Tryptophan depletion in normal volunteers produces selective impairments in learning and memory

Park, S.B.; Coull, Jennifer T.; McShane, Rupert; Young, Allan H.; Sahakian, Barbara J.; Robbins, Trevor W.; Cowen, Philip J.

doi:10.1016/0028-3908(94)90089-2

Cited by 302 publications

(331 citation statements)

References 46 publications

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“…This is consistent with the finding that effects of systemic serotonergic manipulations in human volunteers are not specific to the reversal stage of discrimination learning tasks, but extend to simple and compound discrimination learning stages of such tasks (Park et al, 1994;Rogers et al, 1999;Murphy et al, 2002;Chamberlain et al, 2006). In keeping with these findings, ATD enhanced the BOLD response to punishment in a probabilistic reversal-learning paradigm regardless of whether punishment led to switching (Evers et al, 2005).…”

Section: Discussionsupporting

confidence: 90%

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Cools

Robinson

Sahakian

2007

Neuropsychopharmacol

150

154

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Central serotonin (5-HT) has been implicated in emotional and behavioral control processes for many decades, but its precise contribution is not well understood. We used the acute tryptophan depletion procedure in young healthy volunteers to test the hypothesis that central 5-HT is critical for predicting punishment. An observational reversal-learning task was employed that provided separate measures of punishment and reward prediction. Under baseline, subjects made more prediction errors for punishmentassociated stimuli than for reward-associated stimuli. This bias was abolished after central 5-HT depletion, which enhanced the ability to predict punishment while not affecting reward prediction. The selective potentiation of punishment prediction concurs with recent theorizing, suggesting that central 5-HT carries a prediction error for future punishment, but not for future reward (Daw et al, 2002). Furthermore, the finding highlights the importance of central 5-HT in resilience to adversity and may have implications for a variety of neuropsychiatric disorders including depression and anxiety.

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Section: Discussionsupporting

confidence: 90%

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Cools

Robinson

Sahakian

2007

Neuropsychopharmacol

150

154

View full text Add to dashboard Cite

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“…In keeping with the hypothesis that 5-HT is critically involved in the processing of incentive signals, studies in humans have shown that depletion of central 5-HT impairs decision-making in gambling tasks, visual discrimination, and reversal learning, possibly due to deficits in (re)acquiring associations between stimulus and reward values (Park et al, 1994;Rogers et al, 1999Rogers et al, , 2003Murphy et al, 2002). A recent study revealed that 5-HT depletion in healthy volunteers impaired the ability to discriminate between large and small rewards (Rogers et al, 2003).…”

Section: Introductionmentioning

confidence: 85%

Tryptophan Depletion Disrupts the Motivational Guidance of Goal-Directed Behavior as a Function of Trait Impulsivity

Cools

Blackwell

Clark

et al. 2005

Neuropsychopharmacol

140

145

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Serotonin (5-HT) is well known to affect the motivational properties of stimuli predictive of rewards as well as the inhibitory control of behavior. Here, central 5-HT depletion was induced by the acute tryptophan (TRP) depletion (ATD) procedure in young healthy volunteers to examine the role of 5-HT in motivated action and prepotent response inhibition. A novel reaction-time task, tailored to individual differences in general cognitive speed, was employed to measure the guidance of behavior by motivationally relevant signals predictive of reinforcement likelihood, while the stop-signal reaction-time task was used to measure response inhibition. Following the TRP-balancing control drink, cues predictive of high-reinforcement certainty induced faster, but less accurate responses compared with cues predictive of lower reinforcement certainty. Depletion of central 5-HT modulated this coupling between motivation and action by slowing responses and increasing accuracy as a function of incentive certainty. These effects of ATD on motivated action correlated highly with individual differences in the personality trait of Nonplanning Impulsiveness (Barratt Impulsivity Scale (BIS-11)), so that strongest effects on motivated action were observed in high-impulsive individuals. By contrast, ATD left unaltered the ability to inhibit prepotent responses. Our findings may have implications for a variety of neuropsychiatric disorders including impulsive aggressive disorders and depression.

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“…[19][20][21] In addition, it has been reported that tryptophan depletion, the essential amino acid for brain serotonin synthesis, impairs learning and memory in healthy controls. 22 Pharmacological studies have also provided insight into the role of serotonin in ADHD susceptibility. Although the most effective treatments for ADHD are based on the administration of stimulant drugs, there is evidence that some serotonin agonists, including selective serotonin reuptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors, also reduce ADHD symptoms.…”

Section: Introductionmentioning

confidence: 99%

Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB

et al. 2007

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Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in which different genetic and environmental susceptibility factors are involved. Several lines of evidence support the view that at least 30% of ADHD patients diagnosed in childhood continue to suffer the disorder during adulthood and that genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. Genetic, biochemical and pharmacological studies support the idea that the serotonin system participates in the etiology of ADHD. Based on these data, we aimed to analyze single nucleotide polymorphisms across 19 genes involved in the serotoninergic neurotransmission in a clinical sample of 451 ADHD patients (188 adults and 263 children) and 400 controls using a population-based association study. Several significant associations were found after correcting for multiple testing: (1) the DDC gene was strongly associated with both adulthood (P = 0.00053; odds ratio (OR) = 2.17) and childhood ADHD (P = 0.0017; OR = 1.90); (2) the MAOB gene was found specifically associated in the adult ADHD sample (P = 0.0029; OR = 1.90) and (3) the 5HT2A gene showed evidence of association only with the combined ADHD subtype both in adults (P = 0.0036; OR = 1.63) and children (P = 0.0084; OR = 1.49). Our data support the contribution of the serotoninergic system in the genetic predisposition to ADHD, identifying common childhood and adulthood ADHD susceptibility factors, associations that are specific to ADHD subtypes and one variant potentially involved in the continuity of the disorder throughout lifespan.

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Tryptophan depletion in normal volunteers produces selective impairments in learning and memory

Cited by 302 publications

References 46 publications

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Tryptophan Depletion Disrupts the Motivational Guidance of Goal-Directed Behavior as a Function of Trait Impulsivity

Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB

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