E2 ModeratePreliminaryPEM not requiredCross-SectionalPeer-reviewedReviewed
In Schizophrenia, Depression, Anxiety, and Physiosomatic Symptoms Are Strongly Related to Psychotic Symptoms and Excitation, Impairments in Episodic Memory, and Increased Production of Neurotoxic Tryptophan Catabolites: a Multivariate and Machine Learning Study.
Kanchanatawan, Buranee, Thika, Supaksorn, Sirivichayakul, Sunee et al. · Neurotoxicity research · 2018 · DOI
Quick Summary
This study examined 80 people with schizophrenia and 40 healthy controls to understand why schizophrenia patients often experience depression, anxiety, and physical symptoms like those seen in chronic fatigue. The researchers found that these symptoms were linked to changes in how the body breaks down tryptophan (an amino acid), problems with memory, and the severity of psychotic symptoms. The findings suggest that toxic byproducts from tryptophan metabolism may contribute to depression, anxiety, and physical symptoms in schizophrenia.
Why It Matters
Although this study focuses on schizophrenia rather than ME/CFS, it provides important evidence that depression, anxiety, and physical symptoms can be driven by both cognitive impairment and dysregulated tryptophan metabolism—mechanisms potentially relevant to ME/CFS pathophysiology. The identification of tryptophan catabolites as contributors to systemic symptoms suggests a metabolic pathway that warrants investigation in ME/CFS populations.
Observed Findings
- Regression models explained 58.9% of depression variance through excitement, TRYCAT ratios, word list memory, and verbal fluency.
- 29.9% of anxiety variance was explained by psychotic symptoms and elevated noxious/protective TRYCAT ratios.
- 45.5% of physiosomatic symptom variance was explained by psychotic symptoms, TRYCAT ratios, and word list memory impairment.
- Noxious tryptophan catabolites (picolinic, quinolinic, and xanthurenic acid) were elevated in association with symptom burden.
Inferred Conclusions
- Depression, anxiety, and physical symptoms in schizophrenia are driven by a combination of psychotic/excitation symptoms, episodic memory impairment (especially false memory creation), and dysregulated tryptophan metabolism.
- Increased production of neurotoxic tryptophan catabolites may be a shared metabolic driver of cognitive and psychiatric symptom dimensions.
- Tryptophan catabolite patterning and cognitive dysfunction may represent mechanistic targets for symptom management in psychotic disorders.
Remaining Questions
- Does tryptophan dysmetabolism precede symptom onset, or does it develop secondarily to psychotic illness?
- Are the identified tryptophan catabolite abnormalities specific to schizophrenia or present across conditions featuring depression, anxiety, and physiosomatic symptoms?
What This Study Does Not Prove
This study does not establish causality; the cross-sectional design cannot determine whether tryptophan dysmetabolism causes symptoms or results from them. The findings are specific to schizophrenia and cannot be directly applied to ME/CFS without replication in ME/CFS cohorts. The study does not assess whether these mechanisms are unique to schizophrenia or shared across conditions with similar symptom profiles.
Tags
Symptom:Cognitive DysfunctionPainFatigue
Biomarker:MetabolomicsAutoantibodiesBlood Biomarker
Method Flag:Weak Case DefinitionSmall SampleMixed Cohort
Metadata
- DOI
- 10.1007/s12640-018-9868-4
- PMID
- 29380275
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 12 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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