PMID- 37674553
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230919
IS  - 1664-0640 (Print)
IS  - 1664-0640 (Electronic)
IS  - 1664-0640 (Linking)
VI  - 14
DP  - 2023
TI  - Evidence for increased DNA damage repair in the postmortem brain of the high 
      stress-response group of schizophrenia.
PG  - 1183696
LID - 10.3389/fpsyt.2023.1183696 [doi]
LID - 1183696
AB  - BACKGROUND: Schizophrenia (SZ) is a disorder diagnosed by specific symptoms and 
      duration and is highly heterogeneous, clinically and pathologically. Although 
      there are an increasing number of studies on the association between genetic and 
      environmental factors in the development of SZ, the actual distribution of the 
      population with different levels of influence of these factors has not yet been 
      fully elucidated. In this study, we focused on stress as an environmental factor 
      and stratified SZ based on the expression levels of stress-responsive molecules 
      in the postmortem prefrontal cortex. METHODS: We selected the following 
      stress-responsive molecules: interleukin (IL) -1beta, IL-6, IL-10, tumor necrosis 
      factor-alpha, interferon-gamma, glucocorticoid receptor, brain-derived neurotrophic 
      factor, synaptophysin, S100 calcium-binding protein B, superoxide dismutase, 
      postsynaptic density protein 95, synuclein, apolipoprotein A1 (ApoA1), ApoA2, and 
      solute carrier family 6 member 4. We performed RNA sequencing in the prefrontal 
      gray matter of 25 SZ cases and 21 healthy controls and conducted a hierarchical 
      cluster analysis of SZ based on the gene expression levels of stress-responsive 
      molecules, which yielded two clusters. After assessing the validity of the 
      clusters, they were designated as the high stress-response SZ group and the low 
      stress-response SZ group, respectively. Ingenuity Pathway Analysis of 
      differentially expressed genes (DEGs) between clusters was performed, and 
      Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      staining was conducted on four cases each in the high and low stress-response SZ 
      groups to validate DNA damage. RESULTS: We found higher prevalence of family 
      history of SZ in the low stress-response SZ group (0/3 vs. 5/4, p = 0.04). 
      Pathway analysis of DEGs between clusters showed the highest enrichment for DNA 
      double-strand break repair. TUNEL staining showed a trend toward a lower 
      percentage of TUNEL-positive cells in the high stress-response SZ group. 
      CONCLUSION: Our results suggest that there are subgroups of SZ with different 
      degrees of stress impact. Furthermore, the pathophysiology of these subgroups may 
      be associated with DNA damage repair. These results provide new insights into the 
      interactions and heterogeneity between genetic and environmental factors.
CI  - Copyright (c) 2023 Shishido, Kunii, Hino, Izumi, Nagaoka, Hayashi, Kakita, Tomita 
      and Yabe.
FAU - Shishido, Risa
AU  - Shishido R
AD  - Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, 
      Fukushima, Japan.
FAU - Kunii, Yasuto
AU  - Kunii Y
AD  - Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, 
      Fukushima, Japan.
AD  - Department of Disaster Psychiatry, International Research Institute of Disaster 
      Science, Tohoku University, Sendai, Japan.
FAU - Hino, Mizuki
AU  - Hino M
AD  - Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, 
      Fukushima, Japan.
AD  - Department of Disaster Psychiatry, International Research Institute of Disaster 
      Science, Tohoku University, Sendai, Japan.
FAU - Izumi, Ryuta
AU  - Izumi R
AD  - Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, 
      Fukushima, Japan.
FAU - Nagaoka, Atsuko
AU  - Nagaoka A
AD  - Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, 
      Fukushima, Japan.
FAU - Hayashi, Hideki
AU  - Hayashi H
AD  - Department of Pathology, Brain Research Institute, Niigata University, Niigata, 
      Japan.
FAU - Kakita, Akiyoshi
AU  - Kakita A
AD  - Department of Pathology, Brain Research Institute, Niigata University, Niigata, 
      Japan.
FAU - Tomita, Hiroaki
AU  - Tomita H
AD  - Department of Disaster Psychiatry, International Research Institute of Disaster 
      Science, Tohoku University, Sendai, Japan.
FAU - Yabe, Hirooki
AU  - Yabe H
AD  - Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, 
      Fukushima, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230822
PL  - Switzerland
TA  - Front Psychiatry
JT  - Frontiers in psychiatry
JID - 101545006
PMC - PMC10478254
OTO - NOTNLM
OT  - DNA double-strand break
OT  - DNA double-strand break repair by homologous recombination
OT  - RNA-Seq
OT  - environmental factor
OT  - heterogeneity
OT  - postmortem brain
OT  - schizophrenia
OT  - stress
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/09/07 06:42
MHDA- 2023/09/07 06:43
PMCR- 2023/08/22
CRDT- 2023/09/07 03:59
PHST- 2023/03/10 00:00 [received]
PHST- 2023/06/12 00:00 [accepted]
PHST- 2023/09/07 06:43 [medline]
PHST- 2023/09/07 06:42 [pubmed]
PHST- 2023/09/07 03:59 [entrez]
PHST- 2023/08/22 00:00 [pmc-release]
AID - 10.3389/fpsyt.2023.1183696 [doi]
PST - epublish
SO  - Front Psychiatry. 2023 Aug 22;14:1183696. doi: 10.3389/fpsyt.2023.1183696. 
      eCollection 2023.