Individual differences in threat sensitivity predict serotonergic modulation of amygdala response to fearful faces

MRC Behavioural and Clinical Neuroscience Centre.
Psychopharmacology (Impact Factor: 3.88). 09/2005; 180(4):670-9. DOI: 10.1007/s00213-005-2215-5
Source: PubMed


In this study we used functional magnetic resonance imaging (fMRI) to examine the effects of acute tryptophan depletion (ATD), a well-recognised method for inducing transient cerebral serotonin depletion, on brain activation to fearful faces.
We predicted that ATD would increase the responsiveness of the amygdala to fearful faces as a function of individual variation in threat sensitivity.
Twelve healthy male volunteers received a tryptophan depleting drink or a tryptophan balancing amino acid drink (placebo) in a double-blind crossover design. Five hours after drink ingestion participants were scanned whilst viewing fearful, happy and neutral faces.
Consistent with previous findings, fearful faces induced significant signal change in the bilateral amygdala/hippocampus as well as the fusiform face area and the right dorsolateral prefrontal cortex. Furthermore, ATD modulated amygdala/hippocampus activation in response to fearful relative to happy faces as a function of self-reported threat sensitivity (as measured with the Behavioral Inhibition Scale; Carver CS, White TL (1994) Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: the BIS/BAS scales. J Pers Soc Psychol 67:319-333).
The data support the hypothesis that individual variation in threat sensitivity interacts with manipulation of 5-HT function to bias the processing of amygdala-dependent threat-relevant stimuli.

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    • "Facial displays of emotion have been heavily-used in this regard (Haxby et al., 2000; Phillips et al., 2003). Clinical populations shows comparable biases toward aversive relative to appetitive face across behavioral and neural dimensions (Blair et al., 2008; Roy et al., 2008), as do individuals with increased dispositional anxiety (Cools et al., 2005; Telzer et al., 2008). A wealth of research demonstrates that anxious individuals display an attention bias towards threatening sources of information, and this effect is less consistent or typically not observed in nonanxious individuals (Bar-Haim et al., 2007; Mogg and Bradley, 1998). "
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    ABSTRACT: Literacy: Many studies have been showing that anxious individuals display attention biases including preferential engagement, difficulty in disengagement, or attention avoidance. Research in patients suggests that pathological anxiety may specifically impair spatial short-term and long-term episodic memory. Recently, many authors have emphasized the role of aversive stimulation on attention, working memory and anxiety. Purpose: The present study investigated the influence of anxiety on memory and attention, to contribute to our understanding of the anxiety effects on cognitive function. Methods: 130 students were included in this study (57 male and 73 female). Procedure: Each subject completed the State-Trait Anxiety Inventory (STAI). After this measure, only 41 participants with the highest (n=21) and the lowest (n=20) levels of anxiety complete the Trail Making Test A-B, Attentive Matrices Test, Babcock Story Recall Test and Short-Term Visual Memory Test. Results: Less anxious participants showed best memory capacity and less attention biases than more anxious participants.
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    • "Although previous studies were not consistent in replication (negative association studies e.g.: Gillespie et al. 2005; Willis-Owen et al. 2005; Surtees et al. 2006), some studies provided evidence for an association of the 5-HTTLPR s-allele with traits related to neuroticism and anxiety hypothesized to be modulated by serotonin (Schinka et al. 2004; Sen et al. 2004; Gonda et al. 2009; Munafò et al. 2009) as well as psychiatric disorders, particularly affective disorders (Hauser et al. 2003; Lotrich and Pollock 2004; Lasky-Su et al. 2005; Dorado et al. 2007; Kiyohara and Yoshimasu 2010; Karg et al. 2011). Similar to altered amygdala response during face-emotion processing in anxiety prone subjects, some studies observed differences in amygdala activity in response to emotional faces when contrasting subjects taking selective 5-HT reuptake inhibitors compared to subjects taking placebos (Cools et al. 2005; Del- Ben et al. 2005; Harmer et al. 2006; Van der Veen et al. 2007). This points towards a pivotal role of 5-HT in emotional expression processing within the amygdala. "
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    ABSTRACT: The s/s-genotype of the 5-HTTLPR polymorphism and the personality trait of neuroticism have both been associated with experiences of negative affect, anxiety and mood disorders, as well as an emotional processing bias towards negative facial emotions. On a neural level, this bias can be characterized by altered amygdala and fusiform gyrus (FFG) activity during perception of negative facial expressions. Using resting-state functional magnetic resonance imaging in a multi-center-sample of 178 healthy subjects of European descent, this study investigated the association of 5-HTTLPR (short s- and long l-allele) including the genotype of the single nucleotide polymorphism (SNP) rs25531 (A/G) within this region polymorphism, and trait neuroticism on resting-state functional connectivity (rs-FC) between amygdala and the FFG. Moreover, we aimed to identify additional brain regions with associations of 5-HTTLPR/rs25531 (combined according to its expression; low: s/s; high: lA/lA; intermediate: s/lA, s/lG, lG/lG, lA/lG) and trait neuroticism to amygdala rs-FC. Separate analyses for 5-HTTLPR/rs25531 and neuroticism (controlling for age, gender, handedness, and research site) revealed that s/s-homozygotes and individuals high in neuroticism obtained altered amygdala rs-FC in the right occipital face area, which is considered to be a "core component" of the face processing system. Importantly, effects of neuroticism were replicated across three independent research sites. Additionally, associations of 5-HTTLPR/rs25531 genotype and amygdala rs-FC were observed in the anterior and posterior cingulate cortex, whereas neuroticism was not related to rs-FC in these areas. The presented data implies that 5-HTTLPR/rs25531 variants and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus and suggests that variants of 5-HTTLPR/rs25531 genotype and different levels of neuroticism may partly account for altered processing of negative facial emotions.
    Brain Structure and Function 05/2014; 220(4). DOI:10.1007/s00429-014-0782-0 · 5.62 Impact Factor
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    • "These findings are consistent with LumiVida™ increasing serotoninergic activity in pathways processing emotional stimuli, leading to a potential anti-depressant like activity of a shift in emotional processing away from negative bias (Bari et al. 2010). Importantly, we controlled for any influence of neuroticism here, as such a 'threat sensitivity' aspect of personality has been shown to interact with serotoninergic modulation of brain processing of emotional expressions (Cools et al. 2005). It is worth emphasising that, although the group receiving the effective 2 g dose was also the least neurotic and aggressive of the three groups, these personality differences were adjusted for by analysis of covariance , and either had no impact, or, if anything, strengthened the effect of that dose. "
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    ABSTRACT: Rationale Effective functioning of the neurotransmitter serotonin is important for optimal cognitive and emotional function. Dietary supplements able to increase availability to the brain of the precursor amino acid, tryptophan (TRP), and thereby enhance serotonin synthesis, can have measurable impact on these psychological processes. Objectives This study involves a randomised controlled trial of a TRP-rich egg-white protein hydrolysate (DSM Nutritional Products Ltd., Switzerland) on plasma amino acids, cognition, mood and emotional processing in older women. Methods Following a baseline test day without treatment, 60 healthy women aged 45–65 years received drinks containing either 2 or 4 g of TRP-rich protein hydrolysate product or 3.11 g casein hydrolysate as a control. One hour later, they undertook a 2-h battery of cognitive and emotional tests. Results The TRP-rich protein hydrolysate produced the expected dose-dependent increase in the ratio of plasma TRP to competing large neutral amino acids. TRP-rich protein hydrolysate (2 g only) prevented both the decline in wellbeing and increase in fatigue seen over the test session in the control group. This treatment dose resulted in a significant shift in emotional processing towards positive words and reduced negative bias in assessing negative facial expressions. Effects on cognition were small and not statistically reliable and are not reported here. However, there was no evidence for any adverse effects. Conclusions Consumption of a low dose of TRP-rich protein hydrolysate may have beneficial effects on emotional function that could promote feelings of wellbeing, possibly conferring resistance to deterioration in mood in healthy subjects or depressive episodes.
    Psychopharmacology 05/2014; 231(24). DOI:10.1007/s00213-014-3609-z · 3.88 Impact Factor
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