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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 ,
Keith H. Nuechterlein ,
Catherine A. Sugar ,
Kenneth L. Subotnik ,
Thomas Kubarych ,
Michael C. Neale ,
Kenneth S. Kendler  and
Robert F. Asarnow
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
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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.

Keywords

Attentionchildhood-onset schizophreniaendophenotypesfacial memoryfamilial transmissionschizophreniaverbal learningverbal recognitionworking memory
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 10 , July 2020 , pp. 1672 - 1679
Copyright
Copyright © Cambridge University Press 2019

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References

American Psychiatric Association. & American Psychiatric Association. Work Group to Revise DSM-III (1987) Diagnostic and Statistical Manual of Mental Disorders : DSM-III-R. Washington, DC: American Psychiatric Association.Google Scholar
Andersson, F, Glaser, B, Spiridon, M, Debbane, M, Vuilleumier, P and Eliez, S (2008) Impaired activation of face processing networks revealed by functional magnetic resonance imaging in 22q11.2 deletion syndrome. Biological Psychiatry 63, 49–57.CrossRefGoogle ScholarPubMed
Army Individual Test Battery (1944) Army Individual Test Battery: Manual of Directions and Scoring. Washington, DC: War Department, Adjutant General's Office.Google Scholar
Asarnow, RF and MacCrimmon, DJ (1978) Residual performance deficit in clinically remitted schizophrenics: a marker of schizophrenia? Journal of Abnormnal Psychology 87, 597–608.CrossRefGoogle ScholarPubMed
Asarnow, RF, Nuechterlein, KH, Fogelson, D, Subotnik, KL, Payne, DA, Russell, AT, Asamen, J, Kuppinger, H and Kendler, KS (2001) Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study. Archives of General Psychiatry 58, 581–588.CrossRefGoogle ScholarPubMed
Bartfai, A, Pedersen, NL, Asarnow, RF and Schalling, D (1991) Genetic factors for the span of apprehension test: a study of normal twins. Psychiatry Research 38, 115–124.CrossRefGoogle ScholarPubMed
Beaty, TH and Liang, KY (1987) Robust inference for variance components models in families ascertained through probands: I. Conditioning on proband's phenotype. Genetic Epidemiology 4, 203–210.CrossRefGoogle ScholarPubMed
Bertisch, H, Li, D, Hoptman, MJ and DeLisi, LE (2010) Heritability estimates for cognitive factors and brain white matter integrity as markers Of schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 53B, 885–894.CrossRefGoogle Scholar
Blangero, J and Almasy, L (1996) Solar: sequential oligogenic linkage analysis routines. Population Genetics Laboratory Technical Report.Google Scholar
Calkins, ME, Gur, RC, Ragland, JD and Gur, RE (2005) Face recognition memory deficits and visual object memory performance in patients with schizophrenia and their relatives. American Journal of Psychiatry 162, 1963–1966.CrossRefGoogle ScholarPubMed
Delis, DC, Kramer, JH, Kaplan, E and Ober, BA (2000) Manual for the California Verbal Learning Test, (CVLT-II). San Antonio, TX: The Psychological Corporation.Google Scholar
Dougherty, CC, Evans, DW, Katuwal, GJ and Michael, AM (2016) Asymmetry of fusiform structure in autism spectrum disorder: trajectory and association with symptom severity. Molecular Autism 7, 28.CrossRefGoogle ScholarPubMed
Gottesman, II and Gould, TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636–645.CrossRefGoogle ScholarPubMed
Greenwood, TA, Braff, DL, Light, GA, Cadenhead, KS, Calkins, ME, Dobie, DJ, Freedman, R, Green, MF, Gur, RE, Gur, RC, Mintz, J, Nuechterlein, KH, Olincy, A, Radant, AD, Seidman, LJ, Siever, LJ, Silverman, JM, Stone, WS, Swerdlow, NR, Tsuang, DW, Tsuang, MT, Turetsky, BI and Schork, NJ (2007) Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia. Archives of General Psychiatry 64, 1242–1250.CrossRefGoogle Scholar
Greenwood, TA, Swerdlow, NR, Gur, RE, Cadenhead, KS, Calkins, ME, Dobie, DJ, Freedman, R, Green, MF, Gur, RC, Lazzeroni, LC, Nuechterlein, KH, Olincy, A, Radant, AD, Ray, A, Schork, NJ, Seidman, LJ, Siever, LJ, Silverman, JM, Stone, WS, Sugar, CA, Tsuang, DW, Tsuang, MT, Turetsky, BI, Light, GA and Braff, DL (2013) Genome-wide linkage analyses of 12 endophenotypes for schizophrenia from the consortium on the genetics of schizophrenia. American Journal of Psychiatry 170, 521–532.CrossRefGoogle Scholar
Greenwood, TA, Lazzeroni, LC, Calkins, ME, Freedman, R, Green, MF, Gur, RE, Gur, RC, Light, GA, Nuechterlein, KH, Olincy, A, Radant, AD, Seidman, LJ, Siever, LJ, Silverman, JM, Stone, WS, Sugar, CA, Swerdlow, NR, Tsuang, DW, Tsuang, MT, Turetsky, BI and Braff, DL (2016 a) Genetic assessment of additional endophenotypes from the consortium on the genetics of schizophrenia family study. Schizophrenia Research 170, 30–40.CrossRefGoogle Scholar
Greenwood, TA, Light, GA, Swerdlow, NR, Calkins, ME, Green, MF, Gur, RE, Gur, RC, Lazzeroni, LC, Nuechterlein, KH, Olincy, A, Radant, AD, Seidman, LJ, Siever, LJ, Silverman, JM, Stone, WS, Sugar, CA, Tsuang, DW, Tsuang, MT, Turetsky, BI, Freedman, R and Braff, DL (2016 b) Gating deficit heritability and correlation with increased clinical severity in schizophrenia patients With positive family history. American Journal of Psychiatry 173, 385–391.CrossRefGoogle ScholarPubMed
Gur, RE, Calkins, ME, Gur, RC, Horan, WP, Nuechterlein, KH, Seidman, LJ and Stone, WS (2007) The consortium on the genetics of schizophrenia: neurocognitive endophenotypes. Schizophrenia Bulletin 33, 49–68.CrossRefGoogle Scholar
Kendler, KS and Diehl, SR (1993) The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophrenia Bulletin 19, 261–285.CrossRefGoogle ScholarPubMed
Kendler, KS and Neale, MC (2009) ‘Familiality’ or heritability. Archives of General Psychiatry 66, 452–453.CrossRefGoogle ScholarPubMed
Kim, J, Glahn, DC, Nuechterlein, KH and Cannon, TD (2004) Maintenance and manipulation of information in schizophrenia: further evidence for impairment in the central executive component of working memory. Schizophrenia Research 68, 173–187.CrossRefGoogle ScholarPubMed
Kremen, WS, Panizzon, MS, Franz, CE, Spoon, KM, Vuoksimaa, E, Jacobson, KC, Vasilopoulos, T, Xian, H, McCaffery, JM, Rana, BK, Toomey, R, McKenzie, R and Lyons, MJ (2014) Genetic complexity of episodic memory: a twin approach to studies of aging. Psychology and Aging 29, 404–417.CrossRefGoogle Scholar
McCabe, KL, Marlin, S, Cooper, G, Morris, R, Schall, U, Murphy, DG, Murphy, KC and Campbell, LE (2016) Visual perception and processing in children with 22q11.2 deletion syndrome: associations with social cognition measures of face identity and emotion recognition. Journal of Neurodevelopmental Disorders 8, 30.CrossRefGoogle ScholarPubMed
Nuechterlein, KH, Parasuraman, R and Jiang, Q (1983) Visual sustained attention: image degradation produces rapid sensitivity decrement over time. Science 220, 327–329.CrossRefGoogle ScholarPubMed
Nuechterlein, KH, Edell, WS, Norris, M and Dawson, ME (1986) Attentional vulnerability indicators, thought disorder, and negative symptoms. Schizophrenia Bulletin 12, 408–426.CrossRefGoogle ScholarPubMed
Nuechterlein, KH, Dawson, ME, Gitlin, M, Ventura, J, Goldstein, MJ, Snyder, KS, Yee, CM and Mintz, J (1992) Developmental processes in schizophrenic disorders: longitudinal studies of vulnerability and stress. Schizophrenia Bulletin 18, 387–425.CrossRefGoogle ScholarPubMed
Nuechterlein, KH, Asarnow, RF, Subotnik, KL, Fogelson, DL, Payne, DL, Kendler, KS, Neale, MC, Jacobson, KC and Mintz, J (2002) The structure of schizotypy: relationships between neurocognitive and personality disorder features in relatives of schizophrenic patients in the UCLA family study. Schizophrenia Research 54, 121–130.CrossRefGoogle ScholarPubMed
Patriquin, MA, DeRamus, T, Libero, LE, Laird, A and Kana, RK (2016) Neuroanatomical and neurofunctional markers of social cognition in autism spectrum disorder. Human Brain Mapping 37, 3957–3978.CrossRefGoogle ScholarPubMed
Ramsay, MC and Reynolds, CR (1995) Separate digits tests: a brief history, a literature review, and a reexamination of the factor structure of the Test of Memory and Learning (TOMAL). Neuropsychology Reviews 5, 151–171.CrossRefGoogle Scholar
Shields, J and Gottesman, II (1972) Cross-national diagnosis of schizophrenia in twins. The heritability and specificity of schizophrenia. Archives of General Psychiatry 27, 725–730.CrossRefGoogle ScholarPubMed
Stone, WS, Giuliano, AJ, Tsuang, MT, Braff, DL, Cadenhead, KS, Calkins, ME, Dobie, DJ, Faraone, SV, Freedman, R, Green, MF, Greenwood, TA, Gur, RE, Gur, RC, Light, GA, Mintz, J, Nuechterlein, KH, Olincy, A, Radant, AD, Roe, AH, Schork, NJ, Siever, LJ, Silverman, JM, Swerdlow, NR, Thomas, AR, Tsuang, DW, Turetsky, BI and Seidman, LJ (2011) Group and site differences on the California verbal learning test in persons with schizophrenia and their first-degree relatives: findings from the Consortium on the Genetics of Schizophrenia (COGS). Schizophrenia Research 128, 102–110.CrossRefGoogle Scholar
Subotnik, KL, Nuechterlein, KH, Asarnow, RF, Fogelson, DL, Goldstein, MJ and Talovic, SA (1997) Depressive symptoms in the early course of schizophrenia: relationship to familial psychiatric illness. American Journal of Psychiatry 154, 1551–1556.CrossRefGoogle ScholarPubMed
Tulsky, DS, Zhu, J and Lebetter, M (1997) Wechsler Adult Intelligence Scale-(WAIS-III), Wechsler Memory Scale-Third Scale (WMS-III): Technical Manual. San Antonio, TX: Harcourt Brace.Google Scholar
Weigelt, S, Koldewyn, K and Kanwisher, N (2012) Face identity recognition in autism spectrum disorders: a review of behavioral studies. Neuroscience and Biobehavioral Reviews 36, 1060–1084.CrossRefGoogle ScholarPubMed