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Schizophrenia Bulletin Advance Access originally published online on May 17, 2006
Schizophrenia Bulletin 2006 32(3):507-524; doi:10.1093/schbul/sbj078
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© The Author 2006. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Neuropsychological Functioning in Adolescents and Young Adults at Genetic Risk for Schizophrenia and Affective Psychoses: Results from the Harvard and Hillside Adolescent High Risk Studies

Larry J. Seidman1,2–4, Anthony J. Giuliano2, Christopher W. Smith5, William S. Stone2,4, Stephen J. Glatt6,7, Eric Meyer2, Stephen V. Faraone8, Ming T. Tsuang2–4,6 and Barbara Cornblatt5
2 Department of Psychiatry, Harvard Medical School, Massachusetts Mental Health Center Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA
3 Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston
4 Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, MA
5 Department of Psychiatry Research, Zucker Hillside Hospital, North Shore–Long Island Jewish Health System (NSLIJHS), Glen Oaks, NY
6 Department of Psychiatry, Center for Behavior Genomics, University of California, San Diego, La Jolla, CA
7 Veterans Medical Research Foundation, San Diego, CA
8 Medical Genetics Research Center and Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY

1To whom correspondence should be addressed; e-mail: lseidman{at}bidmc.harvard.edu

Siblings and offspring of persons with schizophrenia carry elevated genetic risk for the illness and manifest attentional and memory impairments. Because less is known about other neuropsychological functions and their specificity in adolescents, we conducted a genetic high-risk (HR) study of schizophrenia (HR-SCZ) and affective psychosis (HR-AFF). Participants (ages 12–25) were from the Harvard Adolescent High-Risk and Hillside Family studies, including 73 HR-SCZ, 18 HR-AFF, and 84 community controls (CCs) recruited in metropolitan Boston and New York. Groups were compared on overall neurocognitive functioning, 6 domains, and 13 test scores, controlling for age, parental education, and correlated data within families. The HR-SCZ group was significantly impaired overall, while the HR-AFF group demonstrated a trend toward overall impairment. HR-SCZ subjects showed significantly lower Verbal Ability (d = .73) and Executive Functioning/Working Memory (d = .47) than CCs. HR-AFF subjects showed reduced Verbal Ability (d = .64) compared to CCs. Excluding 12 CCs with a parental history of depression (without psychosis) led to larger differences between HR and CC groups across domains. Moreover, HR-SCZ and CC group differences in Verbal Memory (d = .39) and Visual-Spatial (d = .34) became statistically significant. There were no significant differences between HR-SCZ and HR-AFF groups. Data support a modest neuropsychological deficit in persons at genetic HR for psychosis, with a broader range of deficits in HR-SCZ. Future work should assess the relationship of neurocognition to adaptive functioning and possible onset of psychosis in HR samples. Ascertainment criteria for controls may markedly influence results and interpretation of group differences.

Keywords: schizophrenia / affective psychoses / genetics / neurocognition / intelligence


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