PMID- 38340697
OWN - NLM
STAT- MEDLINE
DCOM- 20240226
LR  - 20240406
IS  - 1879-1379 (Electronic)
IS  - 0022-3956 (Print)
IS  - 0022-3956 (Linking)
VI  - 171
DP  - 2024 Mar
TI  - Cerebrospinal fluid proteomic signatures are associated with symptom severity of 
      first-episode psychosis.
PG  - 306-315
LID - S0022-3956(24)00064-5 [pii]
LID - 10.1016/j.jpsychires.2024.02.002 [doi]
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 x 10(-4)) and neuron-derived neurotrophic factor (NDNF: 
      SMD = -1.03, p = 4.52 x 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.
CI  - Copyright (c) 2024 Elsevier Ltd. All rights reserved.
FAU - Haroon, Humza
AU  - Haroon H
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic 
      College of Medicine and Science, Rochester, MN, USA.
FAU - Ho, Ada Man-Choi
AU  - Ho AM
AD  - Department of Psychiatry and Psychology, Mayo Clinic College of Medicine and 
      Science, Rochester, MN, USA.
FAU - Gupta, Vinod K
AU  - Gupta VK
AD  - Division of Surgery Research, Department of Surgery, Rochester, MN, USA; 
      Microbiome Program, Center for Individualized Medicine, Rochester, MN, USA.
FAU - Dasari, Surendra
AU  - Dasari S
AD  - Division of Biomedical Statistics and Informatics, Mayo Clinic College of 
      Medicine and Science, Rochester, MN, USA.
FAU - Sellgren, Carl M
AU  - Sellgren CM
AD  - Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 
      Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, 
      Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, 
      Stockholm, Sweden.
FAU - Cervenka, Simon
AU  - Cervenka S
AD  - Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska 
      Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; 
      Department of Medical Sciences, Psychiatry, Uppsala University, Uppsala, Sweden.
FAU - Engberg, Goran
AU  - Engberg G
AD  - Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Eren, Feride
AU  - Eren F
AD  - Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Erhardt, Sophie
AU  - Erhardt S
AD  - Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Sung, Jaeyun
AU  - Sung J
AD  - Division of Surgery Research, Department of Surgery, Rochester, MN, USA; 
      Microbiome Program, Center for Individualized Medicine, Rochester, MN, USA; 
      Division of Rheumatology, Department of Internal Medicine, Rochester, MN, USA.
FAU - Choi, Doo-Sup
AU  - Choi DS
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic 
      College of Medicine and Science, Rochester, MN, USA; Department of Psychiatry and 
      Psychology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; 
      Neuroscience Program, Mayo Clinic College of Medicine and Science, Rochester, MN, 
      USA. Electronic address: choids@mayo.edu.
LA  - eng
GR  - R01 AA029258/AA/NIAAA NIH HHS/United States
GR  - R01 AG072898/AG/NIA NIH HHS/United States
GR  - R21 AA028968/AA/NIAAA NIH HHS/United States
PT  - Journal Article
DEP - 20240202
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
SB  - IM
MH  - Humans
MH  - Proteomics
MH  - *Psychotic Disorders/diagnosis
MH  - *Schizophrenia/cerebrospinal fluid
PMC - PMC10995989
MID - NIHMS1976687
OTO - NOTNLM
OT  - Cerebrospinal fluid
OT  - First-episode psychosis
OT  - Proteomics
OT  - Schizophrenia
COIS- Declaration of competing interest All authors declare that the research was 
      conducted without commercial or financial relationships that could be construed 
      as a potential conflict of interest.
EDAT- 2024/02/11 07:42
MHDA- 2024/02/26 06:43
PMCR- 2025/03/01
CRDT- 2024/02/10 18:14
PHST- 2023/09/18 00:00 [received]
PHST- 2024/01/04 00:00 [revised]
PHST- 2024/02/01 00:00 [accepted]
PHST- 2025/03/01 00:00 [pmc-release]
PHST- 2024/02/26 06:43 [medline]
PHST- 2024/02/11 07:42 [pubmed]
PHST- 2024/02/10 18:14 [entrez]
AID - S0022-3956(24)00064-5 [pii]
AID - 10.1016/j.jpsychires.2024.02.002 [doi]
PST - ppublish
SO  - J Psychiatr Res. 2024 Mar;171:306-315. doi: 10.1016/j.jpsychires.2024.02.002. 
      Epub 2024 Feb 2.