Intranasal Oxytocin Reduces Negative Effects, Improves Cognitive Function in Schizophrenia

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Adjunctive intranasal oxytocin was administered to participants with chronic schizophrenia for 12 weeks.

Adjunctive intranasal oxytocin improves symptoms of schizophrenia, particularly negative symptoms, and these improvements may be related to the gray matter volume of the anterior cingulated cortex and insula, according to an open-label, nonrandomized, 12-week study published in Postgraduate Medicine.  In addition, oxytocin may improve verbal fluency in patients with schizophrenia.

Miho Ota, MD, PhD, of the department of mental disorder research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan, and colleagues evaluated the effects of intranasal oxytocin on cognition and clinical symptoms in 16 patients with schizophrenia. Patients received 12 international units of oxytocin intransally twice daily and remained on their pre-study medication regimen throughout the trial period. Of these, 15 subjects also underwent 3-Tesla magnetic resonance imaging (MRI).  The investigators then evaluated the possible relationship between treatment response to oxytocin and brain structure as assessed by MRI.

Previous studies have shown that plasma oxytocin concentrations in patients with schizophrenia were lower than those in normal subjects and were negatively correlated with psychotic symptoms, and that cerebrospinal fluid oxytocin concentrations were negatively correlated with Positive and Negative Syndrome Scale (PANSS) subscale scores. Furthermore, it is known that oxytocin has an anorexigenic effect, which may be of benefit in schizophrenic patients as they are known to have a high risk for obesity.

The investigators detected a significant reduction of PANSS total score (f value =20.4, partial η2 =0.58; P <.001), and significant reductions of the positive (f value =7.3, partial η2 =0.33; P <.001), negative (f value =17.9, partial η2 =0.54; P <.001), and general (f value =13.1, partial η2 = 0.47; P <.001) scale scores. There were significant reductions of blunted effect, emotional withdrawal, lack of spontaneity, and flow of conversation (all P <.001). However, changes in the other subscale scores of PANSS negative were not significant. 

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Regarding cognitive scores, the investigators found a significant increase in category fluency derived from the Brief Assessment of Cognition in Schizophrenia-Japanese (BACS) during treatment (t = –2.86; P =.012 by paired t-test; effect size = 0.53).  However, there was no significant improvement in social cognition and no significant changes in body mass index during the study period. The investigators noted, however, that these participants were only slightly overweight, with an average BMI of 27.9 kg/m2. They also found that the larger the anterior cingulated cortex  and right insula were on MRI, the greater the improvement in clinical symptoms in response to oxytocin.

Study limitations include the small sample size and low degree of freedom, the open-label design, and the fact that study participants had already been treated with antipsychotics.


Ota M, Yosida S, Nakata M, Yada T, Kunugi H. The effects of adjunctive intranasal oxytocin in patients with schizophrenia. Postgrad Med.  2018;130:122-128.