Allelic variation in 5-HTTLPR and the effects of citalopram on the emotional neural network
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Background: Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, which selectively block serotonin transporter (5-HTT) activity, are widely used in the treatment of depression and anxiety disorders. Numerous neuroimaging studies have examined the effects of SSRIs on emotional processes. However, there are considerable inter-individual differences in SSRI effect, and a recent meta-analysis further revealed discrepant effects of acute SSRI administration on neural responses to negative emotions in healthy adults. Aims: We examined how a variant of the serotonin-transporter polymorphism (5-HTTLPR), which affects the expression and function of 5-HTT, influenced the acute effects of an SSRI (citalopram) on emotion-related brain activity in healthy adults. Method: Combining genetic neuroimaging, pharmacological technique and a psychological paradigm of emotion recognition, we scanned the short/short (s/s) and long/long (l/l) variants of 5-HTTLPR during perception of fearful, happy and neutral facial expressions after the acute administration of an SSRI (i.e. 30mg citalopram administered orally) or placebo administration. Results: We found that 5-HTTLPR modulated the acute effects of citalopram on neural responses to negative emotions. Specifically, relative to placebo, citalopram increased amygdala and insula activity in l/l but not s/s homozygotes during perception of fearful faces. Similar analyses of brain activity in response to happy faces did not show any significant effects. Conclusions: Our combined pharmacogenetic and functional imaging results provide a neurogenetic mechanism for discrepant acute effects of SSRIs.
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Amygdala activity was modulated following a single dose of citalopram in men homozygous for the long allele of the common polymorphism in the promotor region of the serotonin transporter gene (5HTTLPR), but not in those homozygous for the short allele.
“For example, a recent study found that amygdala activity was modulated following a single dose of citalopram in men homozygous for the long allele of the common polymorphism in the promotor region of the serotonin transporter gene (5HTTLPR), but not those who were homozygous for the short allele.56”
From The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment (2015) · cites this paper as [56]
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- Authors
- Ma, Y., Li, B., Wang, C., Zhang, W., Rao, Y., & Han, S.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Ma, Yina
- Venue
- British Journal of Psychiatry
- Publisher
- Royal College of Psychiatrists
- Published
- 2015-05
- Volume
- 206
- Issue
- 5
- Pages
- 385-392
- ISSN
- 0007-1250 (ISSN-L)
- 1472-1465
- OpenAlex
- W2118910004
- Cited by
- 23
- References
- 51
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 5 · 2015: 6
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The British Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (973 Program, 31421003, 91332125, 31421003, 31470986, 31470986, 91332125)
- Ministry of Education of the People's Republic of China (20130001110049)
- National Key Research and Development Program of China (2010CB833901, 2010CB833903.)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- 5-HTTLPR, serotonin transporter gene, citalopram, selective serotonin reuptake inhibitors, allelic variation, amygdala, insula, facial expression perception, fear, pharmacogenetics, anxiety
- MeSH terms
- Adolescent, Alleles, Amygdala, Emotions, Facial Expression, Fear, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Citalopram, Selective Serotonin Reuptake Inhibitors, Serotonin Plasma Membrane Transport Proteins, Young Adult, Healthy Volunteers
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