Friedman Joseph I, Carpenter David, Lu Jing, Fan Jin, Tang Cheuk Y, White Leonard, Parrella Michael, Bowler Stephanie, Elbaz Zeinab, Flanagan Lauren, Harvey Philip D
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Clin Psychopharmacol. 2008 Feb;28(1):59-63. doi: 10.1097/jcp.0b013e318161318f.
Relationships between altered prefrontal cortical dopamine, norepinephrine, and some of the cognitive impairments of schizophrenia support an approach for pharmacological remediation of cognitive symptoms through manipulations of prefrontal cortical dopamine and norepinephrine. Atomoxetine, a selective norepinephrine reuptake inhibitor, produces a widespread increase in brain norepinephrine and a secondary and selective increase in prefrontal dopamine. Given this, we evaluated atomoxetine's cognitive effects in a pilot placebo-controlled trial in patients with schizophrenia. Moreover, a functional magnetic resonance imaging investigation was undertaken to assess the neural mechanisms underlying the cognitive effects of atomoxetine. Twenty participants with schizophrenia were randomized to treatment with placebo or atomoxetine 80 mg daily for an 8-week parallel-designed treatment trial. Cognitive performance was assessed with the Brief Assessment of Cognition in Schizophrenia. No significant cognitive improvement was associated with atomoxetine treatment. However, atomoxetine treatment was associated with significantly greater increases in working memory-related activation of the left dorsolateral prefrontal and left posterior cingulate cortices. The negative results of this study conflict with the effectiveness of amphetamine in enhancing the cognitive abilities of schizophrenic patients and may be related to the differential pattern of cortical activation and deactivation produced by amphetamine.
前额叶皮质多巴胺和去甲肾上腺素的改变与精神分裂症的一些认知障碍之间的关系支持了一种通过调节前额叶皮质多巴胺和去甲肾上腺素来对认知症状进行药物治疗的方法。托莫西汀是一种选择性去甲肾上腺素再摄取抑制剂，可使大脑去甲肾上腺素广泛增加，并使前额叶多巴胺继发且选择性增加。鉴于此，我们在一项针对精神分裂症患者的安慰剂对照试验中评估了托莫西汀的认知效应。此外，还进行了一项功能磁共振成像研究，以评估托莫西汀认知效应背后的神经机制。20名精神分裂症患者被随机分为两组，分别接受安慰剂治疗或每天80毫克托莫西汀治疗，进行为期8周的平行设计治疗试验。使用精神分裂症认知简短评估量表评估认知表现。托莫西汀治疗未带来显著的认知改善。然而，托莫西汀治疗与左背外侧前额叶和左后扣带回皮质与工作记忆相关的激活显著增加有关。本研究的阴性结果与苯丙胺增强精神分裂症患者认知能力的有效性相矛盾，可能与苯丙胺产生的皮质激活和失活的不同模式有关。
