Boldrini Maura, Butt Tanya H, Santiago Adrienne N, Tamir Hadassah, Dwork Andrew J, Rosoklija Gorazd B, Arango Victoria, Hen René, Mann J John
Division of Molecular Imaging and Neuropathology and New York State Psychiatric Institute,New York, NY,USA.
Department of Psychiatry,Columbia University,New York, NY,USA.
Int J Neuropsychopharmacol. 2014 Dec;17(12):1923-33. doi: 10.1017/S1461145714000844. Epub 2014 Jun 27.
Modest antidepressant response rates of mood disorders (MD) encourage benzodiazepine (BZD) co-medication with debatable benefit. Adult hippocampal neurogenesis may underlie antidepressant responses, but diazepam co-administration impairs murine neuron maturation and survival in response to fluoxetine. We counted neural progenitor cells (NPCs), mitotic cells, and mature granule neurons post-mortem in dentate gyrus (DG) from subjects with: untreated Diagnostic and Statistical Manual of Mental Disorders (DSM) IV MD (n = 17); antidepressant-treated MD (MDADT, n = 10); benzodiazepine-antidepressant-treated MD (MDADTBZD, n = 7); no psychopathology or treatment (controls, n = 18). MDADTBZD had fewer granule neurons vs. MDADT in anterior DG and vs. controls in mid DG, and did not differ from untreated-MD in any DG subregion. MDADT had more granule neurons than untreated-MD in anterior and mid DG and comparable granule neuron number to controls in all dentate subregions. Untreated-MD had fewer granule neurons than controls in anterior and mid DG, and did not differ from any other group in posterior DG. MDADTBZD had fewer NPCs vs. MDADT in mid DG. MDADT had more NPCs vs. untreated-MD and controls in anterior and mid DG. MDADTBZD and MDADT had more mitotic cells in anterior DG vs. controls and untreated-MD. There were no between-group differences in mid DG in mitotic cells or in posterior DG for any cell type. Our results in mid-dentate, and to some degree anterior dentate, gyrus are consistent with murine findings that benzodiazepines counteract antidepressant-induced increases in neurogenesis by interfering with progenitor proliferation. We also confirmed, in this expanded sample, our previous finding of granule neuron deficit in untreated MD.
心境障碍(MD)的抗抑郁反应率不高,这促使苯二氮䓬类药物(BZD)联合用药,但其益处存在争议。成年海马神经发生可能是抗抑郁反应的基础,但地西泮联合使用会损害小鼠神经元在氟西汀作用下的成熟和存活。我们在死后对齿状回(DG)中的神经祖细胞(NPC)、有丝分裂细胞和成熟颗粒神经元进行计数,这些受试者包括:未接受治疗的精神疾病诊断与统计手册(DSM)IV心境障碍患者(n = 17);接受抗抑郁治疗的心境障碍患者(MDADT,n = 10);接受苯二氮䓬类 - 抗抑郁治疗的心境障碍患者(MDADTBZD,n = 7);无精神病理学问题或未接受治疗的对照组(n = 18)。与MDADT相比,MDADTBZD在前部DG中的颗粒神经元数量更少,与对照组相比,在中部DG中的颗粒神经元数量更少,并且在任何DG亚区域与未治疗的MD没有差异。MDADT在前部和中部DG中的颗粒神经元数量比未治疗的MD更多,并且在所有齿状亚区域中与对照组的颗粒神经元数量相当。未治疗的MD在前部和中部DG中的颗粒神经元数量比对照组少,并且在后部DG中与其他任何组没有差异。与MDADT相比,MDADTBZD在中部DG中的NPC数量更少。与未治疗的MD和对照组相比,MDADT在前部和中部DG中的NPC数量更多。与对照组和未治疗的MD相比,MDADTBZD和MDADT在前部DG中的有丝分裂细胞更多。在中部DG中的有丝分裂细胞或后部DG中的任何细胞类型上,组间没有差异。我们在齿状回中部以及在某种程度上在前部齿状回中的结果与小鼠研究结果一致,即苯二氮䓬类药物通过干扰祖细胞增殖来抵消抗抑郁药诱导的神经发生增加。我们还在这个扩大的样本中证实了我们之前关于未治疗的MD中颗粒神经元缺陷的发现。