Altemus M, Swedo S E, Leonard H L, Richter D, Rubinow D R, Potter W Z, Rapoport J L
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Md.
Arch Gen Psychiatry. 1994 Oct;51(10):794-803. doi: 10.1001/archpsyc.1994.03950100042004.
This study examined the effect of long-term (mean, 19 months) treatment with clomipramine hydrochloride on cerebrospinal fluid (CSF) levels of several neuropeptides and monoamine metabolites in children and adolescents with obsessive-compulsive disorder.
The CSF levels of corticotropin-releasing hormone, vasopressin, somatostatin, and oxytocin and of the monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in 17 children and adolescents with obsessive-compulsive disorder before and after long-term treatment with clomipramine.
Treatment resulted in significant decreases in CSF levels of corticotropin-releasing hormone (mean +/- SD, 175 +/- 32 vs 152 +/- 25 pmol/L, P < .03) and vasopressin (mean +/- SD, 1.30 +/- 0.57 vs 0.86 +/- 0.54 pmol/L, P < .02) and a trend toward a decrease in somatostatin levels (mean +/- SD, 21.3 +/- 8.5 vs 15.3 +/- 9.8 pmol/L, P < .06). Treatment also significantly increased CSF oxytocin levels (mean +/- SD, 6.05 +/- 1.60 vs 6.70 +/- 1.44 pmol/L, P < .01). Significant changes in CSF monoamine metabolite levels with treatment included significant decreases in CSF levels of 5-hydroxyindoleacetic acid (mean +/- SD, 109 +/- 31 vs 77 +/- 23 pmol/mL, P < .001), CSF homovanillic acid (mean +/- SD, 273 +/- 111 vs 237 +/- 101 pmol/mL, P < .04), and 3-methoxy-4-hydroxyphenylglycol (mean +/- SD, 42.4 +/- 10.2 vs 36.1 +/- 4.8 pmol/L, P < .02) and a significant increase in the homovanillic acid-5-hydroxyindoleacetic acid ratio (mean +/- SD, 2.44 +/- 0.46 vs 3.42 +/- 0.84, P < .0001).
These neuropeptide results coupled with evidence that central administration of corticotropin-releasing hormone, vasopressin, and somatostatin to laboratory animals increases arousal and acquisition of conditioned behaviors whereas central administration of oxytocin has opposite behavioral effects are consistent with a role for these neuropeptides in the pathophysiologic processes and pharmacologic treatment of obsessive-compulsive disorder.
本研究探讨了盐酸氯米帕明长期（平均19个月）治疗对强迫症儿童和青少年脑脊液中几种神经肽和单胺代谢产物水平的影响。
测定了17例强迫症儿童和青少年在长期接受氯米帕明治疗前后脑脊液中促肾上腺皮质激素释放激素、血管加压素、生长抑素、催产素以及单胺代谢产物5-羟吲哚乙酸、高香草酸和3-甲氧基-4-羟基苯乙二醇的水平。
治疗后，脑脊液中促肾上腺皮质激素释放激素水平显著降低（均值±标准差，175±32 vs 152±25 pmol/L，P<.03），血管加压素水平显著降低（均值±标准差，1.30±0.57 vs 0.86±0.54 pmol/L，P<.02），生长抑素水平有降低趋势（均值±标准差，21.3±8.5 vs 15.3±9.8 pmol/L，P<.06）。治疗还显著提高了脑脊液中催产素水平（均值±标准差，6.05±1.60 vs 6.70±1.44 pmol/L，P<.01）。治疗后脑脊液中单胺代谢产物水平的显著变化包括脑脊液中5-羟吲哚乙酸水平显著降低（均值±标准差，109±31 vs 77±23 pmol/mL，P<.001），脑脊液中高香草酸水平显著降低（均值±标准差，273±111 vs 237±101 pmol/mL，P<.04），3-甲氧基-4-羟基苯乙二醇水平显著降低（均值±标准差，42.4±10.2 vs 36.1±4.8 pmol/L，P<.02），以及高香草酸与5-羟吲哚乙酸比值显著升高（均值±标准差，2.44±0.46 vs 3.42±0.84，P<.0001）。
这些神经肽的研究结果，再加上向实验动物中枢给予促肾上腺皮质激素释放激素、血管加压素和生长抑素会增加觉醒和条件性行为的获得，而给予催产素则产生相反的行为效应这一证据，与这些神经肽在强迫症病理生理过程和药物治疗中的作用是一致的。
