Elevation and reduction of plasma tryptophan and their effects on aggression and perceptual sensitivity in normal males

Data from experimental animals suggest that 5-hydroxytryptamine (5HT) may have an inhibitory effect on aggression, while clinical studies have found a correlation between pathological aggression and low brain 5HT. To investigate this relationship further we used amino acid mixtures designed to raise or lower the levels of the 5HT precursor, tryptophan. Normal male subjects were given tryptophan-depleted, balanced, or tryptophan-supplemented ammo acid mixtures and tested for aggression 5 hours later. The balanced amino acid mixture served as a control for the tryptophan depletion and supplementation. Testing for aggression was done using the Buss paradigm in which subjects deliver electric shocks to a (nonexistent) partner in response to stimulus tones. Duration and intensity of shock delivered were the measures of aggression, while responsivity to the stimulus tones was the measure of perceptual sensitivity. Neither tryptophan supplementation nor tryptophan depletion had any effect on these measures of aggression or perceptual sensitivity. We conclude that raising or lowering the synthesis of brain 5HT through alterations in tryptophan availability does not influence aggression in normal males as measured by the Buss task.     

Emotionally controlled decision-making and a gene variant related to serotonin synthesis in women with borderline personality disorder

The Iowa Gambling Task (IGT) was used to examine (i) social decision-making in women with borderline personality disorder (BPD), and (ii) the relationship between impaired decision-making and the tryptophan hydroxylase-1 (TPH-1) gene, involved in serotonin synthesis. Forty-two women with BPD and a history of suicide attempts were genotyped, and the frequency of a TPH-1 haplotype previously uniquely associated with BPD was calculated. The BPD group scored significantly lower than a control group in the IGT. Furthermore, the TPH-1 haplotype displayed a significantly higher frequency in BPD participants with impaired decision making, compared to BPD participants with normal scores. These findings suggest that impaired decision-making as determined by the IGT is a feature of BPD and may be (i) associated with serotonin dysfunction, and (ii) possibly relevant for suicidal behavior.     

Meta-Analysis of Neuropsychological Symptoms of Adolescents and Adults with PKU

Phenylketonuria (PKU; OMIM 261600) is an autosomal recessive inborn error of phenylanaline metabolism. PKU is characterized by deficient or defective phenylalanine hydroxylase activity and persistantly increased levels of the essential amino acid phenylalanine in the circulation. The present article examines current understanding of the etiology of PKU, along with a meta-analysis examining neuropsychological and intellectual presentations in continuously treated adolescents and adults. Patients with PKU differed significantly from controls on Full-Scale IQ, processing speed, attention, inhibition, and motor control. Future research utilizing an integrative approach and detailed analysis of specific cognitive domains will assist both the scientist and clinician, and ultimately the patient.     

The effects of acute plasma tryptophan manipulation on hostile mood: The influence of trait hostility

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. © 1998 Wiley-Liss, Inc.     

Association between intermale aggression and genetically-defined tryptophan hydroxylase activity in the mouse brain

The relationship between the genetically defined intensity of intermale aggression and the activity of brain tryptophan hydroxylase (TPH) has been studied in inbred mice. No association between the enzyme activity and the percentage of aggressive mice (reflecting the predisposition to aggressive reaction) was revealed. However, a significant positive interstrain correlation between brain TPH activity and accumulated attacking time (reflecting fight intensity) was identified. No correlation was found between TPH activity and the accumulated attacking time in segregating F2 (BALB × C57BL) mice. In conclusion, TPH is an important, but not the only factor controlling the intensity of intermale aggression in mice. © 1996 Wiley-Liss, Inc.     

Serotonin metabolism and serotonergic receptors in Norway rats selected for low aggressiveness to man

Selection of Norway rats (24–27 generations) for low aggressiveness to man resulting in the loss of aggressive responding to handling markedly influences the brain serotonergic system. In “domesticated” Norway rats levels of serotonin in the midbrain and hypothalamus and 5-hydroxyindole acetic acid in the hypothalamus were higher than in non-selected aggressive rats. The activity of the key enzyme in serotonin biosynthesis, tryptophan hydroxylase, in midbrain of rats with genetically determined lack of aggressiveness to man was higher than in aggressive animals, although there was no difference in tryptophan hydroxylase activity in the hypothalamus. B_max and K_D of [³H]spiperone-specific binding in frontal cortex membranes were increased in tame rats. No significant differences in B_max and K_D were found between “domesticated” and aggressive rats in [³H]serotonin binding in the frontal cortex.     

Tyrosine hydroxylase activities in the brains of wild Norway rats and silver foxes selected for reduced aggressiveness towards humans

Tyrosine hydroxylase (TH) activity was measured in brains from Norway rats and silver foxes showing wild type aggressiveness and from their counterparts selected over 20-25 generations for reduced aggressiveness towards humans (tameness). TH activity in the brain stem and cortex was increased in tame animals of both species compared with aggressive counterparts. Selection increased hypothalamic TH activity in foxes, but decreased it in rats. There was no difference in TH activity in corpus striatum between the tame and aggressive animals. Fetal TH activity in the posterior part of the brain was higher in tame than aggressive rats at day 20 of embryogensis. Increased TH activity in the brain stem and cortex of adult aggressive rats was observed after treatment of their mothers with hydrocortisone on the days 16 and 18 of pregnancy. This elevation in TH activity was associated with attenuation of the defense behavior of aggressive rats. The data suggested that alterations in neural TH activity in tame rats and foxes may be part of the neurochemical basis of their behavioral phenotype which is developed by selection. © 1994 Wiley-Liss, Inc.