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Obsessive-compulsive disorder, serotonin and oxytocin: treatment response and side effects
Örebro University, School of Medical Sciences.ORCID iD: 0000-0001-6726-7787
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.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 148
Keyword [en]
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
Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-51438ISBN: 978-91-7529-153-6 (print)OAI: oai:DiVA.org:oru-51438DiVA: diva2:949869
Public defence
2016-09-26, Campus USÖ, hörsal C3, Södra Grev Rosengatan, Örebro, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-07-25 Created: 2016-07-25 Last updated: 2017-10-17Bibliographically approved
List of papers
1. The Brief Obsessive-Compulsive Scale (BOCS): a self-report scale for OCD and obsessive-compulsive related disorders
Open this publication in new window or tab >>The Brief Obsessive-Compulsive Scale (BOCS): a self-report scale for OCD and obsessive-compulsive related disorders
Show others...
2014 (English)In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 68, no 8, 549-559 p.Article in journal (Refereed) Published
Abstract [en]

Background: The Brief Obsessive Compulsive Scale (BOCS), derived from the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the children's version (CY-BOCS), is a short self-report tool used to aid in the assessment of obsessive-compulsive symptoms and diagnosis of obsessive-compulsive disorder (OCD). It is widely used throughout child, adolescent and adult psychiatry settings in Sweden but has not been validated up to date.

Aim: The aim of the current study was to examine the psychometric properties of the BOCS amongst a psychiatric outpatient population.

Method: The BOCS consists of a 15-item Symptom Checklist including three items (hoarding, dysmorphophobia and self-harm) related to the DSM-5 category "Obsessive-compulsive related disorders", accompanied by a single six-item Severity Scale for obsessions and compulsions combined. It encompasses the revisions made in the Y-BOCS-II severity scale by including obsessive-compulsive free intervals, extent of avoidance and excluding the resistance item. 402 adult psychiatric outpatients with OCD, attention-deficit/hyperactivity disorder, autism spectrum disorder and other psychiatric disorders completed the BOCS.

Results: Principal component factor analysis produced five subscales titled "Symmetry", "Forbidden thoughts", "Contamination", "Magical thoughts" and "Dysmorphic thoughts". The OCD group scored higher than the other diagnostic groups in all subscales (P < 0.001). Sensitivities, specificities and internal consistency for both the Symptom Checklist and the Severity Scale emerged high (Symptom Checklist: sensitivity = 85%, specificities = 62-70% Cronbach's alpha = 0.81; Severity Scale: sensitivity = 72%, specificities = 75-84%, Cronbach's alpha = 0.94).

Conclusions: The BOCS has the ability to discriminate OCD from other non-OCD related psychiatric disorders. The current study provides strong support for the utility of the BOCS in the assessment of obsessive-compulsive symptoms in clinical psychiatry.

Place, publisher, year, edition, pages
Informa Healthcare, 2014
Keyword
Attention deficit hyperactivity disorder, Autism, Assessment, Compulsive behaviour, Obsessions
National Category
Psychiatry
Research subject
Psychiatry
Identifiers
urn:nbn:se:oru:diva-39459 (URN)10.3109/08039488.2014.884631 (DOI)000343980600005 ()24568661 (PubMedID)
Available from: 2014-12-10 Created: 2014-12-10 Last updated: 2017-12-05Bibliographically approved
2. Reactivity of serotonin in whole blood: relationship with drug response in obsessive-compulsive disorder
Open this publication in new window or tab >>Reactivity of serotonin in whole blood: relationship with drug response in obsessive-compulsive disorder
2001 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 49, no 4, 360-368 p.Article in journal (Refereed) Published
Abstract [en]

Background: Obsessive-compulsive disorder responds almost only to potent serotonin reuptake inhibitors. Previous studies have suggested a relation between serotonergic function and clinical outcome in serotonin reuptake inhibitor treatment of obsessive-compulsive disorder.

Methods: In a randomized, double-blind trial, comparing clomipramine, paroxetine, and a placebo in obsessive-compulsive disorder, serotonin levels in whole blood (WB-5-HT) were measured at baseline, after 1 week, and after 4 weeks of treatment and related to clinical outcome in 36 patients.

Results: In patients treated with serotonin reuptake inhibitors there was a pronounced decrease of WB-5-HT, variable after 1 week and uniformly maximal after 4 weeks. The decrease of WB-5-HT after 1 week of serotonin reuptake inhibitor treatment correlated negatively with clinical outcome after 12 weeks (r = -.61, p =.0006); hence, patients with slower WB-5-HT reactivity eventually responded better to treatment. Baseline WB-5-HT, but not WB-5-HT reactivity, was related to season. Depression, autistic traits, and previous serotonin reuptake inhibitor treatment predicted nonresponse.

Conclusions: A fast decrease of WB-5-HT was associated with poor clinical outcome. This may be related to faster serotonin efflux from platelets, which has previously been linked to autism. Further studies are necessary to identify the underlying mechanism and discern whether serotonin reuptake inhibitor-induced WB-5-HT decrease is clinically useful.

Place, publisher, year, edition, pages
New York, USA: Elsevier, 2001
Keyword
Obsessive-compulsive disorder, serotonin, kinetics, serotonin reuptake inhibitors, autism, prediction of response, randomized controlled trial
National Category
Medical and Health Sciences Psychiatry Neurology
Identifiers
urn:nbn:se:oru:diva-50184 (URN)10.1016/S0006-3223(00)00956-2 (DOI)000167183100007 ()11239907 (PubMedID)2-s2.0-0035865647 (Scopus ID)
Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2017-11-30Bibliographically approved
3. Reactivity of serotonin in whole blood: response to Mulder et al.
Open this publication in new window or tab >>Reactivity of serotonin in whole blood: response to Mulder et al.
2002 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 51, no 3, 267-268 p.Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2002
National Category
Psychiatry Neurosciences
Identifiers
urn:nbn:se:oru:diva-51955 (URN)10.1016/S0006-3223(01)01316-6 (DOI)000173811000011 ()
Available from: 2016-09-05 Created: 2016-09-05 Last updated: 2017-11-21Bibliographically approved
4. Plasma oxytocin changes and anti-obsessive response during serotonin reuptake inhibitor treatment: a placebo controlled study
Open this publication in new window or tab >>Plasma oxytocin changes and anti-obsessive response during serotonin reuptake inhibitor treatment: a placebo controlled study
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.

Keyword
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
Identifiers
urn:nbn:se:oru:diva-33285 (URN)10.1186/1471-244X-13-344 (DOI)000329160000001 ()24359174 (PubMedID)2-s2.0-84890670310 (Scopus ID)
Funder
Swedish Research Council, 2011-3646
Note

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

Available from: 2014-01-24 Created: 2014-01-24 Last updated: 2017-12-06Bibliographically approved
5. Orgasm, Serotonin Reuptake Inhibition, and Plasma Oxytocin in Obsessive-Compulsive Disorder. Gleaning From a Distant Randomized Clinical Trial
Open this publication in new window or tab >>Orgasm, Serotonin Reuptake Inhibition, and Plasma Oxytocin in Obsessive-Compulsive Disorder. Gleaning From a Distant Randomized Clinical Trial
2016 (English)In: Sexual medicine, ISSN 2050-1161, Vol. 4, no 3, e145-e155 p.Article in journal (Refereed) Published
Abstract [en]

Introduction: Serotonin reuptake inhibitors (SRIs) are widely used for the treatment of psychiatric disorders, including obsessive-compulsive disorder (OCD). SRIs commonly cause delayed orgasm, the mechanism of which is poorly understood. Oxytocin is involved in sexual function and is interconnected with serotonin within the brain. SRIs are reported to affect the oxytocin system, but possible relations between SRI-induced changes of sexual function and oxytocin are unexplored in humans. In a randomized, double-blinded, placebo-controlled trial of OCD, the anti-obsessive efficacy and adverse events of SRIs and oxytocin measurements were studied.

Aims: To identify possible correlates between oxytocin levels and sexual function; find out whether sexual side effects correlate with levels of oxytocin and/or paroxetine and clomipramine; and test whether changes in sexual functioning are related to an anti-obsessive response.

Methods Reported sexual function and oxytocin plasma levels at rest were studied in 31 adults (15 men and 16 women) with OCD who participated in a randomized, double-blinded trial comparing the SRIs clomipramine and paroxetine with placebo. Sexual adverse effects were quantified by a clinician-administered semistructured interview. Anti-obsessive response was based on the Yale-Brown Obsessive-Compulsive Scale.

Main outcome measures: Ratings on the Sexual Symptom Checklist, plasma oxytocin, serum paroxetine and clomipramine levels, and Yale-Brown Obsessive-Compulsive Scale scores.

RESULTS: Baseline oxytocin levels were positively correlated with baseline OCD severity, but not with sexual functioning. Impaired orgasm at week 6 was reported by 73% of SRI-treated and 20% of placebo-treated patients (P = .03). Impaired orgasm was related to higher oxytocin levels after 4 weeks of SRI treatment (P < .01) but not to SRI concentrations. In men, an association between impaired orgasm and anti-obsessive treatment response was found (P = .028).

CONCLUSION: This pilot study suggests that some collateral effects of SRIs, particularly delayed orgasm, might be influenced by changes within the oxytocinergic system and are related to anti-obsessive mechanisms. Early-onset delayed orgasm in SRI-treated patients could serve as a predictor for OCD treatment response.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Elsevier, 2016
Keyword
Obsessive-Compulsive Disorder; Oxytocin/Plasma; Serotonin; Clomipramine; Paroxetine; Serotonin Uptake Inhibitors; Response Prediction; Adverse Effects; Randomized Controlled Trial; Sexual Physiology
National Category
Psychiatry Family Medicine
Identifiers
urn:nbn:se:oru:diva-50976 (URN)10.1016/j.esxm.2016.04.002 (DOI)000389259700003 ()27320409 (PubMedID)2-s2.0-85006216627 (Scopus ID)
Available from: 2016-06-21 Created: 2016-06-21 Last updated: 2017-10-18Bibliographically approved

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