{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:38:10Z","timestamp":1788910690219,"version":"build-2803163510"},"reference-count":155,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H03028"],"award-info":[{"award-number":["21H03028"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biological Psychiatry Global Open Science"],"published-print":{"date-parts":[[2022,4]]},"DOI":"10.1016\/j.bpsgos.2021.08.005","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T23:24:38Z","timestamp":1630452278000},"page":"95-105","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"title":["Genetic and Environmental Contributions to Autism Spectrum Disorder Through Mechanistic Target of Rapamycin"],"prefix":"10.1016","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3032-3738","authenticated-orcid":false,"given":"Atsushi","family":"Sato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-0278","authenticated-orcid":false,"given":"Kazutaka","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bpsgos.2021.08.005_bib1","series-title":"Diagnostic and Statistical Manual of Mental Disorders","year":"2013"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib2","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/S2215-0366(15)00376-4","article-title":"Prevalence of autism spectrum disorder phenomenology in genetic disorders: A systematic review and meta-analysis","volume":"2","author":"Richards","year":"2015","journal-title":"Lancet Psychiatry"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib3","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3389\/fncel.2019.00385","article-title":"Genetic causes and modifiers of autism spectrum disorder","volume":"13","author":"Rylaarsdam","year":"2019","journal-title":"Front Cell Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib4","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1001\/jama.2013.2270","article-title":"Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism","volume":"309","author":"Christensen","year":"2013","journal-title":"JAMA"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib5","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2018-0134","article-title":"Prevalence of autism spectrum disorder in preterm infants: A meta-analysis","volume":"142","author":"Agrawal","year":"2018","journal-title":"Pediatrics"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib6","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1152\/physrev.00038.2014","article-title":"mTOR in brain physiology and pathologies","volume":"95","author":"Bockaert","year":"2015","journal-title":"Physiol Rev"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib7","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.cub.2004.06.054","article-title":"Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton","volume":"14","author":"Sarbassov","year":"2004","journal-title":"Curr Biol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib8","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.molcel.2015.04.031","article-title":"Molecular basis of the rapamycin insensitivity of target of rapamycin complex 2","volume":"58","author":"Gaubitz","year":"2015","journal-title":"Mol Cell"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib9","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S1470-2045(07)70411-4","article-title":"Possible mechanisms of disease development in tuberous sclerosis","volume":"9","author":"Jozwiak","year":"2008","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib10","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.tcb.2015.06.002","article-title":"Regulation of mTORC1 by PI3K signaling","volume":"25","author":"Dibble","year":"2015","journal-title":"Trends Cell Biol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib11","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.tibs.2011.03.006","article-title":"The Ras-ERK and PI3K-mTOR pathways: Cross-talk and compensation","volume":"36","author":"Mendoza","year":"2011","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib12","doi-asserted-by":"crossref","first-page":"671","DOI":"10.3389\/fcell.2020.00671","article-title":"Insight on transcriptional regulation of the energy sensing AMPK and biosynthetic mTOR pathway genes","volume":"8","author":"Sukumaran","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib13","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/ncb999","article-title":"Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins","volume":"5","author":"Zhang","year":"2003","journal-title":"Nat Cell Biol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20110892","article-title":"Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks","volume":"441","author":"Magnuson","year":"2012","journal-title":"Biochem J"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib15","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1080\/15384101.2016.1151581","article-title":"4E-BP 1, a multifactor regulated multifunctional protein","volume":"15","author":"Qin","year":"2016","journal-title":"Cell Cycle"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib16","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.3390\/cancers11101422","article-title":"The emerging roles of mTORC1 in macromanaging autophagy","volume":"11","author":"Dossou","year":"2019","journal-title":"Cancers"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib17","doi-asserted-by":"crossref","first-page":"107623","DOI":"10.1016\/j.pharmthera.2020.107623","article-title":"FK506 binding proteins and inflammation related signalling pathways; Basic biology, current status and future prospects for pharmacological intervention","volume":"215","author":"Annett","year":"2020","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib18","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1093\/neuonc\/nov152","article-title":"Differentiating the mTOR inhibitors everolimus and sirolimus in the treatment of tuberous sclerosis complex","volume":"17","author":"MacKeigan","year":"2015","journal-title":"Neuro Oncol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib19","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13045-019-0754-1","article-title":"Targeting mTOR for cancer therapy","volume":"12","author":"Hua","year":"2019","journal-title":"J\u00a0Hematol Oncol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib20","first-page":"81","article-title":"Scl\u00e9rose tub\u00e9reuse des circonvolutions c\u00e9r\u00e9brales: idiotie et \u00e9pilepsie h\u00e9mipl\u00e9gique","volume":"1","author":"Bourneville","year":"1880","journal-title":"Arch Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib21","first-page":"1","article-title":"A\u00a0case of congenital adenoma sebaceum","volume":"2","author":"Pringle","year":"1890","journal-title":"Br J Dermatol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib22","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1126\/science.277.5327.805","article-title":"Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34","volume":"277","author":"van Slegtenhorst","year":"1997","journal-title":"Science"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib23","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/0092-8674(93)90618-Z","article-title":"Identification and characterization of the tuberous sclerosis gene on chromosome 16","volume":"75","year":"1993","journal-title":"Cell"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib24","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.pediatrneurol.2013.08.001","article-title":"Tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference","volume":"49","author":"Northrup","year":"2013","journal-title":"Pediatr Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib25","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/S0140-6736(05)78872-3","article-title":"Prevalence of tuberous sclerosis estimated by capture-recapture analysis","volume":"351","author":"O\u2019Callaghan","year":"1998","journal-title":"Lancet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib26","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1185\/03007995.2011.586687","article-title":"Burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: Systematic review","volume":"27","author":"Hallett","year":"2011","journal-title":"Curr Med Res Opin"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib27","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.pediatrneurol.2013.08.002","article-title":"Tuberous sclerosis complex surveillance and management: Recommendations of the 2012 International tuberous sclerosis Complex Consensus Conference","volume":"49","author":"Krueger","year":"2013","journal-title":"Pediatr Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib28","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S1474-4422(15)00069-1","article-title":"Neurological and neuropsychiatric aspects of tuberous sclerosis complex","volume":"14","author":"Curatolo","year":"2015","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib29","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s00787-006-0570-3","article-title":"The psychopathologies of\u00a0children and adolescents with tuberous sclerosis complex (TSC): A\u00a0postal survey of UK families","volume":"16","author":"de Vries","year":"2007","journal-title":"Eur Child Adolesc Psychiatry"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib30","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.jaac.2017.03.013","article-title":"What is the male-to-female ratio in autism spectrum disorder? A systematic review and meta-analysis","volume":"56","author":"Loomes","year":"2017","journal-title":"J\u00a0Am Acad Child Adolesc Psychiatry"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib31","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1093\/hmg\/6.12.2155","article-title":"Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis","volume":"6","author":"Jones","year":"1997","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib32","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1086\/316951","article-title":"Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs","volume":"68","author":"Dabora","year":"2001","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib33","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1136\/jmg.2003.012757","article-title":"Genotype and psychological phenotype in tuberous sclerosis","volume":"41","author":"Lewis","year":"2004","journal-title":"J\u00a0Med Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib34","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1212\/WNL.0b013e3182104347","article-title":"Identification of risk factors for autism spectrum disorders in tuberous sclerosis complex","volume":"76","author":"Numis","year":"2011","journal-title":"Neurology"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib35","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/ng0195-70","article-title":"A\u00a0germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer","volume":"9","author":"Kobayashi","year":"1995","journal-title":"Nat Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib36","first-page":"1206","article-title":"Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice","volume":"59","author":"Kobayashi","year":"1999","journal-title":"Cancer Res"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib37","doi-asserted-by":"crossref","first-page":"8762","DOI":"10.1073\/pnas.151033798","article-title":"A\u00a0germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice","volume":"98","author":"Kobayashi","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib38","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/ana.21317","article-title":"Cognitive deficits in Tsc1+\/- mice in the absence of cerebral lesions and seizures","volume":"62","author":"Goorden","year":"2007","journal-title":"Ann Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib39","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1172\/JCI7319","article-title":"Tsc2+\/- mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background","volume":"104","author":"Onda","year":"1999","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib40","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nm1788","article-title":"Reversal of learning deficits in a Tsc2+\/- mouse model of tuberous sclerosis","volume":"14","author":"Ehninger","year":"2008","journal-title":"Nat Med"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib41","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1038\/ncomms2295","article-title":"Rapamycin reverses impaired social interaction in mouse models of tuberous sclerosis complex","volume":"3","author":"Sato","year":"2012","journal-title":"Nat Commun"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib42","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s10519-010-9399-0","article-title":"Epilepsy and Tsc2 haploinsufficiency lead to autistic-like social deficit behaviors in rats","volume":"41","author":"Waltereit","year":"2011","journal-title":"Behav Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib43","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00406-016-0703-8","article-title":"mTOR inhibitor reverses autistic-like social deficit behaviours in adult rats with both Tsc2 haploinsufficiency and developmental status epilepticus","volume":"267","author":"Schneider","year":"2017","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib44","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nature11310","article-title":"Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice","volume":"488","author":"Tsai","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib45","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.nbd.2012.10.014","article-title":"Loss of Tsc2 in Purkinje cells is associated with autistic-like behavior in a mouse model of tuberous sclerosis complex","volume":"51","author":"Reith","year":"2013","journal-title":"Neurobiol Dis"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib46","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/ana.21331","article-title":"Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex","volume":"63","author":"Zeng","year":"2008","journal-title":"Ann Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib47","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/hmg\/ddq491","article-title":"Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex","volume":"20","author":"Zeng","year":"2011","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib48","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1093\/hmg\/8.8.1461","article-title":"PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome","volume":"8","author":"Marsh","year":"1999","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib49","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1086\/377109","article-title":"Germline PTEN promoter mutations and deletions in Cowden\/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase\/Akt pathway","volume":"73","author":"Zhou","year":"2003","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib50","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1086\/379382","article-title":"Germline inactivation of PTEN and dysregulation of the phosphoinositol-3-kinase\/Akt pathway cause human Lhermitte-Duclos disease in adults","volume":"73","author":"Zhou","year":"2003","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib51","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1136\/jmg.2004.024646","article-title":"Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations","volume":"42","author":"Butler","year":"2005","journal-title":"J\u00a0Med Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib52","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/aur.132","article-title":"Confirmation study of PTEN mutations among individuals with autism or developmental delays\/mental retardation and macrocephaly","volume":"3","author":"McBride","year":"2010","journal-title":"Autism Res"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib53","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/ejhg.2008.162","article-title":"PTEN hamartoma tumor syndromes","volume":"16","author":"Blumenthal","year":"2008","journal-title":"Eur J Hum Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib54","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/GIM.0b013e31818fd762","article-title":"The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly","volume":"11","author":"Varga","year":"2009","journal-title":"Genet Med"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib55","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.conb.2012.05.004","article-title":"PTEN signaling in autism spectrum disorders","volume":"22","author":"Zhou","year":"2012","journal-title":"Curr Opin Neurobiol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib56","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/s41398-019-0588-1","article-title":"Neurobehavioral phenotype of autism spectrum disorder associated with germline heterozygous mutations in PTEN","volume":"9","author":"Busch","year":"2019","journal-title":"Transl Psychiatry"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib57","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1177\/1947601911407325","article-title":"PTEN tumor suppressor network in PI3K-Akt pathway control","volume":"1","author":"Georgescu","year":"2010","journal-title":"Genes Cancer"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib58","doi-asserted-by":"crossref","first-page":"3490","DOI":"10.1093\/hmg\/ddu057","article-title":"Pten haploinsufficient mice show broad brain overgrowth but selective impairments in autism-relevant behavioral tests","volume":"23","author":"Clipperton-Allen","year":"2014","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib59","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0136494","article-title":"Social behavioral deficits coincide with the onset of seizure susceptibility in mice lacking serotonin receptor 2c","volume":"10","author":"S\u00e9journ\u00e9","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib60","doi-asserted-by":"crossref","first-page":"13421","DOI":"10.1038\/ncomms13421","article-title":"Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly\/autism syndrome","volume":"7","author":"Huang","year":"2016","journal-title":"Nat Commun"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib61","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.neuron.2006.03.023","article-title":"Pten regulates neuronal arborization and social interaction in mice","volume":"50","author":"Kwon","year":"2006","journal-title":"Neuron"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib62","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1523\/JNEUROSCI.5685-08.2009","article-title":"Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice","volume":"29","author":"Zhou","year":"2009","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib63","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1038\/s41591-019-0608-y","article-title":"Therapeutic inhibition of mTORC2 rescues the behavioral and neurophysiological abnormalities associated with Pten-deficiency","volume":"25","author":"Chen","year":"2019","journal-title":"Nat Med"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib64","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1542\/peds.2013-4301","article-title":"Fragile X syndrome: A review of associated medical problems","volume":"134","author":"Kidd","year":"2014","journal-title":"Pediatrics"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib65","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/0092-8674(91)90397-H","article-title":"Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome","volume":"65","author":"Verkerk","year":"1991","journal-title":"Cell"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib66","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/0092-8674(91)90283-5","article-title":"Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox","volume":"67","author":"Fu","year":"1991","journal-title":"Cell"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib67","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.ajhg.2009.09.018","article-title":"A\u00a0distinct DNA-methylation boundary in the 5\u2032-upstream sequence of the FMR1 promoter binds nuclear proteins and is lost in fragile X syndrome","volume":"85","author":"Naumann","year":"2009","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib68","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/ajmg.b.30910","article-title":"The FMR1 gene and fragile X-associated tremor\/ataxia syndrome","volume":"150B","author":"Brouwer","year":"2009","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib69","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1002\/ajmg.a.36511","article-title":"Epidemiology of fragile X syndrome: A systematic review and meta-analysis","volume":"164A","author":"Hunter","year":"2014","journal-title":"Am J Med Genet A"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib70","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/nrn4001","article-title":"Dysregulation and restoration of translational homeostasis in fragile X syndrome","volume":"16","author":"Richter","year":"2015","journal-title":"Nat Rev Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib71","doi-asserted-by":"crossref","first-page":"17065","DOI":"10.1038\/nrdp.2017.65","article-title":"Fragile X syndrome","volume":"3","author":"Hagerman","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib72","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.cell.2008.07.031","article-title":"The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP","volume":"134","author":"Napoli","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib73","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev-med-081117-041238","article-title":"Metformin for treatment of fragile X syndrome and other neurological disorders","volume":"70","author":"Gantois","year":"2019","journal-title":"Annu Rev Med"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib74","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.neuron.2012.07.022","article-title":"Genetic removal of P70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice","volume":"76","author":"Bhattacharya","year":"2012","journal-title":"Neuron"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib75","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1037\/a0035988","article-title":"Fmr1 and Nlgn3 knockout rats: Novel tools for investigating autism spectrum disorders","volume":"128","author":"Hamilton","year":"2014","journal-title":"Behav Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib76","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.neuron.2007.12.001","article-title":"Correction of fragile X syndrome in mice","volume":"56","author":"D\u00f6len","year":"2007","journal-title":"Neuron"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib77","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00213-011-2375-4","article-title":"Group I metabotropic glutamate receptor antagonists alter select behaviors in a mouse model for fragile X syndrome","volume":"219","author":"Thomas","year":"2012","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib78","doi-asserted-by":"crossref","first-page":"6352","DOI":"10.1523\/JNEUROSCI.0995-04.2004","article-title":"Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression","volume":"24","author":"Hou","year":"2004","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib79","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s13041-020-00706-1","article-title":"Identification of FMRP target mRNAs in the developmental brain: FMRP might coordinate Ras\/MAPK, Wnt\/\u03b2-catenin, and mTOR signaling during corticogenesis","volume":"13","author":"Casingal","year":"2020","journal-title":"Mol Brain"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib80","doi-asserted-by":"crossref","first-page":"10624","DOI":"10.1523\/JNEUROSCI.0402-10.2010","article-title":"Excess phosphoinositide 3-kinase subunit synthesis and activity as a novel therapeutic target in fragile X syndrome","volume":"30","author":"Gross","year":"2010","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib81","doi-asserted-by":"crossref","first-page":"15616","DOI":"10.1523\/JNEUROSCI.3888-10.2010","article-title":"Hypersensitivity to mGluR5 and ERK1\/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome","volume":"30","author":"Osterweil","year":"2010","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib82","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1523\/JNEUROSCI.3696-09.2010","article-title":"Dysregulation of mTOR signaling in fragile X syndrome","volume":"30","author":"Sharma","year":"2010","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib83","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nn.3033","article-title":"Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome","volume":"15","author":"Ronesi","year":"2012","journal-title":"Nat Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib84","doi-asserted-by":"crossref","first-page":"452","DOI":"10.3389\/fnmol.2017.00452","article-title":"Negative effects of chronic rapamycin treatment on behavior in a mouse model of fragile X syndrome","volume":"10","author":"Sar\u00e9","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib85","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.clindermatol.2020.03.010","article-title":"RASopathies","volume":"38","author":"Jafry","year":"2020","journal-title":"Clin Dermatol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib86","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1080\/14728222.2018.1465931","article-title":"Emerging therapeutic targets for neurofibromatosis type 1","volume":"22","author":"Walker","year":"2018","journal-title":"Expert Opin Ther Targets"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib87","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/dmcn.12043","article-title":"Autism and other psychiatric comorbidity in neurofibromatosis type 1: Evidence from a population-based study","volume":"55","author":"Garg","year":"2013","journal-title":"Dev Med Child Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib88","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/dmcn.12038","article-title":"Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1","volume":"55","author":"Walsh","year":"2013","journal-title":"Dev Med Child Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib89","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/0092-8674(90)90150-D","article-title":"The Gap-related domain of the neurofibromatosis type 1 gene product interacts with ras p21","volume":"63","author":"Martin","year":"1990","journal-title":"Cell"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib90","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/ng0397-281","article-title":"A\u00a0mouse model for the learning and memory deficits associated with neurofibromatosis type I","volume":"15","author":"Silva","year":"1997","journal-title":"Nat Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib91","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1038\/nn.3822","article-title":"Social learning and amygdala disruptions in Nf1 mice are rescued by blocking p21-activated kinase","volume":"17","author":"Molosh","year":"2014","journal-title":"Nat Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib92","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/gbb.12305","article-title":"Brain and behaviour phenotyping of a mouse model of neurofibromatosis type-1: An MRI\/DTI study on social cognition","volume":"15","author":"Petrella","year":"2016","journal-title":"Genes Brain Behav"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib93","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/aur.1853","article-title":"Characterization of early communicative behavior in mouse models of neurofibromatosis type 1","volume":"11","author":"Maloney","year":"2018","journal-title":"Autism Res"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib94","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/S1474-4422(15)00314-2","article-title":"Valproic acid after five decades of use in epilepsy: Time to reconsider the indications of a time-honoured drug","volume":"15","author":"Tomson","year":"2016","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib95","first-page":"CD010611","article-title":"Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults","volume":"6","author":"Linde","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib96","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1016\/S0140-6736(20)31544-0","article-title":"Bipolar disorders","volume":"396","author":"McIntyre","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib97","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1212\/WNL.0000000000001182","article-title":"IQ at 6 years after in utero exposure to antiepileptic drugs: A controlled cohort study","volume":"84","author":"Baker","year":"2015","journal-title":"Neurology"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib98","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1056\/NEJMoa0907328","article-title":"Valproic acid monotherapy in pregnancy and major congenital malformations","volume":"362","author":"Jentink","year":"2010","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib99","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1111\/epi.13021","article-title":"Valproate in the treatment of epilepsy in girls and women of childbearing potential","volume":"56","author":"Tomson","year":"2015","journal-title":"Epilepsia"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib100","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.expneurol.2017.04.017","article-title":"The valproic acid-induced rodent model of autism","volume":"299","author":"Nicolini","year":"2018","journal-title":"Exp Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib101","doi-asserted-by":"crossref","first-page":"36734","DOI":"10.1074\/jbc.M101287200","article-title":"Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen","volume":"276","author":"Phiel","year":"2001","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib102","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1017\/S1461145711001714","article-title":"Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid","volume":"16","author":"Kataoka","year":"2013","journal-title":"Int J Neuropsychopharmacol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib103","doi-asserted-by":"crossref","first-page":"999","DOI":"10.2353\/ajpath.2009.080537","article-title":"Valproic acid activates the PI3K\/Akt\/mTOR pathway in muscle and ameliorates pathology in a mouse model of Duchenne muscular dystrophy","volume":"174","author":"Gurpur","year":"2009","journal-title":"Am J Pathol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib104","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.mcn.2016.06.004","article-title":"Valproic acid exposure sequentially activates Wnt and mTOR pathways in rats","volume":"75","author":"Qin","year":"2016","journal-title":"Mol Cell Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib105","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13041-018-0423-2","article-title":"Effects of rapamycin on social interaction deficits and gene expression in mice exposed to valproic acid in utero","volume":"12","author":"Kotajima-Murakami","year":"2019","journal-title":"Mol Brain"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib106","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3389\/fncel.2020.00070","article-title":"mTOR suppresses macroautophagy during striatal postnatal development and is hyperactive in mouse models of autism spectrum disorders","volume":"14","author":"Lieberman","year":"2020","journal-title":"Front Cell Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib107","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1523\/JNEUROSCI.0093-05.2005","article-title":"Postadolescent changes in regional cerebral protein synthesis: An in\u00a0vivo study in the FMR1 null mouse","volume":"25","author":"Qin","year":"2005","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib108","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nature10658","article-title":"Mutations causing syndromic autism define an axis of synaptic pathophysiology","volume":"480","author":"Auerbach","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib109","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/jnc.14311","article-title":"Decreased rates of cerebral protein synthesis measured in\u00a0vivo in a mouse model of tuberous sclerosis complex: Unexpected consequences of reduced tuberin","volume":"145","author":"Sar\u00e9","year":"2018","journal-title":"J\u00a0Neurochem"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib110","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nature11628","article-title":"Autism-related deficits via dysregulated eIF4E-dependent translational control","volume":"493","author":"Gkogkas","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib111","doi-asserted-by":"crossref","first-page":"11125","DOI":"10.1523\/JNEUROSCI.4615-14.2015","article-title":"Inhibition of group I metabotropic glutamate receptors reverses autistic-like phenotypes caused by deficiency of the translation repressor eIF4E binding protein 2","volume":"35","author":"Aguilar-Valles","year":"2015","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib112","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nature11782","article-title":"Exaggerated translation causes synaptic and behavioural aberrations associated with autism","volume":"493","author":"Santini","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib113","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aan0665","article-title":"Reducing eIF4E-eIF4G interactions restores the balance between protein synthesis and actin dynamics in fragile X syndrome model mice","volume":"10","author":"Santini","year":"2017","journal-title":"Sci Signal"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib114","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib115","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1091\/mbc.e08-12-1248","article-title":"Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy","volume":"20","author":"Hosokawa","year":"2009","journal-title":"Mol Biol Cell"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib116","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1080\/15548627.2017.1378838","article-title":"Autophagy pathway: Cellular and molecular mechanisms","volume":"14","author":"Yu","year":"2018","journal-title":"Autophagy"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib117","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.neuron.2014.07.040","article-title":"Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits","volume":"83","author":"Tang","year":"2014","journal-title":"Neuron"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib118","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1093\/hmg\/ddu101","article-title":"Neuronal Tsc1\/2 complex controls autophagy through AMPK-dependent regulation of ULK1","volume":"23","author":"Di Nardo","year":"2014","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib119","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1172\/JCI73939","article-title":"mTOR: A pharmacologic target for autophagy regulation","volume":"125","author":"Kim","year":"2015","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib120","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1001627","article-title":"Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling","volume":"11","author":"Potter","year":"2013","journal-title":"PLoS Biol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib121","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/npp.2017.295","article-title":"mGluR5 modulation of behavioral and epileptic phenotypes in a mouse model of tuberous sclerosis complex","volume":"43","author":"Kelly","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib122","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1128\/MCB.00201-08","article-title":"mGluR-dependent long-term depression is associated with increased phosphorylation of S6 and synthesis of elongation factor 1A but remains expressed in S6K-deficient mice","volume":"28","author":"Antion","year":"2008","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib123","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1124\/mol.109.056127","article-title":"Increased GABA(B) receptor-mediated signaling reduces the susceptibility of fragile X knockout mice to audiogenic seizures","volume":"76","author":"Pacey","year":"2009","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib124","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/nrd.2017.221","article-title":"Drug development for neurodevelopmental disorders: Lessons learned from fragile X syndrome","volume":"17","author":"Berry-Kravis","year":"2018","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib125","doi-asserted-by":"crossref","first-page":"321ra5","DOI":"10.1126\/scitranslmed.aab4109","article-title":"Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials","volume":"8","author":"Berry-Kravis","year":"2016","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib126","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s11689-016-9181-6","article-title":"Arbaclofen in fragile X syndrome: Results of phase 3 trials","volume":"9","author":"Berry-Kravis","year":"2017","journal-title":"J\u00a0Neurodev Disord"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib127","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0209984","article-title":"Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in fragile X syndrome","volume":"14","author":"Hessl","year":"2019","journal-title":"PLoS One"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib128","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.atherosclerosis.2004.04.017","article-title":"Simvastatin suppresses coronary artery endothelial tube formation by disrupting Ras\/Raf\/ERK signaling","volume":"175","author":"Miura","year":"2004","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib129","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1016\/j.cub.2005.09.043","article-title":"The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1","volume":"15","author":"Li","year":"2005","journal-title":"Curr Biol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib130","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/1471-2377-13-131","article-title":"Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1","volume":"13","author":"Mainberger","year":"2013","journal-title":"BMC Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib131","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/acn3.288","article-title":"A\u00a0randomized placebo-controlled lovastatin trial for neurobehavioral function in neurofibromatosis I","volume":"3","author":"Bearden","year":"2016","journal-title":"Ann Clin Transl Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib132","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/acn3.50976","article-title":"Visual spatial learning outcomes for clinical trials in neurofibromatosis type 1","volume":"7","author":"Ullrich","year":"2020","journal-title":"Ann Clin Transl Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib133","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1001\/jama.300.3.287","article-title":"Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: A randomized controlled trial","volume":"300","author":"Krab","year":"2008","journal-title":"JAMA"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib134","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/S1474-4422(13)70227-8","article-title":"Simvastatin for cognitive deficits and behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): A randomised, placebo-controlled trial","volume":"12","author":"van der Vaart","year":"2013","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib135","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13229-018-0190-z","article-title":"Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA)","volume":"9","author":"Stivaros","year":"2018","journal-title":"Mol Autism"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib136","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13041-016-0222-6","article-title":"Everolimus improves neuropsychiatric symptoms in a patient with tuberous sclerosis carrying a novel TSC2 mutation","volume":"9","author":"Hwang","year":"2016","journal-title":"Mol Brain"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib137","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1089\/cap.2016.0100","article-title":"Beneficial effects of everolimus on autism and attention-deficit\/hyperactivity disorder symptoms in a group of patients with tuberous sclerosis complex","volume":"27","author":"Kilincaslan","year":"2017","journal-title":"J\u00a0Child Adolesc Psychopharmacol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib138","doi-asserted-by":"crossref","first-page":"4071","DOI":"10.1158\/1078-0432.CCR-11-0445","article-title":"Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: A phase 2 trial","volume":"17","author":"Davies","year":"2011","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib139","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/ana.23960","article-title":"Everolimus treatment of refractory epilepsy in tuberous sclerosis complex","volume":"74","author":"Krueger","year":"2013","journal-title":"Ann Neurol"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.braindev.2018.07.003","article-title":"Everolimus for epilepsy and autism spectrum disorder in tuberous sclerosis complex: EXIST-3 substudy in Japan","volume":"41","author":"Mizuguchi","year":"2019","journal-title":"Brain Dev"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib141","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1056\/NEJMoa1001671","article-title":"Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis","volume":"363","author":"Krueger","year":"2010","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib142","doi-asserted-by":"crossref","first-page":"e200","DOI":"10.1212\/WNL.0000000000007749","article-title":"A\u00a0randomized controlled trial with everolimus for IQ and autism in tuberous sclerosis complex","volume":"93","author":"Overwater","year":"2019","journal-title":"Neurology"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib143","doi-asserted-by":"crossref","first-page":"100733","DOI":"10.1016\/j.conctc.2021.100733","article-title":"A\u00a0randomized double-blind controlled trial of everolimus in individuals with PTEN mutations: Study design and statistical considerations","volume":"21","author":"Hardan","year":"2021","journal-title":"Contemp Clin Trials Commun"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib144","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1073\/pnas.0804428106","article-title":"Haploinsufficiency for Pten and serotonin transporter cooperatively influences brain size and social behavior","volume":"106","author":"Page","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib145","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/npp.2015.339","article-title":"Autistic-like traits and cerebellar dysfunction in Purkinje cell PTEN knock-out mice","volume":"41","author":"Cupolillo","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib146","article-title":"Mitochondrial dysfunction in Pten haplo-insufficient mice with social deficits and repetitive behavior: Interplay between Pten and p53","volume":"7","author":"Napoli","year":"2021","journal-title":"PLoS One"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib147","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3389\/fnmol.2014.00027","article-title":"Deletion of PTEN produces autism-like behavioral deficits and alterations in synaptic proteins","volume":"7","author":"Lugo","year":"2014","journal-title":"Front Mol Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib148","doi-asserted-by":"crossref","first-page":"5880","DOI":"10.1523\/JNEUROSCI.5462-11.2012","article-title":"Pten deletion in adult hippocampal neural stem\/progenitor cells causes cellular abnormalities and alters neurogenesis","volume":"32","author":"Amiri","year":"2012","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib149","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1002\/aur.1641","article-title":"Autism-relevant behaviors are minimally impacted by conditional deletion of Pten in oxytocinergic neurons","volume":"9","author":"Clipperton-Allen","year":"2016","journal-title":"Autism Res"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib150","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.celrep.2015.04.019","article-title":"The parvalbumin\/somatostatin ratio is increased in Pten mutant mice and by human PTEN ASD alleles","volume":"11","author":"Vogt","year":"2015","journal-title":"Cell Rep"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib151","first-page":"505","article-title":"PTEN activity defines an axis for plasticity at cortico-amygdala synapses and influences social behavior","volume":"30","author":"S\u00e1nchez-Puelles","year":"2020","journal-title":"Cereb Cortex"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib152","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3389\/fnbeh.2013.00172","article-title":"Hyperactivity, perseveration and increased responding during attentional rule acquisition in the Fragile X mouse model","volume":"7","author":"Kramvis","year":"2013","journal-title":"Front Behav Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib153","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3389\/fncel.2014.00070","article-title":"2-Methyl-6-(phenylethynyl) pyridine (MPEP) reverses maze learning and PSD-95 deficits in Fmr1 knock-out mice","volume":"8","author":"Gandhi","year":"2014","journal-title":"Front Cell Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib154","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1021\/acschemneuro.0c00482","article-title":"Glyoxalase 1 inhibitor alleviates autism-like phenotype in a prenatal valproic acid-induced mouse model","volume":"11","author":"Wang","year":"2020","journal-title":"ACS Chem Neurosci"},{"key":"10.1016\/j.bpsgos.2021.08.005_bib155","doi-asserted-by":"crossref","first-page":"113094","DOI":"10.1016\/j.bbr.2020.113094","article-title":"Combined the GABA-A and GABA-B receptor agonists attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism","volume":"403","author":"Yang","year":"2021","journal-title":"Behav Brain Res"}],"container-title":["Biological Psychiatry Global Open Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2667174321001063?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2667174321001063?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T07:41:46Z","timestamp":1757403706000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2667174321001063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4]]},"references-count":155,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["S2667174321001063"],"URL":"https:\/\/doi.org\/10.1016\/j.bpsgos.2021.08.005","relation":{},"ISSN":["2667-1743"],"issn-type":[{"value":"2667-1743","type":"print"}],"subject":[],"published":{"date-parts":[[2022,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Genetic and Environmental Contributions to Autism Spectrum Disorder Through Mechanistic Target of Rapamycin","name":"articletitle","label":"Article Title"},{"value":"Biological Psychiatry Global Open Science","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bpsgos.2021.08.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 THE AUTHORS. Published by Elsevier Inc on behalf of the Society of Biological Psychiatry.","name":"copyright","label":"Copyright"}]}}