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

ABSTRACT: 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).

SUBMITTER: Nomoto M

PROVIDER: S-EPMC8346854 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Nomoto Munetaka M Konopaske Glenn T GT Yamashita Naoya N Aoki Reina R Jitsuki-Takahashi Aoi A Nakamura Haruko H Makihara Hiroko H Saito Mari M Saigusa Yusuke Y Nakamura Fumio F Watanabe Keisuke K Baba Toshihiko T Benes Francine M FM Tobe Brian T D BTD Pernia Cameron D CD Coyle Joseph T JT Sidman Richard L RL Hirayasu Yoshio Y Snyder Evan Y EY Goshima Yoshio Y

Proceedings of the National Academy of Sciences of the United States of America 20210801 31

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 u ...[more]

PMID: 34330827

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Dataset Information

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

Publications

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

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