Relationship of plasma oxytocin levels to baseline symptoms and symptom changes during three weeks of daily oxytocin administration in people with schizophrenia

Abstract

Several clinical studies have found an inverse relationship between clinical symptoms and peripheral oxytocin (OT) levels in people with schizophrenia. As oxytocin is a putative treatment for schizophrenia, the effect of repeated dosing of OT on OT levels, clinical symptoms and the relationship between the two is of interest. In a, randomized, double blind, parallel group 3 week study (N = 28) with daily administration of intranasal OT (20 IU twice daily) or placebo (PBO), we examined the effect of OT administration on the correlation between the change in peripheral OT levels and change in clinical symptoms in patients with schizophrenia. At baseline, there were no significant treatment group differences in OT levels. There were no significant associations between baseline OT levels and any symptom measures. After 3 weeks of OT/PBO dosing, there was no significant difference in the magnitude of change in OT levels between the two treatment groups. Correlations between changes in peripheral OT levels and changes in the BPRS total and negative symptom scores were not different between treatment groups. Larger studies are needed to examine the effect of exogenous OT on peripheral OT levels and the relationship between the latter and clinical symptoms.

Clinical Trials.gov = NCT00884897.

Introduction

Early clinical trials of intranasal oxytocin (OT) in individuals with schizophrenia (SZ) suggest short-term benefits for positive, negative, and cognitive symptoms (N = 15, 3 weeks; N = 14, 6 weeks; N = 40, 8 weeks; N = 20, 2 weeks) (Feifel et al., 2010, Gibson et al., 2014, Modabbernia et al., 2013, Pedersen et al., 2011), respectively. However, more recent, larger clinical trials do not show robust benefits for positive or negative symptoms, either with OT alone (N = 58, 6 weeks) (Buchanan et al., 2015, Weiser et al., 2015), or with social skills (N = 48, 3 weeks) (Weiser et al., 2015) or social cognitive training (N = 52, 6 weeks) (Cacciotti-Saija et al., 2015). We completed a pilot 3-week randomized, double-blind clinical trial (Lee et al., 2013) of OT vs. placebo (PBO). Negative symptoms improved only in inpatients who received OT.

It is important to understand the relationship between peripheral OT levels, symptoms and treatment response. Evidence remains equivocal regarding whether there are differences in peripheral levels of OT in individuals with SZ compared to controls, with some studies reporting higher levels (Strauss et al., 2015a, Strauss et al., 2015b, Strauss et al., 2015c), lower levels (Goldman et al., 2008, Jobst et al., 2014) or no difference (Rubin et al., 2014, Rubin et al., 2013, Rubin et al., 2010). There are mixed results also reported for central levels in individuals with SZ (Beckmann et al., 1985, Glovinsky et al., 1994, Linkowski et al., 1984). There are associations between plasma OT levels and symptoms as well as social cognitive measures. OT levels either in plasma or CSF are inversely correlated with negative symptoms in men with SZ (Jobst et al., 2014, Keri et al., 2009, Sasayama et al., 2012). Lower plasma OT levels are also associated with more asociality and poorer accuracy for olfactory identification in individuals with SZ (Rubin et al., 2010, Strauss et al., 2015b). Lower peripheral levels of OT are associated with more severe positive symptoms, general psychopathology and poorer perception of emotion in women, but not men, with SZ (Rubin et al., 2011, Rubin et al., 2010, Strauss et al., 2015c).

There are no studies that examine the effects of repeated OT dosing versus PBO on 1) peripheral OT levels and 2) the relationship between changes in peripheral OT levels and changes in clinical symptoms. At baseline, we hypothesized that there would be a negative correlation between peripheral levels of OT and positive and negative symptoms of SZ. After repeated OT dosing compared to PBO, peripheral OT levels would increase with the increase in peripheral OT levels after 3 weeks significantly correlated with the improvement in positive and negative symptoms of SZ.