Table 1.
Overview of IN-OT research on social cognition in humans (organized by life phase)
| Reference | Age (range and/or mean; in years) | Sex | Dosage & Frequency | Regimen & Duration | Design | Main Finding(s) |
|---|---|---|---|---|---|---|
| EARLY LIFE | ||||||
| PWS (Includes some mixed-age samples) | ||||||
| Einfeld et al., 2014 | 12–29; 17.8 | M/F | 24 and 40 IU (for 16+ year-olds); 18 and 32 IU (for 13–15 year-olds), BID | Repeated, 8 weeks | Double-blind, randomized, placebo-controlled, crossover | IN-OT increased temper outbursts with higher doses; no IN-OT effects on social cognition |
| Kuppens et al., 2016 | 6–13.7; 9.3 (median age) | M/F | 12, 16, 20, or 24 IU, BID | Repeated, 4 weeks | Double-blind, randomized, placebo-controlled, crossover | IN-OT reduced anger, sadness, conflicts, and improved social behavior in children younger than 11 years; no IN-OT effects in children older than 11 years |
| Miller et al., 2017 | 5–11; 8.2 | M/F | 16 IU, once a day | Repeated, 5 days | Double-blind, randomized, placebo-controlled, crossover | IN-OT improved socialization, anxiety, and repetitive behaviors |
| Tauber et al., 2017 | 0.8–5.7 months; 3.9 months | M/F | Step 1: 4 IU, every other day; Step 2: 4 IU, every day; Step 3: 4 IU, BID | Repeated, 7 days | Proof-of-concept, monocentric phase 2 escalating dose | IN-OT improved social withdrawal behavior and mother-infant interactions; increased neural network connectivity correlated with changes in social behavior |
| ASD in Youth | ||||||
| Guastella et al., 2010 | 12–19; 14.88 | M | 18 IU (for 12–15 year-olds); 24 IU (for 16–19 year-olds), once | Acute | Double-blind, randomized, placebo-controlled, crossover | IN-OT improved emotion recognition |
| Gordon et al., 2013 | 8–16.5; 13.2 | M/F | 12 IU (for 7–11 year-olds); 18 IU (for 12–15 year-olds); 24 IU (for 16+ year-olds), once | Acute | Double-blind, randomized, placebo-controlled, crossover | IN-OT increased activity for social judgments, but decreased activity for non-social judgments, in regions of the striatum, middle frontal gyrus, mPFC, orbitofrontal cortex, and superior temporal sulcus |
| Tachibana et al., 2013 | 10–14.5; 11.93 | M | 8, 16, 24 IU, BID (increased every 2 months) | Repeated, ~7 months | Open-label trial | IN-OT improved communication and social interactions; no IN-OT effects on other behavioral outcomes |
| Anagnostou et al., 2014 | 10–17 | M/F | 0.2, 0.26, 0.33, 0.4 IU/kg, BID | Repeated, 12 weeks | Modified Maximum Tolerated Dose Open-label trial | IN-OT improved scores and performance in some reassures of social function and social cognition |
| Dadds et al., 2014 | 7–16; 11.79 (OT), 10.74 (P) | M | 12 IU (for under 40 kg); 24 IU (for over 40 kg), once a day | Repeated, 4 days | Double-blind, randomized, placebo-controlled, between-groups | No IN-OT effects on emotion recognition, social interaction skills, or general behavioral adjustment |
| Guastella et al., 2015 | 12–18; 13.85 (OT), 14 (P) | M | 18 IU (for 12–15 year-olds); 24 IU (for 16–18 year-olds), BID | Repeated, 8 weeks | Double-blind, randomized, placebo‐controlled, between-groups | No IN-OT effects on social behavior |
| Gordon et al., 2016 | 8–16.5; 13.16 | M/F | 24 IU (for 16–19 years); 18 IU (for 12–15 year-olds); 12 IU once (for 7–11 year-olds), once a day | Repeated, 21 days | Double-blind, randomized, placebo-controlled, crossover | IN-OT enhanced connectivity between reward and socioemotional processing related regions especially for social (vs. non-social) stimuli |
| Munesue et al., 2016 | 15–45; 22.5 | M | 8 IU, BID | Repeated, 8 weeks | Double-blind, randomized, placebo-controlled, crossover | IN-OT increased reciprocal social interactions; no IN-OT effects on core social symptoms |
| Yatawara et al., 2016 | 3–8; 6.2 | M/F | 12 IU, BID | Repeated, 5 weeks | Double-blind, randomized, placebo-controlled, crossover | IN-OT increased caregiver-rated social responsiveness |
| Parker et al., 2017 | 6–12; 9.35 (OT), 8.13 (P) | M/F | 24 IU, BID | Repeated, 4 weeks | Double-blind, randomized, placebo-controlled, parallel-groups | IN-OT enhanced social abilities, especially among those with the lowest levels of pre-treatment endogenous OT concentrations; no IN-OT effects on in repetitive behaviors or anxiety |
| YOUNG/MIDDLE ADULTHOOD | ||||||
| Healthy Populations | ||||||
| Kosfeld et al., 2005 | 22 | M | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, between-groups | IN-OT increased trust in others |
| Kirsch et al., 2005 | 18–40; 26.7 | M | 27 IU; once | Acute | Double-blind, randomized, placebo-controlled, crossover | IN-OT reduced amygdala activation to fearful faces |
| Baumgartner et al., 2008 | 21.7 | M | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, between-groups | IN-OT reduced fear of social betrayal and activation in regions involved in fear processing (amygdala and midbrain regions) and post-feedback adaptations (dorsal striatum) |
| Bos et al., 2018 | 19–24; 20.2 | F | 24 IU, once | Acute | Placebo-controlled, within-groups | IN-OT was associated with activation in reward and salience processing regions in response to viewing infants’ faces |
| Bartz et al., 2019 | 18–40; 22.7 (M), 21.6 (F) | M/F | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, crossover | IN-OT selectively improved empathic accuracy for less socially proficient males (vs. more proficient); no IN-OT effects on empathic accuracy for females |
| Quintana et al., 2019 | 20–30; 23.81 | M | 8 IU intranasally; 24 IU intranasally; 1 IU intravenously, once | Acute | Double-blind, randomized, double-dummy, crossover | 8 IU IN-OT reduced pupil dilation and resulted in a positive association with pupil dilation and right amygdala activation when processing social (faces) and non-social (shapes) stimuli; no OT-related effects were obtained for other doses |
| Tabak et al., 2019 | 18–31; 20.88 | M/F | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, between-groups | No IN-OT effects on various tasks tapping into different constructs (e.g., deception detection, empathy, working memory) and involving various stimuli (e.g., social and non-social) |
| Sheng et al. (2013) | 18–26; 21.88 | M | 32 IU, once | Acute | Double-blind, randomized, placebo-controlled, within-groups | OT elicited larger ERPs (P2) to painful than neutral faces of racial in-group but not racial out-group faces. OT resulted in positive correlation between P2 amplitudes and implicit attitude toward in-group members. |
| Xue et al., 2020 | 21.7 | M | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, between-groups | IN-OT resulted in faster perception and larger pupil dilation for social (vs. non-social) stimuli in an interocular suppression task tapping into conscious visual awareness |
| Clinical Populations | ||||||
| ASD | ||||||
| Anagnostou et al., 2012 | 18–60; 33 | M | 24 IU, BID | Repeated, 6 weeks | Double-blind, randomized, placebo-controlled, parallel-groups | IN-OT improved social perception measured by RMET, repetitive behaviors, and emotional well-being |
| Domes et al., 2013 | 24 (ASD); 24.3 (HC) | M | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, between-groups | IN-OT increased right amygdala activity to faces |
| Aoki et al., 2014 | 22–41, 30.8 | M | 24 IU, once | Acute | Double-blind, placebo-controlled, crossover | IN-OT increased accuracy for inferring others’ social emotions and increased right anterior insula activation |
| Watanabe et al., 2015 | 24–43; 32.2 | M | 24 IU, BID | Repeated, 6 weeks | Double-blind, randomized, placebo-controlled, crossover | IN-OT reduced symptoms relating to social reciprocity and increased resting-state functional connectivity between anterior cingulate cortex and dorsomedial prefrontal cortex |
| Kruppa et al., 2019 | 18–26, 21.79 (ASD); 18–25, 22.09 (HC) | M | 20 IU, once | Acute | Double-blind, randomized, placebo-controlled, crossover | IN-OT selectively enhanced reinforcement learning associated with social (vs. non-social) stimuli along with increased brain activity in the nucleus accumbens during social (vs. non-social) feedback |
| Bernaerts et al., 2020 | 18–35; 25 (OT), 24 (P) | M | 24 IU, once a day | Repeated, 4 weeks | Double-blind, randomized, placebo-controlled, parallel-groups | IN-OT was associated with a reduction in self-reported repetitive behaviors and feelings of avoidance towards others; no IN-OT effects on core social symptoms |
| SCZ | ||||||
| Guastella et al., 2015 | 22–57; 37.42 | M | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, within-groups | IN-OT enhanced higher-order social cognition performance; no IN-OT effects on general neurocognition |
| Jarskog et al., 2017 | 18–65; 41.9 (OT), 36.1 (P) | M/F | 24 IU, BID | Repeated, 12 weeks | Double-blind, randomized, placebo-controlled, between-groups | IN-OT improved negative symptoms only in individuals with SCZ but not schizoaffective disorder; no IN-OT effects on social cognition |
| Bradley et al., 2019 | 40.3 (SCZ); 39.8 (HC) | M | 40 IU, once | Acute | Double-blind, randomized, placebo-controlled, crossover | IN-OT increased fixation time on the eyes (eye gaze); higher attachment anxiety and greater symptom severity were predictive of greater eye fixation time |
| De Coster et al., 2019 | 35.3 (SCZ); 27.96 (HC) | M | 40 IU, once | Acute | Double-blind, randomized, placebo-controlled, crossover | IN-OT increased ToM accuracy and right TPJ activation during ToM tasks |
| Lee et al., 2019 | 44.74 (SCZ); 35.07 (HC) | M/F | 20 IU, BID | Repeated, 3 weeks | Double-blind, randomized, placebo-controlled, parallel-groups | No IN-OT effects on social cognition and functioning |
| PWS | ||||||
| Tauber et al., 2011 | 18.7–43.6; 28.5 (median age) | M/F | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, between-groups | IN-OT increased trust in others and lowered sadness and disruptive behavior; no IN-OT effects on other social skill tests |
| OLDER ADULTHOOD | ||||||
| Healthy Populations | ||||||
| Barraza et al., 2013 | 60–95; 80.33 | M/F | 40 IU, once a day | Repeated, 10 days | Double-blind, randomized, placebo-controlled, between-groups | IN-OT increased dispositional gratitude and reduced self-reported physical decline and fatigue; no IN-OT effects on social activities/engagement or other affective measures |
| Campbell et al., 2014 | 19.68 (YA), 72.07 (OA) | M/F | 20 IU, once | Acute | Double-blind, randomized, placebo-controlled, between-groups | IN-OT improved emotion recognition in older males but not in older females |
| Ebner et al., 2015 | 22.4 (YA), 71.2 (OA) | M/F | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, between-groups | IN-OT increased self-reported attention to own feelings only in older males |
| Ebner et al., 2016 | 22.7 (YA), 71.2 (OA) | M/F | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, between-groups | IN-OT increased resting-state amygdala-mPFC connectivity (trend-wise) in older males |
| Grainger et al., 2018 | 18–26, 20.18 (YA); 65–90, 73.25 (OA) | M/F | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, within-groups | IN-OT improved ToM ability irrespective of age |
| Grainger et al. 2019 | 18–26, 20.18 (YA); 65–90, 73.37 (OA) | M/F | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, within-groups | No IN-OT effects on judgments of facial trustworthiness |
| Horta et al., 2019 | 18–31, 22.4 (YA); 63–81, 71.2 (OA) | M/F | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, between-groups | IN-OT was associated with a large scale amygdalar network in OA for anger, fear, and happiness |
| Clinical Populations | ||||||
| Jesso et al., 2011 | 64.40 | M/F | 24 IU, once | Acute | Double-blind, randomized, placebo-controlled, crossover | IN-OT associated with reduced recognition of angry faces in patients with bvFTD; IN-OT-related improvement in scores on NPI |
| Finger et al., 2015 | 62.1–69.9, 66 (OT); 53.4–69.9, 61.1 (P) | M/F | 24, 48, or 72 IU, BID | Repeated, 1 week | Double-blind, randomized, placebo-controlled, parallel-groups | Trends of improvement were observed for the IN-OT group on the measures of apathy and empathy in patients with bvFTD |
Abbreviations: ASD: Autism Spectrum Disorder, BID: Twice-a-day, bvFTD: Behavioral Variant of Frontotemporal Dementia, ERPs=Event-related potentials; F: Female, HC: Healthy controls, IN-OT: Intranasal Oxytocin, IU: International Units, M: Male, mPFC: Medial Prefrontal Cortex, NPI: Neuropsychiatric Inventory, OA: Older Adults, OT: Oxytocin, P: Placebo, PWS: Prader-Willi Syndrome, RMET: Reading the Mind in the Eyes Test, SCZ: Schizophrenia, ToM: Theory of mind, TPJ: Temporoparietal Junction, YA: Younger adults.
Note: For regimen, “Acute” refers to the administration of IN-OT as a single dose; “Repeated” refers to the administration of IN-OT in chronic (e.g., daily administration) or intermittent (e.g., administration once every other day or once every week) fashion.