title: 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.affiliation: aMolecular Neuropsychiatry Unit bClinical Research Unit, Sha'ar Menashe Brain Behavior Laboratory, Sha'ar Menashe Mental Health Center cEve Topf and National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel dDepartment of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Silver
authors.forename: Nina
authors.initials: N
authors.lastname: Mandiuk
authors.forename: Reef
authors.initials: R
authors.lastname: Einoch
authors.forename: Ehud
authors.initials: E
authors.lastname: Susser
authors.forename: Lena
authors.initials: L
authors.lastname: Danovich
authors.forename: Warren
authors.initials: W
authors.lastname: Bilker
authors.forename: Moussa
authors.initials: M
authors.lastname: Youdim
authors.forename: Orly
authors.initials: O
authors.lastname: Weinreb
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D004359:Drug Therapy, Combination; D005260:Female; D016666:Fluvoxamine / Q000008:administration & dosage; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome; D014706:Verbal Learning / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D016666:Fluvoxamine; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D017367:Selective Serotonin Reuptake Inhibitors; C579455:BDNF protein, human