Swedo SE, Leonard HL, Kruesi MJ, Rettew DC, Listwak SJ, Berrettini
W, Stipetic M, Hamburger S, Gold PW, Potter WZ, et al.
fluid neurochemistry in children and adolescents with obsessive-compulsive disorder.
Gen Psychiatry. 1992 Jan;49(1):29-36.
"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." [Abstract]
M, Pigott T, Kalogeras KT, Demitrack M, Dubbert B, Murphy DL, Gold PW.
in the regulation of vasopressin and corticotropin releasing factor secretion
in obsessive-compulsive disorder.
Arch Gen Psychiatry. 1992
"In light of prior data that the central administration
of vasopressin in animals is associated with abnormal persistence of behaviors
acquired under aversive conditioning, we studied the secretion of arginine vasopressin
into the cerebrospinal fluid and plasma in patients with obsessive-compulsive
disorder and controls. Patients with obsessive-compulsive disorder had significantly
elevated basal levels of arginine vasopressin in the cerebrospinal fluid and significantly
increased secretion of arginine vasopressin into the plasma in response to hypertonic
saline administration. Moreover, seven of 12 patients with obsessive-compulsive
disorder showed a loss of the normal linear relationship between plasma arginine
vasopressin level and osmolality. In addition, cerebrospinal fluid corticotropin
releasing hormone, which has synergistic effects with arginine vasopressin centrally
and at the pituitary gland, was also significantly elevated in patients with obsessive-compulsive
disorder compared with controls." [Abstract]
Leckman JF, Goodman WK, North WG, Chappell PB, Price
LH, Pauls DL, Anderson GM, Riddle MA, McSwiggan-Hardin M, McDougle CJ, et al.
cerebrospinal fluid levels of oxytocin in obsessive-compulsive disorder. Comparison
with Tourette's syndrome and healthy controls.
Psychiatry. 1994 Oct;51(10):782-92.
"BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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." [Abstract]
Ferris CF, Rasmussen MF, Messenger T, Koppel G.
flank marking in golden hamsters is suppressed by drugs used in the treatment
of obsessive-compulsive disorder.
BMC Neurosci. 2001;2(1):10.
Epub 2001 Aug 15.
"BACKGROUND: Alterations in arginine vasopressin regulation
and secretion have been proposed as one possible biochemical abnormality in patients
with obsessive-compulsive disorder. In golden hamsters, arginine vasopressin microinjections
into the anterior hypothalamus trigger robust grooming and flank marking, a stereotyped
scent marking behaviors. The intensity and repetition of the behaviors induced
by arginine vasopressin is somewhat reminiscent of Obsessive Compulsive Disorder
in humans. The present experiments were carried out to test whether pharmacological
agents used to alleviate obsessive compulsive disorder could inhibit arginine
vasopressin-induced flank marking and grooming. RESULTS: Male golden hamsters
were treated daily for two weeks with either vehicle, fluoxetine, clomipramine,
or desipramine (an ineffective drug), before being tested for arginine vasopressin-induced
flank marking and grooming. Flank marking was significantly inhibited in animals
treated with fluoxetine or clomipramine but unaffected by treatment with desipramine.
Grooming behavior was not affected by any treatment. CONCLUSION: These data suggest
that arginine vasopressin-induced flank marking may serve as an animal model for
screening drugs used in the control of Obsessive Compulsive Disorder." [Full
Altemus M, Swedo SE, Leonard HL, Richter
D, Rubinow DR, Potter WZ, Rapoport JL.
Changes in cerebrospinal fluid
neurochemistry during treatment of obsessive-compulsive disorder with clomipramine.
Gen Psychiatry. 1994 Oct;51(10):794-803.
"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."
M, Cizza G, Gold PW.
Chronic fluoxetine treatment reduces hypothalamic
vasopressin secretion in vitro.
Brain Res. 1992 Oct 16;593(2):311-3.
with obsessive-compulsive disorder (OCD) hypersecrete the arousal producing neurohormone
arginine vasopressin (AVP) into the cerebrospinal fluid and plasma. Because OCD
responds preferentially to potent serotonin uptake inhibitors, we compared the
effect of chronic fluoxetine treatment to that of other antidepressants (trazodone
and desipramine) on AVP release from rat hypothalamic organ culture and showed
that only fluoxetine significantly reduced in vitro AVP release." [Abstract]
HG, Grozdanovic Z.
Role of serotonin in obsessive-compulsive
Br J Psychiatry Suppl. 1998;(35):13-20.
Serotonin may play a role in the pathophysiology of obsessive-compulsive disorder
(OCD) because of the anti-obsessional effect of selective serotonin reuptake inhibitors
(SSRIs). METHOD: The literature is reviewed on knowledge of the role of serotonergic
neurons in brain function, studies on monoamine metabolites in cerebrospinal fluid
(CSF), various stress neuropeptides, neuroendocrine and behavioural challenge
after administration of direct and indirect serotomimetic compounds, and neuroanatomical
data on brain circuits organising behaviour. RESULTS: In most of the OCD cases
analysed, CSF 5-hydroxyindoleacetic acid and homovanillic acid concentrations
do not significantly differ from age-corrected controls. However, a relationship
appears to exist between pre-treatment levels of these metabolites and clinical
response to drugs acting on the serotonin transporter. Abnormalities in CSF arginine
vasopressin, corticotropin-releasing hormone, oxytocin and somatostatin levels
have been reported in OCD. Long-term treatment with high-doses of clomipramine,
fluvoxamine, and fluoxetine tend to correct these neuropeptide abnormalities.
CONCLUSIONS: We hypothesise that continuous treatment with SSRIs alters serotonin
turnover and neuropeptide expression patterns in OCD-entertaining functional forebrain/midbrain