Cited by 1,216Schizophrenia research and treatmentGenetic Associations and EpidemiologyNeurotransmitter Receptor Influence on Behavior

Intermediate phenotypes and genetic mechanisms of psychiatric disorders

Meyer-Lindenberg, Andreas, Weinberger, Daniel R.·2006·Nature reviews. Neuroscience

Abstract

Genes are major contributors to many psychiatric diseases, but their mechanisms of action have long seemed elusive. The intermediate phenotype concept represents a strategy for characterizing the neural systems affected by risk gene variants to elucidate quantitative, mechanistic aspects of brain function implicated in psychiatric disease. Using imaging genetics as an example, we illustrate recent advances, challenges and implications of linking genes to structural and functional variation in brain systems related to cognition and emotion.

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Crossref · 10.1038/nrn1993

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97 of 97 references verified0 citation errors · 0 not checkable

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  • Developmental cognitive science could serve as a link between molecular pathobiology and clinical behavior.

    “It is in this context that developmental cognitive science may provide the necessary bridge between molecular pathobiology and clinical behavior 6-7.”
  • The COMT enzyme mediates the degradation of catecholamines, in particular dopamine.

    “The gene coding for the catechol-O-methyltransferase (COMT) enzyme, which mediates the degradation of catecholamines, in particular dopamine, has attracted considerable attention as a promising candidate gene for studying variance in cognitive function and mental illness (1,2).”
  • Met/Met adults are thought to be near the apex of the inverted U curve, while Val carriers lie towards the lower end because of the increased dopamine metabolism rate associated with the Val allele.

    “Met/Met adults are thought to be near the apex of this curve, while Val carriers lay towards the lower end because of the increased dopamine metabolism rate associated with the Val allele (2,26,27).”
  • PFC functioning and WM performance have been suggested to follow an inverted-U curve function of dopamine levels, with adult rs4680 Met/Met individuals near the apex of this curve.

    “PFC functioning and WM performance have been suggested to follow an inverted-U curve function of dopamine levels (24), with adult rs4680 Met/Met individuals near the apex of this curve (2).”

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Authors
Meyer-Lindenberg, A., & Weinberger, D. R.
Affiliations
National Institutes of Health (US)
Corresponding author
Weinberger, Daniel R.
Venue
Nature reviews. Neuroscience
Published
2006-10
Volume
7
Issue
10
Pages
818-827
ISSN
  • 1471-003X (ISSN-L)
  • 1471-0048
OpenAlex
W2118136004
Cited by
1,216
References
97
Citations by year
2026: 14 · 2025: 20 · 2024: 23 · 2023: 18 · 2022: 31 · 2021: 54 · 2020: 78 · 2019: 58 · 2018: 36 · 2017: 56 · 2016: 75 · 2015: 93 · 2014: 88 · 2013: 85 · 2012: 97
FWCI
9.76
Type
journal article
Language
en
Open access
closed
Locations
  • Nature reviews. Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
endophenotypes, schizophrenia, imaging genetics, brain structure, brain function, cognition, emotions, neural systems
MeSH terms
Animals, Mental Disorders, Diagnostic Imaging, Genotype, Humans, Models, Genetic, Phenotype, Genetic Variation, Genetic Predisposition to Disease

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