Increased expression of activity-dependent genes in cerebellar glutamatergic neurons of patients with schizophrenia

Am J Psychiatry. 2006 Oct;163(10):1829-31. doi: 10.1176/ajp.2006.163.10.1829.


Objective: The purpose of this study was to evaluate the functional state of glutamatergic neurons in the cerebellar cortex of patients with schizophrenia.

Method: The authors measured messenger ribonucleic acid (mRNA) levels of three activity-dependent genes expressed by glutamatergic neurons in the cerebellar cortex (GAP-43, BDNF, and GABA OLE_LINK2>(A)-delta subunit) in the tissues of 14 patients with schizophrenia and 14 matched nonpsychiatric comparison subjects. Since its level of expression does not change in response to neuronal activity, gamma-aminobutyric acid(A)-alpha6 subunit mRNA was used as a control.

Results: The levels of GAP-43 and BDNF mRNAs were significantly elevated in patients with schizophrenia, and a similar finding was observed for GABA(A)-delta mRNA. In contrast, the levels of the GABA(A)-alpha6 subunit mRNA, which is expressed in cerebellar granule cells in an activity-independent manner, did not differ from comparison subjects.

Conclusions: These results suggest that glutamatergic neurons may be hyperactive in the cerebellar cortices of patients with schizophrenia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cerebellar Cortex / metabolism
  • Cerebellum / chemistry
  • Cerebellum / metabolism*
  • Female
  • GAP-43 Protein / metabolism
  • Gene Expression Regulation / genetics
  • Glutamic Acid / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Neurons / chemistry
  • Neurons / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Brain-Derived Neurotrophic Factor
  • GAP-43 Protein
  • RNA, Messenger
  • Receptors, GABA-A
  • Glutamic Acid
  • gamma-Aminobutyric Acid