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.

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.

• Authors: Henry Silver, Nina Mandiuk, Reef Einoch, Ehud Susser, Lena Danovich, Warren Bilker, Moussa Youdim, Orly Weinreb
• Journal: International clinical psychopharmacology (Int Clin Psychopharmacol) Vol. 30 Issue 3 Pg. 158-66 (May 2015) ISSN: 1473-5857 [Electronic] England
• PMID: 25756551 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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, metabolism)
• Male
• Memory (drug effects, physiology)
• RNA, Messenger (biosynthesis)
• Receptors, GABA-A (biosynthesis)
• Schizophrenia (blood, drug therapy)
• Selective Serotonin Reuptake Inhibitors (administration & dosage)
• Treatment Outcome
• Verbal Learning (drug effects, physiology)
• Young Adult