Psychotic disorders are mental illnesses with psychosis, which includes schizophrenia. It can often be difficult to pinpoint the underlying disorder due to symptom overlap and being confounded by the patient’s delusional mindset. In order to identify at-risk patients, researchers have been investigating potential biomarkers. This work has primarily been focused on blood biomarkers, as these samples are easily obtained. However, it is appreciated that the changes in the blood biochemistry do not always reflect the changes in the brain biochemistry. Therefore, it is important to identify changes in the brain biochemistry of individuals with psychotic disorders, as this may be driving disease pathogenesis or could be used clinically for diagnosis or targeted therapeutics.
Dr. Troels Boldt Rømer and colleagues recently published a meta-analysis of perturbations in the cerebral spinal fluid (CSF) composition of patients with psychotic disorders with the goal of compiling a comprehensive list of potential biomarkers that can be used to diagnose patients. In this study data from 145 studies were included, which is an impressive number of studies, but as the authors point out, for many potential biomarkers there was a lack of overlap to make conclusive results. However, of the biomarkers that had ample representation, inflammatory cytokines, kynurenine (KYN), and kynurenic acid (KYNA) levels were elevated in the CSF of patients compared to healthy controls. Additionally, this study highlights findings of noradrenergic disturbances and dysfunction of the blood-brain barrier, as evident by increased noradrenaline levels as well as albumin and IgG CSF to serum ratios in psychotic disorder patients.
It is interesting to note that this study labeled KYNA as “proinflammatory” which contradicts with what the current literature knows about KYNA in terms of immune modulation. Although KYNA can increase production of the pro-inflammatory cytokine IL-6 via Aryl hydrocarbon Receptor, at physiological relevant concentration during inflammation, several studies showed that KYNA can mediate immunosuppression (i.e. anti-inflammation) by at least 2 mechanisms: 1) TNF-stimulated gene 6; and 2) G Protein-coupled Receptor 35. Read more about the role of KYNA in immune modulation here. Whether KYNA plays a pro- or anti- inflammatory role in psychosis warrants further investigation.
Regardless of the authors conclusions on KYNA, the authors do bring up valid limitations that we should consider when designing our experiments. First, identifying the best population of controls especially in CSF studies where obtaining samples from healthy controls may be limited. Second, ideally would be to try to optimize a standard analysis method, but at the very least detailed reporting of the range of detection and samples outside of that range should be included in the results. While research has started to point to potential biomarkers, there is a clear need for further research in order to concretely identify biomarkers that can be used to identify individuals suffering from psychosis.