063_ Proteomic blood biomarker signature for prediction of poor clinical outcome in affective and non-affective Psychosis: Pilot Study
Research Question and Aims
The aim of the proposed analysis is to measure proven blood biomarkers of neuronal damage and microglial activation (neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP)) using 4th-generation immunoassays (single-molecule array, Simoa) [Khalil 2018] in a longitudinal and transdiagnostic approach within the PsyCourse Study. NfL levels in blood plasma and cerebrospinal fluid (CSF) are highly correlated [Mielke 2019]. Elevated plasma NfL is a prognostic marker of short-term cognitive decline and associated with decline in hippocampal volume, cortical thickness, fractional anisotropy (FA) in the corpus callosum and global cognition in healthy older adults [Mielke 2019]. GFAP is a component of the astrocyte cytoskeleton and relevant for the structural and functional integrity of astrocytes and may be even better detectable in in the peripheral blood than in cerebrospinal fluid and reflect changes of the central nervous system. It is involved in many processes in the central nervous system like cell communication and functioning of the blood brain barrier, which have been described as impaired in neuropsychiatric disorders [Garden 2016][Kealy 2020]. Glial-mediated processes of inflammation are also coming increasingly to the fore in psychiatric disorders such as, in particular, schizophrenia and affective psychoses [Watkins 2014][Jeppesen 2022]. Increasingly, glial-mediated pathways of inflammation are becoming the focus of the development of new innovative drugs. For this reason, it is important to identify which patients suffer from glial-mediated neuroinflammation as well as which patients might respond to glial-mediated therapy. Since it is currently not possible to measure all PsyCourse participants without research funding, we have decided on the following approach for our pilot study:
We have identified 40 patients in the PsyCourse Study whose performance in Verbal Learning (cognitive test: VLMT) declined over a one-year observation period (comparing visit 2 and visit 4). We then matched a comparison group of patients who improved in Verbal Learning over the same one-year period with respect to age, sex, diagnosis and medication (number of antidepressant and number of antipsychotics). These two subsamples will be compared cross-sectionally and, even more important, longitudinally where are each patient can act as his or her own control. Secondary analyses will compare other cognitive tests in this subsample, and analyze possible relations to NfL and GFAP levels.
We will perform inhouse measurement of two plasma blood biomarkers (NfL and GFAP) with ultra-sensitive SIMOA® technology using the “Human Neurology 2-Plex” assay. Measurements will be twofold on the same Duplex plates.
The hypotheses of the primary analyses would be:
a) both groups differ significantly in cross-sectional blood concentrations of NfL and GFAP, and
b) in the group with a decrease in cognitive performance there is also an increase (NfL) or decrease (GFAP) in the measured parameters associated with cognitive performance.
In secondary analyses it will be tested if the plasma blood biomarkers are associated with the magnitude of cognitive decline.