GABAergic promoter hypermethylation as a model to study the neurochemistry of schizophrenia vulnerability

Erminio Costa, Ying Chen, Erbo Dong, Dennis R. Grayson, Marija Kundakovic, Ekrem Maloku, William Ruzicka, Rosalba Satta, Marin Veldic, Adrian Zhubi, Alessandro Guidotti

Research output: Contribution to journalReview articlepeer-review

54 Scopus citations


The neuronal GABAergic mechanisms that mediate the symptomatic beneficial effects elicited by a combination of antipsychotics with valproate (a histone deacetylase inhibitor) in the treatment of psychosis (expressed by schizophrenia or bipolar disorder patients) are unknown. This prompted us to investigate whether the beneficial action of this combination results from a modification of histone tail covalent esterification or is secondary to specific chromatin remodeling. The results suggest that clozapine, or sulpiride associated with valproate, by increasing DNA demethylation with an unknown mechanism, causes a chromatin remodeling that brings about a beneficial change in the epigenetic GABAergic dysfunction typical of schizophrenia and bipolar disorder patients.

Original languageEnglish (US)
Pages (from-to)87-98
Number of pages12
JournalExpert review of neurotherapeutics
Issue number1
StatePublished - Jan 2009


  • Antipsychotic
  • Chromatin remodeling
  • DNA demethylase
  • DNA methyltransferase inhibitor
  • GABAergic neurotransmission
  • GAD
  • Histone deacetylase inhibitor
  • Psychosis
  • Reelin
  • Valproate

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Pharmacology (medical)


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