TY - JOUR
T1 - Cerebrospinal fluid proteomic signatures are associated with symptom severity of first-episode psychosis
AU - Haroon, Humza
AU - Ho, Ada Man Choi
AU - Gupta, Vinod K.
AU - Dasari, Surendra
AU - Sellgren, Carl M.
AU - Cervenka, Simon
AU - Engberg, Göran
AU - Eren, Feride
AU - Erhardt, Sophie
AU - Sung, Jaeyun
AU - Choi, Doo Sup
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2024/3
Y1 - 2024/3
N2 - Apart from their diagnostic, monitoring, or prognostic utility in clinical settings, molecular biomarkers may be instrumental in understanding the pathophysiology of psychiatric disorders, including schizophrenia. Using untargeted metabolomics, we recently identified eight cerebrospinal fluid (CSF) metabolites unique to first-episode psychosis (FEP) subjects compared to healthy controls (HC). In this study, we sought to investigate the CSF proteomic signatures associated with FEP. We employed 16-plex tandem mass tag (TMT) mass spectrometry (MS) to examine the relative protein abundance in CSF samples of 15 individuals diagnosed with FEP and 15 age-and-sex-matched healthy controls (HC). Multiple linear regression model (MLRM) identified 16 differentially abundant CSF proteins between FEP and HC at p < 0.01. Among them, the two most significant CSF proteins were collagen alpha-2 (IV) chain (COL4A2: standard mean difference [SMD] = −1.12, p = 1.64 × 10−4) and neuron-derived neurotrophic factor (NDNF: SMD = −1.03, p = 4.52 × 10−4) both of which were down-regulated in FEP subjects compared to HC. We also identified several potential CSF proteins associated with the pathophysiology and the symptom profile and severity in FEP subjects, including COL4A2, NDNF, hornerin (HRNR), contactin-6 (CNTN6), voltage-dependent calcium channel subunit alpha-2/delta-3 (CACNA2D3), tropomyosin alpha-3 chain (TPM3 and TPM4). Moreover, several protein signatures were associated with cognitive performance. Although the results need replication, our exploratory study suggests that CSF protein signatures can be used to increase the understanding of the pathophysiology of psychosis.
AB - Apart from their diagnostic, monitoring, or prognostic utility in clinical settings, molecular biomarkers may be instrumental in understanding the pathophysiology of psychiatric disorders, including schizophrenia. Using untargeted metabolomics, we recently identified eight cerebrospinal fluid (CSF) metabolites unique to first-episode psychosis (FEP) subjects compared to healthy controls (HC). In this study, we sought to investigate the CSF proteomic signatures associated with FEP. We employed 16-plex tandem mass tag (TMT) mass spectrometry (MS) to examine the relative protein abundance in CSF samples of 15 individuals diagnosed with FEP and 15 age-and-sex-matched healthy controls (HC). Multiple linear regression model (MLRM) identified 16 differentially abundant CSF proteins between FEP and HC at p < 0.01. Among them, the two most significant CSF proteins were collagen alpha-2 (IV) chain (COL4A2: standard mean difference [SMD] = −1.12, p = 1.64 × 10−4) and neuron-derived neurotrophic factor (NDNF: SMD = −1.03, p = 4.52 × 10−4) both of which were down-regulated in FEP subjects compared to HC. We also identified several potential CSF proteins associated with the pathophysiology and the symptom profile and severity in FEP subjects, including COL4A2, NDNF, hornerin (HRNR), contactin-6 (CNTN6), voltage-dependent calcium channel subunit alpha-2/delta-3 (CACNA2D3), tropomyosin alpha-3 chain (TPM3 and TPM4). Moreover, several protein signatures were associated with cognitive performance. Although the results need replication, our exploratory study suggests that CSF protein signatures can be used to increase the understanding of the pathophysiology of psychosis.
KW - Cerebrospinal fluid
KW - First-episode psychosis
KW - Proteomics
KW - Schizophrenia
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U2 - 10.1016/j.jpsychires.2024.02.002
DO - 10.1016/j.jpsychires.2024.02.002
M3 - Article
C2 - 38340697
AN - SCOPUS:85184779868
SN - 0022-3956
VL - 171
SP - 306
EP - 315
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -