Profiling classical neuropsychiatric biomarkers across biological fluids and following continuous lumbar puncture: A guide to sample type and time

Abstract

Identification of putative biomarkers for neuropsychiatric disorders has produced a diverse list of analytes involved in inflammation, hypothalamic–pituitary–adrenal axis (HPA) regulation, growth factor and metabolic pathways. However, translation of these findings to accurate and robust assays has been stalled, affecting objective diagnoses, tracking relapse/remission, and prediction/monitoring of drug affect. Two important factors to control are the sample matrix (e.g. serum, plasma, saliva, or cerebrospinal fluid) and time of sample collection. Additionally, sample collection procedures may affect analyte level. In this study, a panel of 14 core neuropsychiatric biomarkers was measured in serum, plasma, saliva, and cerebrospinal fluid (CSF), all collected from 8 healthy volunteers at the same time. In a second cohort of 7 healthy volunteers, 6 analytes were measured in serum and CSF collected at 13 timepoints over a 24-h period after catheter placement. We found that many of the analytes were quantifiable in all sample types examined, but often at quite different concentrations and without correlation between the sample types. After catheter placement, a diurnal pattern was observed for cortisol and interleukin-6 in serum, and transient spikes were observed in interleukin-1β. In CSF, a chronic elevation of several cytokines was observed instead, perhaps due to the continuous sampling procedure. These findings enable more informed decision-making around sample type and collection time, which can be implemented in future biomarker studies. Clinicaltrial.gov identifiers: NCT02933762, NCT02475148.

Keywords

• Neuropsychiatric disorders
• Neuropsychiatric biomarkers
• Diurnal pattern