Changes in cerebrospinal fluid neurochemistry during treatment of obsessive-compulsive disorder with clomipramine.
BACKGROUND
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.


METHODS
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.


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-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).


CONCLUSIONS
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.
Altemus
M
M
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Md.
Swedo
S E
SE
Leonard
H L
HL
Richter
D
D
Rubinow
D R
DR
Potter
W Z
WZ
Rapoport
J L
JL
D000293:Adolescent; D002648:Child; D002997:Clomipramine / Q000494:pharmacology / Q000627:therapeutic use*; D003346:Corticotropin-Releasing Hormone / Q000134:cerebrospinal fluid* / Q000502:physiology; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D009771:Obsessive-Compulsive Disorder / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000503:physiopathology; D013004:Somatostatin / Q000134:cerebrospinal fluid* / Q000502:physiology; D016896:Treatment Outcome; D014667:Vasopressins / Q000134:cerebrospinal fluid* / Q000502:physiology
D014667:Vasopressins; D013004:Somatostatin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D003346:Corticotropin-Releasing Hormone; D002997:Clomipramine; D006719:Homovanillic Acid