NAAG, Glutamate, and GABA in OCD

描述（由申请人提供）：强迫症（OCD）被世界卫生组织列为收入损失和生活质量下降的前20名致残疾病之一。许多强迫症患者对血清素再摄取抑制剂（SRIs）治疗反应良好；然而，20%到40%的强迫症患者对SRIs有抵抗力，并且人们认为除了血清素外，神经递质系统的异常可能是这些患者强迫症症状的原因。本研究提出测量神经递质谱（由3种具有先进磁共振波谱（MRS）技术可获得的神经递质特性的物质组成）-谷氨酸（Glu）， 3-氨基丁酸（GABA）和N-乙酰天冬氨酸谷氨酸（NAAG）。假设与治疗反应者或对照组相比，抗SRIs的强迫症患者将具有较低水平的GABA（抑制性神经递质），较高水平的Glu（兴奋性神经递质）和较低水平的NAAG （Glu的前体）。使用最先进的光谱编辑MRS技术，将在强迫症的两个关键大脑区域进行测量：前扣带（ACC），基底神经节和丘脑（BG-TH）。总共48名受试者将在2年内进行研究，其中16名为对照组，16名有强迫症反应者和16名无强迫症反应者。这一建议有望提高对谷氨酸能和gaba能系统在强迫症患者中的作用的理解，从长远来看，可能会导致强迫症新治疗策略的发展。

DESCRIPTION (provided by applicant): Obsessive compulsive disorder (OCD) is ranked by the World Health Organization as one of the top 20 disabling illnesses in terms of lost income and diminished quality of life. Many OCD patients respond well to treatment with serotonin reuptake inhibitors (SRIs); however 20% to 40 % of OCD patients are resistant to SRIs, and is believed that abnormalities in neurotransmitter systems other than serotonin may be responsible for OCD symptoms in these patients. This study proposes to measure neurotransmitter profiles (consisting of 3 substances with neurotransmitter properties accessible by advanced magnetic resonance spectroscopy (MRS) techniques) - glutamate (Glu), 3-aminobutyric acid (GABA), and N- acetyl aspartyl glutamate (NAAG). It is hypothesized that SRIs resistant OCD patients will have lower levels GABA (an inhibitory neurotransmitter), higher levels of Glu (an excitatory neurotransmitter (Glu), and lower levels of NAAG (a precursor of Glu) as compared to treatment responders, or control subjects. Measurements will be made in 2 key brain regions in OCD: anterior cingulated (ACC), combined basal ganglia and thalamus (BG-TH) at 3T using state-of-the-art spectral-editing MRS techniques. In total 48 subjects will be studied over 2 years, 16 controls, 16 OCD responders and 16 OCD non-responders. This proposal promises to improve understanding of the role of the glutamatergic and GABAergic systems in OCD patients and, in the long term, may lead to the development of new therapeutic strategies for OCD. PUBLIC HEALTH RELEVANCE: Twenty to 40 % of obsessive-compulsive disorder (OCD) patients are resistant to treatment with serotonin reuptake inhibitors (SRIs). We sought to explore the role of the Glutamatergic and 3-aminobutyric acid (GABAergic) neurotransmitters in 2 brain regions of the brain in OCD and to correlate it to treatment resistance. In the long term, this research may lead to a better understanding of schizophrenia and treatment approaches.