Catherine Lord

Weill Cornell Medical College, New York, New York, United States

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Publications (209)1200.39 Total impact


  • No preview · Conference Paper · Oct 2011

  • No preview · Conference Paper · Oct 2011
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    ABSTRACT: Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
    Full-text · Article · Oct 2011 · Human Genetics
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    Catherine Lord
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    ABSTRACT: Although genes associated with human autism spectrum disorders have been identified, bridging the gap between genetics and the patchwork of behavioral deficits associated with the disease remains an enormous challenge. Peñagarikano et al. (2011) now show that mice lacking CNTNAP2, a gene that causes a rare form of epilepsy associated with autistic features and language impairment, display similar phenotypes to their human counterparts, raising hopes that such models may speed the identification of neuronal circuitries underlying the core features of autism.
    Preview · Article · Sep 2011 · Cell
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    So Hyun Kim · Catherine Lord
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    ABSTRACT: Purpose of this study was to systematically examine combined use of the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) for children under age 4 using newly developed and revised diagnostic algorithms. Single and combined use of the ADI-R and ADOS algorithms were compared to clinical best estimate diagnoses for 435 children with autism spectrum disorders (ASD), 113 children with nonspectrum disorders, and 47 children with typical development from 12 to 47 months of age. Sequential strategies to reach a diagnostic decision by prioritizing administrations of instruments were also evaluated. Well-balanced sensitivities and specificities above 80% were obtained for ASD diagnoses using both instruments. Specificities significantly improved when both instruments were used compared to one. Scores that can be used to systematically prioritize administrations of instruments were identified. The ADI-R and ADOS make independent, additive contributions to more accurate diagnostic decisions for clinicians evaluating toddlers and young preschoolers with ASD. Sequential assessment strategies using the scores identified may be appropriate for some children.
    Preview · Article · Sep 2011 · Journal of Child Psychology and Psychiatry
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    Deborah K Anderson · Melissa P Maye · Catherine Lord
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    ABSTRACT: The current study prospectively examined trajectories of change in symptoms of irritability, hyperactivity, and social withdrawal, as well as predictors of such behaviors, for ages 9-18 years for youths with autism spectrum disorder and a comparison group with nonspectrum developmental delays. Children with more severe core features of autism had consistently higher irritability and hyperactivity scores over time than those with broader autism spectrum disorder and nonspectrum delays. Across all diagnoses, behaviors related to hyperactivity showed the greatest improvement. Social withdrawal worsened with age for a substantial proportion of youths with autism spectrum disorder but not for the nonspectrum comparison group. Compared with youths without autism spectrum disorder, children with the disorder showed greater heterogeneity in trajectories for maladaptive behaviors.
    Preview · Article · Sep 2011 · American Journal on Intellectual and Developmental Disabilities
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    Somer L Bishop · Whitney Guthrie · Mia Coffing · Catherine Lord
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    ABSTRACT: Despite widespread use of the Mullen Scales of Early Learning (MSEL; E. M. Mullen, 1995 ) as a cognitive test for children with autism spectrum disorders and other developmental disabilities, the instrument has not been independently validated for use in these populations. Convergent validity of the MSEL and the Differential Ability Scales (DAS; C. D. Elliott, 1990 , 2007 ) was examined in 53 children with autism spectrum disorder and 19 children with nonspectrum diagnoses. Results showed good convergent validity with respect to nonverbal IQ (NVIQ), verbal IQ (VIQ), and NVIQ-VIQ profiles. These findings provide preliminary support for the practice of using MSEL age-equivalents to generate NVIQ and VIQ scores. Establishing convergent validity of cognitive tests is needed before IQs derived from different tests can be conceptualized as a uniform construct.
    Full-text · Article · Sep 2011 · American Journal on Intellectual and Developmental Disabilities
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    ABSTRACT: We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6-12.0, p = 2.4 × 10(-7)). We estimate there are 130-234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1.
    Full-text · Article · Jun 2011 · Neuron
  • Catherine Lord

    No preview · Article · Jun 2011 · Nature
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    ABSTRACT: Siblings of probands with autism spectrum disorders are at higher risk for developing the broad autism phenotype (BAP). We compared the linguistic abilities (i.e., pragmatic language, school achievements, and underling reading processes) of 35 school-age siblings of children with autism (SIBS-A) to those of 42 siblings of children with typical development. Results indicated lower pragmatic abilities in a subgroup of SIBS-A identified with BAP related difficulties (SIBS-A-BAP) whereas school achievements and reading processes were intact. Furthermore, among SIBS-A-BAP, significant negative correlations emerged between the severity scores on the Autism Diagnostic Observation Schedule and full and verbal IQ scores. These results are discussed in the context of the developmental trajectories of SIBS-A and in relation to the BAP.
    Full-text · Article · Jun 2011 · Journal of Autism and Developmental Disorders
  • Amy N Esler · V. Hus · Susan Ellis Weismer · Catherine Lord
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    ABSTRACT: Standardized calibrated severity scores (CSS) have been created for Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) Modules 1-4 as a metric of the relative severity of autism-specific behaviors. Total and domain CSS were created for the Toddler Module to facilitate comparison to other modules. Analyses included 388 children with ASD age 12-30 months and were replicated on 435 repeated assessments from 127 children with ASD. Compared to raw scores, associations between total and domain CSS and participant characteristics were reduced in the original sample. Verbal IQ effects on Social Affect-CSS were not reduced in the replication sample. Toddler Module CSS increases comparability of ADOS-2 scores across modules and allows studies of symptom trajectories to extend to earlier ages.
    No preview · Conference Paper · May 2011
  • Katherine Gotham · Somer L. Bishop · Catherine Lord

    No preview · Chapter · May 2011
  • So Hyun Kim · Catherine Lord
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    ABSTRACT: Autism Diagnostic Interview-Revised (Rutter et al. in Autism diagnostic interview-revised. Western Psychological Services, Los Angeles, 2003) diagnostic algorithms specific to toddlers and young preschoolers were created using 829 assessments of children aged from 12 to 47 months with ASD, nonspectrum disorders, and typical development. The participants were divided into three more homogeneous groups by language level and age. Items that best differentiated the diagnostic groups were selected and arranged into domains based on multifactor item-response analyses. Using the new algorithms for toddlers and preschool children, we were able to improve sensitivity and specificity compared to the previously developed algorithm.
    No preview · Article · Mar 2011 · Journal of Autism and Developmental Disorders
  • Vanessa Hus · Amanda Taylor · Catherine Lord
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    ABSTRACT: Delays in development are a fundamental feature in diagnosing autism spectrum disorders (ASD). Age of language acquisition, usually obtained through retrospective caregiver report, is currently used to distinguish between categories within ASD. Research has shown that caregivers often report children as having acquired developmental milestones earlier or later than they were actually achieved. The current study examines the extent to which this phenomenon, referred to as 'telescoping,' impacts retrospective reports provided by caregivers of children with ASD. Participants were 127 caregivers of children referred for possible ASD or non-spectrum developmental delay. Caregivers were interviewed when children were 2, 3, 5, and 9 years of age. Caregiver-reported ages of first concern, language and non-diagnostic developmental milestones and interviewer-estimated age of onset were compared over time using linear models. Significant telescoping of language milestones resulted in more children meeting language delay criteria as they grew older, in spite of original reports that their language was not delayed. There was little evidence of consistent telescoping of caregiver-reported ages of first concern, daytime bladder control, and independent walking. With time, the interviewers' judged ages of symptom onset increased, but remained prior to age three. Telescoping of caregiver-reported ages of language acquisition has implications for both clinical diagnosis and genetic studies using these milestones to increase homogeneity of samples. Results support proposals to remove specific age-based criteria in the diagnosis of ASD. Telescoping should be considered when working with any clinical population in which retrospectively recalled events are used in diagnosis.
    No preview · Article · Mar 2011 · Journal of Child Psychology and Psychiatry
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    Full-text · Article · Feb 2011 · Journal of the American Academy of Child and Adolescent Psychiatry
  • So Hyun Kim · Catherine Lord

    No preview · Chapter · Jan 2011
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    ABSTRACT: The study's objectives were to assess diagnostic stability of initial autism spectrum disorder (ASD) diagnoses in community settings and identify factors associated with diagnostic instability using data from a national Web-based autism registry. A Cox proportional hazards model was used to assess the relative risk of change in initial ASD diagnosis as a function of demographic characteristics, diagnostic subtype, environmental factors and natural history. Autistic disorder was the most stable initial diagnosis; pervasive developmental disorder-not otherwise specified was the least stable. Additional factors such as diagnosing clinician, region, when in time a child was initially diagnosed, and history of autistic regression also were significantly associated with diagnostic stability in community settings. Findings suggest that the present classification system and other secular factors may be contributing to increasing instability of community-assigned labels of ASD.
    No preview · Article · Jan 2011 · Journal of Autism and Developmental Disorders
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    ABSTRACT: Models of autism spectrum disorders (ASD) as neural disconnection syndromes have been predominantly supported by examinations of abnormalities in corticocortical networks in adults with autism. A broader body of research implicates subcortical structures, particularly the striatum, in the physiopathology of autism. Resting state functional magnetic resonance imaging has revealed detailed maps of striatal circuitry in healthy and psychiatric populations and vividly captured maturational changes in striatal circuitry during typical development. Using resting state functional magnetic resonance imaging, we examined striatal functional connectivity (FC) in 20 children with ASD and 20 typically developing children between the ages of 7.6 and 13.5 years. Whole-brain voxelwise statistical maps quantified within-group striatal FC and between-group differences for three caudate and three putamen seeds for each hemisphere. Children with ASD mostly exhibited prominent patterns of ectopic striatal FC (i.e., functional connectivity present in ASD but not in typically developing children), with increased functional connectivity between nearly all striatal subregions and heteromodal associative and limbic cortex previously implicated in the physiopathology of ASD (e.g., insular and right superior temporal gyrus). Additionally, we found striatal functional hyperconnectivity with the pons, thus expanding the scope of functional alterations implicated in ASD. Secondary analyses revealed ASD-related hyperconnectivity between the pons and insula cortex. Examination of FC of striatal networks in children with ASD revealed abnormalities in circuits involving early developing areas, such as the brainstem and insula, with a pattern of increased FC in ectopic circuits that likely reflects developmental derangement rather than immaturity of functional circuits.
    Full-text · Article · Dec 2010 · Biological psychiatry
  • Bryan H King · Catherine Lord
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    ABSTRACT: With the ongoing consideration of the diagnostic criteria for mental disorders that is active in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and International Classification of Diseases (ICD-11) revision processes, it is timely to review the phenomenological overlap between autism and schizophrenia. These disorders have at various times been regarded alternatively as closely related and as non-overlapping and incompatible. Nevertheless, there are several reports in the literature that have described individuals with both autism and schizophrenia, and the broader phenotypes of these disorders clearly intersect. Recent studies reveal theory of mind deficits in both disorders, and mirror neuron impairments also appear to be shared. There also may be similar connectivity deficits emerging in functional imaging studies, and both disorders share several genetic signals that are being identified through detection of copy number variants. Taken together, these data suggest that it may be time to revisit the possibility that these disorders are related.
    No preview · Article · Nov 2010 · Brain research
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    Catherine E Lord
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    ABSTRACT: Autism is the most commonly studied of a spectrum of developmental disorders that are believed to be neurobiologically based but which, at this point, for lack of good biomarkers, are defined purely by behavior. In the last 20 years, the definition of autism has shifted in emphasis from extreme aloofness and positive signs of abnormality in repetitive and sensorimotor behaviors to a greater awareness of the importance of more subtle reciprocal social communication deficits as core features. Standard diagnostic instruments were developed for research purposes to acquire information both through caregiver interviews and direct clinical observation. Use of these instruments in clinical practice resulted in major improvements, which in turn affected research results. These results yielded further improvements that led to changes in clinical practice over time. The synergism between research and clinical practice in the understanding of autism is discussed.
    Preview · Article · Nov 2010 · American Psychologist

Publication Stats

27k Citations
1,200.39 Total Impact Points

Institutions

  • 2011-2016
    • Weill Cornell Medical College
      • Department of Psychiatry
      New York, New York, United States
  • 2011-2015
    • New York Presbyterian Hospital
      • Center for Autism and the Developing Brain
      New York, New York, United States
  • 2013-2014
    • Columbia University
      New York, New York, United States
  • 2002-2014
    • University of Michigan
      • Department of Psychology
      Ann Arbor, Michigan, United States
  • 2007-2013
    • Cornell University
      Итак, New York, United States
  • 2012
    • University of Pittsburgh
      • Department of Psychiatry
      Pittsburgh, PA, United States
  • 2007-2011
    • Center for Autism and Related Disorders
      Burbank, California, United States
  • 2006-2010
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 1994-2006
    • University of Chicago
      • Department of Human Genetics
      Chicago, Illinois, United States
  • 1997
    • University of Illinois at Chicago
      • Institute for Juvenile Research
      Chicago, Illinois, United States
  • 1991-1993
    • University of North Carolina at Chapel Hill
      • Department of Psychiatry
      Chapel Hill, NC, United States
  • 1983-1990
    • Glenrose Rehabilitation Hospital
      Edmonton, Alberta, Canada