Tryptophan depletion decreases the recognition of fear in female volunteers.

RATIONALE: Serotonergic processes have been implicated in the modulation of fear conditioning in humans, postulated to occur at the level of the amygdala. The processing of other fear-relevant cues, such as facial expressions, has also been associated with amygdala function, but an effect of serotonin depletion on these processes has not been assessed. OBJECTIVE: The present study investigated the effects of reducing serotonin function, using acute tryptophan depletion, on the recognition of basic facial expressions of emotions in healthy male and female volunteers. METHODS: A double-blind between-groups design was used, with volunteers being randomly allocated to receive an amino acid drink specifically lacking tryptophan or a control mixture containing a balanced mixture of these amino acids. Participants were given a facial expression recognition task 5 h after drink administration. This task featured examples of six basic emotions (fear, anger, disgust, surprise, sadness and happiness) that had been morphed between each full emotion and neutral in 10% steps. As a control, volunteers were given a famous face classification task matched in terms of response selection and difficulty level. RESULTS: Tryptophan depletion significantly impaired the recognition of fearful facial expressions in female, but not male, volunteers. This was specific since recognition of other basic emotions was comparable in the two groups. There was also no effect of tryptophan depletion on the classification of famous faces or on subjective state ratings of mood or anxiety. CONCLUSIONS: These results confirm a role for serotonin in the processing of fear related cues, and in line with previous findings also suggest greater effects of tryptophan depletion in female volunteers. Although acute tryptophan depletion does not typically affect mood in healthy subjects, the present results suggest that subtle changes in the processing of emotional material may occur with this manipulation of serotonin function

Tryptophan depletion alters the decision-making of healthy volunteers through altered processing of reward cues.

While accumulating evidence suggests that effective real-life decision-making depends upon the functioning of the orbitofrontal cortex, much less is known about the involvement of the monoamine neurotransmitter systems and, in particular, serotonin. In the present study, we explored the impact of depleting the serotonin precursor, tryptophan, on human decision-making. Eighteen healthy volunteers consumed an amino-acid drink containing tryptophan and 18 healthy volunteers consumed an amino-acid drink without tryptophan, before choosing between simultaneously presented gambles, differing in the magnitude of expected gains (ie reward), the magnitude of expected losses (ie punishment), and the probabilities with which these outcomes were delivered. Volunteers also chose between gambles probing identified non-nomative biases in human decision-making, namely, risk-aversion when choosing between gains and risk-seeking when choosing between losses. Tryptophan-depleted volunteers showed reduced discrimination between magnitudes of expected gains associated with different choices. There was little evidence that tryptophan depletion was associated with altered discrimination between the magnitudes of expected losses, or altered discrimination between the relative probabilities with which these positive or negative outcomes were delivered. Risk-averse and risk-seeking biases were also unchanged. These results suggest that serotonin mediates decision-making in healthy volunteers by modulating the processing of reward cues, perhaps represented within the orbitofrontal cortex. It is possible that such a change in the cognition mediating human choice is one mechanism associated with the onset and maintenance of anhedonia and lowered mood in psychiatric illness

Neural correlates of reward processing in adults with 22q11 deletion syndrome

BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission. The functional anatomy of the brain reward circuitry has not yet been investigated in 22q11DS. METHODS: This study aims to investigate neural activity during anticipation of reward and loss in adult patients with 22q11DS. We measured blood-oxygen-level dependent (BOLD) activity in 16 patients with 22q11DS and 12 healthy controls during a monetary incentive delay task using a 3T Philips Intera MRI system. Data were analysed using SPM8. RESULTS: During anticipation of reward, the 22q11DS group alone displayed significant activation in bilateral middle frontal and temporal brain regions. Compared to healthy controls, significantly less activation in bilateral cingulate gyrus extending to premotor, primary motor and somatosensory areas was found. During anticipation of loss, the 22q11DS group displayed activity in the left middle frontal gyrus and anterior cingulate cortex, and relative to controls, they showed reduced brain activation in bilateral (pre)cuneus and left posterior cingulate. Within the 22q11DS group, COMT Val hemizygotes displayed more activation compared to Met hemizygotes in right posterior cingulate and bilateral parietal regions during anticipation of reward. During anticipation of loss, COMT Met hemizygotes compared to Val hemizygotes showed more activation in bilateral insula, striatum and left anterior cingulate. CONCLUSIONS: This is the first study to investigate reward processing in 22q11DS. Our preliminary results suggest that people with 22q11DS engage a fronto-temporal neural network. Compared to healthy controls, people with 22q11DS primarily displayed reduced activity in medial frontal regions during reward anticipation. COMT hemizygosity affects responsivity of the reward system in this condition. Alterations in reward processing partly underlain by the dopamine system may play a role in susceptibility for psychosis in 22q11DS