Intermediate phenotypes and genetic mechanisms of psychiatric disorders
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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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.”
From Parsing Heterogeneity in Autism Spectrum Disorders: Visual Scanning of Dynamic Social Scenes in School-Aged Children (2012) · cites this paper as [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).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [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).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [2]
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).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [2]
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“The lack of a genotype effect on baseline WM performance may be attributed to a lack of sensitivity at a behavioral level (Meyer-Lindenberg and Weinberger, 2006).”
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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
- Licence
- www.springer.com/tdm (tdm)
- 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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