Aggressive behavior and Brunner syndrome: no evidence for the C936T mutation in a population sample.
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Aggression↗
Biomedical subjects
R M Palmour
Publications and source records attributed to R M Palmour.
Depressive relapse following acute tryptophan depletion in patients with major depressive disorder.
Acute tryptophan depletion (ATD) lowers serotonin synthesis and elicits depressive symptoms in some, though not all, remitted patients with major depressive disorder (MDD). In the present study, eight medication-free remitted patients with MDD, seasonal pattern, were tested twice, once following the ingestion of a tryptophan-containing mixture, once following ATD. ATD significantly increased Hamilton depression scores (p < 0.001). Four of the patients had a family history of psychiatric disorders: substance abuse (n = 4), mood disorders (n = 3) or Cluster B personality disorders (n = 3). The mood-lowering response to ATD was significantly greater in those patients with, than without, affected relatives (p < 0.001). These preliminary findings (1) support the hypothesis that depressed states are related to disturbed serotonin neurotransmission and (2) suggest that depressive symptoms following ATD might identify a subgroup of patients at high genetic risk for disorders associated with affective lability and dysregulated impulse-control, conditions thought to be related to low serotonin neurotransmission.
Adult↗
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↗
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↗
Research on genes: promises and limitations.
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Humans↗
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↗
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↗
Development of a sensitive and specific assay system for cholecystokinin tetrapeptide.
Cholecystokinin is a gastrointestinal and neuropeptide which has been implicated in a wide range of physiological and behavioral processes. We have developed a sensitive and specific assay system to measure the various forms of cholecystokinin (CCK) in human plasma. This 3-step system involves i) extraction of CCK fragments from plasma using reverse phase chromatography; ii) separation of peptides by high performance liquid chromatography; and iii) detection and quantification of peptides with a double-antibody radioimmunoassay, using an antibody raised against cholecystokinin tetrapeptide (CCK-4) coupled to thyroglobulin and 125I Bolton-Hunter CCK-4 as tracer. The antibody detects CCK-4, sulfated CCK-8 (CCK-8S) and nonsulfated CCK-8 (CCK-8ns) with equal affinity. The lower limit of detection is 2.7 fmol, with an ED50 of 10.6 +/- 2.2 fmol. Mean CCK-like immunoreactivity (CCK-LI) in the plasma of 12 healthy subjects was determined to be 12.9 +/- 2.1 pM CCK-4 equivalents. Concentrations of each individual peptide in plasma were determined to be 1.0 +/- 0.2 pM, 3.4 +/- 0.8 pM and 1.9 +/- 0.4 pM for CCK-4, CCK-8s and CCK-8ns respectively.
Adult↗
The effect of tryptophan depletion on mood in medication-free, former patients with major affective disorder.
Acute tryptophan depletion (ATD) induces transient clinical relapse in medicated patients with major affective disorder. Our objective was to determine whether this effect persists once patients are euthymic and off antidepressants. Thus, we examined the effects of ATD in fully remitted, medication-free, former patients with major depression (n = 14). ATD had no significant effect on mood. These results suggest that the previous report that ATD substantially lowers mood in pharmacologically treated patients reflects a reversal of mechanisms involved in the therapeutic effects of antidepressants. Alternatively, ATD might induce clinical relapse only in subgroups that have yet to be identified.
Adult↗
Of monkeys and men: vervets and the genetics of human-like behaviors.
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Alcohol Drinking↗
Altered dopamine transporter densities in alcohol-preferring vervet monkeys.
Altered dopamine (DA) transporter densities have been implicated in mechanisms of vulnerability and relapse in human alcoholics. The regional distribution and density of the DA transporter was studied in alcohol-preferring vervet monkeys to investigate baseline status and regulation of the DA transporter at different stages of chronic alcohol drinking. Combined ligand binding and in vitro autoradiography of the cocaine congener [125I]RTI-55 (beta-CIT) demonstrated a significant increase in DA transporter densities in abstinent alcohol-preferring monkeys over those in alcohol-avoiding monkeys. Chronic alcohol consumption down-regulated DA transporter densities, and this effect was reversed by acute withdrawal. These results demonstrate that the DA transporter is regulated by alcohol exposure and suggest that increased DA transporter densities may be a phenotypic marker of alcohol preference in vulnerable monkeys.
Alcohol Drinking↗
Mood response to acute tryptophan depletion in healthy volunteers: sex differences and temporal stability.
We investigated (1) the mood response of normal women, without a family history of major affective disorder, to acute tryptophan depletion, and (2) the temporal stability of the mood change, within subjects, when rechallenged at least 1 month later. To deplete tryptophan, a tryptophan deficient amino acid mixture was ingested. The control treatment was a nutritionally balanced amino acid mixture containing tryptophan. A marked lowering of plasma tryptophan (80% to 90%) was achieved by both depletions. Compared to the balanced condition, the women exhibited a significant lowering of mood after the first tryptophan depletion on the elation-depression (p < .05), energetic-tired (p < .005), confident-unsure (p < .01), and clearheaded-confused (p < .01) scales of the bipolar profile of mood states. Whereas a lowering of mood was not found in a comparable sample of males studied earlier, these results were similar to those obtained in healthy males at genetic risk for major affective disorder (MAD). Inasmuch as a family history of MAD and female sex are predisposing factors to depression, these results suggest that a mood-lowering response to acute tryptophan depletion may occur preferentially in subjects with a susceptibility to lowered mood. However, the mood response to tryptophan depletion exhibited poor temporal stability in individual subjects.
Adolescent↗
Tryptophan depletion in stable lithium-treated patients with bipolar disorder in remission.
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Adult↗
Caffeine and propranolol block the increase in rat pineal melatonin production produced by stimulation of adenosine receptors.
The adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) injected i.p. during the light period increased rat pineal melatonin levels and this increase was blocked by simultaneous administration of the non-selective adenosine receptor antagonist caffeine. A single dose of the adenosine A1 agonist cyclopentyladenosine had no effect on nocturnal melatonin production. The NECA-stimulated increase was also blocked by the beta-adrenergic receptor antagonist propranolol. Given alone, neither caffeine nor propranolol had any effect on melatonin levels. The results point to an intermediate role for beta-adrenergic receptors in the adenosine-stimulated increase of melatonin production.
Adenosine↗
Mood-lowering effect of tryptophan depletion. Enhanced susceptibility in young men at genetic risk for major affective disorders.
METHODS: A double-blind placebo-controlled cross-over study in which plasma tryptophan was manipulated by administration of a tryptophan-deficient amino acid mixture. In the placebo condition, all subjects received a nutritionally balanced amino acid mixture that contained tryptophan. To further standardize baseline amino acids, each subject was provided with a low-protein diet the day before amino acid challenges. Subjects were euthymic, healthy men aged 18 to 30 years with either a multigenerational family history of affective illness or no family history of psychiatric illness in the present or in the two previous generations. Each subject was screened with a structured clinical interview to rule out a personal history of psychiatric illness. RESULTS: Plasma tryptophan was reduced by 89% 5 hours after the administration of the tryptophan-deficient amino acid mixture. Six of 20 subjects with a family history of affective illness and none of 19 subjects without a family history of psychiatric illness showed a lowering of mood of 10 or more points on the Profile of Mood States depression scale (P = .012, Fisher's Exact Test) 5 hours after tryptophan depletion. No significant mood changes were observed following the control treatment (balanced amino acid mixture) in either group. CONCLUSIONS: Our data support the hypothesis that subjects with no prior depressive episodes but with a multigenerational family history of major affective disorder show a greater reduction in mood after tryptophan depletion. They are also consistent with theories that implicate deficient serotonergic function as one possible etiological factor in major depressive disorders.
Adolescent↗
A contribution to the differential diagnosis of the "group of schizophrenias": structural abnormality of chromosome 4.
A structural abnormality of chromosome 4 [inv 4 (p15.2; q21.3)] is reported in a male presenting with DSM-III-R schizophrenia, undifferentiated type (295.94) and in his mother, who displayed symptoms associated with schizotypal personality disorder (DSM-III-R 301.22). The proband had a performance IQ of 91, poor motor coordination, stature in the lowest quartile and an impaired sense of time. There were no diagnostic physical or neurological abnormalities. Mild ventricular enlargement and prominent sulci were found on computed tomography. Both he and his chromosomally normal father had strabismus which required surgical correction. This case joins the long list of chromosomal abnormalities previously reported to confer an increased risk of mental illness and emphasizes the importance of a sophisticated differential diagnosis in evaluating patients who present with symptoms of schizophrenia. The implications for recent initiatives which attempt to localize genes conferring susceptibility to schizophrenia and other major mental illnesses are discussed.
Chromosome Aberrations↗
Voluntary alcohol consumption in vervet monkeys: individual, sex, and age differences.
The patterns of voluntary alcohol consumption were studied in 35 vervet monkeys (Cercopithecus aethiops), classified into four groups. Each monkey showed a fairly steady rate during the studied period, resulting in individual differences that became more evident as the treatment evolved. Females showed higher alcohol intake frequencies than males. This sexual difference was maintained among adults and juveniles. Age differences were also observed: juveniles showed higher frequencies of intake than adults, both in general and in each sex group. Intake frequency was not related to age in prepubertal subjects, neither in general nor in each particular sex. The origin of these sex and age alcohol consumption differences remains to be studied, but differences in alcohol metabolism and factors related to puberty are possible influences.
Aging↗
Voluntary consumption of beverage alcohol by vervet monkeys: population screening, descriptive behavior and biochemical measures.
Seventeen percent of 196 feral vervet monkeys (Cercopithecus aethiops) spontaneously drank appreciable quantities of beverage alcohol in 3% sucrose in preference to 3% sucrose alone. Ethanol consumption increased over time, as did the concentration of ethanol tolerated. Willingness to select ethanol was stable over a three-year period, as measured by periodic retesting. Individual patterns of drinking and behavioral responses to ethanol were quite variable. Upon occasion, some animals drank to ataxia and unconsciousness; signs of withdrawal, including tremulousness, pacing, irritability and increased aggression, followed the abrupt discontinuation of ethanol availability. A variety of changes in social interaction, including increased orientation to external stimulus, increased incidence of stereotyped aggression and of other stereotyped behaviors and decreased frequency of affiliative behaviors were observed during ethanol periods, as compared to baseline scoring periods. In a small number of alcohol-preferring animals, CSF amine metabolites (5-hydroxyindoleacetic acid and homovanillic acid) were raised by drinking alcohol. These studies suggest that the alcohol-selecting vervet monkey may be complementary to established primate models of alcoholism.
Alcohol Drinking↗