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Elevated urine levels of bufotenine in patients with autistic spectrum disorders and schizophrenia

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Abstract

Previous studies have suggested that the endogeneous psychotomimetic molecule bufotenine (N-N-dimethyl-5-idroxytryptamine) may play a role in the pathogenesis of severe mental disorders. The potential association of bufotenine with the clinical features of autism and schizophrenia is not entirely understood. In this study, we measured urinary levels of bufotenine in subjects with autistic spectrum disorder (ASD), schizophrenia and healthy comparison subjects free of psychiatric symptoms. We also sought to assess whether urine concentrations of this molecule may be associated with the clinical characteristics of psychiatric patients. Urine bufotenine levels were measured using a high-performance liquid chromatography-mass spectrometry (HPLC-MS) assay in young adults with severe ASD (n=15), patients with schizophrenia (n=15), and healthy control subjects (n=18). The Vineland Adaptive Behavior Scale was used to measure adaptive behaviors in ASD individuals. The Brief Psychiatric Rating Scale (BPRS) was used for patients with schizophrenia. Urine bufotenine levels were significantly higher in ASD subjects (3.30 +/- 0.49 microg/L, p<0.05) and patients with schizophrenia (4.39 +/- 0.43 microg/L, p<0.001) compared with controls (1.53 +/- 0.30 microg/L). Among patients with ASD, there was a significant positive correlation between urine bufotenine and hyperactivity scores on the Vineland Adaptive Behavior Scale (r=0.479, p<0.05). No other associations were detected. Our results indicate that elevated urine levels of the endogeneous psychotomimetic molecule bufotenine may play a role in ASD and schizophrenia, and can be correlated with hyperactivity scores in autism.
To cite this article:
Neuroendocrinol Lett 2010; 31(1):101–105
ORIGINAL ARTICLE
Neuroendocrinology Letters Volume 31 No. 1 2010
Elevated urine levels of bufotenine in patients with
autistic spectrum disorders and schizophrenia
Enzo E, Roberto C, Valentina M, Natascia B,
Mara M, Marianna B, Francesco B, Pierluigi P
Department of Health Sciences, Section of Psychiatry, University of Pavia, Pavia, Italy.
Correspondence to: Enzo Emanuele, MD.
Department of Health Sciences, Section of Psychiatry,
University of Pavia, Via Bassi, 21, I-27100, Pavia, Italy.
: +39 0382 987 940; : +39 0382 526 723; -: enzo.em@libero.it
Submitted: 2009-08-06 Accepted: 2009-11-11 Published online: 2010-00-00
Key words: bufotenine; autism; schizophrenia; high-performance liquid chromatography-
mass spectrometry
Neuroendocrinol Lett 2010; 31(1):101–105 PMID: ----- NEL310110AXX © 2010 Neuroendocrinology Letters www.nel.edu
Abstract
OBJECTIVE: Previous studies have suggested that the endogeneous psychoto-
mimetic molecule bufotenine (N-N-dimethyl-5-idroxytryptamine) may play a
role in the pathogenesis of severe mental disorders. The potential association of
bufotenine with the clinical features of autism and schizophrenia is not entirely
understood. In this study, we measured urinary levels of bufotenine in subjects
with autistic spectrum disorder (ASD), schizophrenia and healthy comparison
subjects free of psychiatric symptoms. We also sought to assess whether urine
concentrations of this molecule may be associated with the clinical characteristics
of psychiatric patients.
DESIGN: Urine bufotenine levels were measured using a high-performance liquid
chromatography-mass spectrometry (HPLC-MS) assay in young adults with
severe ASD (n=15), patients with schizophrenia (n=15), and healthy control sub-
jects (n=18). The Vineland Adaptive Behavior Scale was used to measure adaptive
behaviors in ASD individuals. The Brief Psychiatric Rating Scale (BPRS) was used
for patients with schizophrenia.
RESULTS: Urine bufotenine levels were significantly higher in ASD subjects
(3.30 ± 0.49 g/L, p<0.05) and patients with schizophrenia (4.39 ± 0.43 g/L,
p<0.001) compared with controls
(1.53 ± 0.30 g/L). Among patients with ASD, there was a significant positive
correlation between urine bufotenine and hyperactivity scores on the Vineland
Adaptive Behavior Scale (r=0.479, p<0.05). No other associations were detected.
CONCLUS IONS: Our results indicate that elevated urine levels of the endogeneous
psychotomimetic molecule bufotenine may play a role in ASD and schizophrenia,
and can be correlated with hyperactivity scores in autism.
102
Copyright © 2010 Neuroendocrinology Letters ISSN 0172–780X www.nel.edu
Enzo Emanuele, Roberto Colombo, Valentina Martinelli, Natascia Brondino, Mara Marini, Marianna Boso, Francesco Barale, Pierluigi Politi
INTRODUCTION
Previous studies have suggested that endogenous
psychotomimetic molecules may be involved in the
pathogenesis of major psychiatric disorders (Osmond
& Smythies 1952; Smythies 1983; Ciprian-Ollivier et al.
1988). Bufotenine (5-hydroxy-N,N-dimetyltryptamine)
is a tryptamine alkaloid derived from the double meth-
ylation of serotonin commonly found in a number of
mammals and in several amphibian groups (Takeda
1994). There is evidence to suggest that bufotenine has
potent psychotropic actions in humans, probably due to
its similar physiological and structural features to LSD
on the 5HT2 receptor (McBride 2000). Interestingly, an
endogenous production of bufotenine has been previ-
ously reported in patients with several psychiatric dis-
ease, and urine levels of this molecule have been found
to be elevated in subjects with schizophrenia in numer-
ous (Fischer & Spatz 1968; Räisänen et al. 1984; Fischer
et al. 1971; Narasimhachari & Himwich 1972; Cottrell et
al. 1977) but not all (Perry et al. 1966; Siegel 1956; Rod-
night 1956; Wyatt et al. 1973) studies. Of interest is also
the observation that bufotenine has been reported to be
higher in the urine of patients with autistic spectrum
disorder (ASD) (Piggott 1979; Himwich et al. 1972)
as well as their parents (Narasimhachari & Himwich
1975). Notably, a previous study has detected bufotenine
at significant amounts in 32/47 autistic patients and in
18/18 patients with mental retardation, whereas it was
found in only 2 out of 200 controls (Takeda et al. 1995).
Urinary excretion of bufotenine has been also found to
be higher in drug-free violent offenders, and levels of
this molecule have been found to positively associated
with suspiciousness and aggression and negatively with
socialization scores (Kärkkäinen et al. 1995; Räisänen
et al. 1984). In this study, we assessed urine levels of
bufotenine in subjects with autistic spectrum disorder
(ASD), schizophrenia and healthy comparison subjects
free of psychiatric symptoms. We also sought to investi-
gate whether urine bufotenine levels may be associated
with the clinical characteristics of psychiatric patients.
MATERIALS AND METHODS
Subjects
We measured urine bufotenine levels in the following
three groups of subjects: adults with severe ASD (n =15;
13 males and 2 females, mean age: 31.0 ± 7.5 years),
patients with schizophrenia (n=15, 10 males and 5
females, mean age: 32.7 ± 8.6 years), and normal con-
trol subjects (n=18; 15 males and 3 females, mean age
31.9 ± 8.0 years). Patients with ASD were recruited from
a single farm community center specifically designed
for individuals with autism (Cascina Rossago, San
Ponzo Semola, Pavia, Italy). The diagnosis of ASD was
confirmed in all participants jointly by two indepen-
dent psychiatrists specializing in autism who made the
diagnosis according to the guidelines of the Structured
Clinical Interview for Axis I DSM-IV Disorders, Clini-
cal Version (First et al. 1996). All patients in the present
study scored more than 30 on the Childhood Autism
Rating Scale (CARS) (Schopler et al. 1988), the standard
threshold used to distinguish autism. The Vineland
Adaptive Behavior Scale (Sparrow et al. 1984) was used
to measure adaptive behaviors in ASD individuals.
Patients with schizophrenia were recruited from
the Department of Psychiatry at the Pavia University
School of Medicine and from Outpatients Departments
from which we receive referrals. Each patient was given
a diagnostic assessment by an experienced psychiatrist
based on the Structured Clinical Interview for DSM-IV
(American Psychiatric Association 2005). The psycho-
pathological status of patients with schizophrenia was
assessed using the Brief Psychiatric Rating Scale (BPRS)
(Ventura et al. 2000). All psychiatric patients were either
medication-naive (first-onset) or medication-free for at
least four months. Control subjects were recruited from
healthy blood donors or volunteers who had helped in
other studies within our institutions. Comparison sub-
jects were drawn from the same geographical area as
our patient group, aiming to recover the basic demo-
graphics of the regions from which the patients were
recruited. All controls had no past or present history
of any psychiatric disease and none of them had ever
taken medications for psychiatric conditions. Addition-
ally, subjects with axis-I diagnosis of first degree rela-
tives were not included in this group.
The study was approved by the local ethics com-
mittee in accordance to the Helsinki Declaration and
written informed consent was obtained from all partici-
pants or legal guardians.
Laboratory methods
Specimens of the middle urinary flow were collected
using a standard sterile urine container, transported
in the dark in a refrigerated bag and frozen at –40 °C
within 3 hours of collection. Bufotenine concentrations
in urine were determined using a high-performance
liquid chromatography-mass spectrometry (HPLC-
MS) method as previously described (Kärkkäinen et al.
2005), with slight modifications. Urine bufotenine was
determined in a quality control sample with within-
series and between-series coefficients of variation of
3.8 and 4.6%, respectively. Since laboratory personnel
were blinded to the clinical status of the study partici-
pants, any possible measurement error was likely to be
non-differential.
Data analysis
Continuous variables were tested for normal distribu-
tion with the Kolmogorov–Smirnov statistics. Since all
variables were normally distributed only parametric
statistics were used. Continuous data are expressed as
means ± standard deviations. Comparison of categori-
cal variables was generated by the χ2 test. For three
group comparisons of quantitative variables, a one-way
103
Neuroendocrinology Letters Vol. 31 No. 1 2010 • Article available online: http://node.nel.edu
Elevated urine levels of bufotenine in patients with autistic spectrum disorders and schizophrenia
analysis of variance (ANOVA) with post-hoc Dunns
testing was performed. Correlations among variables
were computed with the use of Pearsons correlation
coefficients. All statistical analyses were carried out
using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA)
and GraphPad Prism version 4.0 (GraphPad Software
Inc., San Diego, CA, USA). A two-tailed p-value <0.05
was considered statistically significant.
RESULTS
The general characteristics of the study partici-
pants are depicted in Table 1. No significant differ-
ences in demographic and clinical parameters were
detected among different groups. Urine bufotenine
levels were significantly higher in the ASD group
(3.30 ± 0.49 g/L, p<0.05) and in patients with schizo-
phrenia (4.39 ± 0.43 g/L, p<0.001) compared with
controls (1.53 ± 0.30 g/L, Figure 1). Although there
was a trend towards higher levels of urine bufotenine
in patients with schizophrenia than in ASD, this differ-
ence failed to reach the statistical significance thresh-
old. Among patients with ASD, there was a significant
positive correlation between urine bufotenine and
hyperactivity scores on the Vineland Adaptive Behav-
ior Scales (r=0.479, p<0.05). No significant correlations
were found between BPRS scores and urine bufotenine
levels in patients with schizophrenia (data not shown).
DISCUSSION
The present study provides evidence of a significant ele-
vation of urine bufotenine levels in patients with ASD
and schizophrenia compared with a matched control
population. Additionally, concentrations of bufotenine
in urine were found to be positively associated with
hyperactivity scores on the Vineland Adaptive Behav-
ior Scales in ASD subjects. Although no correlation was
evident between urinary levels of this molecule and the
severity of schizophrenia symptoms, our data point to a
subtle but definite role of this endogenous pyschotomi-
metic molecule in ASD and schizophrenia.
Subtle alterations in serotonin metabolism have
been suggested to occur and play a role in the patho-
genesis of schizophrenia and autism. Bufotenine has
been found to act as a potent endogenous hallucino-
genic factor, with an activity similar to LSD at the pur-
ported hallucinogenic serotonin receptors, 5HT2A and
Tab. 1. General characteristics of the study participants.
ASD patients
(n=15)
Schizophrenia
(n=15)
Controls
(n=18) p-value
Age, years 31.0 ± 7.5 32.7 ± 8.6 31.9 ± 8.0 0.59
Males/females 13/2 10/5 15/3 0.35
Body mass index, kg/m2 23.9 ± 3.3 24.7 ± 3.6 24.6 ± 3.4 0.47
Glucose, mmol/L 4.6 ± 0.7 4.5 ± 0.6 4.7 ± 0.7 0.77
Creatinine, mg/dL 0.82 ± 0.14 0.84 ± 0.18 0.83 ± 0.19 0.61
Total cholesterol, mmol/L 4.6 ± 0.7 4.8 ± 0.8 4.7 ± 0.7 0.69
LDL cholesterol, mmol/L 2.8 ± 0.8 2.9 ± 1.0 3.1 ± 1.0 0.30
HDL cholesterol, mmol/L 1.4 ± 0.4 1.5 ± 0.4 1.4 ± 0.5 0.89
Triglycerides, mmol/L 1.6 ± 0.9 1.6 ± 1.0 1.5 ± 1.1 0.67
Serum sodium, mmol/L 141.9 ± 3.2 142.0 ± 3.5 140.8 ± 3.0 0.91
Serum potassium, mmol/L 4.1 ± 0.5 4.0 ± 0.5 4.0 ± 0.6 0.84
Systolic blood pressure, mmHg 128 ± 9 130 ± 10 126 ± 7 0.21
Diastolic blood pressure, mmHg 82 ± 7 84 ± 11 81 ± 6 0.18
Urine bufotenine, μg/L 3.30 ± 0.49 4.39 ± 0.43 1.53 ± 0.30 < 0.001
p-values are calculated by means of ANOVA or χ2 test, as appropriate.
Bufotenin [μg/L]
autistics controls schizophrenics
0
2
4
6
8
Fig. 1. Scatter diagram for urine bufotenine in the three study
groups (ASD, controls, and schizophrenia). Horizontal lines
across the scatter diagram represent mean values.
104
Copyright © 2010 Neuroendocrinology Letters ISSN 0172–780X www.nel.edu
Enzo Emanuele, Roberto Colombo, Valentina Martinelli, Natascia Brondino, Mara Marini, Marianna Boso, Francesco Barale, Pierluigi Politi
5HT2C (McBride 2000). Although some reports have
reported detectable levels of urinary bufotenine in sev-
eral groups of patients with major psychiatric illnesses
(Fischer & Spatz 1968; Räisänen et al. 1984; Fischer et
al. 1971; Narasimhachari & Himwich 1972; Cottrell
et al. 1977), other authors were unable to confirm the
presence of this molecule (Perry et al. 1966; Siegel 1956;
Rodnight 1956; Wyatt et al. 1973). One of the reasons
for such discrepancy may be the lack of standardization
of methods for the determination of urinary bufoten-
ine levels and different ways in which urine samples are
handled. In this study, we used an HPLC-MS method to
detect urine bufotenine as previously described (Kärk-
käinen et al. 2005). Of note, we were able to confirm the
presence of a detectable amounts of bufotenine not only
in patients with psychiatric disorders, but also in con-
trols. This result is in keeping with those obtained by
Kärkkäinen and coworkers (Kärkkäinen et al. 2005), but
conflict with those obtained by earlier studies (Perry et
al. 1966; Siegel 1956; Rodnight 1956; Wyatt et al. 1973).
An improved sensitivity of the laboratory techniques
used to assess urine bufotenine may account for such
findings.
In our study, we found that urine bufotenine was sig-
nificantly higher in patients with ASD and schizophre-
nia compared with controls. These findings were in line
with those obtained by previous studies in schizophre-
nia and autism (Fischer & Spatz 1968; Räisänen 1984;
Fischer et al. 1971; Narasimhachari & Himwich 1972;
Cottrell et al. 1977, Himwich et al. 1972; Piggott 1979).
However, previous studies did not clarify whether urine
bufotenine might be associated with the clinical features
of major psychiatric illnesses. In our report, a signifi-
cant positive correlation between hyperactivity scores
and urine bufotenine levels was evident in patients with
ASD. It is feasible to hypothesize that increased levels of
bufotenin in autistic subjects with hyperactivity can be
a biological correlate of their behavior or – more specu-
latively – be a causal factor. Intriguingly, our data paral-
lel those of Kärkkäinen et al. (1995) who showed that
violent offenders with paranoid personality traits have
higher urinary levels of bufotenine than other violent
offenders. Additionally, Räisänen et al. have suggested
that urinary excretion of bufotenine is increased in
violent offenders with paranoid symptoms and family
violence (Räisänen et al. 1984). Although these findings
may prompt intriguing hypotheses on the possible asso-
ciation of bufotenine levels in urine and aberrant behav-
iors, further investigations are needed in larger sample
size to draw a more definite conclusion on this issue.
Caveats of this study merit consideration. The chief
limitations of our report are the small sample size and
its cross-sectional design. We thus observed associa-
tions, not prediction or causation. Therefore, it remains
to be established whether increased bufotenine level
observed in autism is a cause or a consequence of dis-
ease. In addition, we limited our analysis to bufotenine
levels as measured in the urine. In light of this limita-
tion, it remains to be established whether the increase
of peripheral bufotenine observed in autism may be
paralleled by similar changes in the central nervous
system. In this regard, it has been previously suggested
that the CNS is a favored site for the accumulation of
bufotenine, probably because of the lipophilic propteri-
ties of this substance and the slow catabolism of methyl-
ated indolamines in the brain (Kärkkäinen et al. 2005).
The presence of a significantly higher urinary bufoten-
ine concentration is another evidence of the complex
serotoninergic alterations occurring in autism and
schizophrenia, which probably includes an abnormal
methylation of this neurotransmitter.
In summary, our results indicate that elevated urine
bufotenine levels may play a role in schizophrenia and
ASD and may be correlated with hyperactivity scores
in autism.
ACKNOWLEDGEMENTS
The excellent nursing assistance of Roberto Albasi is
gratefully acknowledged.
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... Patients diagnosed with Autism Spectrum Disorder and Schizophrenia exhibited transmethylation of serotonin as demonstrated by the presence of 5-OH-DMT in the urine. Therefore, bufotenin has diagnostic potential as a tracer molecule for detecting such diseases linked to the transmethylation of serotonin, indicated by the presence of 5-OH-DMT in the urine of these patients (Siegel, 1965;Faurbye and Pind, 1968;Carpenter et al., 1975;McLeod and Sitaram, 1985;Takeda, 1994;Takeda et al., 1995;Emanuele et al., 2010). ...
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The family Myristicaceae harbour mind-altering phenylpropanoids like myristicin, elemicin, safrole, tryptamine derivatives such as N,N-dimethyltryptamine (DMT) and 5-methoxy N,N-dimethyltryptamine (5-MeO-DMT) and β-carbolines such as 1-methyl-6-methoxy-dihydro-betacarboline and 2-methyl-6-methoxy-1,2,3,4-tetrahydro-β-carboline. This study aimed to systematically review and propose the hypothetical biosynthetic pathways of hallucinogenic metabolites of Myristicaceae which have the potential to be used pharmaceutically. Relevant publications were retrieved from online databases, including Google Scholar, PubMed Central, Science Direct and the distribution of the hallucinogens among the family was compiled. The review revealed that the biosynthesis of serotonin in plants was catalysed by tryptamine 5-hydroxylase (T5H) and tryptophan 5-hydroxylase (TPH), whereas in invertebrates and vertebrates only by tryptophan 5-hydroxylase (TPH). Indolethylamine-N-methyltransferase catalyses the biosynthesis of DMT in plants and the brains of humans and other mammals. Caffeic acid 3-O-methyltransferase catalyses the biosynthesis of both phenylpropanoids and tryptamines in plants. All the hallucinogenic markers exhibited neuropsychiatric effects in humans as mechanistic convergence. The review noted that DMT, 5-MeO-DMT, and β-carbolines were natural protectants against both plant stress and neurodegenerative human ailments. The protein sequence data of tryptophan 5-hydroxylase and tryptamine 5-hydroxylase retrieved from NCBI showed a co-evolutionary relationship in between animals and plants on the phylogenetic framework of a Maximum Parsimony tree. The review also demonstrates that the biosynthesis of serotonin, DMT, 5-MeO-DMT, 5-hydroxy dimethyltryptamine, and β-carbolines in plants, as well as endogenous secretion of these compounds in the brain and blood of humans and rodents, reflects co-evolutionary mutualism in plants and humans.
... Bufotenin is found in higher concentrations in people with autism and schizophrenia(Emanuele et al., 2010). ...
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The Sonoran Desert Toad (Incilius alvarius) is the only vertebrate known to produce the powerful psychedelic, 5-MeO-DMT, which is easily-accessible form the animal's exterior glands. This paper seeks to present the biocultural (ecological and cultural) history, and conservation concerns of I. alvarius. Discovery of 5-MeO-DMT in I. alvarius was first reported in 1965 and 1967 (Erspamer et al.), and eventually led to the popular psychedelic use of this species after a pamphlet was published in 1984 (Most). Its mostly unmitigated use in for-profit spirituality, wellness, and adventurism has driven erroneous, coerced, and exploitive narratives of ancient Indigenous use – increasing: exploitation of I. alvarius, biocultural erosion, and malpractice of 5-MeO-DMT. Reconciliation of diverse needs is intellectually and financially challenging. It must be careful of approaches that are implicitly biased by a demand that extracts, appropriates, and trades in Indigenous and wellness motifs – but can be reached from the reconciliation and intersection of Indigenous and Western science and priorities. Few conservation-oriented studies and outreach elements concerning I. alvarius exist, and most have been supported by crowdfunding.
... Bufotenin has been tested in animals against rabies (Vigerelli et al. 2014) which might lead to applications of bufotenin in humans. Plasma levels of bufotenin were elevated in patients with autism and schizophrenia (Emanuele et al. 2010) and from our data one might hypothesize that these high levels of bufotenin might lead to tachycardia in untreated patients. Hence, it might be worthwhile to help some of these patients with 5-HT 4 receptor antagonists. ...
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It is unclear whether bufotenin (= N,N-dimethyl-serotonin = 5-hydroxy-N,N-dimethyl-tryptamine), a hallucinogenic drug, can act on human cardiac serotonin 5-HT4 receptors. Therefore, the aim of the study was to examine the cardiac effects of bufotenin and for comparison tryptamine in transgenic mice that only express the human 5-HT4 receptor in cardiomyocytes (5-HT4-TG), in their wild-type littermates (WT) and in isolated electrically driven (1 Hz) human atrial preparations. In 5-HT4-TG, we found that both bufotenin and tryptamine enhanced the force of contraction in left atrial preparations (pD2 = 6.77 or 5.5, respectively) and the beating rate in spontaneously beating right atrial preparations (pD2 = 7.04 or 5.86, respectively). Bufotenin (1 µM) increased left ventricular force of contraction and beating rate in Langendorff perfused hearts from 5-HT4-TG, whereas it was inactive in hearts from WT animals, as was tryptamine. The positive inotropic and chronotropic effects of bufotenin and tryptamine were potentiated by an inhibitor of monoamine oxidases (50 µM pargyline). Furthermore, bufotenin concentration- (0.1-10 µM) and time-dependently elevated force of contraction in isolated electrically stimulated musculi pectinati from the human atrium and these effects were likewise reversed by tropisetron (10 µM). We found that bufotenin (10 µM) increased the phosphorylation state of phospholamban in the isolated perfused hearts, left and right atrial muscle strips of 5-HT4-TG but not from WT and in isolated human right atrial preparations. In summary, we showed that bufotenin can increase the force of contraction via stimulation of human 5-HT4 receptors transgenic mouse cardiac preparations but notably also in human atrial preparations.
... Bufotenin was found to be present in urine samples of schizophrenic patients and autistic children but not in normal controls [56]. Elevated levels of bufotenine in the urine of schizophrenic patients were later confirmed by Kärkkäinen, J. (1988) (GC-MS) [57] and Emanuele E. (2010) (HPLC-MS) [58], but both studies demonstrated reduced (but detectable) amounts of bufotenine in the urine of healthy individuals. The connection between the appearance of bufotenin in the urine and psychiatric disorders is still unknown. ...
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Schizophrenia is one of the most severe chronic mental disorders that is currently diagnosed and categorized through subjective clinical assessment of complex symptoms. At present, there is a recognized need for an objective, unbiased clinical test for schizophrenia diagnosis at an early stage and categorization of the disease. This can be achieved by assaying low-molecular-weight biomarkers of the disease. Here we give an overview of previously conducted research on the discovery of biomarkers of schizophrenia and focus on the studies implemented with the use of GC-MS and the least invasiveness of biological samples acquisition. The presented data demonstrate that GC-MS is a powerful instrumental platform for investigating dysregulated biochemical pathways implicated in schizophrenia pathogenesis. With this platform, different research groups suggested a number of low molecular weight biomarkers of schizophrenia. However, we recognize an inconsistency between the biomarkers or biomarkers patterns revealed by different groups even in the same matrix. Moreover, despite the importance of the problem, the number of relevant studies is limited. The intensification of the research, as well as the harmonization of the analytical procedures to overcome the observed inconsistencies, can be indicated as future directions in the schizophrenia bio-markers quest.
... • Bufotenine, and its methoxy analogue, O-methylbufotenine, are potent hallucinogenic compounds that act as nonselective serotoninergic ligands. 52 • Caffeine is the most widely consumed CNS stimulant of the methylxanthine class, 53 eliminated in the liver via cytochrome P450. 54,55 • Cocaine is a potent addictive stimulant having many short-and long-term effects on users. ...
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The presence of positron emission tomography (PET) centers at most major hospitals worldwide, along with the improvement of PET scanner sensitivity and the introduction of total body PET systems, has increased the interest in the PET tracer development using the short-lived radionuclides carbon-11. In the last few decades, methodological improvements and fully automated modules have allowed the development of carbon-11 tracers for clinical use. Radiolabeling natural compounds with carbon-11 by substituting one of the backbone carbons with the radionuclide has provided important information on the biochemistry of the authentic compounds and increased the understanding of their in vivo behavior in healthy and diseased states. The number of endogenous and natural compounds essential for human life is staggering, ranging from simple alcohols to vitamins and peptides. This review collates all the carbon-11 radiolabeled endogenous and natural exogenous compounds synthesised to date, including essential information on their radiochemistry methodologies and preclinical and clinical studies in healthy subjects.
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La Serpiente y el Arco Iris (1988) de Wes Craven supone un modelo docente atractivo que combina la farmacología y las alteraciones fisiológicas en muchos sistemas funcionales. Basada en un hecho real, este clásico del terror convertido en una película de culto analiza como el método científico es capaz de dar respuestas al mito del muerto viviente, a través del vudú en la población de Haití, por la inhalación de una potente droga en polvo que contiene altas dosis de tetrodotoxina. Este filme simula el estado agudo de catalepsia de los pacientes y las pruebas sometidas para certificar la aparente defunción tras la confirmación del cese irreversible de las funciones cardiorrespiratorias o encefálica, debido a la ausencia de reflejos troncoencefálicos a causa de los efectos a largo plazo que presenta la droga. Además, a pesar de que el paciente no fallece y es enterrado siendo consciente de todo el proceso, el filme permite reflexionar en los estudiantes la alta carga psicológica, tanto del propio paciente como de la población, que profundiza en los estados de terror al suponer que es un esclavo retornado de la muerte sin alma y sin voluntad.
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Hallucinogenic drugs are used because they have effects on the central nervous system. Their hallucinogenic effects probably occur via stimulation of serotonin receptors, namely, 5-HT2A-serotonin receptors in the brain. However, a close study reveals that they also act on the heart, possibly increasing the force of contraction and beating rate and may lead to arrhythmias. Here, we will review the inotropic and chronotropic actions of bufotenin, psilocin, psilocybin, lysergic acid diethylamide (LSD), ergotamine, ergometrine, N,N-dimethyltryptamine, and 5-methoxy-N,N-dimethyltryptamine in the human heart.
Article
Mit einer quantitativen Methode haben wir bei Nicht-Schizophrenen eine Bufoteninausscheidung durch den Harn zwischen 1,2 und 8,9 mcg-%, mit einem Durchschnittswert von 3,6 mcg-%, festgestellt. Bei akuten unbehandelten, nicht, oder nicht lnger als 24 Std internierten Schizophreniefllen lagen die Werte bei 83% der Flle oberhalb 10 mcg-%, der hchste Wert entsprach 37,5 mcg-%, der Durchschnitt 17,2 mcg-%. Vorbehandelte chronische Flle von Schizophrenie zeigten nur in einem Prozentsatz von 26,6 erhhte Werte. Die erhhte Bufoteninausscheidung hat nichts mit einer Medikation oder Internierung zu tun und die Bufoteninausscheidung scheint auch von der Dit unabhngig zu sein.By means of a quantitative method we found in non schizophrenic subjects a urinary elimination of Bufotenin between 1.2 and 8.9 mcg-%, with a mean value of 3.6 mcg-%. In acute not medicated and not or not longer than 24 hr interned cases of schizophrenia the values were in 83% higher than 10 mcg-%, the highest value corresponded to 37.5 mcg-% and the mean to 17.2 mcg-%. Chronic and medicated cases of schizophrenia showed only in 26.6% high values. The elevated urinary elimination of bufotenin has nothing to do with medication or hospitalization and seems not to depend on the diet.
Article
A pilot study designed to determine whether patients with a diagnosis of infantile autism excreted N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine and bufotenin, as do some chronic adult schizophrenic patients, is presented and discussed. Twenty-four-hour urinary collections from 12 children and adolescents, 10 boys and 2 girls, were made at their homes. Subsequently, 24-hour samples were also collected during 14 consecutive days from the 6 children who were possibly autistic and on controlled diet at the hospital. At home, samples of the normal controls and of 2 possibly autistic patients were negative for bufotenin. In the hospital, those of 5 of the 6 were positive. It is suggested that some patients with a diagnosis of early infantile autism excrete bufotenin, an ability they share with schizophrenic patients.
Article
In our hands, methods purporting to detect 35 μg and 400 μg/1. quantities of bufotenin in schizophrenic urine cannot be confirmed. Criticism was offered of these methods which would tend to make suspect any conclusions drawn from their use. A chemical method which claimed to detect 50 μg of bufotenin per 1. of normal urine was shown to be erroneous in its conclusions. A method was presented which is sensitive to at least 1 μg of bufotenin per 1. of urine. By this method, in not one of five normals nor in any of 21 schizophrenics could any bufotenin be detected. These results indicate that bufotenin cannot be measurably present in urine of schizophrenic patients, nor do they support a hypothesis involving bufotenin in the etiology of schizophrenia.
Article
Basic research in autism is reviewed. There is mounting indication, but as yet inconclusive evidence, of unique physiologic disturbances etiologically related to autism. Additionally there is indication that some of the physiologic disturbances found in autistic children are also present in children with other developmental disorders. Children called autistic probably represent a complex of clinically similar manifestations in a variety of different subgroups of children, each subgroup representing a basically different physiologic disturbance. However, the possibility remains that there is only one basic disturbance that in varying degrees affects many body systems and thus manifests in a variety of overlapping syndromes. Objective markers are needed so as to allow the demarcation of subgroups of autistic children for further study. Possible markers may be decreased duration of postrotatory nystagmus, auditory evoked response deviations, lymphocytic hyporesponsivity, increased blood platelet serotonin efflux, and/or the presence of urinary DMT or bufotenin.
Article
The authors present a preliminary report which suggests that a bufotenin-like substance is present in the urine of many patients with a schizophrenic illness. They have used a simple and sensitive assay system that eliminates some of the defects of previous studies.
Article
The hypothesis that endogenously formed, N-methylated metabolites of indoleamines may play a role in the pathogenesis of schizophrenia was reviewed. Although N-methylated indoleamines can be produced in vivo and have significant psychotomimetic effects, there is little evidence for a specific increase in the methylation of indoleamines in schizophrenic patients. It was noted that even if the relationship between schizophrenia and N-methylated indoleamines had existed, nicotinic acid would not be an appropriate therapeutic agent.
Article
In four series of studies on schizophrenic patients and normals we found that all the schizophrenics eliminated N, N-dimethyltryptamines in their urine while none of the normals did so. Similarly, with early infantile autism (Studies I and II) and normal controls, this separation between patiens and normals still held. But ten parents of the five autistic children positive for bufotenin revealed that one or both parents, i.e., seven of ten were positive. The Psychiatric Assessment Interview, the Minnesota Multiphasic Personality Index, and the Rorschach indicated no significant evidence of psychopathology. Thus, individuals who revealed no psychopathology could still be positive for bufotenin. In studies III and V, 1 of 13 normals and 13 of 27 normals were positive, respectively. Study IV showed that 6 of 18 autistic children were positive for bufotenin.