Mintzopoulos Dionyssios, Gillis Timothy E, Robertson Holly R, Dalia Triana, Feng Guoping, Rauch Scott L, Kaufman Marc J
Biol Psychiatry Cogn Neurosci Neuroimaging. 2016 Jan 1;1(1):39-48. doi: 10.1016/j.bpsc.2015.10.001.
Obsessive compulsive disorder (OCD) is a debilitating condition with lifetime prevalence of 1-3%. OCD typically arises in youth but delays in diagnosis impede optimal treatment and developmental studies of the disorder. Research using genetically modified rodents may provide models of etiology that enable earlier detection and intervention. The SAPAP3 knockout (KO) transgenic mouse was developed as an animal model of OCD and related disorders (OCRD). KO mice exhibit compulsive self-grooming behavior analogous to behaviors found in people with OCRD. Striatal hyperactivity has been reported in these mice and in humans with OCD.
Striatal and medial frontal cortex 9.4 Tesla proton spectra were acquired from young adult SAPAP3 KO and wild-type control mice to determine whether KO mice have metabolic and neurochemical abnormalities.
Young adult KO mice had lower striatal lactate (=0.006) and glutathione (=0.039) levels. Among all mice, striatal lactate and glutathione levels were associated (R=0.73, =0.007). We found no group differences in medial frontal cortex metabolites. At the age range studied, only 1 of 8 KO mice had skin lesions indicative of severe compulsive grooming.
Young adult SAPAP3 KO mice have striatal but not medial frontal cortex MRS abnormalities that may reflect striatal hypermetabolism accompanied by oxidative stress. These abnormalities typically preceded the onset of severe compulsive grooming. Our findings are consistent with striatal hypermetabolism in OCD. Together, these results suggest that striatal MRS measures of lactate or glutathione might be useful biomarkers for early detection of risk for developing compulsive behavior disorders.
强迫症（OCD）是一种使人衰弱的疾病，终生患病率为1%-3%。强迫症通常在青少年时期出现，但诊断延迟会妨碍对该疾病的最佳治疗和发育研究。使用基因改造啮齿动物的研究可能会提供病因模型，从而实现更早的检测和干预。SAPAP3基因敲除（KO）转基因小鼠被开发为强迫症及相关疾病（OCRD）的动物模型。基因敲除小鼠表现出强迫性自我梳理行为，类似于OCRD患者的行为。据报道，这些小鼠以及患有强迫症的人类存在纹状体活动亢进。
从年轻成年SAPAP3基因敲除小鼠和野生型对照小鼠获取纹状体和内侧前额叶皮质的9.4特斯拉质子谱，以确定基因敲除小鼠是否存在代谢和神经化学异常。
年轻成年基因敲除小鼠的纹状体乳酸（=0.006）和谷胱甘肽（=0.039）水平较低。在所有小鼠中，纹状体乳酸和谷胱甘肽水平相关（R=0.73，=0.007）。我们发现内侧前额叶皮质代谢物在组间无差异。在所研究的年龄范围内，8只基因敲除小鼠中只有1只出现了表明严重强迫性梳理的皮肤损伤。
年轻成年SAPAP3基因敲除小鼠存在纹状体而非内侧前额叶皮质磁共振波谱异常，这可能反映了纹状体代谢亢进并伴有氧化应激。这些异常通常在严重强迫性梳理发作之前出现。我们的研究结果与强迫症中的纹状体代谢亢进一致。总之，这些结果表明，纹状体磁共振波谱测量的乳酸或谷胱甘肽可能是早期检测强迫行为障碍发病风险的有用生物标志物。
