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. The 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. Neural Network analysis shows that the total HR-Qol score is best predicted by (in descending order) HAMA, FF, HAMD, and psychosis. Partial least Squares (PLS) analysis shows that 56.7% of the variance in the WHO-QoL scores is explained by PHEMN / DAPS symptoms, while 64.3% of the variance in those symptoms is explained by TRYCAT patterning and episodic/semantic memory impairments. IgA responses to picolinic acid, xanthurenic acid and 3-hydroxy-kynurenine (all negatively) and anthranilic acid (positively) have highly significant indirect effects on WHO-QoL scores, which are completely mediated by cognitive impairments and PHEMN / DAPS symptoms. The results show that lowered HR-Qol in schizophrenia is strongly associated with noxious TRYCATs and that these effects are mediated by impairments in episodic / semantic memory and schizophrenia phenomenology, especially physio-somatic and anxiety symptoms. Mucosal activation of the TRYCAT pathway combined with a deficit in natural IgM isotype antibodies to TRYCATs determine cognitive impairments and DAPS/PHEMN symptoms, which together determine to a large extent lowered HR-QoL in schizophrenia.