Glutamate abnormalities in obsessive compulsive disorder: Neurobiology, pathophysiology, and treatment

被引:249
作者
Pittenger, Christopher [1 ,2 ,3 ]
Bloch, Michael H. [1 ,2 ]
Williams, Kyle [1 ,2 ]
机构
[1] Yale Univ, Dept Psychiat, Sch Med, New Haven, CT 06520 USA
[2] Yale Univ, Ctr Child Study, Sch Med, New Haven, CT 06520 USA
[3] Yale Univ, Interdept Neurosci Program, Sch Med, New Haven, CT 06520 USA
关键词
Obsessive-compulsive disorder; OCD; Glutamate; MAGNETIC-RESONANCE-SPECTROSCOPY; TRANSPORTER GENE SLC1A1; OPEN-LABEL TRIAL; N-ACETYL CYSTEINE; ANTIGLUTAMATERGIC AGENT RILUZOLE; COGNITIVE-BEHAVIORAL THERAPY; ANTERIOR CINGULATE GLUTAMATE; COMORBID TOURETTES-SYNDROME; FAMILY-BASED ASSOCIATION; PLACEBO-CONTROLLED TRIAL;
D O I
10.1016/j.pharmthera.2011.09.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 dys-regulated 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. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:314 / 332
页数:19
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