Improvement in verbal memory following SSRI augmentation of antipsychotic treatment is associated with changes in the expression of mRNA encoding for the GABA-A receptor and BDNF in PMC of schizophrenic patients

Int Clin Psychopharmacol. 2015 May;30(3):158-66. doi: 10.1097/YIC.0000000000000070.

Abstract

Verbal memory impairment in schizophrenia is associated with abnormalities in gamma-aminobutyric acid (GABA)-ergic and brain-derived neurotrophic factor (BDNF) systems. Recent evidence from animal and clinical studies that adding fluvoxamine to antipsychotics alters the expression of transcripts encoding for the GABA-A receptor and BDNF led us to postulate that fluvoxamine augmentation may improve memory in schizophrenia. To test this, we examined the effect of add-on fluvoxamine on verbal memory and other cognitive functions and related it to the expression of mRNA coding for the GABA-A receptor and BDNF in peripheral mononuclear cells (PMC) of schizophrenic patients. Twenty-nine patients completed a 6-week study in which fluvoxamine (100 mg/day) was added to ongoing antipsychotic treatment. Verbal memory, abstraction working memory, object and face recognition, and psychomotor speed and clinical symptoms were assessed at baseline and after 3 and 6 weeks of treatment. Blood samples were taken at baseline and weeks 1, 3, and 6 and PMC was assayed for the GABA-A beta3 receptor and BDNF mRNA by quantitative real-time reverse transcription-PCR. Associative and logical verbal memory improved significantly and showed a significant correlation with changes in PMC BDNF and GABA-A beta3 receptor mRNA, which increased during treatment. Abstraction and object recognition improved, but this did not correlate with PMC measures. Negative and positive symptoms improved significantly; the latter showed significant correlations with changes in PMC measures. Addition of fluvoxamine to antipsychotics improves verbal memory. It is postulated that the mechanism involves enhanced GABA-A receptor/BDNF-dependent synaptic plasticity in the hippocampus.

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage*
  • Brain-Derived Neurotrophic Factor / biosynthesis*
  • Drug Therapy, Combination
  • Female
  • Fluvoxamine / administration & dosage
  • Gene Expression Regulation
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • RNA, Messenger / biosynthesis
  • Receptors, GABA-A / biosynthesis*
  • Schizophrenia / blood*
  • Schizophrenia / drug therapy
  • Serotonin Uptake Inhibitors / administration & dosage*
  • Treatment Outcome
  • Verbal Learning / drug effects
  • Verbal Learning / physiology
  • Young Adult

Substances

  • Antipsychotic Agents
  • Brain-Derived Neurotrophic Factor
  • RNA, Messenger
  • Receptors, GABA-A
  • Serotonin Uptake Inhibitors
  • BDNF protein, human
  • Fluvoxamine