Serotonin transporter genotype differentially modulates neural responses to emotional words following tryptophan depletion in patients recovered from depression and healthy volunteers
Open accessAbstract
Previous studies have suggested that polymorphism in the serotonin transporter gene (5-HTTLPR) influences responses to serotonergic manipulation, with opposite effects in patients recovered from depression (rMDD) and controls. Here we sought to clarify the neurocognitive mechanisms underpinning these surprising results. Twenty controls and 23 rMDD subjects completed the study; functional magnetic resonance imaging (fMRI) and genotype data were available for 17 rMDD subjects and 16 controls. Following tryptophan or sham depletion, subjects performed an emotional-processing task during fMRI. Although no genotype effects on mood were identified, significant genotype*diagnosis*depletion interactions were observed in the hippocampus and subgenual cingulate in response to emotionally valenced words. In both regions, tryptophan depletion increased responses to negative words, relative to positive words, in high-expression controls, previously identified as being at low-risk for mood change following this procedure. By contrast, in higher-risk low-expression controls and high-expression rMDD subjects, tryptophan depletion had the opposite effect. Increased neural responses to negative words following tryptophan depletion may reflect an adaptive mechanism promoting resilience to mood change following perturbation of the serotonin system, which is reversed in sub-groups vulnerable to developing depressive symptoms. However, this interpretation is complicated by our failure to replicate previous findings of increased negative mood following tryptophan depletion.
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Lowering brain serotonin using acute tryptophan depletion leads to an increased negative affective bias as a result of a change in the connectivity between mPFC and amygdala, which has been associated with the risk of depression.
“Lowering brain serotonin using acute tryptophan depletion leads to an increased negative affective bias as a result of a change in the connectivity between mPFC and amygdala (Robinson et al., 2013), which has been associated with the risk of depression (Roiser et al., 2012).”
From Social functioning in major depressive disorder (2016) · cites this paper as Roiser et al., 2012
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Self-citation
- Authors
- Roiser, J. P., Levy, J., Fromm, S. J., Goldman, D., Hodgkinson, C. A., Hasler, G., Sahakian, B. J., & Drevets, W. C.
- Affiliations
- National Institutes of Health (US)
- University of Cambridge (GB)
- ORCID
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2012-04-10
- Volume
- 26
- Issue
- 11
- Pages
- 1434-1442
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- PMC
- PMC3506165
- OpenAlex
- W2169077853
- Cited by
- 18
- References
- 47
- Citations by year
- 2024: 2 · 2023: 2 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 5 · 2014: 1
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- BORIS (University Library Bern) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (086041)
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (Z01AA000301, K24AA000301, Z01AA000306)
- National Institute of Mental Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- serotonin transporter gene, 5-HTTLPR, tryptophan depletion, remitted depression, emotional word processing, hippocampus, subgenual cingulate, serotonergic system, genetic polymorphism
- MeSH terms
- Adult, Affect, Major Depressive Disorder, Emotions, Female, Genotype, Gyrus Cinguli, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Polymorphism, Genetic, Tryptophan, Case-Control Studies, Serotonin Plasma Membrane Transport Proteins, Young Adult
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