Cardiovascular protein profiling in patients with first-episode psychosis

Abstract

Patients with schizophrenia have a threefold higher mortality from cardiovascular disease than people in the general population. Atherosclerosis is linked to immune activation, a process tentatively entwined with the underlying pathophysiological mechanisms of schizophrenia. The aim of the present study was to investigate an extensive array of cardiovascular biomarkers in individuals experiencing their first episode of psychosis (FEP), either drug-naïve or exposed to short-term antipsychotic treatment, alongside a group of healthy controls (HC). Using the OLINK Proximity Extension Assay, Cardiovascular II Panel, we analyzed plasma from 72 FEP patients, including 42 later diagnosed with schizophrenia and 54 HCs. Biomarker levels, that significantly differed between patients and controls, were correlated with symptom severity, cognitive performance and cardiovascular risk factors. Fifteen out of 92 cardiovascular biomarkers were higher in individuals with FEP compared to HC, and one biomarker was lower in FEP patients compared to HC. BMI, waist size, blood pressure, fp-glucose, HbA1c and serum lipid levels were similar between the groups. No correlations that held for multiple comparisons were seen between biomarker concentrations and symptom severity, cognitive performance or cardiovascular risk factors in FEP patients. Higher concentrations of several cardiovascular biomarkers were observed in individuals with FEP compared to in HC. This suggests that patients with FEP are at an increased risk of developing cardiovascular disease from the onset of psychosis, even before changes in traditional biomarkers are detectable. It underscores the need for innovative approaches to detect and monitor this risk early.

Fig. 1. Differences in plasma cardiovascular proteins in patients with first episode psychosis vs. healthy controls.

Ninety-one biomarkers are presented in a volcano plot with log₂ fold change between FEP patients and HC. Log₂ fold changes between groups and p values are calculated with the limma package in R and adjusted for plate, age, gender, and nicotine use. Adjustment for multiple comparisons was performed using the Benjamini–Hochberg correction method and was corrected for 91 tests. Significance level chosen for adjusted p value is <0.05.

Fig. 2. OLINK cardiovascular protein profiling in plasma of patients with first episode psychosis vs. healthy controls.

Scatter dot plots display 16 biomarkers that show significant differences between FEP patients and HC. The horizontal line represents the median value. HC healthy controls, FEP first episode psychosis patients.

Fig. 3. Correlations of significantly different biomarkers in plasma (NPX values) and clinical rating scores (PANSS, GAF, and CGI) in patients with first episode psychosis.

Correlation analysis was performed using Spearman correlation (r_s) and numbers in the heat map boxes indicate r_s values. The color represents the value of the Spearman’s rank coefficient, and red is a positive correlation and blue a negative correlation. The asterisk indicates a significant correlation (p < 0.05). None of the correlations remained significant after correction for multiple analysis with Benjamini–Hochberg’s method. PANSS positive and negative syndrome scale, CGI clinical global impression, GAF global assessment of functioning.

Fig. 4. Correlations of significantly different biomarkers in plasma (NPX) and cognitive measures (MATRICS) in patients with first episode psychosis.

Correlation analysis was performed using Spearman correlation (r_s) and numbers in the heat map boxes indicate r_s values. The color represents the value of the Spearman’s rank coefficient, and red is a positive correlation and blue a negative correlation. The asterisk indicates a significant correlation (p < 0.05). None of the correlations remained significant after correction for multiple analysis with Benjamini–Hochberg’s method. TMT trail making test, Part A, BACS SC brief assessment of cognition in schizophrenia, symbol coding, HVLT-R Hopkins verbal learning test-revised, WMS III SS Wechsler memory scale–3rd edition: spatial span, LNS letter-number span, NAB-MAZES neuropsychological assessment battery: Mazes, BVMT-R brief visuospatial memory test revised, Fluency category fluency: animal naming, MSCEIT ME Mayer–Salovey–Caruso emotional intelligence test: managing emotions, and CPT continuous performance test-identical pairs.