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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References
Hippocampal Volume Is Reduced in Schizophrenia and Schizoaffective Disorder But Not in Psychotic Bipolar I Disorder Demonstrated by Both Manual Tracing and Automated Parcellation (FreeSurfer)
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TL;DR: Findings from a large psychosis sample support decreased hippocampal volume as a putative biomarker for schizophrenia and schizoaffective disorder, but not for psychotic bipolar I disorder, and may reflect a cumulative effect of divergent primary disease processes and/or lifetime medication use.
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Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis.
Richard S.E. Keefe,Larry J. Seidman,Bruce K. Christensen,Robert M. Hamer,Tonmoy Sharma,Margriet M. Sitskoorn,Stephanie L. Rock,Sandra Woolson,Mauricio Tohen,Gary D. Tollefson,Todd M. Sanger,Jeffrey A. Lieberman +11 more
TL;DR: Both antipsychotic agents appeared to improve neurocognitive functioning among first-episode psychosis patients with schizophrenia.
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Intelligence quotient and Neuropsychological profiles in patients with schizophrenia and in normal volunteers
William S. Kremen,William S. Kremen,Larry J. Seidman,Larry J. Seidman,Stephen V. Faraone,Stephen V. Faraone,Ming T. Tsuang,Ming T. Tsuang +7 more
TL;DR: The results strengthen the argument that neurocognitive deficits are core deficits of schizophrenic illness, as neuropsychological patterns in schizophrenia tend to be consistent at different IQ levels.
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Longitudinal Volume Reductions in People at High Genetic Risk of Schizophrenia as They Develop Psychosis
Andrew M. McIntosh,David G. C. Owens,William J. Moorhead,Heather C. Whalley,Andrew C. Stanfield,Jeremy Hall,Eve C. Johnstone,Stephen M. Lawrie +7 more
TL;DR: People at high genetic risk of schizophrenia had significantly greater reductions over time than the control group for whole brain volume and left and right prefrontal and temporal lobes and these changes were significantly associated with increasing severity of psychotic symptoms.
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A comparison of cognitive structure in schizophrenia patients and healthy controls using confirmatory factor analysis
TL;DR: Cognitive ability, as reflected in test performance, appears to be more unitary in schizophrenia than in healthy subjects, and this finding may have measurement and treatment implications.
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