Table 1.

Overview of Clinical Trials of the Effect of Oxytocin on Social Cognition and Psychopathology in Schizophrenia

Study	Sample*	Oxytocin (OT) Intranasal Dose	Design	Outcome Measure	Results
Goldman et al. (2008)	13 SZ 5 with PD; age=53+/−3; males=3 8 without PD; age=44+/−9; males=4 11 HCs (age=38+/− 13; males=4)	10 IU or 20 IU once a week	Double-blind, placebo-controlled crossover 3-week trial	Facial affect recognition	Facial affect intensity was greater in patients with PD compared to HCs across the treatment conditions but there was no difference between the two patients groups. The low OT dose (10 IU) increased intensity in the PD group compared to HCs but not to the nonPD group. The 20 IU dose showed a decrease in intensity in the PD group relative to the nonPD group but there were no differences compared to the HCs. Among emotions, only ‘fear’ was altered by OT: PD patients showed a reduction in fear compared to the nonPD patients. Recognition deteriorated in both SZ groups on the 10 IU dose but improved with 20 IU dose in SZ with PD. Overall emotion recognition improved with the 20 IU dose in the PD patients compared to the nonPD patients.
Feifel et al. (2010)	15 SZ 6 in the OT group 9 in the placebo group Sample age=48+/−8.9; males=12	20 IU twice a day (first week); 40 IU twice a day for the subsequent two weeks	Double-blind, placebo-controlled crossover 3-week trial	Positive And Negative Symptoms Scale (PANSS) Clinical Global Impression (CGI)	Reduction of symptoms with improvement of PANSS and CGI scores at the 3 week endpoint in OT group vs the placebo group. Study supports the hypothesis that OT has antipsychotic properties with effects on both negative and positive symptoms but more statistically robust for positive symptoms
Pederson et al. 2011	20 SZ 11 in the OT group; age=39+/− 11.2; males=9 9 in the placebo group age=35.8+/− 9.5; males=8	24 IU twice daily	Randomize d, double-blind, placebo-controlled 2-week trial	Brune Theory of Mind Picture Stories Task Trustworthiness Task Positive And Negative Symptoms Scale (PANSS) Paranoia Scale	The OT group improved in accurate identification in second order false beliefs (Brune Task) but there were no other significant differences in other measures of the Brune Task. The OT group also showed reduction in PANSS (positive, total, general subscale and suspiciousness/persecutory items) and Paranoia Scale scores.
Averback et al 2012	21 SZ 10 in the OT group 11 in the placebo group Sample age=38.2+/− 1.8; males=21	24 IU single dose	Double-blind, placebo-controlled crossover 2-week trial	Facial Affect Recognition: facial expression of emotion in still images from the standardized items developed by Ekman	The OT group showed an overall better performance on facial emotion recognition, but none of the individual emotions showed a significant difference. The OT group performance remained lower compared to that of a control group used in a previous experiment in the study.
Feifel 2012	15 SZ 6 in the OT group 9 placebo in the placebo group Sample age=48+/−8.9; males=12	20 IU twice a day (first week); 40 IU twice a day for the other two weeks	Double-blind, placebo-controlled crossover study	Verbal memory: California Verbal Learning Test (CVLT) Working Memory: LNS (from WAIS- III)	The OT group vs the placebo groups showed significant effect on CVLT but not on LNS. The effect of OT was significant in CVLT total recall trials 1–5, short delayed free recall and total recall discrimination. However, it was stronger for short-term recall than for long-term. Authors suggest that this might be due to the fact that OT modulates only neural processes involved in short-term verbal memory.
Modabbernia et al 2012	40 SZ 20 in the OT group age=32.3+/− 7.4; males=17 20 in the placebo group age=33.2+/− 6.9; males=16	20 IU twice daily for the 1st week; 40 IU twice daily for the following 7 weeks	Randomize d, double-blind, placebo-controlled 8-week trial	Positive And Negative Symptoms Scale (PANSS) Extrapyramidal Symptom Rating Scale (ESRS)	OT group showed improvement in PANSS total score by week 4 with a total 11.2% symptoms reduction from baseline. Positive and negative symptoms and general psychopathology subscale scores showed that in the OT group at the study endpoint there was a symptoms reduction (of 20%, 7% and 8% respectively) starting from week 6. No changes were detected in ESRS score between the OT and the placebo group.
Davis et al 2013	23 SZ 11 in the OT group age=48.6+/− 6.6; males=11 12 in the placebo group age=48.9+/− 9.1; males=12	Single dose of 40 IU	Randomize d, double-blind, placebo-controlled study	Theory of mind: The Awareness of Social Inference Test (TASIT-III) Empathy: Emotional Perspective Taking Task (EPTT) Social Perception: Half Profile of Nonverbal Sensitivity (Half-PONS) Facial affect recognition: assessed asking participants to identify facial expression of emotion in still images from the standardized items developed by Ekman	OT did not significantly improve performance either in the social composite measure (combination of all the social tasks) or in the low-level processes score (TASIT- Part III detection of lies, Half-PONS and Facial Affect Recognition Task). However, OT significantly improved performance on high-level social cognition (TASIT-Part III detection of sarcasm, EPTT) with a large effect size (d=1.0). No improvement on positive, negative or general symptoms.
Fischer- Shoftly et al. 2013a	35 SZ age=32.4+/− 6.4; males=31 48 HCs age=30.4+/− 5.8; males=39	24 IU single dose	Double-blind, within-subjects crossover 2-week trial	Social Perception: the Interpersonal Perception Task (IPT). Participants needed to discriminate between 2 categories of relationship: kinship (familial relationship) and intimacy (romantic relationship) Depression: Depression Adjective Check List (DACL)	There was no general effect of OT on mood. However a positive effect on social perception performance was found after administration in the OT group compared to placebo. In patients, the OT and placebo group significantly differed in the identification of kinship relationships but not intimacy while no such effect was detected in the control group.
Fischer- Shoftly et al. 2013b	30 SZ age=31.8+/− 6.5; males=27 35 HCs age=29.5+/− 5.6; males=32	24 IU single dose	Double-blind, within-subjects crossover 2-week trial	Facial Emotion Recognition: the Facemorphing Task Depression: Depression Adjective Check List (DACL)	There was no general effect of OT on mood. In all participants, regardless of their psychiatric status, the OT administration showed higher accuracy recognition for the ‘fearful’ but not for ‘happy’ faces. Also, independently of psychiatric status, OT administration improved the performance of those participants whose basic fear recognition was below the median.
Lee et al. (2013)	28 SZ or SAD 13 (6 inpatients and 7 outpatients) in the OT group; age=44.7+/− 11.8; males=9 15 (6 inpatients and 9 outpatients) in the placebo groups; age=35.1+/− 8.2; males=11	20 IU twice daily	Randomize d, double-blind, placebo-controlled 3-week trial	Olfactory identification ability (neutral, pleasant and unplesant odors): the University of Pennsylvania Smell Identification Test (UPSIT) Symptomatology: Brief Psychiatric Rating Scale (BPRS) Scale for the Assessment of Negative Symptoms (SANS)	Improvement in the OT group in the total UPSIT score and in the subscore for the pleasant smells (no effects for neutral or unpleasant smells). The placebo group showed improved global symptomatology (BPRS). The inpatient group that received OT had a better total SANS (d=.85) at week 3 while no differences were detected for the outpatient group. The motivational/pleasure subscale of the SANS showed improvement in the OT inpatient group (d=.74).

SZ= Schizophrenia; SAD=Schizoaffective; HCs= Healthy Controls; PD= polydipsia OT=oxytocin; IU=International Unit

^*All SZ subjects across the clinical trials reported in the table maintained their pre-study antipsychotic medication