Depressive, anxiety and hypomanic symptoms in schizophrenia may be driven by tryptophan catabolite (TRYCAT) patterning of IgA and IgM responses directed to TRYCATs

Abstract

The aim of this study was to delineate the associations between the tryptophan catabolite (TRYCAT) pathway and affective symptoms in schizophrenia. Towards this end we measured immunoglobulin (Ig)A and IgM responses to relatively noxious TRYCATs, namely quinolinic (QA), xanthurenic (XA), picolinic (PA) acid and 3-OH-kynurenine (3HK), and generally protective TRYCATs, namely anthranilic (AA) and kynurenic (KA) acid in 80 patients with schizophrenia and 40 healthy controls. The Hamilton Rating Scale for Depression (HDRS) and anxiety (HAMA), Young Mania Rating Scale (YMRS) as well as the Positive and Negative Symptoms Scale of Schizophrenia (PANSS) were measured. Depression, anxiety and hypomanic as well as negative and positive symptoms were associated with increased IgA responses to PA. Increased IgA responses to XA were associated with anxiety, hypomanic and negative symptoms. Moreover, depressive, anxiety, hypomanic and negative symptoms were characterized by increased IgA responses to the noxious (XA+3HK+QA+PA)/protective (AA+KA) TRYCAT ratio. All symptom dimensions were associated with increased IgM responses to QA, while depressive, anxiety, positive and negative symptoms were accompanied by lowered IgM responses to 3HK. Hypomanic symptoms were additionally accompanied by lowered IgM responses to AA, and negative symptoms by increased IgM responses to KA. In conclusion, both shared and distinct alterations in the activity of the TRYCAT pathway, as well as its regulatory factors and consequences, may underpin affective and classical psychotic symptoms of schizophrenia. Increased mucosa-generated production of noxious TRYCATs, especially PA, and specific changes in IgM-mediated regulatory activities may be associated with the different symptom dimensions of schizophrenia.

Effects of inflammation on the kynurenine pathway in schizophrenia — a systematic review

“…The negative symptoms of schizophrenia are significantly and positively correlated with increased IgA responses directed against PIC and inversely with AA, whereas no significant associations between positive symptoms and IgA responses to TRYCATs were found [41,42].…”

“…The authors tried to delineate the differences in tryptophan catabolites' (TRYCATs) profile between both groups in comparison with healthy controls (n = 40). Deficit schizophrenia was accompanied by an activated TRYCATs pathway when compared to controls and the non-deficit schizophrenia subgroup [41,42]. Moreover, both schizophrenia subgroups showed increased IgA responses to 3-OH-kynurenine as compared to controls while KYNA and anthranilic acid (AA) were relatively lowered in the combined schizophrenia groups versus controls with respect to increased levels of noxious TRYCATs [41,42].…”

“…The non-deficit schizophrenia patient subgroup versus healthy controls was characterized by relatively increased PIC but lowered QUIN levels [41,42].…”

“…Interestingly, deficit schizophrenia showed much higher IgA responses to PIC, xanthurenic acid (XA), and QUIN; an increased QUIN/KYNA ratio; relatively lowered AA and KYNA levels; and lowered IgA responses to both acids as compared to non-deficit schizophrenia [41,42].…”

Chronic Fatigue and Fibromyalgia Symptoms are Key Components of Deficit Schizophrenia and are Strongly Associated with Activated Immune-Inflammatory Pathways

“…Moreover, IRS activation in schizophrenia (including Th-1 and M1 macrophage) may cause stimulation of peripheral IDO (indoleamine 2,3-dioxygenase), which causes an increased catabolism of tryptophan into tryptophan catabolites (TRYCATs), some of which are neurotoxic, e.g. picolinic acid (PA), xanthurenic acid (XA), kynurenine (KYN) and quinolinic acid (QA) (Kanchanatawan et al, 2018c;2018d). Importantly, increased levels of IgA directed to those TRYCATs (indicating TRYCAT pathway activation) in schizophrenia are significantly associated not only with PHEM, negative, affective and neurocognitive symptoms but also with physiosomatic symptoms (Kanchanatawan et al, 2017;2018a;2018b;2018g), indicating that the latter may be immune-mediated.…”