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Plasma oxytocin changes and anti-obsessive response during serotonin reuptake inhibitor treatment: a placebo controlled study
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Psychiatric Research Centre, Örebro, Sweden.ORCID iD: 0000-0001-6726-7787
Swedish University of Agricultural Sciences, Skara, Sweden .
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Psychiatric Research Centre, Örebro County Council, Örebro, Sweden.
Karolinska Institutet, Stockholm, Sweden.ORCID iD: 0000-0002-3587-6075
2013 (English)In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 13, 344- p.Article in journal (Refereed) Published
Abstract [en]

Background: The drug treatments of choice for obsessive-compulsive disorder (OCD) are serotonin reuptake inhibitors (SRIs). However, a correlation between the neuropeptide oxytocin in cerebrospinal fluid and the severity of OCD has previously been shown, and oxytocin and serotonin are interconnected within the brain. Few studies have investigated whether SRIs have any effect on oxytocin; thus, our aim was to explore the possibility that oxytocinergic mechanisms contribute to the anti-obsessive effect of SRIs.

Method: In a randomized, double-blind trial, comparing SRIs (clomipramine and paroxetine) with placebo in 36 adults with OCD (characterized for subtypes), plasma oxytocin was measured with radioimmunoassay after plasma extraction, at baseline, after 1 week, and after 4 weeks of treatment, and related to baseline severity and clinical response after 12 weeks, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).

Results: Baseline oxytocin levels correlated positively with baseline Y-BOCS ratings, but only among the future SRI responders. Patients with early onset of OCD had higher baseline oxytocin. During treatment, plasma oxytocin did not differ between SRI and placebo treatment. In SRI responders, plasma oxytocin first decreased and then increased; in non-responders (to SRI as well as to placebo), the reverse was the case. After 4 weeks, treatment responders had attained higher oxytocin levels compared to non-responders. The intra-individual range (i.e. the variability) of plasma oxytocin between measurements was the measure that best differentiated responders from non-responders. This range was higher in responders than non-responders, and lower in patients with autistic traits.

Conclusions: SRIs have highly variable effects on plasma oxytocin between individuals. The associations between baseline oxytocin and OCD severity and between oxytocin changes and treatment response support the notions that oxytocin is involved in OCD pathophysiology, and that the anti-obsessive effects of SRIs are partly exerted through oxytocinergic mechanisms.

Place, publisher, year, edition, pages
2013. Vol. 13, 344- p.
Keyword [en]
Obsessive-compulsive disorder, Oxytocin/plasma, Serotonin, Serotonin uptake inhibitors, Treatment response, Randomized controlled trial, Autism spectrum disorder, Placebo response
National Category
Medical and Health Sciences Psychiatry
URN: urn:nbn:se:oru:diva-33285DOI: 10.1186/1471-244X-13-344ISI: 000329160000001PubMedID: 24359174ScopusID: 2-s2.0-84890670310OAI: diva2:690785
Swedish Research Council, 2011-3646

Funding Agency: Örebro County Council; Örebro University (se även Forskningsfinansiär)

Available from: 2014-01-24 Created: 2014-01-24 Last updated: 2016-09-06Bibliographically approved
In thesis
1. Obsessive-compulsive disorder, serotonin and oxytocin: treatment response and side effects
Open this publication in new window or tab >>Obsessive-compulsive disorder, serotonin and oxytocin: treatment response and side effects
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obsessive-compulsive disorder (OCD), with a prevalence of 1-2 %, frequently leads a chronic course. Persons with OCD are often reluctant to seek help and, if they do, their OCD is often missed. This is unfortunate, since active treatment may substantially improve social function and quality of life. Serotonin reuptake inhibitors (SRIs) have welldocumented efficacy in OCD, but delayed response may be problematic. Methods to predict response have been lacking. Because SRIs are effective, pathophysiological research on OCD has focussed on serotonin. However, no clear aberrations of serotonin have been found, thus other mechanisms ought to be involved.

Our aims were to facilitate clinical detection and assessment of OCD, to search for biochemical correlates of response and side-effects in SRI treatment of OCD and to identify any possible involvement of oxytocin in the pathophysiology of OCD.

In study I, we tested in 402 psychiatric out-patients the psychometric properties of a concise rating scale, “Brief Obsessive Compulsive Scale” (BOCS). BOCS was shown to be easy to use and have excellent discriminant validity in relation to other common psychiatric diagnoses.

Studies II-V were based on 36 OCD patients from a randomised controlled trial of paroxetine, clomipramine or placebo. In study II, contrary to expectation, we found that the change (decrease) of serotonin in whole blood was most pronounced in non-responders to SRI. This is likely to reflect inflammatory influence on platelet turnover rather than serotonergic processes within the central nervous system.

In studies IV-V, we found relations between changes of oxytocin in plasma and the anti-obsessive response, and between oxytocin and the SRI related delay of orgasm, respectively. In both cases, the relation to central oxytocinergic mechanisms is unclear. In males, delayed orgasm predicted anti-obsessive response.

Place, publisher, year, edition, pages
Örebro: Örebro university, 2016. 133 p.
Örebro Studies in Medicine, ISSN 1652-4063 ; 148
Adverse effects, Obsessive-compulsive disorder, Orgasm, Oxytocin, Randomised controlled trial, Rating scale, Response prediction, Serotonin, Serotonin uptake inhibitors, Sexual function
National Category
Psychiatry Family Medicine
Research subject
urn:nbn:se:oru:diva-51438 (URN)978-91-7529-153-6 (ISBN)
Public defence
2016-09-26, Campus USÖ, hörsal C3, Södra Grev Rosengatan, Örebro, 13:00 (Swedish)
Available from: 2016-07-25 Created: 2016-07-25 Last updated: 2016-09-05Bibliographically approved

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