Silver Henry, Mandiuk Nina, Einoch Reef, Susser Ehud, Danovich Lena, Bilker Warren, Youdim Moussa, Weinreb Orly
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.
Int Clin Psychopharmacol. 2015 May;30(3):158-66. doi: 10.1097/YIC.0000000000000070.
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.
精神分裂症患者的言语记忆障碍与γ-氨基丁酸（GABA）能系统和脑源性神经营养因子（BDNF）系统异常有关。动物和临床研究的最新证据表明，在抗精神病药物中添加氟伏沙明会改变GABA-A受体和BDNF编码转录本的表达，这使我们推测氟伏沙明增效可能改善精神分裂症患者的记忆。为了验证这一点，我们研究了加用氟伏沙明对言语记忆和其他认知功能的影响，并将其与精神分裂症患者外周血单个核细胞（PMC）中GABA-A受体和BDNF编码mRNA的表达相关联。29名患者完成了一项为期6周的研究，在持续的抗精神病治疗基础上加用氟伏沙明（100mg/天）。在基线以及治疗3周和6周后评估言语记忆、抽象工作记忆、物体和面部识别、精神运动速度及临床症状。在基线以及第1、3和6周采集血样，通过定量实时逆转录PCR检测PMC中的GABA-Aβ3受体和BDNF mRNA。联想和逻辑言语记忆显著改善，且与治疗期间PMC中BDNF和GABA-Aβ3受体mRNA的变化显著相关，二者均增加。抽象和物体识别能力有所改善，但这与PMC检测指标无关。阴性和阳性症状显著改善；阳性症状与PMC检测指标的变化显著相关。在抗精神病药物治疗中加用氟伏沙明可改善言语记忆。推测其机制涉及增强海马体中GABA-A受体/BDNF依赖性突触可塑性。
