論文

国際誌
2021年8月3日

Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia.

Proceedings of the National Academy of Sciences of the United States of America
  • Munetaka Nomoto
  • ,
  • Glenn T Konopaske
  • ,
  • Naoya Yamashita
  • ,
  • Reina Aoki
  • ,
  • Aoi Jitsuki-Takahashi
  • ,
  • Haruko Nakamura
  • ,
  • Hiroko Makihara
  • ,
  • Mari Saito
  • ,
  • Yusuke Saigusa
  • ,
  • Fumio Nakamura
  • ,
  • Keisuke Watanabe
  • ,
  • Toshihiko Baba
  • ,
  • Francine M Benes
  • ,
  • Brian T D Tobe
  • ,
  • Cameron D Pernia
  • ,
  • Joseph T Coyle
  • ,
  • Richard L Sidman
  • ,
  • Yoshio Hirayasu
  • ,
  • Evan Y Snyder
  • ,
  • Yoshio Goshima

118
31
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.2100032118

There are no validated biomarkers for schizophrenia (SCZ), a disorder linked to neural network dysfunction. We demonstrate that collapsin response mediator protein-2 (CRMP2), a master regulator of cytoskeleton and, hence, neural circuitry, may form the basis for a biomarker because its activity is uniquely imbalanced in SCZ patients. CRMP2's activity depends upon its phosphorylation state. While an equilibrium between inactive (phosphorylated) and active (nonphosphorylated) CRMP2 is present in unaffected individuals, we show that SCZ patients are characterized by excess active CRMP2. We examined CRMP2 levels first in postmortem brains (correlated with neuronal morphometrics) and then, because CRMP2 is expressed in lymphocytes as well, in the peripheral blood of SCZ patients versus age-matched unaffected controls. In the brains and, more starkly, in the lymphocytes of SCZ patients <40 y old, we observed that nonphosphorylated CRMP2 was higher than in controls, while phosphorylated CRMP2 remained unchanged from control. In the brain, these changes were associated with dendritic structural abnormalities. The abundance of active CRMP2 with insufficient opposing inactive p-CRMP2 yielded a unique lowering of the p-CRMP2:CRMP2 ratio in SCZ patients, implying a disruption in the normal equilibrium between active and inactive CRMP2. These clinical data suggest that measuring CRMP2 and p-CRMP2 in peripheral blood might reflect intracerebral processes and suggest a rapid, minimally invasive, sensitive, and specific adjunctive diagnostic aid for early SCZ: increased CRMP2 or a decreased p-CRMP2:CRMP2 ratio may help cinch the diagnosis in a newly presenting young patient suspected of SCZ (versus such mimics as mania in bipolar disorder, where the ratio is high).

リンク情報
DOI
https://doi.org/10.1073/pnas.2100032118
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34330827
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346854
ID情報
  • DOI : 10.1073/pnas.2100032118
  • PubMed ID : 34330827
  • PubMed Central 記事ID : PMC8346854

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