Amygdala Function and 5-HTT Gene Variants in Adolescent Anxiety and Major Depressive Disorder
Open accessAbstract
Background Associations between a functional polymorphism in the serotonin transporter gene and amygdala activation have been found in healthy, depressed, and anxious adults. This study explored these gene-brain associations in adolescents by examining predictive effects of serotonin transporter gene variants (S and L(G) allele carriers vs. L(A) allele homozygotes) and their interaction with diagnosis (healthy vs. patients) on amygdala responses to emotional faces.Methods Functional magnetic resonance data were collected from 33 healthy adolescents (mean age: 13.71, 55% female) and 31 medication-free adolescents with current anxiety or depressive disorders (or both; mean age: 13.58, 56% female) while viewing fearful, angry, happy, and neutral facial expressions under varying attention states.Results A significant three-way genotype-by-diagnosis-by-face-emotion interaction characterized right amygdala activity while subjects monitored internal fear levels. This interaction was decomposed to map differential gene-brain associations in healthy and affected adolescents. First, consistent with healthy adult data, healthy adolescents with at least one copy of the S or L(G) allele showed stronger amygdala responses to fearful faces than healthy adolescents without these alleles. Second, patients with two copies of the L(A) allele exhibited greater amygdala responses to fearful faces relative to patients with S or L(G) alleles. Third, although weaker, genotype differences on amygdala responses in patients extended to happy faces. All effects were restricted to the fear-monitoring attention state.Conclusions S/L(G) alleles in healthy adolescents, as in healthy adults, predict enhanced amygdala activation to fearful faces. Contrary findings of increased activation in patients with L(A)L(A) relative to the S or L(G) alleles require further exploration.
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Neuroimaging studies in children and adolescents with MDD show heightened amygdala and OFC activation in response to emotional facial expressions, though conflicting findings exist.
“Neuroimaging studies conducted in children and adolescents with MDD also show heightened activation in the amygdala 56,60,74 and OFC 74 in response to emotional facial expressions (for conflicting findings, see Thomas and colleagues 42 ).”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [60]
During passive viewing paradigms, patients with bipolar disorder and those with MDD demonstrate hypoactivity in the DLPFC and OFC and hyperactivity in the amygdala and anterior cingulate (subgenual and pregenual), although evidence is less consistent for subcortical regions such as the amygdala and paralimbic regions.
“During passive viewing paradigms, patients with bipolar disorder and those with MDD demonstrate hypoactivity in the DLPFC and OFC and hyperactivity in the amygdala and anterior cingulate (subgenual and pregenual), although evidence is less consistent for subcortical regions such as the amygdala and paralimbic regions.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [60]
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- Authors
- Lau, J. Y. F., Goldman, D., Buzas, B., Fromm, S. J., Guyer, A. E., Hodgkinson, C., Monk, C. S., Nelson, E. E., Shen, P.-H., Pine, D. S., & Ernst, M.
- Affiliations
- National Institutes of Health (US)
- University of Michigan (US)
- Corresponding author
- Lau, Jennifer Y.F.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 65
- Issue
- 4
- Pages
- 349-355
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2791528
- OpenAlex
- W2019633593
- Cited by
- 113
- References
- 53
- Citations by year
- 2025: 1 · 2022: 3 · 2021: 2 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 3 · 2013: 24 · 2012: 19
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- amygdala, serotonin transporter gene, 5-HTT polymorphism, adolescent anxiety, major depressive disorder, emotional face processing, fearful faces
- MeSH terms
- Adolescent, Amygdala, Anxiety, Major Depressive Disorder, DNA, Emotions, Facial Expression, Fear, Female, Genotype, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Psychiatric Status Rating Scales, Reaction Time, Social Perception, Serotonin Plasma Membrane Transport Proteins
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