Serotonin transporter genotype differentially modulates neural responses to emotional words following tryptophan depletion in patients recovered from depression and healthy volunteers (original) (raw)
Related papers
The Effects of Tryptophan Depletion on Neural Responses to Emotional Words in Remitted Depression
Biological Psychiatry, 2009
Background-Major depressive disorder (MDD) has been associated with both dysfunction of the central serotonergic system and abnormal responses to emotional stimuli. We used acute tryptophan depletion (ATD) to investigate the effect of temporarily reducing brain serotonin synthesis on neural and behavioural responses to emotional stimuli in remitted MDD subjects (rMDD) and healthy controls.
Biological Psychology, 2008
Individual differences in brain response to emotional stimuli have previously been associated with gene variations within the serotonin transporter (5-HTT) and tryptophan hydroxylase-2 (TPH2) genes. We recently reported that these two genes exhibit an additive effect, based on recordings of event-related potentials (ERPs) from individuals viewing emotional scenes. The current study was designed to replicate and extent this initial report in an independent study sample, and use functional magnetic resonance imaging (fMRI) to identify specific neural loci that may mediate the 5-HTT-TPH2 additive effect. Furthermore, we sought to obtain convergent evidence for a gene-gene additive effect by collecting fMRI data from the same individuals engaged in two different cognitive-affective tasks, using emotional and neutral facial expressions and word stimuli. We found evidence for an additive effect of 5-HTT-TPH2 genotype, which was most robust in the putamen, a region rich in both 5-HTT and TPH2 protein, but was also observed in the amygdala at a less stringent threshold, and in other cortical regions. The additive effect was more robust effect for visuospatial than for verbal stimuli, and more robust for negatively than for positively valenced stimuli. These findings confirm and extend the additive effect of two critical genes in the serotonergic regulation of neural processing of affective stimuli, and identify the striatum as a critical site where is gene-gene regulation takes place. #
Social cognitive and affective neuroscience, 2013
A functional polymorphism within the serotonin transporter gene (5-HTTLPR) has been reported to modulate emotionality and risk for affective disorders. The short (S) allele has less functional efficacy than the long (L) allele and has been associated with enhanced emotional reactivity. One possible contributing factor to the high emotionality in S carriers may be inefficient use of cognitive strategies such as reappraisal to regulate emotional responses. The aim of the present study was to test whether the 5-HTTLPR genotype modulates the neural correlates of emotion regulation. To determine neural differences between S and L allele carriers during reappraisal of negative emotions, 15 homozygous S (S'/S') and 15 homozygous L (L'/L') carriers underwent functional magnetic resonance imaging (fMRI), while performing an instructed emotion regulation task including downregulation, upregulation and passive viewing of negative emotional pictures. Compared to L'/L' al...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2007
Polymorphism at the serotonin transporter linked polymorphic region (5-HTTLPR) has been associated with neuroticism, increased risk for affective disorders and greater vulnerability to mood change following serotonin (5-HT) depletion. The aim of the present study was to investigate whether the cognitive effects of 5-HT depletion were differentially affected by genotype at the 5-HTTLPR polymorphism, using neuropsychological measures of memory and attention. We utilized the acute tryptophan depletion (ATD) technique to temporarily reduce 5-HT synthesis in two groups of healthy volunteers pre-selected on the basis of 5-HTTLPR genotype, 15 of the ll genotype and 15 of the ss genotype, in a double-blind, placebo-controlled crossover design. As expected, ATD resulted in a robust reduction in plasma tryptophan concentration in both genotype groups. However, the genotype groups differed in terms of the effect of ATD on cognitive performance. The ss genotype group showed impaired verbal reca...
Neuropsychopharmacology, 2008
The processing of affective material is known to be modulated by serotonin (5-HT), but few studies have used neurophysiological measures to characterize the effect of changes in 5-HT on neural responses to emotional stimuli. We used functional magnetic resonance imaging to investigate the effect of acute tryptophan depletion, which reduces central 5-HT synthesis, on neural responses to emotionally-valenced verbal stimuli. Though no participants experienced significant mood change, emotional information processing was substantially modified following 5-HT depletion. A behavioral bias towards positive stimuli was attenuated following depletion, which was accompanied by increased haemodynamic responses during the processing of emotional words in several subcortical structures. Inter-individual differences in tryptophan depletion-elicited anxiety correlated positively with the caudate bias towards negative stimuli. These data suggest that 5-HT may play an important role in mediating automatic negative attentional biases in major depression, as well as resilience against negative distracting stimuli in never-depressed individuals.
Psychiatry Research, 2010
Selective serotonin reuptake inhibitors (SSRIs) are known to influence the information processing of emotional material in depressed patients and healthy controls. The functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to interact with the effectiveness of serotonin reuptake inhibitors. It is not known whether 5-HTTLPR has an influence on emotional processing in healthy controls. We report first data with long-term SSRI administration after genetic characterization of 5-HTTLPR in a randomized, double-blind, placebo-controlled, crossover design. In 30 healthy controls, 15 homozygous for the long and 15 for the short allele of 5-HTTLPR, emotionally valent images were used to elicit positive or negative emotions. We found a diminished perception of sad and fearful information under SSRI which was significant in the long allele group. These findings emphasize the importance of genetic variance in emotion processing research.
PLOS ONE, 2015
Serotonin transporter gene variants are known to interact with stressful life experiences to increase chances of developing affective symptoms, and these same variants have been shown to influence amygdala reactivity to affective stimuli in non-psychiatric populations. The impact of these gene variants on affective neurocircuitry in anxiety and mood disorders has been studied less extensively. Utilizing a triallelic assay (5-HTTLPR and rs25531) to assess genetic variation linked with altered serotonin signaling, this fMRI study investigated genetic influences on amygdala and anterior insula activity in 50 generalized anxiety disorder patients, 26 of whom also met DSM-IV criteria for social anxiety disorder and/or major depressive disorder, and 39 healthy comparison subjects. A Group x Genotype interaction was observed for both the amygdala and anterior insula in a paradigm designed to elicit responses in these brain areas during the anticipation of and response to aversive pictures. Patients who are S/L G carriers showed less activity than their L A /L A counterparts in both regions and less activity than S/L G healthy comparison subjects in the amygdala. Moreover, patients with greater insula responses reported higher levels of intolerance of uncertainty, an association that was particularly pronounced for patients with two L A alleles. A genotype effect was not established in healthy controls. These findings link the serotonin transporter gene to affective circuitry findings in anxiety and depression psychopathology and further suggest that its impact on patients may be different from effects typically observed in healthy populations.
Complex Psychiatry, 2015
Purpose: To study the brief and reversible mood response to acute tryptophan depletion (ATD) as a trait marker in subjects considered at risk for major depressive disorder (MDD). Procedures: ATD was administered to 64 subjects (54 European-Americans and 10 from other races) with a personal and family history of MDD. They were in remission and had been medication-free for at least 3 months. Subjects were randomly assignment to an active or sham condition in a double-blind crossover design. They were genotyped for serotonin-related candidate genes, and mood response was quantified with the Hamilton Depression Rating Scale (HDRS). Data were analyzed using Poisson regression with repeated measures and latent trajectory models. Results: Compared to the sham controls, active ATD caused modest depressive changes showing significant main effects of test condition (χ2 = 5.14, d.f. = 1, p = 0.023) and time (χ2 = 12.22, d.f. = 3, p = 0.007), but no significant interaction of time and test cond...
Cerebral Cortex, 2006
Prior studies reported that functional variants of both the serotonin transporter (5-HTT) and tryptophan hydroxylase-2 genes (TPH2), 2 key regulators of the serotonergic signaling pathway, modulate amygdala activation during emotional processing. We addressed the question whether these 2 gene variants modulate each other, using an emotional picture-processing task. Specifically, we measured event-related potentials (ERPs) during a passive emotional picture perception task, focusing on ERPs for the early posterior negativity (EPN) around 240 ms and for the slow wave starting at 315 ms. We found evidence for increased neural activity at 240 ms in individuals who carried 1 or 2 copies of the low-expression short variant of the 5-HTT. Carriers of T variant of the TPH2 also showed a tendency toward increased neural activity at 240 ms. Moreover, we observed an additive effect of both genotypes for EPN, with highest neural activity to emotional stimuli in individuals carrying combination of both short variant of 5-HTT and T variant of TPH2.