Serotonin transporter genotype differentially modulates neural responses to emotional words following tryptophan depletion in patients recovered from depression and healthy volunteers

Roiser, Jonathan P; Levy, Jamey; Fromm, Stephen J; Goldman, David; Hodgkinson, Colin A; Hasler, Gregor; Sahakian, Barbara J; Drevets, Wayne C (2012). Serotonin transporter genotype differentially modulates neural responses to emotional words following tryptophan depletion in patients recovered from depression and healthy volunteers. Journal of psychopharmacology, 26(11), pp. 1434-42. Los Angeles, Calif.: Sage Publications 10.1177/0269881112442789

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Healthcare Research
UniBE Contributor:	Hasler, Gregor
ISSN:	0269-8811
Publisher:	Sage Publications
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:24
Last Modified:	05 Dec 2022 14:07
Publisher DOI:	10.1177/0269881112442789
PubMed ID:	22495688
Web of Science ID:	000309839100005
URI:	https://boris.unibe.ch/id/eprint/8297 (FactScience: 213814)