Reference Entry10.1002/9781119125556.DEVPSY224
Neuropsychological and Structural Neuroimaging Endophenotypes in Schizophrenia
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TL;DR: This chapter reviews neuropsychological and structural neuroimaging endophenotypes for schizophrenia and for schizophrenia spectrum disorders, with an emphasis on key conceptual criteria for assessing endophenotype relationships, including their relationships to schizophrenia, to non-psychotic relatives, and to heritability.
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Abstract: The limits of the current diagnostic systems have led to a variety of efforts to identify alternate expressions of mental disorders that are broader than the DSM or ICD diagnostic criteria needed to diagnose them (e.g., Research Diagnostic Criteria, or RDoC). These newer approaches reflect a growing consensus that characterizing multiple, dimensional phenotypes can advance the search for identifying etiological or modulatory factors of psychiatric disorders. Moreover, the failure of Mendelian genetics to make progress in psychiatric disorders has led some to propose an alternative genetic focus on the traits associated with illnesses rather than on the diagnosis per se. These alternate phenotypes or endophenotypes (e.g., neuroanatomical, psychophysiological or neuropsychological abnormalities) of disorders may be more specific and amenable to objective measurement than clinical symptoms, and presumably reflect variation among smaller numbers of genes than more complex, clinical symptoms that are hypothesized to be more distal from their genetic origins. This has led to a dramatic growth of using endophenotypes in genetic studies, and consideration of their potential usefulness in the development of targets for early interventions. In this chapter, we review neuropsychological and structural neuroimaging endophenotypes for schizophrenia and for schizophrenia spectrum disorders, with an emphasis on key conceptual criteria for assessing endophenotypes, including their relationships to schizophrenia, to non-psychotic relatives, and to heritability. Future directions for establishing the validity of endophenotype research are also discussed.
Keywords:
endophenotypes;
neuropsychological markers;
neuroimaging markers;
structural magnetic resonance imaging (sMRI);
memory;
executive function;
attention;
schizophrenia
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Citations
Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis.
Gabriëlla A.M. Blokland,Gabriëlla A.M. Blokland,Raquelle I. Mesholam-Gately,Raquelle I. Mesholam-Gately,Timothea Toulopoulou,Timothea Toulopoulou,Timothea Toulopoulou,Elisabetta C. del Re,Elisabetta C. del Re,Max Lam,Lynn E. DeLisi,Lynn E. DeLisi,Gary Donohoe,Gary Donohoe,James T.R. Walters,Larry J. Seidman,Larry J. Seidman,Tracey L. Petryshen,Tracey L. Petryshen +18 more
TL;DR: Heritability estimates were comparable in nonpsychiatric and schizophrenia samples, suggesting that environmental factors and illness-related moderators do not substantially decrease heritability in schizophrenic samples, and that genetic studies in schizophrenia samples are informative for elucidating the genetic basis of cognitive deficits.
Factor structure and heritability of endophenotypes in schizophrenia: findings from the Consortium on the Genetics of Schizophrenia (COGS-1).
Larry J. Seidman,Larry J. Seidman,Gerhard Hellemann,Keith H. Nuechterlein,Tiffany A. Greenwood,David L. Braff,David L. Braff,Kristin S. Cadenhead,Monica E. Calkins,Robert Freedman,Raquel E. Gur,Ruben C. Gur,Laura C. Lazzeroni,Gregory A. Light,Gregory A. Light,Ann Olincy,Allen D. Radant,Allen D. Radant,Larry J. Siever,Jeremy M. Silverman,Joyce Sprock,William S. Stone,William S. Stone,Catherine A. Sugar,Neal R. Swerdlow,Debby W. Tsuang,Debby W. Tsuang,Ming T. Tsuang,Ming T. Tsuang,Bruce I. Turetsky,Michael F. Green +30 more
TL;DR: Neurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia.
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Neurodegenerative model of schizophrenia: Growing evidence to support a revisit
William S. Stone,Michael R. Phillips,Lawrence H. Yang,Lawrence S. Kegeles,Ezra Susser,Jeffrey A. Lieberman +5 more
TL;DR: In this paper , a neurodegenerative hypothesis was proposed to explain some features of chronic schizophrenia, including accelerated aging, than is provided by neurodevelopmental hypotheses, including cognitive and biological integrity.
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Neural correlates of cognitive deficits across developmental phases of schizophrenia
Sinead Kelly,Synthia Guimond,Amanda E. Lyall,William S. Stone,Martha E. Shenton,Matcheri S. Keshavan,Larry J. Seidman +6 more
TL;DR: It is suggested that most cognitive domains are affected across the developmental trajectory of schizophrenia, with corresponding brain structural and/or functional differences.
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Cognitive dysfunction in a psychotropic medication-naïve, clinical high-risk sample from the ShangHai-At-Risk-for-Psychosis (SHARP) study: Associations with clinical outcomes.
HuiRu Cui,Anthony J. Giuliano,Tianhong Zhang,LiHua Xu,YanYan Wei,Yingying Tang,Zhenying Qian,Lena Stone,Huijun Li,Susan Whitfield-Gabrieli,Margaret A. Niznikiewicz,Matcheri S. Keshavan,Martha E. Shenton,Jijun Wang,William S. Stone +14 more
TL;DR: Outcome stratification into remission, symptomatic and poor groups was associated with increasing cognitive deficits in learning and processing speed, and these findings support cross-cultural generalizability and advance understanding of CHR neurocognitive heterogeneity associated with 1-year clinical outcomes.
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Neurocognitive Endophenotypes in a Multiplex Multigenerational Family Study of Schizophrenia
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TL;DR: Examination of computerized neurocognitive measures as candidate endophenotypic markers of liability for schizophrenia in a genetically informative cohort found probands demonstrated greatest impairment relative to comparison subjects, followed by family members.
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Widespread Reductions of Cortical Thickness in Schizophrenia and Spectrum Disorders and Evidence of Heritability
Aaron L. Goldman,Lukas Pezawas,Venkata S. Mattay,Bruce Fischl,Bruce Fischl,Beth A. Verchinski,Qiang Chen,Daniel R. Weinberger,Andreas Meyer-Lindenberg +8 more
TL;DR: The present study provides the first evidence of broadly distributed and heritable reductions of cortical thickness alterations in schizophrenia, since only trend-level reductions of thickness were observed in siblings, and cortical thickness per se is not a strong intermediate phenotype for schizophrenia.
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Attention-deficit/hyperactivity disorder endophenotypes.
Alysa E. Doyle,Erik G. Willcutt,Larry J. Seidman,Larry J. Seidman,Joseph Biederman,Virginie-Anne Chouinard,Julie M. Silva,Stephen V. Faraone +7 more
TL;DR: Existing data on potential endophenotypes for ADHD are reviewed, emphasizing neuropsychological deficits because assessment tools are cost effective and relatively easy to implement, and it is concluded that these endophenotype will not be a quick fix for the field but offer potential if careful consideration is given to issues of heterogeneity, measurement and statistical power.
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Are endophenotypes based on measures of executive functions useful for molecular genetic studies of ADHD
Alysa E. Doyle,Stephen V. Faraone,Larry J. Seidman,Erik G. Willcutt,Joel T. Nigg,Irwin D. Waldman,Bruce F. Pennington,Joanne Peart,Joseph Biederman +8 more
TL;DR: Evidence supporting the use of deficits on neurocognitive measures of executive functions for ADHD is reviewed and empirical strategies that may be necessary to allow such research to progress prior to full resolution of the pathophysiological basis of ADHD are discussed.
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