Catherine Lord

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

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Publications (184)1039.96 Total impact

  • 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.
    Brain research 11/2010; 1380:34-41. DOI:10.1016/j.brainres.2010.11.031 · 2.83 Impact Factor
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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.
    American Psychologist 11/2010; 65(8):815-26. DOI:10.1037/0003-066X.65.8.815 · 6.87 Impact Factor
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    Psychiatric genetics 11/2010; 21(4):212-3. DOI:10.1097/YPG.0b013e328341a323 · 2.27 Impact Factor
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    ABSTRACT: We examined to what extent increased parent reports of autistic traits in some children with Attention Deficit Hyperactivity Disorder (ADHD) are the result of ADHD-related symptoms or qualitatively similar to the core characteristics of autism spectrum disorders (ASD). Results confirm the presence of a subgroup of children with ADHD and elevated ratings of core ASD traits (ADHD(+)) not accounted for by ADHD or behavioral symptoms. Further, analyses revealed greater oppositional behaviors, but not greater ADHD severity or anxiety, in the ADHD(+) subgroup compared to those with ADHD only. These results highlight the importance of specifically examining autistic traits in children with ADHD for better characterization in studies of the underlying physiopathology and treatment.
    Journal of Autism and Developmental Disorders 11/2010; 41(9):1178-91. DOI:10.1007/s10803-010-1135-3 · 3.06 Impact Factor
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    ABSTRACT: Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
    Human Molecular Genetics 10/2010; 19(20):4072-82. DOI:10.1093/hmg/ddq307 · 6.68 Impact Factor
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    ABSTRACT: Healthy individuals show robust functional connectivity during rest, which is stronger in adults than in children. Connectivity occurs between the posterior and anterior portions of the default network, a group of structures active in the absence of a task, including the posterior cingulate cortex and the superior frontal gyrus. Previous studies found weaker posterior-anterior connectivity in the default network in adults and adolescents with autism spectrum disorders (ASD). However, these studies used small a priori regions of interest ("seeds") to calculate connectivity. Since seed location for all participants was chosen based on controls' brains, these studies' analyses are more tailored to controls than individuals with ASD. An alternative is to use a data-driven approach, such as self-organizing maps (SOM), to create a reference for each participant to calculate connectivity. We used individualized resting-state clusters identified by an SOM algorithm to corroborate previous findings of weaker posterior-anterior connectivity in the ASD group and examine age-related changes in the ASD and control groups. Thirty-nine adolescents with ASD and 41 controls underwent a 10-minute, eyes-open, resting-state functional MRI scan. The SOM analysis revealed that adolescents with ASD versus controls have weaker connectivity between the posterior hub of the default network and the right superior frontal gyrus. Additionally, controls have larger increases in connectivity with age compared to the ASD group. These findings indicate that SOM is a complementary method for calculating connectivity in a clinical population. Additionally, adolescents with ASD have a different developmental trajectory of the default network compared to controls.
    Brain research 10/2010; 1380:187-97. DOI:10.1016/j.brainres.2010.10.102 · 2.83 Impact Factor
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    ABSTRACT: Autism spectrum disorders (ASD) involve a core deficit in social functioning and impairments in the ability to recognize face emotions. In an emotional faces task designed to constrain group differences in attention, the present study used functional MRI to characterize activation in the amygdala, ventral prefrontal cortex (vPFC), and striatum, three structures involved in socio-emotional processing in adolescents with ASD. Twenty-two adolescents with ASD and 20 healthy adolescents viewed facial expressions (happy, fearful, sad and neutral) that were briefly presented (250 ms) during functional MRI acquisition. To monitor attention, subjects pressed a button to identify the gender of each face. The ASD group showed greater activation to the faces relative to the control group in the amygdala, vPFC and striatum. Follow-up analyses indicated that the ASD relative to control group showed greater activation in the amygdala, vPFC and striatum (p < .05 small volume corrected), particularly to sad faces. Moreover, in the ASD group, there was a negative correlation between developmental variables (age and pubertal status) and mean activation from the whole bilateral amygdala; younger adolescents showed greater activation than older adolescents. There were no group differences in accuracy or reaction time in the gender identification task. When group differences in attention to facial expressions were limited, adolescents with ASD showed greater activation in structures involved in socio-emotional processing.
    Journal of Child Psychology and Psychiatry 10/2010; 52(3):296-305. DOI:10.1111/j.1469-7610.2010.02317.x · 5.67 Impact Factor
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    So Hyun Kim, Catherine Lord
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    ABSTRACT: Restricted and repetitive behaviors (RRBs) observed during the Autism Diagnostic Observation Schedule [ADOS: Lord et al., 2000] were examined in a longitudinal data set of 455 toddlers and preschoolers (age 8-56 months) with clinical diagnosis of Autism Spectrum Disorders (ASD; autism, n=121 and pervasive developmental disorders-not otherwise specified (PDD-NOS), n=71), a nonspectrum disorder (NS; n=90), or typical development (TD; n=173). Even in the relatively brief semi-structured observations, GEE analyses of the severity and prevalence of RRBs differentiated children with ASD from those with NS and TD across all ages. RRB total scores on the ADOS were stable over time for children with ASD and NS; however, typically developing preschoolers showed lower RRB scores than typically developing toddlers. Nonverbal IQ (NVIQ) was more strongly related to the prevalence of RRBs in older children with PDD-NOS, NS, and TD than younger children under 2 years and those with autism. Item analyses revealed different relationships between individual items and NVIQ, age, diagnosis, and gender. These findings are discussed in terms of their implications for the etiology and treatment of RRBs as well as for the framework of ASD diagnostic criteria in future diagnostic systems.
    Autism Research 08/2010; 3(4):162-73. DOI:10.1002/aur.142 · 4.53 Impact Factor
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    ABSTRACT: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
    Nature 07/2010; 466(7304):368-72. DOI:10.1038/nature09146 · 42.35 Impact Factor
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    ABSTRACT: Cross-sectional magnetic resonance imaging (MRI) studies have long hypothesized that the brain in children with autism undergoes an abnormal growth trajectory that includes a period of early overgrowth; however, this has never been confirmed by a longitudinal study. We performed the first longitudinal study of brain growth in toddlers at the time symptoms of autism are becoming clinically apparent using structural MRI scans at multiple time points beginning at 1.5 years up to 5 years of age. We collected 193 scans on 41 toddlers who received a confirmed diagnosis of autistic disorder at approximately 48 months of age and 44 typically developing controls. By 2.5 years of age, both cerebral gray and white matter were significantly enlarged in toddlers with autistic disorder, with the most severe enlargement occurring in frontal, temporal, and cingulate cortices. In the longitudinal analyses, which we accounted for age and gender effect, we found that all regions (cerebral gray, cerebral white, frontal gray, temporal gray, cingulate gray, and parietal gray) except occipital gray developed at an abnormal growth rate in toddlers with autistic disorder that was mainly characterized by a quadratic age effect. Females with autistic disorder displayed a more pronounced abnormal growth profile in more brain regions than males with the disorder. Given that overgrowth clearly begins before 2 years of age, future longitudinal studies would benefit from inclusion of even younger populations as well as further characterization of genetic and other biomarkers to determine the underlying neuropathological processes causing the onset of autistic symptoms.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 03/2010; 30(12):4419-27. DOI:10.1523/JNEUROSCI.5714-09.2010 · 6.75 Impact Factor
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    Susan Ellis Weismer, Catherine Lord, Amy Esler
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    ABSTRACT: This study characterized early language abilities in toddlers with autism spectrum disorders (n = 257) using multiple measures of language development, compared to toddlers with non-spectrum developmental delay (DD, n = 69). Findings indicated moderate to high degrees of agreement among three assessment measures (one parent report and two direct assessment measures). Performance on two of the three measures revealed a significant difference in the profile of receptive-expressive language abilities for toddlers with autism compared to the DD group, such that toddlers with autism had relatively more severe receptive than expressive language delays. Regression analyses examining concurrent predictors of language abilities revealed both similarities in significant predictors (nonverbal cognition) and differences (frequency of vocalization, imitation) across the diagnostic groups.
    Journal of Autism and Developmental Disorders 03/2010; 40(10):1259-73. DOI:10.1007/s10803-010-0983-1 · 3.06 Impact Factor
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    ABSTRACT: Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces. Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces. In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces. The small sample size may have affected our ability to detect additional group differences. When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.
    Journal of psychiatry & neuroscience: JPN 03/2010; 35(2):105-14. DOI:10.1503/jpn.090085 · 7.49 Impact Factor
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    ABSTRACT: This study examined how restricted and repetitive behaviors and interests (RRBs) developed over time in a sample of children with autism spectrum disorders (ASD). One hundred ninety-two children referred for a diagnosis of autism at age 2, and 22 children with nonspectrum development disorders were evaluated with a battery of cognitive and diagnostic measures at age 2 and subsequently at ages 3, 5, and 9. Factor analysis of the RRB items on the Autism Diagnostic Interview-Revised revealed two RRB factors at each wave of data collection, one comprising "repetitive sensorimotor" (RSM) behaviors and the other "insistence on sameness" (IS) behaviors. For children with ASD, RSM scores remained relatively high over time, indicating consistent severity, whereas IS scores started low and increased over time, indicating worsening. Having a higher nonverbal intelligence (NVIQ) at age 2 was associated with milder concurrent RSM behaviors and with improvement in these behaviors over time. There was no relationship between NVIQ at age 2 and IS behaviors. However, milder social/communicative impairment, at age 2 was associated with more severe concurrent IS behaviors. Trajectory analysis revealed considerable heterogeneity in patterns of change over time for both kinds of behaviors. These findings are discussed in terms of their implications for our understanding of RRBs in ASD and other disorders, making prognoses about how RRBs will develop in children with ASD as they get older, and using RRBs to identify ASD phenotypes in genetic studies.
    Development and Psychopathology 02/2010; 22(1):55-69. DOI:10.1017/S0954579409990265 · 4.89 Impact Factor
  • Catherine Lord, Somer L. Bishop
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    ABSTRACT: Recent prevalence rates for autism spectrum disorders (ASDs) are now estimated at about 1 in 110 children in the U.S. Increases in public awareness and research funding in response to the growing numbers of children and adults with this disorder have led to numerous important scientific advances over the last several years. Nevertheless, because ASD remains a diagnosis that is defined completely on the basis of behavior, diagnostic assessment is both complex and expensive. Appropriate interventions and services are also multi-faceted and costly, and because of the pervasive nature of the disorder, are often required in some form across the lifespan. In the absence of standard societal mechanisms to pay for appropriate assessment and treatment, families must personally shoulder many of the costs associated with securing appropriate services for their children. This "Social Policy" Report summarizes selected recent studies on diagnosis, prevalence, and intervention, and discusses strategies for designing social policies to help improve the outcomes and independence of children and adults with ASDs. (Contains 2 tables and 1 figure.) [Commentaries from Geraldine Dawson, David Mandell, and Fred R. Volkmar are included, and are individually referenced.]
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    ABSTRACT: Autism spectrum disorders (ASD) are associated with disturbances of neural connectivity. Functional connectivity between neural structures is typically examined within the context of a cognitive task, but also exists in the absence of a task (i.e., "rest"). Connectivity during rest is particularly active in a set of structures called the default network, which includes the posterior cingulate cortex (PCC), retrosplenial cortex, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus. We previously reported that adults with ASD relative to controls show areas of stronger and weaker connectivity within the default network. The objective of the present study was to examine the default network in adolescents with ASD. Sixteen adolescents with ASD and 15 controls participated in a functional MRI study. Functional connectivity was examined between a PCC seed and other areas of the default network. Both groups showed connectivity in the default network. Relative to controls, adolescents with ASD showed widespread weaker connectivity in nine of the eleven areas of the default network. Moreover, an analysis of symptom severity indicated that poorer social skills and increases in restricted and repetitive behaviors and interests correlated with weaker connectivity, whereas poorer verbal and non-verbal communication correlated with stronger connectivity in multiple areas of the default network. These findings indicate that adolescents with ASD show weaker connectivity in the default network than previously reported in adults with ASD. The findings also show that weaker connectivity within the default network is associated with specific impairments in ASD.
    Brain research 12/2009; 1313:202-14. DOI:10.1016/j.brainres.2009.11.057 · 2.83 Impact Factor
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    Rhiannon Luyster, Catherine Lord
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    ABSTRACT: Autism spectrum disorders (ASD) have been gaining attention, partly as an example of unusual developmental trajectories related to early neurobiological differences. The present investigation addressed the process of learning new words to explore mechanisms of language delay and impairment. The sample included 21 typically developing toddlers matched on expressive vocabulary with 21 young children with ASD. Two tasks were administered to teach children a new word and were supplemented by cognitive and diagnostic measures. In most analyses, there were no group differences in performance. Children with ASD did not consistently make mapping errors, even in word learning situations that required the use of social information. These findings indicate that some children with ASD, in developmentally appropriate tasks, are able to use information from social interactions to guide word-object mappings. This result has important implications for understanding of how children with ASD learn language.
    Developmental Psychology 11/2009; 45(6):1774-86. DOI:10.1037/a0016223 · 3.21 Impact Factor
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    ABSTRACT: Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success
    Nature 10/2009; 461(7265):802-808. DOI:10.1038/nature08490 · 42.35 Impact Factor
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    ABSTRACT: Autism is a heterogeneous neurodevelopmental disorder of unknown etiology. The amygdala has long been a site of intense interest in the search for neuropathology in autism, given its role in emotional and social behavior. An interesting hypothesis has emerged that the amygdala undergoes an abnormal developmental trajectory with a period of early overgrowth in autism; however this finding has not been well established at young ages nor analyzed with boys and girls independently. We measured amygdala volumes on magnetic resonance imaging scans from 89 toddlers at 1-5 years of age (mean = 3 years). Each child returned at approximately 5 years of age for final clinical evaluation. Toddlers who later received a confirmed autism diagnosis (32 boys, 9 girls) had a larger right (p < .01) and left (p < .05) amygdala compared with typically developing toddlers (28 boys, 11 girls) with and without covarying for total cerebral volume. Amygdala size in toddlers with autism spectrum disorder correlated with the severity of their social and communication impairments as measured on the Autism Diagnostic Interview and Vineland scale. Strikingly, girls differed more robustly from typical in amygdala volume, whereas boys accounted for the significant relationship of amygdala size with severity of clinical impairment. This study provides evidence that the amygdala is enlarged in young children with autism; the overgrowth must begin before 3 years of age and is associated with the severity of clinical impairments. However, neuroanatomic phenotypic profiles differ between males and females, which critically affects future studies on the genetics and etiology of autism.
    Biological psychiatry 09/2009; 66(10):942-9. DOI:10.1016/j.biopsych.2009.07.007 · 9.47 Impact Factor
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    ABSTRACT: The sociocommunicative abnormalities of young children with Williams syndrome (WS) with limited language were compared with those of children with clinical diagnoses of autism, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), or nonspectrum developmental disability. Participants were 30 children with WS and individually matched groups of participants with autism (n = 28), PDD-NOS (n = 17), and mixed etiology nonspectrum developmental disabilities (n = 16). The autism, PDD-NOS, and mixed etiology groups were matched individually to the children with WS for age, sex, and developmental level. All participants were administered the Autism Diagnostic Observation Schedule Module 1 and the Mullen Scales of Early Learning. As a group, children with WS with limited language showed fewer sociocommunicative abnormalities than children with autism, about the same level as children with PDD-NOS, and more abnormalities in reciprocity social interaction than participants in the mixed etiology group. Examination of the subgroup of participants with WS matched and compared with children with PDD-NOS indicated that half of the children showed fewer abnormalities than their individual matches with PDD-NOS, whereas half of the children with WS showed more abnormalities than their matches with PDD-NOS. Sociocommunicative difficulties are present for many children with WS and overlap with the autism spectrum. The results of this investigation suggest that these abnormalities are not accounted for by developmental delay alone, and care should be taken to avoid diagnostic overshadowing in young children with WS.
    Journal of developmental and behavioral pediatrics: JDBP 09/2009; 30(4):289-99. DOI:10.1097/DBP.0b013e3181ad1f9a · 2.12 Impact Factor
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    ABSTRACT: Adaptive social skills were assessed longitudinally at approximately ages 2, 3, 5, 9, and 13 years in a sample of 192 children with a clinical diagnosis of autism (n = 93), PDD-NOS (n = 51), or nonspectrum developmental disabilities (n = 46) at age 2. Growth curve analyses with SAS proc mixed were used to analyze social trajectories over time. Both individual characteristics and environmental resources emerged as key predictors of adaptive social behavior outcome. The gap between children with autism and the other two diagnostic groups widened with time as the social skills of the latter groups improved at a higher rate. However, within diagnostic groups, improvement ranged from minimal to very dramatic. Children with autism most at risk for problems with social adaptive abilities later in life can be identified with considerable accuracy at a very young age so they can be targeted for appropriate early intervention services.
    Journal of Abnormal Child Psychology 07/2009; 37(7):1019-34. DOI:10.1007/s10802-009-9326-0 · 3.09 Impact Factor

Publication Stats

22k Citations
1,039.96 Total Impact Points

Institutions

  • 2011–2015
    • Weill Cornell Medical College
      • Department of Psychiatry
      New York, New York, United States
    • Cincinnati Children's Hospital Medical Center
      Cincinnati, Ohio, United States
  • 2013–2014
    • Columbia University
      New York, New York, United States
    • Florida State University
      Tallahassee, Florida, United States
  • 2004–2014
    • University of Michigan
      • Department of Psychology
      Ann Arbor, Michigan, United States
    • University of California, San Diego
      San Diego, California, United States
  • 2007–2013
    • Cornell University
      Итак, New York, United States
    • Alliant International University
      Los Angeles, California, United States
    • California State University, Northridge
      Northridge, Ohio, United States
  • 2011–2012
    • New York Presbyterian Hospital
      • Center for Autism and the Developing Brain
      New York, New York, United States
  • 2010–2012
    • University of Pittsburgh
      • Department of Psychiatry
      Pittsburgh, PA, United States
  • 2007–2011
    • Center for Autism and Related Disorders
      Burbank, California, United States
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 1994–2006
    • University of Chicago
      • Department of Human Genetics
      Chicago, Illinois, United States
  • 2001
    • Dartmouth Medical School
      • Department of Psychiatry
      Hanover, NH, United States
  • 1997–2000
    • 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
  • 1989–1990
    • Glenrose Rehabilitation Hospital
      Edmonton, Alberta, Canada
    • University of Alberta
      • Department of Pediatrics
      Edmonton, Alberta, Canada