Skip to main content Accessibility help
×
Home

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

  • Tim B. Bigdeli (a1) (a2), Keith H. Nuechterlein (a3) (a4), Catherine A. Sugar (a3) (a5), Kenneth L. Subotnik (a3), Thomas Kubarych (a2), Michael C. Neale (a2), Kenneth S. Kendler (a2) and Robert F. Asarnow (a3) (a4)...

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.

Copyright

Corresponding author

Author for correspondence: Keith H. Nuechterlein, E-mail: keithn@ucla.edu; Robert F. Asarnow, E-mail: rasarnow@mednet.ucla.edu

References

Hide All
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.
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, 4957.
Army Individual Test Battery (1944) Army Individual Test Battery: Manual of Directions and Scoring. Washington, DC: War Department, Adjutant General's Office.
Asarnow, RF and MacCrimmon, DJ (1978) Residual performance deficit in clinically remitted schizophrenics: a marker of schizophrenia? Journal of Abnormnal Psychology 87, 597608.
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, 581588.
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, 115124.
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, 203210.
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, 885894.
Blangero, J and Almasy, L (1996) Solar: sequential oligogenic linkage analysis routines. Population Genetics Laboratory Technical Report.
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, 19631966.
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.
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.
Gottesman, II and Gould, TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636645.
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, 12421250.
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, 521532.
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, 3040.
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, 385391.
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, 4968.
Kendler, KS and Diehl, SR (1993) The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophrenia Bulletin 19, 261285.
Kendler, KS and Neale, MC (2009) ‘Familiality’ or heritability. Archives of General Psychiatry 66, 452453.
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, 173187.
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, 404417.
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.
Nuechterlein, KH, Parasuraman, R and Jiang, Q (1983) Visual sustained attention: image degradation produces rapid sensitivity decrement over time. Science 220, 327329.
Nuechterlein, KH, Edell, WS, Norris, M and Dawson, ME (1986) Attentional vulnerability indicators, thought disorder, and negative symptoms. Schizophrenia Bulletin 12, 408426.
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, 387425.
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, 121130.
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, 39573978.
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, 151171.
Shields, J and Gottesman, II (1972) Cross-national diagnosis of schizophrenia in twins. The heritability and specificity of schizophrenia. Archives of General Psychiatry 27, 725730.
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, 102110.
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, 15511556.
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.
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, 10601084.

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed