Oxytocin and psychotherapy: A pilot study of its physiological, behavioral and subjective effects in males with depression The Effects of Intranasal Oxytocin Administration on Sensitive Caregiving in Mothers with Postnatal Depression Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder Intranasal oxytocin, but not vasopressin, augments neural responses to toddlers in human fathers Effects of oxytocin and vasopressin on the neural response to unreciprocated cooperation within brain regions involved in stress and anxiety in men and women Oxytocin differentially alters resting state functional connectivity between amygdala subregions and emotional control networks: Inverse correlation with depressive traits Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome Intranasal oxytocin administration prior to exposure therapy for arachnophobia impedes treatment response. Sex differences in the neural and behavioral response to intranasal oxytocin and vasopressin during human social interaction Oxytocin increases amygdala reactivity to threatening scenes in females The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample Oxytocin and vasopressin effects on the neural response to social cooperation are modulated by sex in humans A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans. Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial Efficacy of oral transmucosal nicotine lozenge for suppression of withdrawal symptoms in smoking abstinence. Intranasal Oxytocin Enhances Connectivity in the Neural Circuitry Supporting Social Motivation and Social Perception in Children with Autism Oxytocin promotes protective behavior in depressed mothers: a pilot study with the enthusiastic stranger paradigm. Effects of intranasal oxytocin on neural processing within a socially relevant neural circuit Adjuvant occupational therapy improves long-term depression recovery and return-to-work in good health in sick-listed employees with major depression: results of a randomised controlled trial Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment Effects of game-based virtual reality on health-related quality of life in chronic stroke patients: A randomized, controlled study Occupational therapy in spinocerebellar ataxia type 3: an open-label trial. Oxytocin-Augmented Social Cognitive Skills Training in Schizophrenia
Individual psychotherapy is an important treatment for a number of psychiatric conditions and involves a unique form of human attachment . This raises the question of whether oxytocin ( OT ) , the paradigmatic " attachment hormone " , may have benefits in this context . In this r and omized , double-blind , crossover trial , we gave male psychiatric out patients with major depressive disorder 40 IU  intranasal OT or placebo before a videotaped session with a therapist and measured a number of subjective , physiological , and behavioral parameters . We report three main findings . Surprisingly - in contrast to prior reports of OT 's anxiolytic properties - we found OT caused an increase in anxiety over the course of the therapy session . Secondly , though it had no main effect on cortisol , eye contact , or overall behavior , we did find that OT caused a decrease in nonverbal behaviors that cut off social contact , after controlling for level of depressive symptoms . Lastly , we replicated prior findings that OT improves social cognition ( performance on the reading the mind in the eyes test ( RMET ) ) , albeit in a depressed patient group . These results inform future studies of oxytocin and psychotherapy and suggest that in certain clinical population s and context s , OT has heterogeneous subjective effects which may include acute anxiogenesis . Moreover , the similarity of some of these acute effects to those of single-dose serotonergic antidepressants raises interesting questions about the potential antidepressant benefits of chronic OT administration Postnatal depression ( PND ) is common and negatively affects the mother – infant relationship ; oxytocin ( OT ) has been found to have positive effects on parenting , although psychiatric disorders may reduce these effects . Thus , we explored the role of OT in mothers diagnosed with PND . A within-subject , r and omized controlled double-blind design was used to test the effects of nasal administration of OT or placebo on sensitive caregiving . The outcome measures were perceptual and caregiving responses to prerecorded cry sounds , as well as observed maternal sensitivity . We found that in the OT condition mothers with PND were more likely to rate an infant cry as more urgent and they were more likely to indicate they would chose a harsh caregiving strategy in response . There was no effect of OT on maternal sensitive interaction with their own baby . Further research is required prior to consideration of OT administration in depressed mothers of infants The neuropeptide oxytocin ( OT ) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder ( PTSD ) because of its anxiolytic and prosocial properties . We therefore investigated the behavioral and neurobiological effects of a single intranasal OT administration ( 40 IU ) in PTSD patients . We conducted a r and omized , placebo-controlled , cross-over resting-state fMRI study in male and female police officers with ( n=37 , 21 males ) and without PTSD ( n=40 , 20 males ) . We investigated OT administration effects on subjective anxiety and functional connectivity of basolateral ( BLA ) and centromedial ( CeM ) amygdala subregions with prefrontal and salience processing areas . In PTSD patients , OT administration result ed in decreased subjective anxiety and nervousness . Under placebo , male PTSD patients showed diminished right CeM to left ventromedial prefrontal cortex ( vmPFC ) connectivity compared with male trauma-exposed controls , which was reinstated after OT administration . Additionally , female PTSD patients showed enhanced right BLA to bilateral dorsal anterior cingulate cortex ( dACC ) connectivity compared with female trauma-exposed controls , which was dampened after OT administration . Although caution is warranted , our findings tentatively suggest that OT has the potential to diminish anxiety and fear expression of the amygdala in PTSD , either via increased control of the vmPFC over the CeM ( males ) or via decreased salience processing of the dACC and BLA ( females ) . Our findings add to accumulating evidence that OT administration could potentially enhance treatment response in PTSD Abstract This study investigates paternal brain function with the hope of better underst and ing the neural basis for variation in caregiving involvement among men . The neuropeptides oxytocin ( OT ) and vasopressin ( AVP ) are implicated in paternal caregiving in humans and other species . In a double‐blind , placebo‐controlled , within‐subject pharmaco‐functional MRI experiment , we r and omized 30 fathers of 1–2 year old children to receive either 24 IU intranasal OT before one scan and placebo before the other scan ( n = 15 ) or 20 IU intranasal AVP before one scan and placebo before the other scan ( n = 15 ) . Brain function was measured with fMRI as the fathers viewed pictures of their children , unknown children and unknown adults , and as they listened to unknown infant cry stimuli . Intranasal OT , but not AVP , significantly increased the BOLD fMRI response to viewing pictures of own children within the cau date nucleus , a target of midbrain dopamine projections , as well as the dorsal anterior cingulate ( dACC ) and visual cortex , suggesting that intranasal oxytocin augments activation in brain regions involved in reward , empathy and attention in human fathers . OT effects also varied as a function of order of administration such that when OT was given before placebo , it increased activation within several reward‐related structures ( substantia nigra , ventral tegmental area , putamen ) more than when it was given after placebo . Neither OT nor AVP had significant main effects on the neural response to cries . Our findings suggest that the hormonal changes associated with the transition to fatherhood are likely to facilitate increased approach motivation and empathy for children , and call for future research that evaluates the potential of OT to normalize deficits in paternal motivation , as might be found among men suffering from post‐partum depression .  HighlightsOxytocin  increases fathers ' neural response to viewing pictures of their toddlers . Some oxytocin effects are stronger in fathers with lower baseline brain activation . Early life experience modulates oxytocin effects on paternal brain function . Vasopressin does not affect fathers ' neural response to pictures of their toddler Anxiety disorders are characterized by hyperactivity in both the amygdala and the anterior insula . Interventions that normalize activity in these areas may therefore be effective in treating anxiety disorders . Recently , there has been significant interest in the potential use of oxytocin ( OT ) , as well as vasopressin ( AVP ) antagonists , as treatments for anxiety disorders . In this double-blind , placebo-controlled , pharmaco- fMRI study , 153 men and 151 women were r and omized to treatment with either 24 IU intranasal OT , 20 IU intranasal AVP , or placebo and imaged with fMRI as they played the iterated Prisoner ’s Dilemma game with same-sex human and computer partners . In men , OT attenuated the fMRI response to unreciprocated cooperation ( CD ) , a negative social interaction , within the amygdala and anterior insula . This effect was specific to interactions with human partners . In contrast , among women , OT unexpectedly attenuated the amygdala and anterior insula response to unreciprocated cooperation from computer but not human partners . Among women , AVP did not significantly modulate the response to unreciprocated cooperation in either the amygdala or the anterior insula . However , among men , AVP attenuated the BOLD response to CD outcomes with human partners across a relatively large cluster including the amygdala and the anterior insula , which was contrary to expectations . Our results suggest that OT may decrease the stress of negative social interactions among men , whereas these effects were not found in women interacting with human partners . These findings support continued investigation into the possible efficacy of OT as a treatment for anxiety disorders ABSTRACT The hypothalamic neuropeptide oxytocin ( OT ) has received increasing attention for its role in modulating social‐emotional processes across species . Previous studies on using intranasal‐OT in humans point to a crucial engagement of the amygdala in the observed neuromodulatory effects of OT under task and rest conditions . However , the amygdala is not a single homogenous structure , but rather a set of structurally and functionally heterogeneous nuclei that show distinct patterns of connectivity with limbic and frontal emotion‐processing regions . To determine potential differential effects of OT on functional connectivity of the amygdala subregions , 79 male participants underwent resting‐state fMRI following r and omized intranasal‐OT or placebo administration .  In line with previous studies OT increased the connectivity of the total amygdala with dorso‐medial prefrontal regions engaged in emotion regulation . In addition , OT enhanced coupling of the total amygdala with cerebellar regions . Importantly , OT differentially altered the connectivity of amygdala subregions with distinct up‐stream cortical nodes , particularly prefrontal/parietal , and cerebellar down‐stream regions . OT‐induced  increased connectivity with cerebellar regions were largely driven by effects on the centromedial and basolateral subregions , whereas increased connectivity with prefrontal regions were largely mediated by right superficial and basolateral subregions . OT decreased connectivity of the centromedial subregions with core hubs of the emotional face processing network in temporal , occipital and parietal regions . Preliminary findings suggest that effects on the superficial amygdala‐prefrontal pathway were inversely associated with levels of sub clinical depression , possibly indicating that OT modulation may be blunted in the context of increased pathological load . Together , the present findings suggest a subregional‐specific modulatory role of OT on amygdala‐centered emotion processing networks in humans . HighlightsEffects of oxytocin ( OT ) on amygdala subregional rsFC were examined . OT differentially altered rsFC of amygdala subregions . Increased connectivity with PFC regions were driven by SF and BLA.OT  decreased rsFC of the CM with the face processing network . Effects on the SF‐mPFC pathway were associated with depression Fragile X syndrome ( FXS ) is a rare inherited genetic disorder causing severe intellectual disability and autistic-like symptoms . Individuals with FXS , males in particular , often exhibit extreme eye gaze avoidance and hyperarousal when they encounter stressful social situations . We investigated whether oxytocin ( OT ) , a hormone with prosocial and anxiolytic effects , could alleviate symptoms of social anxiety in this population . A r and omized double-blind placebo-controlled single-dose trial was performed with intranasal administration of placebo , 24 IU OT and 48 IU OT . Measures of eye gaze frequency , heart rate , respiratory sinus arrhythmia ( RSA ) , heart rate variability ( HRV ) and salivary cortisol were obtained during a structured social challenge conducted 50 min following OT administration . Ten low-functioning males with FXS ( aged 13 - 28 years ) traveled to Stanford for the initial visit : 8 completed the study .  Eye gaze frequency improved significantly in response to the 24 IU OT dose and salivary cortisol levels decreased significantly in response to the 48 IU OT dose . There was no effect of OT on heart rate , RSA or HRV although individual plots of the heart rate data suggested that OT increased heart rate in some participants and decreased heart rate in others . These findings suggest that intranasal administration of OT may ameliorate some symptoms of social anxiety in patients with FXS . Further double-blind placebo-controlled studies of OT , conducted in combination with behavioral treatment programs , may be warranted BACKGROUND Recent years have seen the emergence of a new paradigm for treatment of anxiety disorders focusing on development of drugs that facilitate psychotherapies via targeted effects on neuroplasticity . One compound that has generated interest in this regard is oxytocin ( OT ) , a mammalian neuropeptide that modulates activity of the neurocircuit mediating fear extinction and memory processes . Recent research in healthy humans has suggested that intranasal OT administered prior to fear extinction training enhances fear extinction performance , supporting its potential to augment exposure-based psychotherapy . Here , we tested the hypothesis that OT treatment would facilitate response to exposure therapy in patients with specific phobia . METHODS We conducted a small proof-of-concept trial investigating the effect of pretreatment intranasal OT administration on a brief , single-session exposure treatment for arachnophobia ( fear of spiders ) . The study was r and omized , double-blind , and placebo controlled ( n = 13 placebo , 11 females ; n = 10 OT , 8 females ) with 1-week and 1-month follow-up assessment s. Dependent measures attended to arachnophobia symptoms ( self-report ) , phobic behavior ( behavioral avoidance of spider task ) , and treatment credibility/therapeutic alliance . RESULTS Administration of OT prior to exposure therapy tended to impede treatment response as measured by self-report of symptoms at both follow-up periods . OT treatment did not significantly affect behavioral measures of fear . Immediately after OT administration but before therapy , the OT group trended toward less confidence in the treatment . The OT group also trended toward lower ratings of therapeutic alliance than placebo . CONCLUSIONS These results suggest that OT administration effects on extinction may vary depending on conditions and population Both oxytocin ( OT ) and vasopressin ( AVP ) are known to modulate social behavior , and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits . In particular , there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders , and preliminary pre- clinical and clinical studies suggest efficacy in alleviating some of the associated symptoms . However , the vast majority of research participants in these studies have been male , and there is evidence for sexually differentiated effects of nonapeptides in both humans and non-human animals . To date , no study has investigated the effect of intranasal OT on brain function in human males and females within the same paradigm . Previously , in a r and omized , placebo-controlled , double-blind fMRI study , we reported effects of intranasal OT and AVP on behavior and brain activity of human males as they played an interactive social game known as the Prisoner 's Dilemma Game . Here , we present findings from an identical study in human females , and compare these with our findings from males . Overall , we find that both behavioral and neural responses to intranasal OT and AVP are highly sexually differentiated . In women , AVP increased conciliatory behavior , and both OT and AVP caused women to treat computer partners more like humans . In men , AVP increased reciprocation of cooperation from both human and computer partners . However , no specific drug effects on behavior were shared between men and women . During cooperative interactions , both OT and AVP increased brain activity in men within areas rich in OT and AVP receptors and in areas playing a key role in reward , social bonding , arousal and memory ( e.g. , the striatum , basal forebrain , insula , amygdala and hippocampus ) , whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women . OT treatment rendered neural responses of males more similar to responses of females in the placebo group and vice versa , raising the prospect of an inverted u-shaped dose response to central OT levels . These findings emphasize the need to fully characterize the effects of intranasal OT and AVP in both males and females and at multiple doses before widespread clinical application will be warranted The neuropeptide oxytocin ( OT ) is well known for its profound effects on social behavior , which appear to be mediated by an OT-dependent modulation of amygdala activity in the context of social stimuli . In humans , OT decreases amygdala reactivity to threatening faces in males , but enhances amygdala reactivity to similar faces in females , suggesting sex-specific differences in OT-dependent threat-processing . To further explore whether OT generally enhances amygdala-dependent threat-processing in females , we used functional magnetic resonance imaging ( fMRI ) in a r and omized within-subject crossover design to measure amygdala activity in response to threatening and non-threatening scenes in 14 females following intranasal administration of OT or placebo .  Participants ' eye movements were recorded to investigate whether an OT-dependent modulation of amygdala activity is accompanied by enhanced exploration of salient scene features . Although OT had no effect on participants ' gazing behavior , it increased amygdala reactivity to scenes depicting social and non-social threat . In females , OT may , thus , enhance the detection of threatening stimuli in the environment , potentially by interacting with gonadal steroids , such as progesterone and estrogen Rationale To improve outcomes for patients undergoing extinction-based therapies ( e.g. , exposure therapy ) for anxiety disorders such as post-traumatic stress disorder ( PTSD ) , there has been interest in identifying pharmaceutical compounds that might facilitate fear extinction learning and recall . Oxytocin ( OT ) is a mammalian neuropeptide that modulates activation of fear extinction-based neural circuits and fear responses . Little is known , however , about the effects of OT treatment on conditioned fear responding and extinction in humans . Objectives The purpose of the present study was to assess the effects of OT in a fear-potentiated startle task of fear conditioning and extinction . Methods A double-blind , placebo-controlled study of 44 healthy human participants was conducted . Participants underwent a conditioned fear acquisition procedure , after which they were r and omized to treatment group and delivered OT ( 24 IU ) or placebo via intranasal ( IN ) spray . Forty-five minutes after treatment , participants underwent extinction training . Twenty-four hours later , subjects were tested for extinction recall . Results Relative to placebo , the OT group showed increased fear-potentiated startle responding during the earliest stage of extinction training relative to placebo ; however , all treatment groups showed the same level of reduced responding by the end of extinction training . Twenty-four hours later , the OT group showed significantly higher recall of extinction relative to placebo . Conclusions The current study provides preliminary evidence that OT may facilitate fear extinction recall in humans . These results support further study of OT as a potential adjunctive treatment for extinction-based therapies in fear-related disorders Recent research has examined the effects of oxytocin ( OT ) and vasopressin ( AVP ) on human social behavior and brain function . However , most participants have been male , while previous research in our lab demonstrated sexually differentiated effects of OT and AVP on the neural response to reciprocated cooperation . Here we extend our previous work by significantly increasing the number of participants to enable the use of more stringent statistical thresholds that permit more precise localization of OT and AVP effects in the brain . In a double-blind , placebo-controlled study , 153 men and 151 women were r and omized to receive 24 IU intranasal OT , 20 IU intranasal AVP or placebo . Afterwards , they were imaged with fMRI while playing an iterated Prisoner ’s Dilemma Game with same-sex partners . Sex differences were observed for effects of OT on the neural response to reciprocated cooperation , such that OT increased the caduate/putamen response among males , whereas it decreased this response among females . Thus , 24 IU OT may increase the reward or salience of positive social interactions among men , while decreasing their reward or salience among women . Similar sex differences were also observed for AVP effects within bilateral insula and right supramarginal gyrus when a more liberal statistical threshold was employed . While our findings support previous suggestions that exogenous nonapeptides may be effective treatments for disorders such as depression and autism spectrum disorder , they caution against uniformly extending such treatments to men and women alike Intranasal oxytocin ( OT ) can modulate social-emotional functioning and related brain activity in humans . Consequently , OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits . However , OT effects are often heterogeneous across individuals . Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene ( OXTR ) . Previously , we conducted a double-blind , placebo-controlled study in which healthy men and women were r and omized to treatment with intranasal OT or placebo . Afterwards , they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner 's Dilemma Game with same-sex partners . Within the left ventral cau date nucleus , intranasal OT treatment increased activation to reciprocated cooperation in men , but tended to decrease activation in women . Here , we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype , and are not found for other genotypes ( rs53576 AA/AG ) . Thus , OT may increase the reward or salience of positive social interactions for male GG homozygotes , while decreasing those processes for female GG homozygotes . These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment UNLABELLED It is unclear if and how exogenous oxytocin ( OT ) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response . To better underst and the delivery routes of intranasal OT administration to the brain and the dose-response , we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging ( fMRI ) in four treatment conditions , including two different doses of intranasal OT using a novel Breath Powered device , intravenous ( IV ) OT , which provided similar concentrations of blood plasma OT , and placebo . We adopted a r and omized , double-blind , double-dummy , crossover design , with 16 healthy male adults administering a single-dose of these four treatments . We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli , with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo . These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT . TRIAL REGISTRATION This trial is registered at the U.S. National Institutes of Health clinical trial registry ( www . clinical trials.gov ; NCT01983514 ) and as EudraCT no. 2013 - 001608 - 12 Nicotine replacement therapy relieves withdrawal symptoms , significantly improving smoking cessation rates . Oral transmucosal nicotine ( OT-NIC ) is a novel nicotine delivery system consisting of a lozenge ( OT-NIC unit ) containing 4 mg of nicotine , which is dissolved in the cheek pouch , releasing nicotine for absorption through the buccal mucosa . Theoretical advantages of OT-NIC include that it does not require special chewing methods or interfere with dental work , it provides sensory oral effect , and it can be dosed to effect . This study aim ed to determine the preliminary safety and efficacy of OT-NIC for suppression of nicotine withdrawal symptoms over 8 days of smoking abstinence and to assess flavor preference , sensory characteristics , and acceptability . In an open-label , within-subjects design , 11 smokers used three different flavors of OT-NIC ad lib in response to withdrawal symptoms and craving . On days 1 and 8 , withdrawal symptoms were measured with pre- and postadministration scores for each of the first three OT-NIC units used ( three different flavors presented in r and om order ) . Flavor preference , desire to smoke , sensory characteristics , acceptability , and overall OT-NIC performance were rated at the end of each day . A generalized estimating equation analysis was conducted to account for the repeated- measures design . Use of OT-NIC result ed in a significant decrease in a composite withdrawal score aggregating scores from all eight symptoms ( decline of.57 units in a possible range of 4 , p<.01 ) . Withdrawal scores for anxiety , craving , difficulty concentrating , impatience , and restlessness significantly decreased . Depressed mood , increased appetite , and irritability did not change . Order of flavor preference was peppermint over cinnamon over plain . Acceptability and ratings for sensory characteristics were favorable , and OT-NIC was well tolerated with no serious adverse effects . In conclusion , OT-NIC showed promise as a potential new aid for smoking cessation Oxytocin ( OT ) has become a focus in investigations of autism spectrum disorder ( ASD ) . The social deficits that characterize ASD may relate to reduced connectivity between brain sites on the mesolimbic reward pathway ( nucleus accumbens ; amygdala ) that receive OT projections and contribute to social motivation , and cortical sites involved in social perception . Using functional magnetic resonance imaging and a r and omized , double blind , placebo-controlled crossover design , we show that OT administration in ASD  increases activity in brain regions important for perceiving social-emotional information . Further , OT  enhances connectivity between nodes of the brain ’s reward and socioemotional processing systems , and does so preferentially for social ( versus nonsocial ) stimuli . This effect is observed both while viewing coherent versus scrambled biological motion , and while listening to happy versus angry voices . Our findings suggest a mechanism by which intranasal OT may bolster social motivation — one that could , in future , be harnessed to augment behavioral treatments for ASD BACKGROUND Successful parenting requires maternal behaviors that promote infant survival such as protection from predators . In animal studies , oxytocin ( OT ) has been linked to maternal aggression to protect offspring . No human study has explored this topic . Mothers with a diagnosis of postnatal depression ( PND ) are at higher risk of neglecting their infants . We hypothesized that intranasal OT administration would increase the protective behaviors of mothers with PND , toward their infants . METHODS Sixteen mothers with a diagnosis of PND participated in a double-blind , r and omized-controlled , within-subject pilot study . Participants received intranasal OT during one visit and placebo spray on the alternate visit . Maternal protective behavior toward their infant was measured , in the presence of a socially intrusive stranger . RESULTS The enthusiastic stranger paradigm stimulated participants ' protective responses in the presence of an intrusive stranger . Furthermore , this protective response of mothers with a diagnosis of PND was increased in the OT condition . CONCLUSIONS The study introduces a new paradigm , the enthusiastic stranger paradigm , which may be used to examine a neglected type of parental behavior , that is , protection of offspring . The protective response of mothers with PND increased , in line with the ' tend and defend ' effects of OT in animal models . In future work it should be tested whether this protection effect can also be found in non clinical sample s , or whether it is specific for clinical ly depressed mothers Dysregulation of the Mirror Neuron System ( MNS ) in schizophrenia ( SCZ ) may underlie the cognitive and behavioral manifestations of social dysfunction associated with that disorder . In healthy subjects  intranasal ( IN ) oxytocin ( OT ) improves neural processing in the MNS and is associated with improved social cognition . OT 's brain effects can be measured through its modulation of the MNS by suppressing EEG mu-b and electrical activity ( 8 - 13Hz ) in response to motion perception . Although IN OT 's effects on social cognition have been tested in SCZ , OT 's impact on the MNS has not been evaluated to date . Therefore , we design ed a study to investigate the effects of two different OT doses on biological motion-induced mu suppression in SCZ and healthy subjects .  EEG recordings  were taken after each subject received a single IN administration of placebo , OT-24IU and OT-48IU in r and omized order in a double-blind crossover design . The results provide support for  OT 's  regulation of the MNS in both healthy and SCZ subjects , with the optimal dose dependent on diagnostic group and sex of subject . A statistically significant response was seen in SCZ males only , indicating a heightened sensitivity to those effects , although sex hormone related effects can not be ruled out . In general , OT appears to have positive effects on neural circuitry that supports social cognition and socially adaptive behaviors Objectives To evaluate whether adjuvant occupational therapy ( OT ) can improve the effectiveness of treatment-as-usual ( TAU ) in sick-listed employees with major depression . Methods In total , 117 employees sick-listed for a median duration of 4.8 months ( IQR=2.6 to 10.1 months ) because of major depression were r and omised to TAU  ( n=39 ) or adjuvant OT ( TAU+OT ; n=78 ) . OT ( 18 sessions ) focussed on a fast return to work ( RTW ) and improving work-related coping and self-efficacy . The primary outcome was work participation ( hours of absenteeism+ duration until partial/full RTW ) . Secondary outcomes were depression , at-work functioning , and health-related functioning . Intermediate outcomes were work-related , coping and self-efficacy . Blinded assessment s occurred at baseline and 6 , 12 and 18 months follow-up . Results The groups did not significantly differ in their overall work participation ( adjusted group difference=−1.9 , 95 % CI −19.9 to + 16.2 ) . However , those in TAU+OT did show greater improvement in depression symptoms ( −2.8 , −5.5 to −0.2 ) , an increased probability of long-term symptom remission ( + 18 % , + 7 % to + 30 % ) , and increased probability of long-term RTW in good health ( GH ) ( + 24 % , 12 % to 36 % ) . There were no significant group differences in the remaining secondary /intermediate outcomes . Conclusions In a highly impaired population , we could not demonstrate significant benefit of adjuvant OT for improving overall work participation . However , adjuvant OT did increase long-term depression recovery and long-term RTW in GH ( ie , full RTW while being remitted , and with better work and role functioning ) . Trial Registration Dutch Trial Register NTR2057 Despite the promise of intranasal oxytocin ( OT ) for modulating social behavior , recent work has provided mixed results . This may relate to suboptimal drug deposition achieved with conventional nasal sprays , inter-individual differences in nasal physiology and a poor underst and ing of how intranasal OT is delivered to the brain in humans . Delivering OT using a novel ‘ Breath Powered ’ nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport , we evaluated dose-dependent effects on social cognition , compared response with intravenous ( IV ) administration of OT , and assessed nasal cavity dimensions using acoustic rhinometry . We adopted a r and omized , double-blind , double-dummy , crossover design , with 16 healthy male adults completing four single-dose treatments ( intranasal 8 IU ( international units ) or 24 IU OT , 1 IU OT IV and placebo ) . The primary outcome was social cognition measured by emotional ratings of facial images . Secondary outcomes included the pharmacokinetics of OT , vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings . Despite the fact that all the treatments produced similar plasma OT increases compared with placebo , there was a main effect of treatment on anger ratings of emotionally ambiguous faces . Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT . In addition , there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment . These findings provide support for a direct nose-to-brain effect , independent of blood absorption , of low-dose OT delivered from a Breath Powered device In the present study , we aim ed to determine whether game-based virtual reality ( VR ) rehabilitation , combined with occupational therapy ( OT ) , could improve health-related quality of life , depression , and upper extremity function . We recruited 35 patients with chronic hemiparetic stroke , and these participants were r and omized into groups that underwent VR rehabilitation plus conventional OT , or the same amount of conventional OT alone , for 20 sessions over 4 weeks . Compared to baseline , the VR rehabilitation plus OT group exhibited significantly improved role limitation due to emotional problems ( p=0.047 ) . Compared to baseline , both groups also exhibited significantly improved depression ( p=0.017 ) and upper extremity function ( p=0.001 ) , although the inter-group differences were not significant . However , a significant inter-group difference was observed for role limitation due to physical problems ( p=0.031 ) . Our results indicate that game-based VR rehabilitation has specific effects on health-related quality of life , depression , and upper extremity function among patients with chronic hemiparetic stroke Occupational therapy ( OT ) is a profession concerned with promoting health and well-being through occupation , by enabling h and icapped people to participate in the activities of everyday life . OT is part of the clinical rehabilitation of progressive genetic neurodegenerative diseases such as spinocerebellar ataxias ; however , its effects have never been determined in these diseases . Our aim was to investigate the effect of OT on both physical disabilities and depressive symptoms of spinocerebellar ataxia type 3 ( SCA3 ) patients . Genomically diagnosed SCA3 patients older than 18 years were invited to participate in the study . Disability , as evaluated by functional independence measurement and Barthel incapacitation score , Hamilton Rating Scale for Depression , and World Health Organization Quality of Life question naire ( WHOQOL-BREF ) , was determined at baseline and after 3 and 6 months of treatment . Twenty-six patients agreed to participate in the study . All were treated because OT prevents blinding of a control group . Fifteen sessions of rehabilitative OT were applied over a period of 6 months . Difficult access to food , clothing , personal hygiene , and leisure were some of the main disabilities focused by these patients . After this treatment , disability scores and quality of life were stable , and the Hamilton scores for depression improved . Since no medication was started up to 6 months before or during OT , this improvement was related to our intervention . No association was found between these endpoints and a CAG tract of the MJD1 gene ( CAGn ) , age , age of onset , or neurological scores at baseline ( Spearman test ) . Although the possibly temporary stabilization of the downhill disabilities as an effect of OT remains to be established , its clear effect on depressive symptoms confirms the recommendation of OT to any patient with SCA3 or spinocerebellar ataxia Impairments in social cognition are common in schizophrenia and predict poor functional outcome . The purpose of this proof-of-concept r and omized , parallel group clinical trial was to assess whether intranasal oxytocin ( OT ) , given before social cognitive training , enhances learning of social cognitive skills .  Twenty seven male out patients with schizophrenia participated in a 6-week ( 12 session ) training on social cognitive skills . Training focused on three domains : facial affect recognition , social perception , and empathy . Subjects were r and omly assigned ( double blind ) to receive either intranasal OTor placebo 30 min before each session . Participants did not receive OT between sessions or on the day of assessment s. We evaluated scores on social-cognition measures , as well as clinical symptoms and neurocognition , at baseline , 1 week following the final training session , and 1 month later . Our prespecified primary outcome measure was a social-cognition composite score comprised of five individual measures . There were main effects of time ( indicating improvement across the combined-treatment groups ) on the social-cognition composite score at both 1 week and 1 month following completion of training . Subjects receiving OT demonstrated significantly greater improvements in empathic accuracy than those receiving placebo at both posttreatment and 1 month follow up . There were no OT-related effects for the other social cognitive tests , clinical symptoms , or neurocognition . This study provides initial support for the idea that OT enhances the effectiveness of training when administered shortly before social cognitive training sessions . The effects were most pronounced on empathic accuracy , a high-level social cognitive process that is not easily improved in current social cognitive remediation programs
Results showed no significant effects on core symptomatology .
In conclusion , up to date , evidence regarding the potential utility of IN-OT in treating anxiety and depression is still inconclusive .
Several studies have demonstrated the neuromodulating function of oxytocin ( OT ) in response to anxiogenic stimuli as well as its potential role in the pathogenesis of depression .
Consequently , intranasal OT ( IN-OT ) has been proposed as a potential treatment of  anxiety and depressive disorders .
The present systematic review aim ed to summarize the r and omized controlled trials ( RCTs ) evaluating the effect of IN-OT on anxiety and depressive symptoms .