Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment.
Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment.
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DOI：
10.1016/j.pharmthera.2011.09.006
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发表时间：
2011-12
影响因子：
13.5
通讯作者：
Williams, Kyle
中科院分区：
文献类型：
--
作者：
Pittenger, Christopher;Bloch, Michael H.;Williams, Kyle
强迫症很普遍，具有致残性，人们对它的了解不完全，并且通常对当前的治疗方法有抵抗力。既定的治疗包括专门的认知行为心理治疗和药物治疗，药物靶向多巴胺能和多巴胺能神经传递。然而，缓解是罕见的，超过四分之一的强迫症患者很少或根本没有从这些方法中受益，即使他们是最佳的交付。迫切需要对这种疾病的新见解和新的治疗策略。最近的证据表明，无处不在的兴奋性神经递质谷氨酸失调的强迫症，这种失调可能有助于疾病的病理生理。在这里，我们回顾了这一证据的现状，包括神经影像学研究，遗传学，神经化学研究和动物模型的见解。最后，我们回顾了谷氨酸调节药物治疗难治性强迫症的小型临床试验的最新发现。谷氨酸失调在强迫症中的确切作用尚不清楚，我们缺乏盲法、对照良好的研究来证明谷氨酸调节剂的治疗益处。然而，支持谷氨酸在疾病中的一些重要扰动的证据越来越强。这种对强迫症病理生理学的新观点补充了对单胺能神经传递的旧关注，构成了当前研究的重要焦点，也是新疗法持续发展的一个有前途的领域。
Obsessive compulsive disorder is prevalent, disabling, incompletely understood, and often resistant to current therapies. Established treatments consist of specialized cognitive-behavioral psychotherapy and pharmacotherapy with medications targeting serotonergic and dopaminergic neurotransmission. However, remission is rare, and more than a quarter of OCD sufferers receive little or no benefit from these approaches, even when they are optimally delivered. New insights into the disorder, and new treatment strategies, are urgently needed. Recent evidence suggests that the ubiquitous excitatory neurotransmitter glutamate is dysregulated in OCD, and that this dysregulation may contribute to the pathophysiology of the disorder. Here we review the current state of this evidence, including neuroimaging studies, genetics, neurochemical investigations, and insights from animal models. Finally, we review recent findings from small clinical trials of glutamate-modulating medications in treatment-refractory OCD. The precise role of glutamate dysregulation in OCD remains unclear, and we lack blinded, well-controlled studies demonstrating therapeutic benefit from glutamate-modulating agents. Nevertheless, the evidence supporting some important perturbation of glutamate in the disorder is increasingly strong. This new perspective on the pathophysiology of OCD, which complements the older focus on monoaminergic neurotransmission, constitutes an important focus of current research and a promising area for the ongoing development of new therapeutics.
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DOI：
10.1176/appi.ajp.2008.08020320
发表时间：
2008-12
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Bloch MH;Landeros-Weisenberger A;Rosario MC;Pittenger C;Leckman JF
通讯作者：
Leckman JF
影响因子：
25
作者：
Aoyama, K;Suh, SW;Swanson, RA
通讯作者：
Swanson, RA
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH
影响因子：
--
作者：
Bloch, Michael H.;Pittenger, Christopher
通讯作者：
Pittenger, Christopher
影响因子：
10.6
作者：
Auer, DP;Pütz, B;Holsboer, F
通讯作者：
Holsboer, F