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.
"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   . "
[Show abstract][Hide abstract] 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. "
"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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