Reference Entry10.1002/9781119125556.DEVPSY224
Neuropsychological and Structural Neuroimaging Endophenotypes in Schizophrenia
16
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.
read more
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
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
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.
60
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.
56
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.
50
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.
31
References
Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia
Stephen M. Lawrie,Heather C. Whalley,Suheib S. Abukmeil,Julia N Kestelman,Lorna Donnelly,Patrick Miller,Jonathan J.K. Best,D. G. C. Owens,Eve C. Johnstone +8 more
TL;DR: The results suggest that some structural abnormalities in subjects at high risk of developing schizophrenia have abnormalities of brain structure similar to but not identical to those found in schizophrenia, and that the development of symptoms is associated with a third overlapping group of structural changes.
294
Effects of Olanzapine, Quetiapine, and Risperidone on Neurocognitive Function in Early Psychosis: A Randomized, Double-Blind 52-Week Comparison
Richard S.E. Keefe,John A. Sweeney,Hongbin Gu,Robert M. Hamer,Diana O. Perkins,Joseph P. McEvoy,Jeffrey A. Lieberman +6 more
TL;DR: Cognitive improvements were modest, their clinical importance was suggested by relationships with improvements in functional outcome, and Statistically significant relationships between improvements in neurocognition and functional outcome were observed.
292
General and specific cognitive deficits in schizophrenia: Goliath defeats David?
Dwight Dickinson,Dwight Dickinson,J. Daniel Ragland,James M. Gold,James M. Gold,Ruben C. Gur,Ruben C. Gur +6 more
TL;DR: The schizophrenia cognitive deficit is largely generalized across performance domains, with small, direct effects of diagnostic group confined to selected domains.
291
Left Hippocampal Volume as a Vulnerability Indicator for Schizophrenia A Magnetic Resonance Imaging Morphometric Study of Nonpsychotic First-Degree Relatives
Larry J. Seidman,Stephen V. Faraone,Jill M. Goldstein,William S. Kremen,Nicholas J. Horton,Nikos Makris,Rosemary Toomey,David N. Kennedy,Verne S. Caviness,Ming T. Tsuang +9 more
TL;DR: Findings suggest that smaller left hippocampi and verbal memory deficits are an expression of early neurodevelopmental compromise, reflecting the degree of genetic liability to schizophrenia.
280
Brain volumes in relatives of patients with schizophrenia - A meta-analysis
TL;DR: In this article, a systematic search was conducted to determine the magnitude and extent of brain volume differences in first-degree relatives of schizophrenic patients, and the largest difference between relatives and healthy control subjects was found in hippocampal volume, with relatives having smaller volumes than controls.
277