Effects of single dose intranasal oxytocin on social cognition in schizophrenia

Department of Veterans Affairs VISN 22 MIRECC, Los Angeles, CA, United States.
Schizophrenia Research (Impact Factor: 3.92). 05/2013; 147(2-3). DOI: 10.1016/j.schres.2013.04.023
Source: PubMed


Deficits in social cognition are common in schizophrenia and predict poor community functioning. Given the current limitations of psychosocial treatments and the lack of pharmacological treatments for social cognitive deficits, the development of novel therapeutic agents could greatly enhance functional recovery in schizophrenia. This study evaluated whether a single dose of intranasal oxytocin acutely improves social cognitive functioning in schizophrenia. Twenty-three male veterans with schizophrenia completed baseline assessments of social cognition that were divided into lower-level (facial affect perception, social perception, detection of lies) and higher-level (detection of sarcasm and deception, empathy) processes. One week later, patients received the same battery after being randomized to a single dose of 40IU intranasal oxytocin or placebo. Though the groups did not differ significantly on the social cognition composite score, oxytocin improved performance for the higher-level social cognitive tasks (Cohen's d=1.0, p=0.045). Subjects were unable to accurately guess which treatment they had received. The improvements found in higher-level social cognition encourage further studies into the therapeutic potential of oxytocin in schizophrenia.

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    • "Insulin is not the only compound to have beneficial effects on cognition with intranasal administration. Oxytocin, exendin, and pituitary adenylate cyclase-activating peptide have also shown improvements on cognition after intranasal administration [23] [43] [44]. "
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    ABSTRACT: Intranasal insulin has shown efficacy in patients with Alzheimer's disease (AD), but there are no preclinical studies determining whether or how it reaches the brain. Here, we showed that insulin applied at the level of the cribriform plate via the nasal route quickly distributed throughout the brain and reversed learning and memory deficits in an AD mouse model. Intranasal insulin entered the blood stream poorly and had no peripheral metabolic effects. Uptake into the brain from the cribriform plate was saturable, stimulated by PKC inhibition, and responded differently to cellular pathway inhibitors than did insulin transport at the blood-brain barrier. In summary, these results show intranasal delivery to be an effective way to deliver insulin to the brain.
    • "Given the number of studies that have now failed to show significant benefit of oxytocin on facial emotion recognition in schizophrenia (Davis et al., 2013; Horta de Macedo et al., 2014; Woolley et al., 2014), we conclude that the consistent benefits of oxytocin identified in healthy control populations on basic facial emotion recognition performance (Shahrestani et al., 2013) do not appear to generalize to schizophrenia populations. Perhaps, more fundamental neurobiological and/ or visual processing deficits underlie impaired lower order social cognition performance in schizophrenia, resulting in a failure to respond to oxytocin treatment. "
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    ABSTRACT: Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 07/2015; DOI:10.1016/j.schres.2015.06.005 · 3.92 Impact Factor
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    • "Future studies assessing receptor function may be valuable in disentangling the meaning of the elevated plasma oxytocin levels. Despite these limitations , oxytocin may represent a novel therapeutic target in SZ given recent evidence for significant improvements in social cognition and social outcome following single or repeated intranasal administration (Feifel et al., 2010; Pedersen et al., 2011; Averbeck et al., 2012; Davis et al., 2013, 2014; Fischer-Shofty et al., 2013a,b; Gibson et al., 2014; Woolley et al., 2014). Table 2 Correlations between social cognition and plasma oxytocin levels. "
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    ABSTRACT: Lower endogenous levels of the neuropeptide oxytocin may be an important biological predictor of social cognition impairments in schizophrenia (SZ). Prior studies have demonstrated that lower-level social cognitive processes (e.g., facial affect perception) are significantly associated with reduced plasma oxytocin levels in SZ; however, it is unclear whether higher-level social cognition, which requires inferential processes and knowledge not directly presented in the stimulus, is associated with endogenous oxytocin. The current study explored the association between endogenous oxytocin levels and lower- and higher-level social cognition in 40 individuals diagnosed with SZ and 22 demographically matched healthy controls (CN). All participants received the Social Cue Recognition Test (SCRT), which presents participants with videotaped interpersonal vignettes and subsequent true/false questions related to concrete or abstract aspects of social interactions in the vignettes. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ and CN did not differ on SCRT hits, but SZ had more false positives and lower sensitivity scores than CN. Higher plasma oxytocin levels were associated with better sensitivity scores for abstract items in CN and fewer false positives for concrete items in individuals with SZ. Findings indicate that endogenous oxytocin levels predict accurate encoding of lower-level socially relevant information in SZ. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 02/2015; 162(1-3). DOI:10.1016/j.schres.2015.01.034 · 3.92 Impact Factor
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