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Evidence of shared familial factors influencing neurocognitive endophenotypes in adult- and childhood-onset schizophrenia

Published online by Cambridge University Press:  31 July 2019

Tim B. Bigdeli
Affiliation:
Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, New York, USA Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
Keith H. Nuechterlein*
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA
Catherine A. Sugar
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA Department of Biostatistics, University of California Los Angeles, Los Angeles, CA, USA
Kenneth L. Subotnik
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA
Thomas Kubarych
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
Michael C. Neale
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
Kenneth S. Kendler
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
Robert F. Asarnow*
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA
*
Author for correspondence: Keith H. Nuechterlein, E-mail: keithn@ucla.edu; Robert F. Asarnow, E-mail: rasarnow@mednet.ucla.edu
Author for correspondence: Keith H. Nuechterlein, E-mail: keithn@ucla.edu; Robert F. Asarnow, E-mail: rasarnow@mednet.ucla.edu

Abstract

Background

The aggregation of neurocognitive deficits among the non-psychotic first-degree relatives of adult- and childhood-onset schizophrenia patients suggests that there may be a common etiology for these deficits in childhood- and adult-onset illness. However, there is considerable heterogeneity in the presentation of neurobiological abnormalities, and whether there are differences in the extent of familial transmission for specific domains of cognitive function has not been systematically addressed.

Methods

We employed variance components analysis, as implemented in SOLAR-Eclipse, to evaluate the evidence of familial transmission for empirically derived composite scores representing attention, working memory, verbal learning, verbal retention, and memory for faces. We contrast estimates for adult- and childhood-onset schizophrenia families and matched community control pedigrees, and compare our findings to previous reports based on analogous neurocognitive assessments.

Results

We observed varying degrees of familial transmission; attention and working memory yielded comparable, significant estimates for adult-onset and community control pedigrees; verbal learning was significant for childhood-onset and community control pedigrees; and facial memory demonstrated significant familial transmission only for childhood-onset schizophrenia. Model-fitting analyses indicated significant differences in familiality between adult- and childhood-onset schizophrenia for attention, working memory, and verbal learning.

Conclusions

By comprehensively assessing a wide range of neurocognitive domains in adult- and childhood-onset schizophrenia families, we provide additional support for specific neurocognitive domains as schizophrenia endophenotypes. Whereas comparable estimates of familial transmission for certain dimensions of cognitive functioning support a shared etiology of adult- and childhood-onset neurocognitive function, observed differences may be taken as preliminary evidence of partially divergent multifactorial architectures.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2019

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