Effects of adjunctive intranasal oxytocin on olfactory identification and clinical symptoms in schizophrenia: Results from a randomized double blind placebo controlled pilot study

Abstract

Background Deficits in olfactory identification have been widely reported in patients with schizophrenia (SZ) and are associated with negative symptomatology. Adjunctive oxytocin delivered intranasally has been shown to improve some aspects of social cognition as well as positive and negative symptoms in patients with schizophrenia. Given the intranasal delivery route of oxytocin to olfactory pathways and that olfactory abnormalities are a potential endophenotype in SZ, we investigated the effect of intranasal oxytocin on olfactory identification as well as positive and negative symptoms in people with schizophrenia. Methods Individuals with schizophrenia or schizoaffective disorder (n=28; 16 outpatients, 12 inpatients) were randomized to receive adjunctive intranasal oxytocin 20 IU BID or placebo for 3 weeks. Results All 28 participants completed the clinical trial. Odor identification performance significantly improved on the University of Pennsylvania Smell Identification Test (UPSIT) total score and subscore for pleasant smells. UPSIT score (F=5.20, df=1,23, p=0.032) and subscore for pleasant smells (F=4.56, df=1,23, p=0.044), in patients treated with oxytocin were compared to placebo from baseline to endpoint. Global symptomatology as well as positive and negative symptoms were not improved by intranasal oxytocin. In fact, global symptoms, not positive or negative symptoms, improved in the placebo group. Secondary analysis shows that intranasal oxytocin improved negative symptoms in the small group of inpatients. Intranasal oxytocin was well tolerated during the three week trial. Conclusion Adjunctive intranasal oxytocin may improve olfactory identification, particularly in items of positive valence. Larger studies are needed to determine the effects of oxytocin on negative symptoms in SZ.

Oxytocin administration selectively improves olfactory detection thresholds for lyral in patients with schizophrenia

“…Our findings extend those of other studies (Lee et al, 2013), and suggest that the oxytocin system plays a role in some aspects of the olfactory deficits in schizophrenia. However, oxytocin did not improve participants' ability to detect anise, suggesting some specificity to its olfaction-enhancing effect.…”

“…Finally, there is growing evidence that oxytocin administration to patients with schizophrenia improves emotion recognition and higher-level social cognition and decreases both positive and negative symptoms (Gumley et al, 2014). Additionally, a recent study that administered 20 IU of oxytocin or placebo twice daily for three weeks to patients with schizophrenia found that oxytocin improved patients' ability to identify pleasant, but not neutral or unpleasant odors (Lee et al, 2013). Taken together, this evidence suggests that oxytocin administration may reduce olfactory deficits in schizophrenia.…”

Efficacy and safety of oxytocin augmentation therapy for schizophrenia: an updated systematic review and meta-analysis of randomized, placebo-controlled trials

“…To date, only 1 meta-analysis of oxytocin for the treatment of schizophrenia has been reported [15]. The previous meta-analysis included four RCTs [8,20,27,31] that evaluated the psychopathology and found that total symptoms, positive symptoms, and negative symptoms improved significantly in the oxytocin group; however, the Positive and Negative Syndrome Scale (PANSS) [18] general subscale scores did not improve in comparison with the placebo group (Table 1). However, seven RCTs with oxytocin have been conducted for the treatment of schizophrenia to date [5,7,8,12,20,27,31].…”

Epistatic and Independent Effects on Schizophrenia-Related Phenotypes Following Co-disruption of the Risk Factors Neuregulin-1 × DISC1

“…Both the animal and human literature has linked oxytocin and vasopressin with social affiliative and agonistic behavior, 41 and intranasal oxytocin administration has been shown to improve negative symptoms in schizophrenia patients. 42 The present study demonstrates that, in general, male mutants were more affected than females by mutation of NRG1, DISC1 or NRG1 × DISC1. Sexually dimorphic effects in genetic mouse models of psychosis are commonly observed.…”