Article

Genetic Architecture of Declarative Memory Implications for Complex Illnesses

1Departments of Psychiatry and Biobehavioral Sciences and Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA.
The Neuroscientist (Impact Factor: 7.62). 08/2011; 18(5):516-32. DOI: 10.1177/1073858411415113
Source: PubMed

ABSTRACT Why do memory abilities vary so greatly across individuals and cognitive domains? Although memory functions are highly heritable, what exactly is being genetically transmitted? Here we review evidence for the contribution of both common and partially independent inheritance of distinct aspects of memory function. We begin by discussing the assessment of long-term memory and its underlying neural and molecular basis. We then consider evidence for both specialist and generalist genes underlying individual variability in memory, indicating that carving memory into distinct subcomponents may yield important information regarding its genetic architecture. And finally we review evidence from both complex and single-gene disorders, which provide insight into the molecular mechanisms underlying the genetic basis of human memory function.

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Available from: Anderson Winkler, Jan 13, 2014
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    • "As already noted, these composites were also created without knowledge of the genetic architecture of the tests. However, episodic memory is a complex construct at both the phenotypic and genetic level (Bearden et al., 2012; Kremen et al., 2014; Papassotiropoulos & de Quervain, 2011). Here we used multivariate genetic approaches to understand more fully the complexity of age-related changes in episodic memory. "
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    ABSTRACT: Episodic memory is a complex construct at both the phenotypic and genetic level. Ample evidence supports age-related cognitive stability and change being accounted for by general and domain-specific factors. We hypothesized that general and specific factors would underlie change even within this single cognitive domain. We examined 6 measures from 3 episodic memory tests in a narrow age cohort at middle and late middle age. The factor structure was invariant across occasions. At both timepoints 2 of 3 test-specific factors (story recall, design recall) had significant genetic influences independent of the general memory factor. Phenotypic stability was moderate to high, and primarily accounted for by genetic influences, except for 1 test-specific factor (list learning). Mean change over time was nonsignificant for 1 test-level factor; 1 declined; 1 improved. The results highlight the phenotypic and genetic complexity of memory and memory change, and shed light on an understudied period of life. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
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    • "Thus the former would be expected to be involved in more pathways within and across diseases of the brain, whereas the latter would be expected to be more specific. The actual selection of the endophenotypes to study would depend upon a ranking system such as the one devised by Glahn et al. (2012) for major depressive disorder , or associated with the in-depth study of a candidate endophenotype such as declarative memory (Bearden et al., 2012), or with a specific pathology observed with brain imaging (e.g., Borgwardt & Fusar-Poli, 2012). The relationships between and among endophenotypes will emerge from empirical research that is not fettered by invalid assumptions about what actually goes with what. "
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    ABSTRACT: Endophenotypes, measurable components unseen by the unaided eye along the pathway between disease or other phenotypes and distal genomics, have emerged as an important concept in the study of complex neuropsychiatric diseases. The term was introduced to psychopathology in 1972 by Gottesman and Shields, and reinvigorated in 2003 by Gottesman and Gould. An endophenotype may be neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological (including configured self-report data) in nature. Endophenotypes represent simpler clues, in principle, to genetic underpinnings than the disease syndrome itself, thus promoting the prescient view embodied in the recent emphasis on new research domain criteria or RDoC that psychiatric diagnoses can be optimally deconstructed in ways that allow discovery of their etiology by focusing on endophenotypic dimensions rather than categories. Endophenotypes differ from other biomarkers in a number of ways, most importantly, they are heritable and thus not the consequence of disease. They are heuristic in the development of animal models of psychopathology. For example, genes implicated in humans can be knocked out or in to observe their effects on animal behaviors and their endophenotypes.Keywords:behavioral genetics;Gottesman, Irving;nature-nurture controversy;neuroscience;research domain criteria (RDoC);Shields, James;systems biology;bipolar;schizophrenia;suicide
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    • "As already noted, these composites were also created without knowledge of the genetic architecture of the tests. However, episodic memory is a complex construct at both the phenotypic and genetic level (Bearden et al., 2012; Kremen et al., 2014; Papassotiropoulos & de Quervain, 2011). Here we used multivariate genetic approaches to understand more fully the complexity of age-related changes in episodic memory. "
    Psychology and Aging 01/2015; · 2.73 Impact Factor
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