Tryptophan as an evolutionarily conserved signal to brain serotonin: Molecular evidence and psychiatric implications (original) (raw)
Related papers
The effect of tryptophan on quarrelsomeness, agreeableness, and mood in everyday life
International Congress Series, 2007
In humans there is an association between low serotonin levels and aggressive behavior, and drugs that increase serotonin function have been used to treat aggression. In monkey alterations in serotonin function seem to influence behavior along the agonistic-affiliative axis, with increases in serotonin function not only decreasing aggression but also increasing the grooming of other animals. Measurement of human social behavior in everyday life has advanced to the stage where it is possible to measure behavior along the agreeable-quarrelsome axis. Therefore we performed two double-blind cross-over studies to compare the effects of tryptophan, the serotonin precursor, with placebo on the social behavior of healthy people. In the first study tryptophan decreased quarrelsome behaviors. In the second study on irritable people tryptophan not only decreased quarrelsome behaviors but also increased agreeable behaviors and improved mood. Our studies suggest that increasing serotonin synthesis with tryptophan moves behavior along the axis that encompasses aggressive, quarrelsome, and agreeable behaviors towards more positive social behavior in healthy people in everyday life. Irritability is a risk factor for various mental and physical disorders. It remains to be seen whether increasing serotonin function in irritable people improves their mental and physical health.
Tryptophan, serotonin and human social behavior
Advances in experimental medicine and biology, 2003
Animals research suggests that increasing serotonin can decrease aggression, increase affiliative behaviors and increase dominant behaviors. We tested the relevance of these data to humans by giving 100 healthy people tryptophan (1 g after each meal) and placebo, each for 12 days in a double-blind cross-over study. Social behaviors were studied using an event sampling method in which subjects filled in a one page questionnaire about their behaviors after each social interaction lasting at least 5 minutes. Tryptophan caused a significant decrease in quarrelsome behaviors and a significant increase in dominant behaviors.
Social behaviour and mood in everyday life: the effects of tryptophan in quarrelsome individuals
Journal of psychiatry & neuroscience : JPN, 2006
We hypothesized that increasing brain serotonin in healthy individuals with high scores on 2 self-report measures of trait quarrelsomeness would reduce quarrelsome behaviours and enhance agreeable behaviours when measured ecologically using an event-contingent recording method. We conducted a double-blind crossover study, in which participants took tryptophan (3 g/d) and placebo for 15 days each and recorded how they behaved, felt and perceived others during everyday social interactions. Tryptophan significantly decreased quarrelsome behaviours and increased agreeable behaviours and perceptions of agreeableness. Men also behaved less dominantly, whereas both men and women perceived others as more dominant. Tryptophan's effects on behaviours and perceptions, while more marked in the men, were generally positive and accompanied by improved affect. Increasing serotonin in quarrelsome people may not only reduce behaviours associated with a predisposition to various mental and physic...
Psychopharmacology, 1995
In order to investigate the link between aggression and 5-HT, we looked at effects of changes in plasma tryptophan on healthy male subjects. Twenty-four with high trait aggression (H) and 24 with low (L) drank an amino acid mixture with (T+) or without (T−) trytophan. These caused plasma tryptophan enhancement and depletion, respectively, at 4.5 h. Group H subjects given T− became more angry, aggressive, annoyed, hostile and quarrelsome on subjective measures, whereas those given T+ responded in the opposite way. On a behavioural measure of aggression, group H subjects responded more aggressively after T− than T+. In contrast, there was no consistent effect on subjective or behavioural aggression in group L subjects. Feelings of well-being in group H were decreased by T− and increased by T+. In group L, T+ reduced feelings of well-being, possibly due to the sedative effect of tryptophan in this group, which correlated positively with plasma trytophan concentration. Changes in plasma tryptophan are probably followed by changes in central 5-HT turnover. We conclude that, in those with pre-existing aggressive traits, acute falls in central 5-HT can cause increased subjective and objective aggression, while rises can have the opposite effect. The absence of changes in a low aggressive group suggests that the primary effect may be on impulsivity, possibly mediated by 5-HT1a receptors, expressing underlying aggressive traits. The findings on mood changes provide support for earlier reports of a lowering of mood with tryptophan depletion.
Tryptophan depletion and its implications for psychiatry
British Journal of Psychiatry, 2001
BackgroundOver the past 10 years the technique of tryptophan depletion has been used increasingly as a tool for studying brain serotonergic systems.AimsTo review the technique of tryptophan depletion and its current status as a tool for investigating psychiatric disorders.MethodSystematic review of preclinical and clinical studies.ResultsTryptophan depletion produces a marked reduction in plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release. In healthy volunteers the effects of tryptophan depletion are influenced by the characteristics of the subjects and include some mood lowering, some memory impairment and an increase in aggression. In patients with depression tryptophan depletion tends to result in no worsening of depression in untreated subjects but a relapse in those who have responded to antidepressants (particularly serotonergic agents). In panic disorder the results are similar.ConclusionsThe findings that tryptophan depletion produces a relapse o...
Tryptophan depletion causes a rapid lowering of mood in normal males
Psychopharmacology, 1985
Normal male human subjects ingested amino acid mixtures which were tryptophan-free, balanced or contained excess tryptophan. The tryptophan-free mixture causes a marked depletion of plasma tryptophan by 5 h. At this time the subjects in the tryptophan-free group had significantly elevated scores on the depression scale of the Multiple Affect Adjective Checklist. The tryptophan-free group also performed worse than the other two groups in a proofreading task carried out while listening to a tape with themes of hopelessness and helplessness (dysphoric distractor). Cognitive theories of depression predict greater distractability of depressed individuals by dysphoric themes. Thus, both measures indicate a rapid mood lowering effect of tryptophan depletion in normal males. This effect is probably mediated by a lowering of brain 5-hydroxytryptamine. Although the mood-lowering effect was not as great as that seen in depressed patients, our results suggest that low brain 5HT might be one factor precipitating depression in some patients.
Annals of Behavioral Medicine, 2006
Background: Dysregulation of central nervous system serotonergic (5-HT) activity is implicated in behavioral states and psychological traits associated with depression and aggression, with some studies suggesting possible gender-related differences. Purpose: This study examined the relation of free plasma tryptophan (TRP) to aggression and depression in a sample of 138 nonsmoking adults recruited from the general community. It was hypothesized that TRP would be associated with anger, hostility, and aggression. Methods: To minimize effects of diurnal variation and menstrual cycle, fasting blood samples were collected in the morning, and, for women, during the follicular phase of the menstrual cycle. Participants were administered questionnaires following blood draw. Plasma TRP was determined by high performance liquid chromatography. Results: In women, but not men, higher levels of TRP were associated with trait hostility, propensity for anger, a tendency to express anger outwardly, and an antagonistic interpersonal style. For men and women, greater severity of depressive symptoms, anger, and the verbal expression of anger were associated with higher TRP. These associations were independent of age, body mass index, fasting albumin, and race and ethnicity. Conclusions: These data suggest that in women, but not men, higher plasma levels of TRP, the precursor to 5-HT, are associated with anger-hostility-aggression and that these associations are independent of various potential confounds. Implications of these observations to studies employing acute TRP depletion studies are discussed.
Neurochemistry International, 2010
Although depression is a heterogeneous disorder with complex molecular pathophysiological mechanisms, a dysfunctional serotonergic neurotransmitter system is widely accepted to be one of the main factors underlying the development of depressive symptomatology . Direct evidence comes from human studies associating depressive symptoms with abnormal physiological parameters related to the serotonergic system . Depressed patients often display disturbances in 5-HT metabolism (van Praag and de Haan, 1979) as indicated by decreased peripheral levels of tryptophan (TRP; , the dietary precursor of serotonin (5-hydroxytryptamine, 5-HT), and diminished levels of 5-hydroxyindoleacetic acid (5-HIAA; , an inactive 5-HT degradation product. Drugs successfully used in the treatment of depression provide direct evidence for the important role of disrupted function of specific pre-and post-synaptic receptors underlying the impaired 5-HT neurotransmission linked to depressive symptomatology . Moreover, variations in genes that regulate the 5-HT system appear to play an important role in the probability of onset and recurrence of depressive episodes and other affective disorders . Therefore, the aetiology of depression is thought to be strongly related to specific factors that predispose subjects to a dysfunctional 5-HT system (Booij and .
The Effect of Tryptophan on Social Interaction in Everyday Life A Placebo-Controlled Study
Neuropsychopharmacology, 2001
In monkeys increasing serotonin function enhances affiliative interactions and promotes the acquisition of dominance. To examine whether similar effects occur in humans, we treated 98 subjects for 12 days with the serotonin precursor tryptophan (1g TID) and for 12 days with placebo in a double-blind, cross over study. Agreeableness/quarrelsomeness and dominance/submission were measured using an event-contingent method, in which subjects reported on various behaviors during important social interactions throughout their day. Tryptophan decreased quarrelsome behavior, but only when placebo was given first, suggesting that a decrease in quarrelsomeness when tryptophan was given first may have carried over into the subsequent placebo period. Tryptophan increased dominant behavior, an effect that was independent of the order of treatment, the broad social context, and the subject's and partner's sex. Our results suggest that serotonin may enhance dominance in humans, as in monkeys, and illustrate the advantages of the event contingent methodology in studying the associations between biology and human social interaction.
Aggressive Behavior, 1998
The effects of acute plasma tryptophan manipulation on changes in hostile, anxious, and depressive mood were studied in 48 males. Subjects consumed tryptophan-free or nutritionally balanced amino acid mixtures as a means of manipulating brain serotonin levels. Mood (hostility, anxiety, depression) was assessed pre-and 5 hr post-ingestion using the Multiple Affect Adjective Checklist. Overall, the tryptophan manipulation resulted in significant changes in hostile mood. Analyses also revealed a stronger association between changes in plasma tryptophan and changes in hostility in subjects with high levels of pre-existing hostile traits compared with low levels of hostile traits, and in subjects with high vs. low antisocial traits. There was no significant association between changes in plasma tryptophan and changes in depression. The results suggest that persons with high levels of trait hostility may be more susceptible to the effects of acute manipulation of plasma tryptophan on hostile mood. Aggr. Behav. 24:173-185, 1998.