Plasma tryptophan levels and tryptophan/neutral amino acid ratios in obsessive-compulsive patients with and without depression

doi:10.1016/S0165-1781(96)02961-7

Psychiatry Research

Volume 69, Issue 1, 3 March 1997, Pages 9-15

https://doi.org/10.1016/S0165-1781(96)02961-7 Get rights and content

Abstract

We have studied fasting plasma tryptophan (TRP) levels and tryptophan/large neutral amino acid ( $TRP LNAA$ ) ratios in 12 patients with obsessive-compulsive disorder (OCD) and 12 patients with OCD and a coexisting current diagnosis of major depressive disorder (OCD-MDD). Assessments were made at baseline and after 6 weeks of treatment with fluvoxamine. OCD-MDD patients had significantly lower baseline TRP levels and $TRP LNAA$ ratios than OCD patients. After 6 weeks of fluvoxamine treatment, OCD-MDD patients had significant increases in plasma TRP and $TRP LNAA$ ratio, whereas OCD patients had non-significant decreases. Our data suggest that a major depressive syndrome could be a state variable affecting the changes in plasma TRP and $TRP LNAA$ ratio in OCD patients.

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Cited by (12)

Tryptophan in health and disease
2020, Advances in Clinical Chemistry
Citation Excerpt :
It is important to note that, in the presence of comorbidities, i.e., aggressive or suicidal behavior, depressed patients show greater reduction in circulating TRP than those without these comorbidities as well as healthy controls [56,78,79,84]. Interestingly, comorbidity with obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD) symptoms or delirium appears to increase TRP [73,76,87,89]. Finally, depression and anxiety commonly occur together (in ~ 50% of patients) and their symptoms can be very similar.
Tryptophan (TRP), an essential amino acid in mammals, is involved in several physiological processes including neuronal function, immunity, and gut homeostasis. In humans, TRP is metabolized via the kynurenine and serotonin pathways, leading to the generation of biologically active compounds, such as serotonin, melatonin and niacin. In addition to endogenous TRP metabolism, resident gut microbiota also contributes to the production of specific TRP metabolites and indirectly influences host physiology.
The variety of physiologic functions regulated by TRP reflects the complex pattern of diseases associated with altered homeostasis. Indeed, an imbalance in the synthesis of TRP metabolites has been associated with pathophysiologic mechanisms occurring in neurologic and psychiatric disorders, in chronic immune activation and in the immune escape of cancer. In this chapter, the role of TRP metabolism in health and disease is presented. Disorders involving the central nervous system, malignancy, inflammatory bowel and cardiovascular disease are discussed.
Simultaneous chemosensing of tryptophan and the bacterial signal molecule indole by boron doped diamond electrode
2018, Electrochimica Acta
Citation Excerpt :
It appeared to us that the detection limit using BDD electrodes in our work would be sufficient for the analysis of indole in such biological samples. The plasma TRP concentrations in case of obsessive-compulsive disorder and major depressive disorder range from 50 to 70 μM [42], significantly higher than the LOD of the bare BDD electrode. However, it is present with two metabolites, 5-hydroxytryptophan, and serotonin at much lower concentrations (ng/mL) in patients affected with different forms of amenorrhea [43].
A simple and robust chemosensing approach using a boron-doped diamond (BDD) electrode has been developed and applied to analyze tryptophan (TRP) and indole during the growth of Escherichia coli in a complex growth medium. The bacterial enzyme tryptophanase catalyzes TRP to indole, an emerging signaling molecule. The process can now be monitored using electrochemistry, in a method far beyond the traditional identification protocols. Electroanalysis in a non-aqueous medium comprising acetonitrile (ACN) and tetrabutylammonium hexafluorophosphate (TBAH) is capable of separating the oxidation peak of TRP from that of indole. Mechanisms are postulated for the electrochemical oxidation of indole and TRP in ACN chosen because of its wider potential range, proton acceptor property, and solubilization of analytes. The electrochemical oxidation of TRP involves the elimination of two electrons. With a detection limit of 0.5 μM for both indole and TRP, this chemosensing approach is sufficient to monitor the level of these two biomolecules during the bacterial growth period.
Nutraceuticals in the treatment of Obsessive Compulsive Disorder (OCD): A review of mechanistic and clinical evidence
2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry
Citation Excerpt :
For this reason, an increase in the systemic concentration of tryptophan may not necessarily result in higher 5-HT synthesis in the brain (Feldman et al., 1997). Considering the evidence that drug-naïve OCD patients have both lower plasma levels of tryptophan and lower tryptophan/LNAA ratios (Bellodi et al., 1997), it could be argued that tryptophan supplementation may more successfully raise brain serotonin levels in OCD patients in comparison to the normal population. However, acute experimentally-induced tryptophan depletion has not been found to lead to increases in OCD symptom severity (Smeraldi et al., 1996); suggesting that tryptophan availability in itself is not directly related to obsessive–compulsive symptom severity.
Obsessive–Compulsive Disorder (OCD) is a debilitating mental illness which has a significant impact on quality of life. First-line SSRI treatments for OCD typically are of limited benefit to only 40–60% of patients, and are associated with a range of adverse side effects. Current preclinical research investigating nutraceuticals (natural products) for OCD, reveals encouraging novel activity in modulating key pathways suggested to be involved in the pathogenesis of OCD (glutamatergic and serotonergic pathway dysregulation). Emerging clinical evidence also appears to tentatively support certain nutrients and plant-based interventions with known active constituents which modulate these pathways: N-acetlycysteine, myo-inositol, glycine, and milk thistle (Silybum marianum). The serotonin precursor tryptophan is unlikely to be of use in treating OCD while 5-HTP may possibly be a more effective precursor strategy. However, there is currently no clinical evidence to test the efficacy of either of these substances. Currently the balance of clinical evidence does not support the use of St. John's wort (Hypericum perforatum) in OCD. While clinical research in this area is in its infancy, further research into nutraceuticals is warranted in light of the promising preclinical data regarding their mechanisms of action and their favourable side effect profiles in comparison to current SSRI treatments. It is recommended that future clinical trials of nutraceutical treatments for OCD utilize randomized placebo-controlled study designs and considerably larger sample sizes in order to properly test for efficacy.
Anorexia and Plasma Levels of Free Tryptophan, Branched Chain Amino Acids, and Ghrelin in Hemodialysis Patients
2009, Journal of Renal Nutrition
The aim of the present cross-sectional study was to assess appetite and to examine at the same time the associations between self-reported appetite and orexigen (ghrelin) and anorexigen (free tryptophan, free tryptophan/large neutral amino acid ratios, low branched chain amino acid levels) substances in chronic hemodialysis patients.
Cross-sectional study.
Patients were recruited from the Catholic University Outpatient Dialysis Clinic.
A total of 59 patients (32 men and 27 women) were included in this study. The mean age was 63.7 ± 13.9 years, and the mean dialytic age was 6.6 ± 5.1 years. Their mean body mass index of the study population was 25.1 ± 4.1 kg/m².
The first question of the Hemodialysis (HEMO) Study Appetite questionnaire was used to assess the appetite of the hemodialysis patients. The multiple-choice answers for the first question, “During the past week, how would you rate your appetite?” were (1) very good, (2) good, (3) fair, (4) poor, or (5) very poor. Plasma amino acid concentrations were measured with the use of liquid chromatography. Ghrelin levels were measured with Ghrelin-RIA (Mediagnost).
According to the questionnaire, in 16 of 59 (27.1%) hemodialysis patients, their appetite was very good (group 1); in 15 (25.4%), it was good (group 2); in another 15 (25.4%), it was fair (group 3); in 10 (16.9%), it was poor; and in 3 (5%), it was very poor. For statistical purposes, patients with a poor or very poor appetite were pooled together into a single group (group 4). Body mass index and serum albumin were significantly lower in patients with a fair and poor/very poor appetite than in patients with a very good or good appetite. According to the Subjective Global Assessment, all patients in groups A and B were well-nourished, whereas most patients in groups C (60%) and D (68%) were severely malnourished. Most of the comorbid conditions were significantly higher in patients of groups C and D. Branched chain amino acids were significantly lower in patients with a fair or poor/very poor appetite with respect to patients with a very good or good appetite. Free tryptophan levels were similar in the four groups of patients. The molar sum in plasma of the other large neutral amino acids (valine, leucine, isoleucine, tyrosin, phenylalanine) (large neutral amino acids) tended to be lower in patients with a fair and poor/very poor appetite than in patients with a very good or good appetite. However, the free tryptophan/large neutral amino acid ratio did not change significantly according to the appetite reported by the patients. Mean ghrelin levels were significantly higher in patients of group D than in other groups and in patients of groups B and C than in patients of group A.
The present study shows that poor appetite is associated with significantly lower branched chain amino acid levels but not with higher free tryptophan levels and higher free tryptophan/large neutral amino acid ratios in hemodialysis patients. In addition, significantly higher levels of ghrelin have been observed in patients with a poor/very poor appetite.
Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently
2001, Biological Psychiatry
Citation Excerpt :
Hence, depressive symptoms occurring in OCD patients appear to be mediated by decreased rather than increased activity in limbic-subcortical circuits. This decrease in subcortical activity might be related to lowered levels of tryptophan in patients with concurrent OCD+MDD compared with patients with OCD alone (Bellodi et al 1997) because tryptophan depletion has been found both to markedly reduce regional metabolism in the caudate, thalamus, and hippocampus in depressed subjects (Bremner et al 1997) and to produce depressive symptoms in nondepressed subjects with OCD who had improved on serotonin reuptake inhibitor medications (Barr et al 1994). This patient sample failed to confirm numerous prior reports of significantly elevated activity in OFC and caudate in subjects with OCD, with or without comorbid MDD, although there was trend toward higher right caudate metabolism in our subjects with OCD alone than in control subjects.
Background: The frequent comorbidity of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) suggests a fundamental relationship between them. We sought to determine whether MDD and OCD have unique cerebral metabolic patterns that remain the same when they coexist as when they occur independently.
Methods: [¹⁸F]-fluorodeoxyglucose positron emission tomography (PET) brain scans were obtained on 27 subjects with OCD alone, 27 with MDD alone, 17 with concurrent OCD+MDD, and 17 normal control subjects, all in the untreated state. Regional cerebral glucose metabolism was compared between groups.
Results: Left hippocampal metabolism was significantly lower in subjects with MDD alone and in subjects with concurrent OCD+MDD than in control subjects or subjects with OCD alone. Hippocampal metabolism was negatively correlated with depression severity across all subjects. Thalamic metabolism was significantly elevated in OCD alone and in MDD alone. Subjects with concurrent OCD+MDD had significantly lower metabolism in thalamus, caudate, and hippocampus than subjects with OCD alone.
Conclusions: Left hippocampal dysfunction was associated with major depressive episodes, regardless of primary diagnosis. Other cerebral metabolic abnormalities found in OCD and MDD occurring separately were not seen when the disorders coexisted. Depressive episodes occurring in OCD patients may be mediated by different basal ganglia-thalamic abnormalities than in primary MDD patients.
Loudness dependence of auditory evoked potentials in obsessive-compulsive disorder: A pilot study
2000, Psychiatry Research
In recent years it has been suggested that a serotonergic dysfunction is involved in the pathogenesis of obsessive–compulsive disorder (OCD). The loudness dependence of auditory evoked potentials (AEPs) is one of the best validated indicators of the activity of the serotonin system in humans. To explore the validity of the hypothesis of a serotonergic dysfunction in OCD, the loudness dependence of AEPs of 22 medication-free OCD patients were compared with those of 22 age- and gender-matched healthy subjects. Auditory evoked N1/P2 activity to tones of increasing intensity was studied using dipole source analysis. Contrary to the hypothesis, OCD patients and healthy controls did not differ in their LDAEPs of the tangential dipole in particular, located in the primary auditory cortex and closely related to central serotonergic activity. Furthermore, no significant correlation was found between the severity of obsessive–compulsive or depressive symptoms and the loudness dependence of AEPs. These findings do not support the hypothesis of a serotonergic dysfunction in OCD patients.

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ArticlePlasma tryptophan levels and tryptophan/neutral amino acid ratios in obsessive-compulsive patients with and without depression

Abstract

J Affect Disord

Psychiatry Res

Psychiatry Res

Life Sci

J Affect Disord

J Affect Disord

Diagnostic and Statistical Manual of Mental Disorders

Tryptophan depletion in patients with obsessive-compulsive dis-order who respond to serotonin reuptake inhibitors

Arch Gen Psychiatry

The serotonin hypothesis of obsessive compulsive disorder: implications of pharmacologic challenge studies

J Clin Psychiatry

Mood-lowering effect of tryptophan depletion

Arch Gen Psychiatry

Effects of acute and chronic treatment with fluvoxamine on extracellular and platelet serotonin in the blood of major depressive patients: relationship to clinical improvement

J Affect Disord

Influence of plasma tryptophan on brain 5HT synthesis and serotonergic activity

Adv Exp Med Biol

Plasma tryptophan and five other amino acids in depressed and normal subjects

Arch Gen Psychiatry

Serotonin function and the mechanism of antidepressant action

Arch Gen Psychiatry

Diet, food intake regulation, and brain serotonin: an overview

Brain serotonin content: physiological dependence on plasma tryptophan levels

Science

Brain serotonin content: increases following ingestion of a carbohydrate diet

Science

Article
Plasma tryptophan levels and tryptophan/neutral amino acid ratios in obsessive-compulsive patients with and without depression