Neurocognitive performance in family-based and case-control studies of schizophrenia

Ruben C. Gur; David L. Braff; Monica E. Calkins; Dorcas J. Dobie; Robert Freedman; Michael F. Green; Tiffany A. Greenwood; Laura C. Lazzeroni; Gregory A. Light; Keith H. Nuechterlein; Ann Olincy; Allen D. Radant; Larry J. Seidman; Larry J. Siever; Jeremy M. Silverman; Joyce Sprock; William S. Stone; Catherine A. Sugar; Neal R. Swerdlow; Debby W. Tsuang; Ming T. Tsuang; Bruce I. Turetsky; Raquel E. Gur

doi:10.1016/j.schres.2014.10.049

Neurocognitive performance in family-based and case-control studies of schizophrenia

Ruben C. Gur, David L. Braff, Monica E. Calkins, Dorcas J. Dobie, Robert Freedman, Michael F. Green, Tiffany A. Greenwood, Laura C. Lazzeroni, Gregory A. Light, Keith H. Nuechterlein, Ann Olincy, Allen D. Radant, Larry J. Seidman, Larry J. Siever, Jeremy M. Silverman, Joyce Sprock, William S. Stone, Catherine A. Sugar, Neal R. Swerdlow, Debby W. TsuangMing T. Tsuang, Bruce I. Turetsky, Raquel E. Gur

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Background: Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. Methods: The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Results: Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Conclusions: Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs.

Original language	English
Pages (from-to)	17-23
Number of pages	7
Journal	Schizophrenia Research
Volume	163
Issue number	1-3
DOIs	https://doi.org/10.1016/j.schres.2014.10.049
State	Published - 1 Apr 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2014.

Funding

Dr. Green has been a consultant to AbbVie, Biogen, DSP, EnVivo/Forum and Roche, and he is on the scientific advisory board of Mnemosyne. He has received research funds from Amgen. Dr. Lazzeroni is an inventor on a patent application filed by Stanford University on genetic polymorphisms associated with depression. Dr. Light has served as a consultant for Astellas, Forum, and Neuroverse. Dr. Nuechterlein has received unrelated research support from Janssen Scientific Affairs, Genentech, and Brain Plasticity, Inc., and has consulted to Genentech, Otsuka, Janssen, and Brain Plasticity, Inc. Dr. Swerdlow has been a consultant for Genco Sciences, Ltd. All other authors declare that they have no conflict of interest. This work was supported by collaborative R01 grants from the National Institute of Mental Health . COGS-1 and COGS-2: MH065571 UCSD, MH065707 UCLA, MH065554 MSSM, MH065578 Penn, MH065558 Washington; COGS-1 Only: MH065588 Colorado, MH065562 Harvard; Seidman and Stone are on a subcontract for COGS-2; COGS-2 Only: MH86135 Stanford.

Funders	Funder number
Otsuka
National Institutes of Health
National Institute of Mental Health	R01MH086135, R01MH093383
Genentech
Janssen Pharmaceuticals
Janssen Scientific Affairs

Keywords

Ascertainment
Case-control
Family-based
Neurocognition
Schizophrenia

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.schres.2014.10.049

Cite this

Gur, R. C., Braff, D. L., Calkins, M. E., Dobie, D. J., Freedman, R., Green, M. F., Greenwood, T. A., Lazzeroni, L. C., Light, G. A., Nuechterlein, K. H., Olincy, A., Radant, A. D., Seidman, L. J., Siever, L. J., Silverman, J. M., Sprock, J., Stone, W. S., Sugar, C. A., Swerdlow, N. R., ... Gur, R. E. (2015). Neurocognitive performance in family-based and case-control studies of schizophrenia. Schizophrenia Research, 163(1-3), 17-23. https://doi.org/10.1016/j.schres.2014.10.049

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title = "Neurocognitive performance in family-based and case-control studies of schizophrenia",

abstract = "Background: Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. Methods: The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Results: Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Conclusions: Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs.",

keywords = "Ascertainment, Case-control, Family-based, Neurocognition, Schizophrenia",

author = "Gur, {Ruben C.} and Braff, {David L.} and Calkins, {Monica E.} and Dobie, {Dorcas J.} and Robert Freedman and Green, {Michael F.} and Greenwood, {Tiffany A.} and Lazzeroni, {Laura C.} and Light, {Gregory A.} and Nuechterlein, {Keith H.} and Ann Olincy and Radant, {Allen D.} and Seidman, {Larry J.} and Siever, {Larry J.} and Silverman, {Jeremy M.} and Joyce Sprock and Stone, {William S.} and Sugar, {Catherine A.} and Swerdlow, {Neal R.} and Tsuang, {Debby W.} and Tsuang, {Ming T.} and Turetsky, {Bruce I.} and Gur, {Raquel E.}",

note = "Publisher Copyright: {\textcopyright} 2014.",

year = "2015",

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doi = "10.1016/j.schres.2014.10.049",

language = "אנגלית",

volume = "163",

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Gur, RC, Braff, DL, Calkins, ME, Dobie, DJ, Freedman, R, Green, MF, Greenwood, TA, Lazzeroni, LC, Light, GA, Nuechterlein, KH, Olincy, A, Radant, AD, Seidman, LJ, Siever, LJ, Silverman, JM, Sprock, J, Stone, WS, Sugar, CA, Swerdlow, NR, Tsuang, DW, Tsuang, MT, Turetsky, BI & Gur, RE 2015, 'Neurocognitive performance in family-based and case-control studies of schizophrenia', Schizophrenia Research, vol. 163, no. 1-3, pp. 17-23. https://doi.org/10.1016/j.schres.2014.10.049

TY - JOUR

T1 - Neurocognitive performance in family-based and case-control studies of schizophrenia

AU - Gur, Ruben C.

AU - Braff, David L.

AU - Calkins, Monica E.

AU - Dobie, Dorcas J.

AU - Freedman, Robert

AU - Green, Michael F.

AU - Greenwood, Tiffany A.

AU - Lazzeroni, Laura C.

AU - Light, Gregory A.

AU - Nuechterlein, Keith H.

AU - Olincy, Ann

AU - Radant, Allen D.

AU - Seidman, Larry J.

AU - Siever, Larry J.

AU - Silverman, Jeremy M.

AU - Sprock, Joyce

AU - Stone, William S.

AU - Sugar, Catherine A.

AU - Swerdlow, Neal R.

AU - Tsuang, Debby W.

AU - Tsuang, Ming T.

AU - Turetsky, Bruce I.

AU - Gur, Raquel E.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Background: Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. Methods: The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Results: Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Conclusions: Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs.

AB - Background: Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. Methods: The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Results: Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Conclusions: Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs.

KW - Ascertainment

KW - Case-control

KW - Family-based

KW - Neurocognition

KW - Schizophrenia

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Neurocognitive performance in family-based and case-control studies of schizophrenia

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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