title: Early developmental trajectories associated with ASD in infants with tuberous sclerosis complex.
abstract: OBJECTIVE
  We performed a longitudinal cohort study of infants with tuberous sclerosis complex (TSC), with the overarching goal of defining early clinical, behavioral, and biological markers of autism spectrum disorder (ASD) in this high-risk population.
  
  
  METHODS
  Infants with TSC and typically developing controls were recruited as early as 3 months of age and followed longitudinally until 36 months of age. Data gathered at each time point included detailed seizure history, developmental testing using the Mullen Scales of Early Learning, and social-communication assessments using the Autism Observation Scale for Infants. At 18 to 36 months, a diagnostic evaluation for ASD was performed using the Autism Diagnostic Observation Schedule.
  
  
  RESULTS
  Infants with TSC demonstrated delays confined to nonverbal abilities, particularly in the visual domain, which then generalized to more global delays by age 9 months. Twenty-two of 40 infants with TSC were diagnosed with ASD. Both 12-month cognitive ability and developmental trajectories over the second and third years of life differentiated the groups. By 12 months of age, the ASD group demonstrated significantly greater cognitive delays and a significant decline in nonverbal IQ from 12 to 36 months.
  
  
  CONCLUSIONS
  This prospective study characterizes early developmental markers of ASD in infants with TSC. The early delay in visual reception and fine motor ability in the TSC group as a whole, coupled with the decline in nonverbal ability in infants diagnosed with ASD, suggests a domain-specific pathway to ASD that can inform more targeted interventions for these high-risk infants.
authors.affiliation: From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA. Sjeste@mednet.ucla.edu.
authors.forename: Shafali
authors.initials: S
authors.lastname: Spurling Jeste
authors.affiliation: From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Wu
authors.affiliation: From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Damla
authors.initials: D
authors.lastname: Senturk
authors.affiliation: From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Kandice
authors.initials: K
authors.lastname: Varcin
authors.affiliation: From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Ko
authors.affiliation: From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Brigid
authors.initials: B
authors.lastname: McCarthy
authors.affiliation: From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Christina
authors.initials: C
authors.lastname: Shimizu
authors.affiliation: From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Kira
authors.initials: K
authors.lastname: Dies
authors.affiliation: From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Vogel-Farley
authors.affiliation: From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sahin
authors.affiliation: From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Nelson
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002652:Child Behavior; D002657:Child Development; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000209:etiology / Q000523:psychology*; D002675:Child, Preschool; D003071:Cognition / Q000502:physiology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D007858:Learning; D008137:Longitudinal Studies; D008297:Male; D009048:Motor Skills / Q000502:physiology; D009483:Neuropsychological Tests; D011446:Prospective Studies; D018401:Sample Size; D014402:Tuberous Sclerosis / Q000150:complications / Q000523:psychology*; D014785:Vision, Ocular / Q000502:physiology
chemical_list: D015415:Biomarkers