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.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    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).
    Psychology and Aging 05/2015; DOI:10.1037/pag0000023 · 2.73 Impact Factor
  • Source
    Psychology and Aging 01/2015; · 2.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Declarative memory (DM) impairments are reported in schizophrenia and in unaffected biological relatives of patients. However, the neural correlates of successful and unsuccessful encoding, mediated by the medial temporal lobe (MTL) memory system, and the influence of disease-related genetic liability remain under explored. This study employed an event-related functional MRI paradigm to compare activations for successfully and unsuccessfully encoded associative face-name stimuli between 26 schizophrenia patients (mean age: 33, 19m/7f), 30 controls (mean age: 29, 24m/6f), and 14 unaffected relatives of patients (mean age: 40, 5m/9f). Compared to controls or unaffected relatives, patients showed hyper-activations in ventral visual stream and temporo-parietal cortical association areas when contrasting successfully encoded events to fixation. Follow-up hippocampal regions-of-interest analysis revealed schizophrenia-related hyper-activations in the right anterior hippocampus during successful encoding; contrasting successful versus unsuccessful events produced schizophrenia-related hypo-activations in the left anterior hippocampus. Similar hippocampal hypo-activations were observed in unaffected relatives during successful versus unsuccessful encoding. Post hoc analyses of hippocampal volume showed reductions in patients, but not in unaffected relatives compared to controls. Findings suggest that DM encoding deficits are attributable to both disease-specific and genetic liability factors that impact different components of the MTL memory system. Hyper-activations in temporo-occipital and parietal regions observed only in patients suggest the influence of disease-related factors. Regional hyper- and hypo-activations attributable to successful encoding occurring in both patients and unaffected relatives suggest the influence of schizophrenia-related genetic liability factors. Copyright © 2014 Elsevier B.V. All rights reserved.
    Schizophrenia Research 12/2014; 161(2-3). DOI:10.1016/j.schres.2014.11.030 · 4.43 Impact Factor