dynorphins and Obsessive-Compulsive-Disorder

Limited neurobiological data have implicated central arginine vasopressin in the pathobiology of obsessive-compulsive disorder (OCD). Based on twin, family genetic, and pharmacological studies, some forms of OCD are etiologically related to Tourette's syndrome. The role of arginine vasopressin and related compounds such as oxytocin in Tourette's syndrome has not been previously explored.. To compare cerebrospinal fluid (CSF) levels of arginine vasopressin and oxytocin, we collected CSF at midday in a standardized fashion from a total of 83 individuals (29 patients with OCD, 23 patients with Tourette's syndrome, and 31 normal controls). We also collected family study data on each subject to determine which subjects had a family history positive for Tourette's syndrome, OCD, or related syndromes.. In contrast to previous reports, we report similar concentrations of arginine vasopressin for all three groups but increased oxytocin levels in patients with OCD. Remarkably, this increase was observed only in a subset of patients with OCD (n = 22) independently identified as being without a personal or family history of tic disorders (P = .0003). In this subgroup of patients, the CSF oxytocin level was correlated with current severity of OCD (n = 19, r = .47, P < .05).. A possible role for oxytocin in the neurobiology of a subtype of OCD is suggested by the elevated CSF levels of oxytocin and by the correlation between CSF oxytocin levels and OCD severity. These findings reinforce the value of family genetic data in identifying biologically homogeneous (and perhaps more etiologically homogeneous) groups of patients with OCD. Together with emerging pharmacological data showing differential responsiveness to treatment of tic-related OCD vs non-tic-related OCD, these data also argue strongly for the incorporation of tic-relatedness as a variable in biological and behavioral studies of patients with OCD.

Topics: Adolescent; Adult; Age of Onset; Arginine Vasopressin; Biogenic Amines; Comorbidity; Dynorphins; Family; Female; Humans; Hydroxyindoleacetic Acid; Male; Mental Disorders; Middle Aged; Obsessive-Compulsive Disorder; Oxytocin; Psychiatric Status Rating Scales; Severity of Illness Index; Tourette Syndrome; Tryptophan

Cerebrospinal fluid hormones, monoaminergic metabolites, and dynorphin A (1-8 sequence) were examined in 43 children with severe, primary obsessive-compulsive disorder. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid were positively correlated with one of eight obsessive-compulsive disorder severity ratings and three of seven measures of improvement following 5 weeks of treatment with clomipramine hydrochloride. Arginine vasopressin concentration was significantly and negatively correlated with several ratings of obsessive-compulsive disorder symptom severity, while oxytocin concentration was positively correlated with depressive symptoms. The ratio of arginine vasopressin to oxytocin was also negatively correlated with obsessive-compulsive disorder and depressive symptoms. Comorbid affective disorder was associated with decreased arginine vasopressin concentrations, while concomitant anxiety disorder was associated with increased oxytocin. Dynorphin A (1-8 sequence), homovanillic acid, corticotropin, 3-methoxy-4-hydroxyphenylglycol, and corticotropin releasing hormone were not significantly related to obsessive-compulsive disorder symptoms. These results seem to indicate that arginine vasopressin may be related to obsessive-compulsive disorder symptom severity, while 5-hydroxyindoleacetic acid might be associated with drug response.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Arginine Vasopressin; Child; Clomipramine; Corticotropin-Releasing Hormone; Dynorphins; Female; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Male; Methoxyhydroxyphenylglycol; Neuropeptides; Obsessive-Compulsive Disorder; Oxytocin; Peptide Fragments; Severity of Illness Index