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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.

SUBMITTER: Lee MR

PROVIDER: S-EPMC4821731 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Lee Mary R MR Wehring Heidi J HJ McMahon Robert P RP Liu Fang F Linthicum Jared J Verbalis Joseph G JG Buchanan Robert W RW Strauss Gregory P GP Rubin Leah H LH Kelly Deanna L DL

Schizophrenia research 20160212 1-3

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 o ...[more]

PMID: 26879587

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Project description:Individuals with schizophrenia have functionally significant deficits in automatic and controlled social cognition, but no currently available pharmacologic treatments reduce these deficits. The neuropeptide oxytocin has multiple prosocial effects when administered intranasally in humans and there is growing interest in its therapeutic potential in schizophrenia.We administered 40 IU of oxytocin and saline placebo intranasally to 29 male subjects with schizophrenia and 31 age-matched, healthy controls in a randomized, double-blind, placebo-controlled, cross-over study. Social cognition was assessed with The Awareness of Social Inference Test (TASIT) and the Reading the Mind in the Eyes Test (RMET). We examined the effects of oxytocin administration on automatic social cognition (the ability to rapidly interpret and understand emotional cues from the voice, face, and body); controlled social cognition (the ability to comprehend indirectly expressed emotions, thoughts, and intentions through complex deliberations over longer time periods); and a control task (the ability to comprehend truthful dialog and perform general task procedures) in individuals with and without schizophrenia using mixed factorial analysis of variance models.Patients with schizophrenia showed significant impairments in automatic and controlled social cognition compared to healthy controls, and administration of oxytocin significantly improved their controlled, but not automatic, social cognition, F(1, 58)=8.75; p=0.004. Conversely, oxytocin administration had limited effects on social cognition in healthy participants. Patients and controls performed equally well and there were no effects of oxytocin administration on the control task.Intact social cognitive abilities are associated with better functional outcomes in individuals with schizophrenia. Our data highlight the potentially complex effects of oxytocin on some but not all aspects of social cognition, and support the exploration of intranasal oxytocin as a potential adjunct treatment to improve controlled social cognition in schizophrenia.

Project description:Abstract Background: A significant proportion of people with schizophrenia are characterized by impaired ability to socially engage with others, which may reflect social aversion secondary to defeatist beliefs; decreased motivation for social interactions; and/or impairment in the normal reinforcement value of social interactions. Unfortunately, pharmacological interventions have limited benefits for impaired social function, whereas psychosocial interventions provide only partial benefit for this critical aspect of the illness. The development of an effective intervention for functional outcomes remains a central therapeutic challenge. The current study assessed whether the addition of intranasal oxytocin to Cognitive Behavioral Social Skills Training (CBSST) improved social function. Methods: Participants with DSM-IV-TR schizophrenia or schizoaffective disorder entered a 24-week, double-blind, placebo-controlled, randomized clinical trial with a 3-month follow-up evaluation. The study was conducted at two sites: Maryland and California. Participants were randomized to either: intranasal oxytocin 36 I.U. (3 sprays) BID (n = 31) or intranasal placebo-oxytocin 3 sprays BID (n = 31). All participants received CBSST, which was delivered in four 6-session modules (cognitive, social, and problem-solving CBSST modules plus a module adapted from Social Cognition and Interaction Training). The modules were delivered twice in biweekly 1-hour sessions, for a total of 48 sessions over 24 weeks. Birchwood Social Functioning Scale (SFS) was used to assess social function; the Defeatist Performance Attitude Scale (DPAS) was used to assess defeatist beliefs; the Asocial Beliefs Scale (ABS) was used to assess social disinterest and aversion; and the Scale for the Assessment of Negative Symptoms (SANS) total score was used to assess negative symptoms. Results: In the intent-to-treat analyses, there were no significant group differences in the SFS total score (Treatment × Week interaction: F = 0.96; df = 2, 40; P = .39) or ABS total score (Treatment × Week interaction: F = .12; df = 2, 39.7; P = .89). There was a trend for a significant reduction in defeatist beliefs among the participants randomized to oxytocin (Treatment × Week interaction: F = 2.86; df = 2, 67.2; P = .07). There were no significant group differences in SANS total score (Treatment × Week interaction: F = 0.96; df = 6, 39.7; P = 0.46), though the interpretation of the effect of oxytocin on SANS total score was complicated by the presence of a significant site effect: there was a significant placebo effect at the California site, which was markedly greater in magnitude than the observed oxytocin effect for these symptoms. Conclusion: The results of the intent-to-treat analyses provide minimal support for the utility of add-on intranasal oxytocin to CBSST for improvement in social function. Oxytocin was associated with trend improvement in defeatist attitudes and greater reduction in negative symptoms at one of the two study sites. (clinicaltrials.gov, trial number: NCT01752712)

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

Publications

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

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