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Changes in Cerebrospinal Fluid Neurochemistry During Treatment of Obsessive-compulsive Disorder With Clomipramine

Margaret Altemus, MD; Susan E. Swedo, MD; Henrietta L. Leonard, MD; Dan Richter; David R. Rubinow, MD; William Z. Potter, MD; Judith L. Rapoport, MD
Arch Gen Psychiatry. 1994;51(10):794-803. doi:10.1001/archpsyc.1994.03950100042004.
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Background:  This study examined the effect of longterm (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.

Methods:  The CSF levels of corticotropin-releasing hormone, vasopressin, somatostatin, and oxytocin and of the monoamine metabolites 5-hydroxyindolacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in 17 children and adolescents with obsessive-compulsive disorder before and after longterm treatment with clomipramine.

Results:  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-hydroxyindolacetic 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-hydroxyin-dolacetic acid ratio (mean±SD, 2.44±0.46 vs 3.42±0.84, P<.0001).

Conclusions:  These neuropeptide results coupled with evidence that central administration of corticotropinreleasing 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.


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