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Biomedical subjects

S N Young

Publications and source records attributed to S N Young.

At least 37 records · Page 2Linked to original sources
PubMed2000

Acute tyrosine depletion and alcohol ingestion in healthy women.

BACKGROUND: Recently we reported that, in vervet monkeys, ingestion of an amino acid mixture deficient in the catecholamine precursors, phenylalanine and tyrosine, produced a decrease in alcohol self-administration. We now report the results of a similar study in humans. METHODS: Three groups of healthy female social drinkers were administered a nutritionally balanced amino acid mixture (B, n = 13), a mixture deficient in the serotonin precursor, tryptophan (Trp-free, n = 14), or a phenylalanine/tyrosine deficient mixture (Phe/Tyr-free, n = 12). Six hours after administration of the amino acid mixture, alcohol ingestion was measured during a free-choice "Taste Test." RESULTS: Compared to the B mixture, Phe/Tyr-free, but not Trp-free, significantly decreased the ingestion of alcohol [p < 0.02]. Neither Phe/Tyr-free nor Trp-free significantly decreased orange juice ingestion or the self-reported "Liking" of either substance. Some subjects experienced transient nausea and/or regurgitated the amino acid mixtures, but excluding these subjects did not change the results. CONCLUSIONS: The results suggest that (a) Phe/Tyr-free may be a suitable method for investigating the role of catecholamines in the self-administration and subjective effects of alcohol, (b) acutely decreased catecholamine neurotransmission might disrupt mechanisms mediating alcohol self-administration, and (c) acutely decreased serotonin neurotransmission seems not to alter alcohol self-administration.

Adult↗
PubMed1999

The effect of acute tryptophan depletion and fenfluramine on quantitative EEG and mood in healthy male subjects.

BACKGROUND: Efforts to model putative serotonergic deficits associated with affective disorders have frequently involved acute tryptophan depletion (ATD) as a manipulation strategy aimed at lowering brain serotonin synthesis. In an attempt to widen the scope of the measurement probes used in these investigations, the central actions of ATD and a subsequent dose of fenfluramine were examined via utilization of quantitative electroencephalography (EEG) and mood ratings. METHODS: Electroencephalograms (EEG) and subjective mood ratings were assessed in 28 healthy men before and after double-blind ingestion of a tryptophan-depleting (T-) amino acid mixture, or a nutritionally balanced (B) amino acid mixture containing tryptophan, and again after a single-blind oral dose of D,L-fenfluramine hydrochloride (60 mg). RESULTS: Compared to the B mixture, the T- mixture reduced total plasma tryptophan by more than 75% 5 hours after ingestion. Tryptophan depletion was associated with a modest lowering of mood and a slowing of EEG as indicated by increases in delta amplitude. Fenfluramine caused no change in mood but increased fast wave (beta) activity in anterior recordings when administered after the T-, but not after the B mixture. CONCLUSIONS: Quantitative EEG measurements may be a promising method for studying the central mechanisms underlying serotonin-mediated changes in mood and behavior.

Adolescent↗
PubMed1999

A placebo-controlled clinical trial of L-tryptophan in premenstrual dysphoria.

BACKGROUND: Antidepressant drugs, including specific serotonin reuptake inhibitors, have been shown to be beneficial in the treatment of premenstrual dysphoric disorders. The present study tests the efficacy of L-tryptophan, which acts specifically on serotonergic neurons, in this disorder. METHODS: In a randomized controlled clinical trial, 37 patients with premenstrual dysphoric disorder were treated with L-tryptophan 6 g per day, and 34 were given placebo. The treatments were administered under double-blind conditions for 17 days, from the time of ovulation to the third day of menstruation, during three consecutive menstrual cycles. RESULTS: The Visual Analogue Scales (VAS) revealed a significant (p = .004) therapeutic effect of L-tryptophan relative to placebo for the cluster of mood symptoms comprising the items of dysphoria, mood swings, tension, and irritability. The magnitude of the reduction from baseline in maximum luteal phase VAS-mood scores was 34.5% with L-tryptophan compared to 10.4% with placebo. CONCLUSIONS: These results suggest that increasing serotonin synthesis during the late luteal phase of the menstrual cycle has a beneficial effect in patients with premenstrual dysphoric disorder.

Adult↗
PubMed1999

A placebo-controlled study of the effects of L-tryptophan in patients with premenstrual dysphoria.

In a randomized controlled clinical trial, 37 patients with premenstrual dysphoric disorder were treated with L-tryptophan 6 g per day and 34 were given placebo. The treatments were given under double-blind conditions for 17 days, from the time of ovulation to the third day of menstruation, during three consecutive cycles. Visual Analog Mood Scales revealed a significant (p = 0.004) therapeutic effect of L-tryptophan relative to placebo for the cluster of mood symptoms comprising the items dysphoria, mood swings, tension and irritability. These results suggest that increasing serotonin synthesis during the late luteal phase of the menstrual cycle is therapeutic in patients with premenstrual dysphoric disorder.

Adult↗
PubMed1999

Pet studies of serotonin synthesis in the human brain.

The method for measuring serotonin synthesis in human brain uses [11C]alpha-methyl-L-tryptophan as a tracer and positron emission tomography. The alpha-methyl-L-tryptophan is converted to alpha-methylserotonin, which is not a substrate for monoamine oxidase and therefore accumulates in the brain. In a pilot study published recently, rates of serotonin synthesis were found to be higher in men than in women. This was due to the lower plasma free tryptophan in the women under the experimental conditions used, and does not necessarily reflect the situation in all circumstances. Acute tryptophan depletion lowered brain serotonin synthesis by 90% or more. Patients with borderline personality disorder, who exhibit emotional lability and impulsivity, may have lower brain serotonin synthesis rates than healthy controls.

Brain↗
PubMed1999

A comparison of the effects of acute tryptophan depletion and acute phenylalanine/tyrosine depletion in healthy women.

Acute tryptophan depletion (ATD), which is thought to lower serotonin levels, can result in a lowering of mood. In the present study we compared the effect of ATD with acute phenylalanine/tyrosine depletion (APTD) in healthy women. Although considerable evidence relates catecholamines to the regulation of anxiety, there was no difference in anxiety responses in the ATD and APTD groups when the women underwent a mildly stressful psychological challenge. Both ATD and APTD caused a similar lowering of mood. Both depletions also increased heart rate. These results suggest that APTD is a useful method for studying the effect of low catecholamine levels in humans, and that catecholamines are involved in the regulation of mood.

Adult↗
PubMed1999

The response of crying newborns to sucrose: is it a "sweetness" effect?

Intraoral sucrose (and other sweet carbohydrates) induce rapid and sustained calming in crying newborns and transiently increase mouthing and hand-mouth contact ("sucrose effects"). To investigate whether these effects are due to the sweetness of sucrose, 60 crying newborns were randomized to receive 250 microL of 24% sucrose solution, 0.12% of aspartame solution of equivalent sweetness (to adults), or 24% polycose, a soluble carbohydrate that is only very slightly sweet (to adults), as well as water in a mixed parallel crossover design. Relative to water, sucrose persistently reduced crying, and transiently increased mouthing and hand-mouth contact, as previously demonstrated. Aspartame also reduced crying, and transiently increased mouthing and hand-mouth contact, virtually mimicking the time course and the magnitude of the effects obtained in response to sucrose. By contrast, polycose solution had no specific effects on crying, mouthing, or hand-mouth contact. The results imply that the responses of crying newborns to intraoral sucrose are neither specific to sucrose nor to the general class of carbohydrates, and that these effects are more appropriately understood as "sweetness" effects.

Administration, Oral↗
PubMed1999

Acute tryptophan depletion in healthy young women with a family history of major affective disorder.

BACKGROUND: Acute tryptophan depletion (ATD), a means of reducing brain serotonin synthesis, lowers mood in normal males with a multi-generational family history of major affective disorder (MAD) and in normal women devoid of any family history of psychiatric illness. As both a family history of MAD and female sex are factors predisposing to depression, the hypothesis that a mood lowering response to ATD may reflect a susceptibility to depression was further investigated in young women with an extensive, multi-generational family history of MAD. In addition, the temporal stability of mood change following repeated trials of ATD was also assessed in this study. METHODS: To deplete tryptophan, a tryptophan deficient amino acid mixture was ingested on two separate occasions. The control treatment, administered on a third occasion, was a nutritionally balanced amino acid mixture containing tryptophan. RESULTS: A marked lowering of plasma tryptophan (85-90 %) was achieved by both depletions. In comparison to the balanced condition, family history positive (FH +) women showed no lowering of mood to either the first or second ATD (N = 13) and N = 12, respectively). Mood change between the two ATD trials (N = 13) exhibited poor temporal stability. CONCLUSIONS: These results may indicate that serotonin responsiveness is not an important characteristic of vulnerability to depression in these women. Alternately, these negative results may be due to the exclusion of a large number of FH + women who had already experienced an episode of depression, resulting in the selection of a biased FH + sample who are resistant to the mood lowering effects of ATD.

Adolescent↗
PubMed1999

Behavioral disinhibition induced by tryptophan depletion in nonalcoholic young men with multigenerational family histories of paternal alcoholism.

OBJECTIVE: A deficit in serotonergic neurotransmission has been linked to impulsive behavior, as well as to disorders characterized by disinhibition. The present study tested the hypothesis that young men at high risk for alcoholism demonstrate greater behavioral disinhibition after acute dietary depletion of tryptophan, the amino acid precursor of serotonin. METHOD: A double-blind, placebo-comparison, between-subjects study design was used. Nonalcoholic young men with a multigenerational paternal family history of alcoholism (N = 13) or with no family history of alcoholism (N = 15) in two previous generations were administered mixtures of tryptophan-deficient amino acid to achieve plasma tryptophan depletion. Comparison subjects with a multigenerational paternal family history of alcoholism (N = 1) and comparison subjects with no family history of alcoholism (N = 18) were given a balanced mixture. Five hours after this, all were tested on a modified Taylor task and a go/ no-go task measuring aggressive response and disinhibition, respectively. RESULTS: Plasma tryptophan levels were reduced by 89% in both groups. Tryptophan depletion had no effect on aggressive response. In contrast, tryptophan-depleted individuals with a family history of alcoholism made more commission errors (responses to stimuli associated with punishment or loss of reward) than did tryptophan-depleted individuals with no family history of alcoholism and those receiving the balanced (comparison) mixture of amino acid in either group. CONCLUSIONS: Low serotonin levels may be implicated in the high disinhibition or impulsivity observed in some individuals with a genetic vulnerability to alcohol abuse or dependence.

Affect↗
PubMed1999

Differential calming responses to sucrose taste in crying infants with and without colic.

BACKGROUND: Colic is a behavioral syndrome of early infancy of unknown etiology whose core symptom is increased crying. Both clinical anecdotal descriptions and controlled observations converge in suggesting that a defining characteristic of the crying behavior is the longer duration of the crying bouts, especially during the second month of life when colic is at its peak. This implies that, once infants with colic begin crying, they do not calm as well as infants without colic. To investigate this difference objectively, we used response to sucrose taste as a probe of colic-normal differences in regulation of crying for three reasons. First, sucrose taste has been shown to be a potent regulator of crying in human newborns. Second, convergent evidence from studies in both nonhuman and human infants suggests that sucrose calming reflects the function of central distress regulatory systems that are opioid-dependent. Third, effectiveness of sucrose calming diminishes in normal infants by 4 to 6 weeks of age, consistent with the developmental increase in crying duration common to infants with and without colic. Consequently we predicted that, if the regulation of crying by sucrose taste is relevant to the crying of infants with colic, calming responses to sucrose taste should be less effective in 6-week-old infants with colic compared with those without. OBJECTIVES: To investigate the clinical observation that infants with and without colic differ in their ability to regulate their crying behavior, our primary objective was to determine if there were differential crying responses to intraoral sucrose tastes (relative to water) in crying infants with and without colic. Based on previous studies of calming responses to sucrose taste, it was predicted that sucrose-specific calming before a feeding would be less effective in infants with colic than in those without. A secondary and more exploratory aim was to assess calming responses to sucrose (relative to water) on spontaneous crying after a feed in both groups. METHODS: Nineteen infants meeting modified Wessel's criteria for colic were compared with 19 age- and sex-matched normal infants without colic in a within-subject controlled observation of calming and mouthing responses to both intraoral sucrose and water tastes. Both before and after two feedings on the same day, each infant was observed until she or he cried continuously for 15 consecutive seconds, at which time three 250-microL tastes of 48% sucrose solution or sterile water were administered 30 seconds apart, and infant responses videotaped. Outcome measures derived from second-by-second coding of the videorecordings were percent time crying per minute for 4 minutes and percent time mouthing per minute for 2 minutes after stimulus administration. RESULTS: As predicted, the crying of infants with colic was less affected than the crying of infants without colic after sucrose but not water tastes before feedings. After feedings, the crying of infants with colic was less affected than the crying of infants without colic for both sucrose and water tastes, and sucrose was more effective than water in both groups of infants. These calming differences could not be attributed to differences in mouthing responses because the calming effects persisted after mouthing ceased, and there were no differences in mouthing responses between groups before or after feedings. CONCLUSIONS: As in newborns, a significant calming effect of sucrose taste that persisted beyond the cessation of mouthing could be elicited in crying 6-week-old infants, but it required a stronger taste stimulus to do so. As predicted, infants with colic were less effectively calmed by sucrose taste than infants without. These differential effects could not be accounted for by differences in crying when the stimulus was applied or by differences in mouthing behavior. Before a feed, these differences in calming were specific to sucrose taste. After a feed, infants with c

Colic↗
PubMed1998

An amino acid mixture deficient in phenylalanine and tyrosine reduces cerebrospinal fluid catecholamine metabolites and alcohol consumption in vervet monkeys.

An amino acid mixture devoid of tryptophan, given orally, was previously shown to reduce cerebrospinal fluid levels of tryptophan and 5-hydroxyindoleacetic acid in vervet monkeys, as compared to a control mixture containing all essential amino acids. In the present study, we tested the possibility that a similar amino acid mixture containing tryptophan, but devoid of phenylalanine and tyrosine (the amino acid precursors of catecholamine neurotransmitters), would influence dopamine and noradrenaline metabolism. Five hours after the administration of this mixture to vervet monkeys, cerebrospinal fluid levels of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol were reduced by 27.4% and 26.9%, respectively. Both effects were statistically significant. Plasma tyrosine (-30%) and the ratio of tyrosine to the sum of other large neutral amino acids (sigmaLNAA) were also significantly reduced. The behavioral efficacy of phenylalanine/tyrosine depletion was compared with that of tryptophan depletion in a primate model of voluntary alcohol consumption. All three drinks lowered alcohol consumption, but the effects of the tryptophan-deficient amino acid mixture were not different from those of the balanced amino acid control. The phenylalanine/tyrosine-deficient drink differentially lowered alcohol consumption, consistent with other data in this species and elsewhere implicating dopamine in the rewarding effects of alcohol.

Alcohol Drinking↗
PubMed1998

The effect of sucrose on acute tobacco withdrawal in women.

Carbohydrate consumption is thought to attenuate symptoms of tobacco withdrawal, but direct evidence for this idea does not exist. Using a 2 x 2 (smoking/smoking deprived x sucrose/placebo) factorial design, we examined in 67 women whether sucrose would decrease acute withdrawal symptoms observed after 12 h of tobacco abstinence. Sucrose decreased tobacco abstinence-induced drowsiness and anxiety and preference for foods high in carbohydrate and fat content. Sucrose, however, had no effect on several other acute withdrawal symptoms, including restlessness, irritability and concentration difficulties. These results provide modest support for the idea that increased carbohydrate intake during tobacco withdrawal reduces certain withdrawal symptoms even after only 12 h of abstinence.

Adult↗
PubMed1998

Tryptophan depletion, executive functions, and disinhibition in aggressive, adolescent males.

Low serotonin has been associated with aggressive behavior and impulsivity. Executive functions (cognitive abilities involved in the initiation/maintenance of goal attainment) have also been related to aggression. We tested whether dietary depletion of tryptophan, the amino acid precursor of serotonin, would increase disinhibition (impulsivity) in aggressive male adolescents. Cognitive-neuropsychological variables predictive of disinhibition were explored. Stable aggressive and nonaggressive adolescent men received balanced and tryptophan-depleted, amino acid mixtures separately (counterbalanced, double-blind). Commission errors on a go/no-go learning task (i.e., failures to inhibit responding to stimuli associated with punishment/nonreward) measured disinhibition. Aggressive adolescent males made more commission errors as compared to nonaggressives. Lower executive functioning was significantly related to commission errors over and above conventional memory abilities. Tryptophan depletion had no effect on commission errors in the aggressive adolescents, possibly because of a ceiling effect.

Adolescent↗
PubMed1998

Effects of electromagnetic fields on the levels of biogenic amine metabolites, quinolinic acid, and beta-endorphin in the cerebrospinal fluid of dairy cows.

Eight multiparous non-lactating pregnant Holstein cows at 198 +/- 35 d of gestation, weighing 608 +/- 24 kg, were confined to wooden metabolic cages in an electric and magnetic field chamber with a 12:12 h light:dark cycle. Subarachnoidal catheters were installed 5 d before the activation of the electric and magnetic fields. The cows were exposed to electric and magnetic fields (60 Hz, 10 kV/m and 30 microT) continuously except for the feeding and cleaning time for an average of 21.44 +/- 1.4 h per day for a period of 30 d. Cerebrospinal fluid samples were collected on three consecutive days before an exposure period of 30 d, on the last 3 d of the exposure period, and for 3 d starting 5 d after the exposure period. The concentrations of beta-endorphin, tryptophan, 5-hydroxyindoleacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylethyleneglycol and quinolinic acid in cerebrospinal fluid were determined. There was a significant increase in quinolinic acid, and a trend towards an increase in tryptophan, findings consistent with a weakening of the blood-brain barrier due to exposure to the electric and magnetic fields.

Animals↗