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Translational psychiatry
02 08, 2021;11 (1): 117.

The microRNA-195 - BDNF pathway and cognitive deficits in schizophrenia patients with minimal antipsychotic medication exposure.

Shujuan Pan, Wei Feng, Yanli Li, Junchao Huang, Song Chen, Yimin Cui, Baopeng Tian, Shuping Tan, Zhiren Wang, Shangwu Yao, Joshua Chiappelli, Peter Kochunov, Shuo Chen, Fude Yang, Chiang-Shan R Li, Li Tian, Yunlong Tan, L Elliot Hong
Author Information
  1. Shujuan Pan: Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
  2. Wei Feng: Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
  3. Yanli Li: Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
  4. Junchao Huang: Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
  5. Song Chen: Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
  6. Yimin Cui: Department of Pharmacy, Peking University First Hospital, Beijing, China.
  7. Baopeng Tian: Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
  8. Shuping Tan: Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
  9. Zhiren Wang: Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
  10. Shangwu Yao: Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
  11. Joshua Chiappelli: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
  12. Peter Kochunov: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
  13. Shuo Chen: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
  14. Fude Yang: Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
  15. Chiang-Shan R Li: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. ORCID
  16. Li Tian: Faculty of Medicine, Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia. ORCID
  17. Yunlong Tan: Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China. yltan21@126.com. ORCID
  18. L Elliot Hong: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
PMID: 33558459 DOI: 10.1038/s41398-021-01240-x

Abstract

Cognitive impairment is a core characteristic of schizophrenia, but its underlying neural mechanisms remain poorly understood. Reduced brain-derived neurotrophic factor (BDNF), a protein critical for neural plasticity and synaptic signaling, is one of the few molecules consistently associated with cognitive deficits in schizophrenia although the etiological pathway leading to BDNF reduction in schizophrenia is unclear. We examined microRNA-195 (miR-195), a known modulator of BDNF protein expression, as a potential mechanistic component. One-hundred and eighteen first-episode patients with schizophrenia either antipsychotic medication-naïve or within two weeks of antipsychotic medication exposure and forty-seven age- and sex-matched healthy controls were enrolled. MiR-195 and BDNF mRNA and BDNF protein levels in peripheral blood were tested. Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). MiR-195 was significantly higher (p = 0.01) whereas BDNF mRNA (p < 0.001) and protein (p = 0.016) levels were significantly lower in patients compared with controls. Higher miR-195 expression was significantly correlated to lower BDNF protein levels in patients (partial r = -0.28, p = 0.003) and lower BDNF protein levels were significantly associated with poorer overall cognitive performance by MCCB and also in speed of processing, working memory, and attention/vigilance domains composite score (p = 0.002-0.004). The subgroup of patients with high miR-195 and low BDNF protein showed the lowest level of cognitive functions, and miR-195 showed significant mediation effects on cognitive functions through BDNF protein. Elevated miR-195 may play a role in regulating BDNF protein expression thereby influencing cognitive impairments in schizophrenia, suggesting that development of cognition enhancing treatment for schizophrenia may consider a micro-RNA based strategy.

References

Biol Psychiatry. 2009 Jun 15;65(12):1006-14 [PMID: 19121517]
Neurosci Lett. 2003 Nov 13;351(2):111-4 [PMID: 14583394]
Psychiatry Res. 2016 Apr 30;238:196-202 [PMID: 27086233]
Int J Neuropsychopharmacol. 2010 May;13(4):535-9 [PMID: 19941699]
J Neurosci. 1999 Nov 15;19(22):RC40 [PMID: 10559430]
PLoS Biol. 2011 Dec;9(12):e1001214 [PMID: 22162950]
Am J Psychiatry. 2008 Feb;165(2):203-13 [PMID: 18172019]
Tumour Biol. 2016 May;37(5):6457-63 [PMID: 26631043]
J Clin Neurosci. 2015 Mar;22(3):570-4 [PMID: 25487174]
Neuropharmacology. 1998 Dec;37(12):1553-61 [PMID: 9886678]
BMC Syst Biol. 2010 Feb 15;4:10 [PMID: 20156358]
Cell. 2009 Jan 23;136(2):215-33 [PMID: 19167326]
J Transl Med. 2016 May 20;14(1):143 [PMID: 27197967]
Sci Rep. 2017 Nov 10;7(1):15328 [PMID: 29127368]
Neuron. 2001 Oct 11;32(1):123-40 [PMID: 11604144]
Cell Mol Life Sci. 2015 Aug;72(16):3127-41 [PMID: 26037721]
Neurosci Lett. 2008 Jul 11;439(2):157-9 [PMID: 18514407]
Am J Psychiatry. 2008 Feb;165(2):214-20 [PMID: 18172018]
Cell. 1999 Sep 17;98(6):739-55 [PMID: 10499792]
J Psychiatr Res. 2014 Jul;54:134-40 [PMID: 24694668]
Neuroimage Clin. 2017 Aug 08;16:248-256 [PMID: 28831376]
Front Cell Neurosci. 2014 Jan 30;8:15 [PMID: 24523674]
Neuron. 1999 Oct;24(2):401-14 [PMID: 10571233]
Schizophr Res. 2015 Dec;169(1-3):109-115 [PMID: 26441005]
J Biochem Mol Toxicol. 2011 Nov-Dec;25(6):404-8 [PMID: 22190509]
JAMA Psychiatry. 2013 Oct;70(10):1107-12 [PMID: 23925787]
Psychoneuroendocrinology. 2020 Sep;119:104748 [PMID: 32559610]
Nucleic Acids Res. 2011 Oct;39(18):8163-72 [PMID: 21724616]
Schizophr Res. 2018 Nov;201:237-242 [PMID: 29954699]
J Psychiatr Res. 2012 Feb;46(2):198-204 [PMID: 22094284]
Eur J Neurosci. 2001 Jul;14(1):135-44 [PMID: 11488957]
Psychiatry Res. 2019 Mar;273:528-536 [PMID: 30710808]
Int J Neuropsychopharmacol. 2011 Apr;14(3):347-53 [PMID: 20604989]
Cell Mol Life Sci. 2014 Nov;71(22):4443-56 [PMID: 24804980]
Hippocampus. 2002;12(4):551-60 [PMID: 12201640]
Psychopharmacology (Berl). 2015 Jan;232(1):223-32 [PMID: 24994553]
Handb Exp Pharmacol. 2014;220:223-50 [PMID: 24668475]
Biochem Pharmacol. 2016 Mar 15;104:1-7 [PMID: 26626188]
Hum Mol Genet. 2008 Oct 1;17(19):3030-42 [PMID: 18632683]
Psychol Methods. 2002 Dec;7(4):422-45 [PMID: 12530702]
World J Biol Psychiatry. 2017 Aug;18(5):401-408 [PMID: 27409727]
Clin Med Insights Pathol. 2013 Aug 26;6:1-11 [PMID: 24031163]

Grants

  1. R01 MH116948/NIMH NIH HHS
  2. R01 EB015611/NIBIB NIH HHS
  3. UL1 TR001863/NCATS NIH HHS
  4. R01 MH112180/NIMH NIH HHS
  5. S10 OD023696/NIH HHS

MeSH Term

Antipsychotic Agents
Brain-Derived Neurotrophic Factor
Cognition
Cognitive Dysfunction
Humans
MicroRNAs
Neuropsychological Tests
Schizophrenia

Chemicals

Antipsychotic Agents
Brain-Derived Neurotrophic Factor
MIRN195 microRNA, human
MicroRNAs
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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