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Kanchanatawan, B.

Publications and source records attributed to Kanchanatawan, B..

2 recordsLinked to original sources
bioRxiv2018

Supervised machine learning to decipher the complex associations between neuro-immune biomarkers and quality of life in schizophrenia

Stable phase schizophrenia is characterized by altered patterning in tryptophan catabolites (TRYCATs) and memory impairments, which are associated with PHEMN (psychosis, hostility, excitation, mannerism and negative) and DAPS (depression, anxiety and physio-somatic) symptoms. This study was carried out to examine the association between TRYCAT patterning, memory impairments, psychopathological features and health-related quality of life (HR-QoL) in schizophrenia.\n\nThe World Health Organization (WHO) QoL instrument-Abbreviated version (WHO-QoL-BREF), IgA/IgM responses to TRYCATs, cognitive tests, Scale for the Assessment of Negative Symptoms (SANS), Hamilton and Depression (HAMD) and Anxiety (HAMA) Rating Scales and the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale (FF) were measured in 80 schizophrenia patients and 40 controls.\n\nNeural Network analysis shows that the total HR-Qol score is best predicted by (in descending order) FF, HAMA and SANS scores, Mini Mental State examination, hostility, ratio noxious/protective TRYCATs and HAMD score. Partial least Squares (PLS) analysis shows that 55.1% of the variance in Domain1 (physical) is predicted by PHEMN and DAPS latent vector (LV) scores, while 57.9% of domain2 (psychological), 32.7% of domain3 (social) and 55.0% of domain4 (environment) are explained by DAPS LV scores. TRYCATs and episodic/semantic memory impairments have specific indirect effects on domains 2, 3 and 4, which are mediated by DAPS symptoms, while the effects of TRYCATs on domain1 are mediated by PHEMN and DAPS symptoms. Picolinic acid, xanthurenic acid and 3-hydroxy-kynurenine decrease WHO-QoL scores, whilst anthranilic acid is protective.\n\nThe results show that lowered HR-Qol in schizophrenia is strongly predicted by noxious TRYCATs, impairments in episodic and semantic memory and DAPS symptoms, especially physio-somatic symptoms and anxiety. Neuro-immune pathways and the consequent cognitive impairments determine to a great extent lowered HR-QoL in schizophrenia.

neuroscience↗
bioRxiv2018

A new schizophrenia model: immune activation is associated with induction of thetryptophan catabolite pathway and increased eotaxin levels which together determinememory impairments and schizophrenia symptom dimensions.

AbstractO_ST_ABSObjectiveC_ST_ABSRecently, we reported that stable-phase schizophrenia is characterized by two interrelated symptom dimensions: PHEMN (psychotic, hostility, excitation, mannerism and negative symptoms); and DAPS (depressive, anxiety and physio-somatic symptoms) and that Major Neuro-Cognitive psychosis (MNP) is the full blown phenotype of schizophrenia (largely overlapping with deficit schizophrenia). Herein we examined the effects of immune activation in association with tryptophan catabolite (TRYCAT) patterning and memory disorders on PHEMN/DAPS dimensions and MNP.\n\nMethodSerum levels of macrophage inflammatory protein-1 (MIP-1), soluble interleukin (IL)-1 receptor antagonist (sIL-1RA), IL-10, eotaxin, IgA/IgM responses to TRYCATs, and Consortium to Establish a Registry for Alzheimers disease (CERAD) tests were assessed in 40 controls and 80 schizophrenia patients.\n\nResultsSchizophrenia and MNP were predicted by significantly increased levels of IL-10, eotaxin and TRYCATs. A large part of the variance in both PHEMN/DAPS symptom dimensions (42.8%) was explained by cytokine levels and TRYCATs combined. The MTP+sTL-1R A+IL-10 composite score and eotaxin explained each around 19% of the variance in symptom dimensions, and approximately 18% of memory deficits. Moreover, MIP+sIL-1RA+IL-10 was significantly associated with elevations in picolinic acid, xanthurenic acid and 3-OH-kynurenine. Partial Least Squares path modeling shows that the highly significant effects of MIP+sIL-1RA+IL-10 on symptomatology are mediated by the effects of noxious TRYCATs on memory deficits.\n\nConclusionsCurrent findings indicate that in schizophrenia, immune activation may underpin activation of indoleamine-2,3-dioxygenase and kynurenine monooxygenase, while impairments in episodic and semantic memory may be caused by the neurotoxic effects of TRYCATs and eotaxin. The combined effects of immune activation, eotaxin and memory defects determine to a large extent PHEMN/DAPS symptoms and the MNP phenotype. These findings indicate that schizophrenia phenomenology is largely mediated by multiple neuro-immune pathways and that immune activation, increased production of eotaxin and neurotoxic TRYCATs (picolinic acid, xanthurenic acid and 3-HO-kynurenine) are new drug targets in schizophrenia and MNP.

neuroscience↗