NAAG, Glutamate, and GABA in OCD

描述(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种致残疾病之一。许多强迫症患者对5-羟色胺再摄取抑制剂(SRIs)的治疗反应良好；然而，20%至40%的OCD患者对SRIs具有抵抗力，人们认为5-羟色胺以外的神经递质系统的异常可能是这些患者出现强迫症症状的原因。这项研究建议测量神经递质谱(由3种具有神经递质特性的物质组成，可通过先进的磁共振波谱(MRS)技术获得)-谷氨酸(Glu)、3-氨基丁酸(GABA)和N-乙酰天冬氨酸谷氨酸(NAAG)。据推测，与治疗应答者或对照组相比，SRIs抵抗的强迫症患者的GABA(抑制性神经递质)水平较低，Glu(兴奋性神经递质(Glu))水平较高，NAAG(Glu的前体)水平较低。在3T时，将使用最先进的光谱编辑MRS技术在强迫症的两个关键脑区进行测量：前扣带回(ACC)，基底节和丘脑(BG-TH)。总共有48名受试者将在两年内接受研究，16名对照组，16名强迫症应答者和16名强迫症无应答者。这项建议有望提高对谷氨酸和GABA能系统在强迫症患者中作用的理解，从长远来看，可能会导致强迫症新治疗策略的发展。 公共卫生相关性：20%至40%的强迫症(OCD)患者对5-羟色胺再摄取抑制剂(SRI)的治疗具有抵抗力。我们试图探索谷氨酸和3-氨基丁酸(GABA能)神经递质在强迫症两个脑区的作用，并将其与治疗耐药性联系起来。从长远来看，这项研究可能会导致更好地理解精神分裂症和治疗方法。

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.