzic B, Pance K, Lee JY, Cui Y, Coulter DA* and Zhou Z* (2017). Loss of CDKL5 in glutamatergic neurons disrupts hippocampal microcircuitry and leads to memory impairment in mice. Journal of Neuroscience, 37(31): 7420-7437.     PMID28674172. https://www.ncbi.nlm.nih.gov/pubmed/28674172

 

Biotin tagging of MeCP2 reveals contextual insights into the Rett syndrome transcriptome

Johnson BS, Zhao Y, Fasolino M, Lamonica JM, Kim YJ, Georgakilas G, Wood KH, Bu D, Cui Y, Goffin D, Vahedi G, Kim TH and Zhou Z* (2017). Biotin tagging of MeCP2 reveals contextual insights into the Rett syndrome transcriptome. Nature Medicine, 23(10): 1203-1214. PMID28920956. https://www.ncbi.nlm.nih.gov/pubmed/28920956

 

Sociability deficits and altered amygdala circuits in mice lacking Pcdh10, an autism associated gene

Schoch H., Kreibich A.S., Ferri S.L., White R.S., Bohorquez D., Banerjee A., Port R.G., Dow H.C., Cordero L., Pallathra A.A., Kim H., Li H., Bilker W.B., Hirano S., Schultz R.T., Borgmann-Winter K., Hahn C.-G., Feldmeyer D., Carlson G.C., Abel T., Brodkin E.S.:  “Sociability deficits and altered amygdala circuits in mice lacking Pcdh10, an autism associated gene.”  Biological Psychiatry, 81:193-202, 2017. https://pubmed.ncbi.nlm.nih.gov/27567313/

 

Increased burden of deleterious variants in essential genes in autism spectrum disorder

Ji X, Kember RL, Brown CD, Bućan M. Increased burden of deleterious variants in essential genes in autism spectrum disorder. Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):15054-15059.

Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model

Monyak RE, Emerson D, Schoenfeld BP, Zheng X, Chambers DB, Rosenfelt C, Langer S, Hinchey P, Choi CH, McDonald TV, Bolduc FV, Sehgal A, McBride SM, Jongens TA. Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model. Molecular psychiatry. 2016. Epub 2016/04/20. doi: 10.1038/mp.2016.51. PubMed PMID: 27090306; PubMed Central PMCID: PMCPmc5071102. https://pubmed.ncbi.nlm.nih.gov/27090306/

Nipped-B Mutants Model Cornelia de Lange Syndrome in Growth and Behavior

Wu Y, Gause M, Xu D, Misulovin Z, Schaaf CA, Mosarla RC, Mannino E, Shannon M, Jones E, Shi M, Chen WF, Katz OL, Sehgal A, Jongens TA, Krantz ID, Dorsett D. Drosophila Nipped-B Mutants Model Cornelia de Lange Syndrome in Growth and Behavior. PLoS genetics. 2015;11(11):e1005655. Epub 2015/11/07. doi: 10.1371/journal.pgen.1005655. PubMed PMID: 26544867; PubMed Central PMCID: PMCPmc4636142. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636142/

Cellular origins of auditory event-related potential deficits in Rett syndrome

Goffin D., Brodkin E.S., Blendy J.A., Siegel S.J., Zhou Z.:  “Cellular origins of auditory event-related potential deficits in Rett syndrome.”  Nature Neuroscience, 17(6):804-806, 2014. https://pubmed.ncbi.nlm.nih.gov/24777420/

Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice

Wang IT, Allen M, Goffin D, Zhu X, Fairless AH, Brodkin ES, Siegel SJ, Marsh ED, Blendy JA, Zhou Z. Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice. Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21516-21. https://pubmed.ncbi.nlm.nih.gov/23236174/

Prevalence and correlates of autism in a state psychiatric hospital

Mandell D.S., Lawer L.J., Branch K., Brodkin E.S., Healey K., Witalec R., Johnson D.N., Gur R.E.:  “Prevalence and correlates of autism in a state psychiatric hospital.” Autism, 16(6):557-567, 2012. https://pubmed.ncbi.nlm.nih.gov/21846667/

The social motivation theory of autism

Chevallier C., Kohls G., Troiani V., Brodkin E.S., Schultz R.T.:  “The social motivation theory of autism.”  Trends in Cognitive Sciences, 16(4):231-239, 2012. https://doi.org/10.1016/j.tics.2012.02.007

 

Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses

Goffin D, Allen M, Zhang L, Amorim M, Wang IT, Reyes AR, Mercado-Berton A, Ong C, Cohen S, Hu L, Blendy JA, Carlson GC, Siegel SJ, Greenberg ME, Zhou Z. Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses. Nat Neurosci. 2011 Nov 27;15(2):274-83. https://pubmed.ncbi.nlm.nih.gov/22119903/

Modulation of dADAR-dependent RNA editing by the Drosophila FMRP

Bhogal B, Jepson JE, Savva YA, Pepper AS, Reenan RA, Jongens TA. Modulation of dADAR-dependent RNA editing by the Drosophila FMRP. Nature neuroscience. 2011;14(12):1517-24. Epub 2011/11/01. doi: 10.1038/nn.2950. PubMed PMID: 22037499; PubMed Central PMCID: PMCPmc3225737.

Pharmacological reversal of synaptic plasticity deficits in the mouse model of fragile X syndrome by group II mGluR antagonist or lithium treatment

Choi CH, Schoenfeld BP, Bell AJ, Hinchey P, Kollaros M, Gertner MJ, Woo NH, Tranfaglia MR, Bear MF, Zukin RS, McDonald TV, Jongens TA, McBride SM. Pharmacological reversal of synaptic plasticity deficits in the mouse model of fragile X syndrome by group II mGluR antagonist or lithium treatment. Brain research. 2011;1380:106-19. Epub 2010/11/17. doi: 10.1016/j.brainres.2010.11.032. PubMed PMID: 21078304; PubMed Central PMCID: PMCPmc3050427. https://pubmed.ncbi.nlm.nih.gov/21078304/

Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes

Bucan, M*., Abrahams*, B. S., Wang*, K., Glessner, J. T., Herman, E. I., Sonnenblick, L. I., Alvarez Retuerto, A. I., Imielinski, M., Hadley, D., Bradfield, J. P., Kim, C., Gidaya, N. B., Lindquist, I., Hutman, T., Sigman, M., Kustanovich, V., Lajonchere, C. M., Singleton, A., Kim, J., Wassink, T. H., McMahon, W. M., Owley, T., Sweeney, J. A., Coon, H., Nurnberger, J. I., Li, M., Cantor, R. M., Minshew, N. J., Sutcliffe, J. S., Cook, E. H., Dawson, G., Buxbaum, J. D., Grant, S. F., Schellenberg, G. D., Geschwind, D. H. and Hakonarson, H.: Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes. PLoS Genet 5(6): e1000536, 2009. PMCID: PMC2695001 https://pubmed.ncbi.nlm.nih.gov/19557195/