2021-10-28

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.

Analytic Plan

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.

Resources needed

v1_id
v1_stat
v1_center
v1_tstlt
v1_interv_date
v1_sex
v1_ageBL
v1_yob
v1_cur_psy_trm
v1_dur_illness
v1_tms_daypat_outpat_trm
v1_cat_daypat_outpat_trm
v1_fam_hist
v1_school
v1_prof_dgr
v1_ed_status
v1_curr_paid
v1_disabl_pens
v1_spec_emp
v1_wrk_abs_pst_5_yrs
v1_cur_work_restr
v1_marital_stat
v1_partner
v1_liv_aln
v1_lftm_alc_dep
v1_evr_ill_drg
v1_scid_dsm_dx
v1_scid_dsm_dx_cat v4_gaf
v2_gaf
v2_cgi_s
v2_cgi_c
v2_panss_sum_pos
v2_panss_sum_neg
v2_panss_sum_gen
v2_idsc_sum
v2_ymrs_sum
v2_Antidepressants
v2_Antipsychotics
v2_Mood_Stabilizers
v2_Tranquilizers
v2_Other_psychiatric
v1_ nrpsy_mwtb
v2_nrpsy_mtv
v2_nrpsy_vlmt_corr
v2_nrpsy_vlmt_lss_d
v2_nrpsy_vlmt_lss_t
v2_nrpsy_vlmt_rec
v2_nrpsy_tmt_A_rt
v2_nrpsy_tmt_B_rt
v2_nrpsy_dgt_sp_frw
v2_nrpsy_dgt_sp_bck
v2_nrpsy_dg_sym
v4_nrpsy_mtv
v4_nrpsy_vlmt_corr
v4_nrpsy_vlmt_lss_d
v4_nrpsy_vlmt_lss_t
v4_nrpsy_vlmt_rec
v4_nrpsy_tmt_A_rt
v4_nrpsy_tmt_B_rt
v4_nrpsy_dgt_sp_frw
v4_nrpsy_dgt_sp_bck
v4_nrpsy_dg_sym
v4_gaf
v4_cgi_s
v4_cgi_c
v4_panss_sum_pos
v4_panss_sum_neg
v4_panss_sum_gen
v4_idsc_sum
v4_ymrs_sum
v4_Antidepressants
v4_Antipsychotics
v4_Mood_Stabilizers
v4_Tranquilizers
v4_Other_psychiatric