scholarly journals The Tryptophan System in Cocaine-Induced Depression

2020 ◽  
Vol 9 (12) ◽  
pp. 4103
Author(s):  
Francina Fonseca ◽  
Joan-Ignasi Mestre-Pintó ◽  
Àlex Gómez-Gómez ◽  
Diana Martinez-Sanvisens ◽  
Rocío Rodríguez-Minguela ◽  
...  
Keyword(s):  
Treatment Approach ◽  
Plasma Concentrations ◽  
Kynurenine Pathway ◽  
Acute Tryptophan Depletion ◽  
Comorbid Condition ◽  
Tryptophan Depletion ◽  
Healthy Controls ◽  
Major Depression Disorder ◽  
Double Blind ◽  
Depression Disorder

Major depression disorder (MDD) is the most prevalent psychiatric comorbid condition in cocaine use disorder (CUD). The comorbid MDD might be primary-MDD (CUD-primary-MDD) or cocaine-induced MDD (CUD-induced-MDD), and their accurate diagnoses and treatment is a challenge for improving prognoses. This study aimed to assess the tryptophan/serotonin (Trp/5-HT) system with the acute tryptophan depletion test (ATD), and the kynurenine pathway in subjects with CUD-primary-MDD, CUD-induced-MDD, MDD and healthy controls. The ATD was performed with a randomized, double-blind, crossover, and placebo-controlled design. Markers of enzymatic activity of indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase, kynurenine aminotransferase (KAT) and kynureninase were also established. Following ATD, we observed a decrease in Trp levels in all groups. Comparison between CUD-induced-MDD and MDD revealed significant differences in 5-HT plasma concentrations (512 + 332 ng/mL vs. 107 + 127 ng/mL, p = 0.039) and the Kyn/5-HT ratio (11 + 15 vs. 112 + 136; p = 0.012), whereas there were no differences between CUD-primary-MDD and MDD. Effect size coefficients show a gradient for all targeted markers (d range 0.72–1.67). Results suggest different pathogenesis for CUD-induced-MDD, with lower participation of the tryptophan system, probably more related to other neurotransmitter pathways and accordingly suggesting the need for a different pharmacological treatment approach.

Biochemical and behavioural effects of acute tryptophan depletion in abstinent bulimic subjects: a pilot study

1995 ◽  
Vol 25 (5) ◽  
pp. 995-1001 ◽  
Author(s):  
A. Oldman ◽  
A. Walsh ◽  
P. Salkovskis ◽  
C. G. Fairburn ◽  
P. J. Cowen
Keyword(s):  
Amino Acid ◽  
Food Intake ◽  
Free Amino ◽  
Acute Tryptophan Depletion ◽  
Tryptophan Depletion ◽  
Healthy Controls ◽  
Behavioural Effects ◽  
Amino Acid Load ◽  
Healthy Female ◽  
Acid Load

SYNOPSISWe studied the effect of acute tryptophan (TRP) depletion in a group of eight abstinent bulimic (BN) subjects and in 12 healthy female controls. Despite being free of episodes of bingeeating and vomiting for a prolonged period, the abstinent BN subjects still appeared to practice dietary restraint as judged by their food intake in a test meal. In addition, their plasma TRP concentrations were significantly lower than those of the controls. Administration of a TRP-free amino acid load (52 g) significantly lowered plasma total and free TRP. However, compared to a balanced amino acid load, this procedure did not have significant effects on mood, appetite or food intake in either the abstinent BN subjects or the healthy controls.

Effects of acute tryptophan depletion on cognitive function in Alzheimer's disease and in the healthy elderly

2002 ◽  
Vol 33 (1) ◽  
pp. 41-49 ◽  
Author(s):  
R. J. PORTER ◽  
B. S. LUNN ◽  
J. T. O'BRIEN
Keyword(s):  
Cognitive Function ◽  
Rating Scales ◽  
Senile Dementia ◽  
Specific Effect ◽  
Acute Tryptophan Depletion ◽  
Elderly Subjects ◽  
Tryptophan Depletion ◽  
Emotional Symptoms ◽  
Double Blind ◽  
Healthy Elderly

Background. The cholinergic system is profoundly impaired in senile dementia of Alzheimer type (SDAT) and replacement therapy produces only modest clinical benefits. The serotonergic system is also impaired and may contribute both to cognitive and non-cognitive symptoms in SDAT. To investigate this further we assessed the effects of lowering brain serotonin using the technique of acute tryptophan depletion on cognitive function in patients with SDAT and in age matched control subjects.Method. Sixteen patients with probable SDAT and 17 healthy elderly subjects received two amino acid drinks in a within subject, double-blind, placebo-controlled, counterbalanced, crossover design. One of the drinks was nutritionally balanced and contained tryptophan (placebo), the other was identical but contained no tryptophan. A battery of detailed neuropsychological tests was performed between 4 and 6 h after the drink. Mood rating scales and other ratings of behavioural and emotional symptoms were also performed on both occasions.Results. Acute tryptophan depletion resulted in impairment on tasks of working memory in both groups. There was no group specific effect. Female SDAT subjects performed better on a task of pattern recognition during acute tryptophan depletion compared with placebo. There were no changes in behavioural symptoms during acute tryptophan depletion in either group.Conclusion. Compromised serotonergic function may be an important contributor to cognitive decline in SDAT and in ageing. Strategies targeting specific 5HT receptors may be helpful in SDAT.

scholarly journals Metabolic dysfunctions in the kynurenine pathway, noradrenergic and purine metabolism in schizophrenia and bipolar disorders

2019 ◽  
Vol 50 (4) ◽  
pp. 595-606 ◽  
Author(s):  
Nils Eiel Steen ◽  
Ingrid Dieset ◽  
Sigrun Hope ◽  
Trude S.J. Vedal ◽  
Olav B. Smeland ◽  
...  
Keyword(s):  
Psychotic Disorders ◽  
Plasma Concentrations ◽  
Bipolar Disorders ◽  
Kynurenine Pathway ◽  
Xanthurenic Acid ◽  
Vanillylmandelic Acid ◽  
Healthy Controls ◽  
Schizophrenia Spectrum Disorders ◽  
Schizophrenia Spectrum ◽  
Metabolic Dysfunctions

AbstractBackgroundWe aimed at exploring potential pathophysiological processes across psychotic disorders, applying metabolomics in a large and well-characterized sample of patients and healthy controls.MethodsPatients with schizophrenia and bipolar disorders (N = 212) and healthy controls (N = 68) had blood sampling with subsequent metabolomics analyses using electrochemical coulometric array detection. Concentrations of 52 metabolites including tyrosine, tryptophan and purine pathways were compared between patients and controls while controlling for demographic and clinical characteristics. Significant findings were further tested in medication-free subsamples.ResultsSignificantly decreased plasma concentrations in patients compared to healthy controls were found for 3-hydroxykynurenine (3OHKY, p = 0.0008), xanthurenic acid (XANU, p = 1.5×10−5), vanillylmandelic acid (VMA, p = 4.5×10−5) and metanephrine (MN, p = 0.0001). Plasma concentration of xanthine (XAN) was increased in the patient group (p = 3.5×10−5). Differences of 3OHKY, XANU, VMA and XAN were replicated across schizophrenia spectrum disorders and bipolar disorders subsamples of medication-free individuals.ConclusionsAlthough prone to residual confounding, the present results suggest the kynurenine pathway of tryptophan metabolism, noradrenergic and purinergic system dysfunction as trait factors in schizophrenia spectrum and bipolar disorders. Of special interest is XANU, a metabolite previously not found to be associated with bipolar disorders.

scholarly journals Depressive symptoms and neurotrophin levels in ostomy patients

2018 ◽  
Vol 67 (3) ◽  
pp. 166-173
Author(s):  
Daniela Vicente Bavaresco ◽  
Mágada Tessmann Schwalm ◽  
Luciano Kurtz Jornada ◽  
Luiz Felipe Andrade Quadros ◽  
Bruna Simon ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Major Depression ◽  
Peripheral Blood ◽  
Healthy Controls ◽  
Major Depression Disorder ◽  
Significant Difference ◽  
Healthy Control ◽  
Axis I ◽  
Cortisol Levels ◽  
Depression Disorder

ABSTRACT Objective: The aim of the present study was to investigate the depressive symptoms and changes in neurotrophins (BDNF, NGF, NT-3), and cortisol levels in serum of peripheral blood from ostomy patients compared to healthy control group. Methods: We evaluated ostomy (n = 29) and healthy control (n = 30) patients. The neurotrophin (BDNF, NGF, NT-3), and cortisol levels were assessed by ELISA in serum of peripheral blood. Depressive symptoms were defined based on the Hamilton Depression Rating Scale (HDRS), and major depression disorder was based on clinical interviews and was confirmed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Results: The results showed a significant decrease in BDNF levels and, a significant increase in NT-3 levels in serum of peripheral blood from ostomy patients when compared to healthy controls. The levels of NGF and cortisol showed no significant differences between groups. The depressive symptom evaluations by HDRS demonstrated a significant increase in ostomy patients when compared to healthy controls. The major depression disorder diagnosis by SCID-I showed no significant difference between groups. Conclusion: Our results suggest ostomy triggers significant depressive symptoms and alterations in neurotrophins levels in serum of peripheral blood samples collected from these patients.

Acute tryptophan depletion and Lewy body dementias

2016 ◽  
Vol 28 (9) ◽  
pp. 1487-1491 ◽  
Author(s):  
Janet L. Mace ◽  
Richard J. Porter ◽  
John C. Dalrymple-Alford ◽  
Chris Collins ◽  
Tim J. Anderson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Cognitive Status ◽  
Acute Tryptophan Depletion ◽  
Dementia Patient ◽  
Tryptophan Depletion ◽  
Double Blind ◽  
People With Dementia

ABSTRACTBackground:Studies using acute tryptophan depletion (ATD) to examine the effects of a rapid reduction in serotonin function have shown a reduction in global cognitive status during ATD in Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the severe cholinergic loss evident in dementia with Lewy bodies (DLB) and Parkinson's disease and dementia (PDD), we predicted that a reduction of global cognitive status during ATD would be greater in these conditions than in AD.Methods:Patients having DLB or PDD underwent ATD in a double-blind, placebo-controlled, randomized, counterbalanced, crossover design.Results:While the study intended to test 20 patients, the protocol was poorly tolerated and terminated after six patients attempted, but only four patients – three with DLB and one with PDD – completed the protocol. The Modified Mini-Mental State Examination (3MSE) score was reduced in all three DLB patients and unchanged in the PDD and dementia patient during ATD compared with placebo.Conclusions:This reduction in global cognitive function and the poor tolerability may fit with the hypothesis that people with dementia with Lewy bodies have sensitivity to the effects of reduced serotonin function.

scholarly journals Effects of Acute Tryptophan Depletion on Human Taste Perception

2020 ◽  
Author(s):  
Sharon A Smith ◽  
Paula D Trotter ◽  
Francis P McGlone ◽  
Susannah C Walker
Keyword(s):  
Depressive Disorders ◽  
Affective State ◽  
Taste Perception ◽  
Controlled Study ◽  
Acute Tryptophan Depletion ◽  
Tryptophan Depletion ◽  
Double Blind ◽  
Detection Thresholds ◽  
Specific Effects ◽  
Taste Detection

Abstract Taste perception has been reported to vary with changes in affective state. Distortions of taste perception, including blunted recognition thresholds, intensity and hedonic ratings have been identified in those suffering from depressive disorders. Serotonin is a key neurotransmitter implicated in the aetiology of anxiety and depression; systemic and peripheral manipulations of serotonin signalling have previously been shown to modulate taste detection. However, the specific effects of central serotonin function on taste processing have not been widely investigated. Here, in a double-blind placebo-controlled study, acute tryptophan depletion was used to investigate the effect of reduced central serotonin function on taste perception. 25 female participants aged 18-28 attended the laboratory on 2 occasions at least 1 week apart. On one visit they received a tryptophan depleting drink and on the other a control drink was administered. Approximately 6 hours after drink consumption they completed a taste perception task which measured detection thresholds and supra-threshold perceptions of the intensity and pleasantness of four basic tastes (sweet, sour, bitter and salt). While acutely reducing central levels of serotonin had no effect on the detection thresholds of sweet, bitter or sour tastes it significantly enhanced detection of salt. For supra-threshold stimuli, acutely reduced serotonin levels significantly enhanced the perceived intensity of both bitter and sour tastes and blunted pleasantness ratings of bitter quinine. These findings show manipulation of central serotonin levels can modulate taste perception and are consistent with previous reports that depletion of central serotonin levels enhances neural and behavioural responsiveness to aversive signals.

scholarly journals Kynurenine pathway: the link between depressive disorders and inflammation

2020 ◽  
Vol 74 ◽  
pp. 331-339
Author(s):  
Justyna Kubacka ◽  
Anna Stefańska ◽  
Grażyna Sypniewska
Keyword(s):  
Genetic Basis ◽  
Depressive Disorders ◽  
Genetic Factors ◽  
Current Knowledge ◽  
Kynurenine Pathway ◽  
Major Depression Disorder ◽  
Pathway Activation ◽  
Neuropsychiatric Diseases ◽  
Depression Disorder

Depression is highly prevalent worldwide and the leading cause of disability. It is believed that currently more than 300 million people of all ages suffer from depression. However, the unambiguous cause of the depression remains unknown. It is suggested that the occurrence of this disease is primarily affected by genetic factors, psychological factors and atypical brain structure or function. Recently, an increasingly important role is attributed to the inflammatory response, which is considered to be the main cause of depression. Activation of the kynurenine pathway (KP) is one of the described mechanisms by which inflammation can induce depression. Kynurenine pathway activation is associated with several neuropsychiatric diseases, including major depression disorder (MDD). The imbalance between the neuroprotective and neurotoxic metabolites in the kynurenine pathway and the associated serotonin and melatonin deficiency, may contribute to the manifestation of depressive symptoms. In this review we discuss the role of the major enzymes of the tryptophan KP: tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) and the role of selected kynurenic metabolites in the depressive disorders. Particular attention was also paid to the genetic basis of depressive disorders and to the summary of current knowledge on the effectiveness of treatment and supplementation with tryptophan and 5-hydroxytryptophan in depression.

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