title: Intranasal adminsitration of oxytocin in postnatal depression: implications for psychodynamic psychotherapy from a randomized double-blind pilot study Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia 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 Something to talk about: Gossip increases oxytocin levels in a near real-life situation The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex. Oxytocin promotes protective behavior in depressed mothers: a pilot study with the enthusiastic stranger paradigm. Oxytocin Modulation of Amygdala Functional Connectivity to Fearful Faces in Generalized Social Anxiety Disorder Oxytocin Selectively Improves Empathic Accuracy The effect of oxytocin on attention to angry and happy faces in chronic depression Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers Intranasal oxytocin administration prior to exposure therapy for arachnophobia impedes treatment response. Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder Cyberostracism: effects of being ignored over the Internet. Fear of Spiders Questionnaire. Intranasal Oxytocin Improves Emotion Recognition for Youth with Autism Spectrum Disorders A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder Oxytocin in postnatally depressed mothers: Its influence on mood and expressed emotion
abstract: Oxytocin is a neuropeptide that is active in the central nervous system and is generally considered to be involved in prosocial behaviors and feelings . In light of its documented positive effect on maternal behavior , we design ed a study to ascertain whether oxytocin exerts any therapeutic effects on depressive symptoms in women affected by maternal postnatal depression . A group of 16 mothers were recruited in a r and omized double-blind study : the women agreed to take part in a brief course of psychoanalytic psychotherapy ( 12 sessions , once a week ) while also being administered , during the 12-weeks period , a daily dose of intranasal oxytocin ( or a placebo ) . The pre-treatment evaluation also included a personality assessment of the major primary -process emotional comm and systems described by Panksepp ( ) and a semi-quantitative assessment by the therapist of the mother ’s depressive symptoms and of her personality . No significant effect on depressive symptomatology was found following the administration of oxytocin ( as compared to a placebo ) during the period of psychotherapy . Nevertheless , a personality trait evaluation of the mothers , conducted in our overall sample group , showed a decrease in the narcissistic trait only within the group who took oxytocin . The depressive ( dysphoric ) trait was in fact significantly affected by psychotherapy ( this effect was only present in the placebo group so it may reflect a positive placebo effect enhancing the favorable influence of psychotherapy on depressive symptoms ) but not in the presence of oxytocin . Therefore , the neuropeptide would appear to play some role in the modulation of cerebral functions involved in the self-centered ( narcissistic ) dimension of the suffering that can occur with postnatal depression . Based on these results , there was support for our hypothesis that what is generally defined as postnatal depression may include disturbances of narcissistic affective balance , and oxytocin supplementation can counteract that type of affective disturbance . The result ing improvements in well-being , reflected in better self-centering in post-partuent mothers , may in turn facilitate better interpersonal acceptance of ( and interactions with ) the child and thereby , improved recognition of the child ’s needs Oxytocin has numerous prosocial and antipsychotic-like effects in animals . Prosocial effects of acute intranasal oxytocin administration have also been reported in human subjects . We conducted a r and omized , placebo-controlled trial testing the effects of twice daily intranasal oxytocin treatment for 14 days on psychotic symptoms and social cognition in patients with schizophrenia .  PANSS scores declined significantly and several social cognition measures improved significantly or nearly significantly in oxytocin ( N=11 ) but not placebo ( N=9 ) recipients . Our results suggest that , in addition to reducing classic psychotic symptoms , oxytocin may diminish certain social cognition deficits that are not improved by current antipsychotic medications 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 Gossip is a pervasive social behavior . Its evolutionary survival seems related to its social functions , such as establishing group rules , punishing trespassers , exercising social influence through reputational systems , and developing and strengthening social bonds . We aim ed at evaluating the effect of gossip on hormones ( oxytocin and cortisol ) and at identifying potential mediators of hormonal response to gossip . Twenty-two female students were r and omly assigned to a  gossip conversation  or to an emotional non-gossip conversation .  Additionally , all participants underwent a neutral conversation on the second day of the study . Salivary oxytocin and cortisol levels were measured . Oxytocin increased significantly in the gossip compared to the emotional non-gossip conversation . A decrease in cortisol levels was observed in all three conditions ( gossip , emotional non-gossip , neutral ) . Change in cortisol levels was similar across conditions . Psychological characteristics ( e.g. empathy , autistic traits , perceived stress , envy ) did not affect oxytocin rise in the gossip condition . Our findings suggest that oxytocin may represent a potential hormonal correlate of gossip behavior Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The neuropeptide oxytocin ( OXT ) plays an important role in complex socio-affective behaviours such as affiliation , attachment , stress and anxiety . Previous studies have focused on the amygdala as an important target of OXT 's effects . However , the effects of OXT on connectivity of the amygdala with cortical regions such as medial frontal cortex , an important mediator of social cognition and emotion regulation , remain unexplored . In a r and omized , double-blind , cross-over design , 15 volunteers received intranasal OXT or placebo prior to resting-state functional magnetic resonance imaging . OXT significantly increased connectivity between both amygdalae and rostral medial frontal cortex ( rmFC ) , while having only negligible effects on coupling with other brain regions . These results demonstrate that OXT is a robust and highly selective enhancer of amygdala connectivity with rmFC , a region critical to social cognition and emotion regulation , and add to our underst and ing of the neural mechanisms by which OXT modulates complex social and cognitive behaviours 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 The neuropeptide oxytocin ( OXT ) is thought to attenuate anxiety by dampening amygdala reactivity to threat in individuals with generalized social anxiety disorder ( GSAD ) . Because the brain is organized into networks of interconnected areas , it is likely that OXT impacts functional coupling between the amygdala and other socio-emotional areas of the brain . Therefore , the aim of the current study was to examine the effects of OXT on amygdala functional connectivity during the processing of fearful faces in GSAD subjects and healthy controls ( HCs ) . In a r and omized , double-blind , placebo (PBO)-controlled , within-subjects design , 18 HCs and 17 GSAD subjects performed a functional magnetic resonance imaging task design ed to probe amygdala response to fearful faces following acute intranasal administration of PBO or OXT . Functional connectivity between the amygdala and the rest of the brain was compared between OXT and PBO sessions using generalized psychophysiological interaction analyses . Results indicated that within individuals with GSAD , but not HCs , OXT enhanced functional connectivity between the amygdala and the bilateral insula and middle cingulate/dorsal anterior cingulate gyrus during the processing of fearful faces . These findings suggest that OXT may have broad pro-social implication s such as enhancing the integration and modulation of social responses Oxytocin is known to regulate prosocial behavior and social cognition in animals ( Ross & Young , 2009 ) , and recent studies suggest that oxytocin may have similar functions in humans . For example , oxytocin increases trust ( Kosfeld , Heinrichs , Zak , Fischbacher , & Fehr , 2005 ) and accuracy in mental-state attribution ( Domes , Heinrichs , Michel , Berger , & Herpertz , 2007 ; Guastella et al. , 2009 ) . These findings have generated excitement about oxytocin ’s potential to ameliorate social deficits in such disorders as social phobia and autism ( Bartz & Holl and er , 2006 ; Guastella et al. , 2009 ; Kosfeld et al. , 2005 ) . This excitement has not been confined to the scientific community : Dubbed the “ hormone of love , ” oxytocin is a common topic in the popular press . Is oxytocin truly a universal social panacea ? Although some studies have shown that oxytocin improves social cognition and empathy ( Domes et al. , 2007 ; Guastella et al. , 2009 ) , others have not ( Singer et al. , 2008 ) . Even studies demonstrating positive effects have ambiguities : Domes et al. ( 2007 ) found that oxytocin improved performance for difficult — but not easy — test items . These observations imply that rather than working universally , oxytocin may selectively facilitate social cognition given certain constraints . For example , by altering specific motivational or cognitive states , oxytocin might increase the salience of social cues , which in turn could improve social-cognitive performance for some individuals , but not others . The effects of oxytocin , then , should be most pronounced in individuals who — at baseline — are less socially proficient ; this would be consistent with broader interactionist views emphasizing that individual differences in competencies interact with situational variables to determine behavior ( Mischel & Shoda , 1995 ) . To test whether normal variance in social proficiency  moderates the effects of oxytocin on social-cognitive performance , we used a r and omized , double-blind , placebo-controlled , crossover challenge in which participants received either intranasal oxytocin or a placebo and performed an empathicaccuracy task that naturalistically measures social-cognitive abilities ( Zaki , Bolger , & Ochsner , 2008 ) . We measured variance in baseline social competencies with the Autism Spectrum Quotient ( AQ ; Baron-Cohen , Wheelwright , Skinner , Martin , & Clubley , 2001 ) , a self-report instrument that predicts social-cognitive performance ( Baron-Cohen , Wheelwright , Hill , Raste , & Plumb , 2001 ) . We hypothesized that drug condition and AQ score would interact to predict performance on the empathic-accuracy task  , with oxytocin having the most pronounced effects for less socially proficient individuals ( i.e. , those with higher AQ scores ) Background Chronic depression is characterized by a high degree of early life trauma , psychosocial impairment , and deficits in social cognition . Undisturbed recognition and processing of facial emotions are basic prerequisites for smooth social interactions . Intranasal application of the neuropeptide oxytocin has been reported to enhance emotion recognition in neuropsychiatric disorders and healthy individuals . We therefore investigated whether oxytocin modulates attention to emotional faces in patients with chronic depression . Methods In this double-blind , r and omized , controlled study , 43 patients received a single dose of oxytocin or placebo nasal spray and were tested while fulfilling a facial dot probe task . We assessed reaction times to  neutral probes  presented at the location of one of two faces depicting happy , angry , or neutral expressions as a prime . Results When comparing reaction times to the congruent ( prime and probe at the same location ) with incongruent presentation of facial emotions , neither the placebo nor oxytocin group showed an attentional preference for emotional facial expressions in terms of a threat bias . However , oxytocin treatment did reveal two specific effects : it generally reduced the allocation of attention towards angry facial expressions , and it increased sustained attention towards happy faces , specifically under conditions of heightened awareness , i.e. trials with longer primes . Conclusions We investigated a heterogeneous group of medicated male and female patients . We conclude that oxytocin does modulate basic factors of facial emotion processing in chronic depression . Our findings encourage further investigations assessing the therapeutic potential of oxytocin in chronic depression . Trial registration EUDRA-CT 2010 - 020956 - 69 . Date registered : 23 February 2011 Abstract Animal studies have shown the role of oxytocin in affiliation and attachment , and recent evidence suggests that oxytocin is also involved in human models of approach behaviour , possibly by modulating the processing of emotionally valenced stimuli . Although oxytocin administration has been reported to decrease neural responses to facial emotional information , the effects on a wider range of behavioural measures of emotional processing shown to be sensitive to antidepressant manipulation have not been examined . The aim of this study was to investigate whether intranasally administered oxytocin affects the processing of positive and negative affective information in healthy male volunteers across tasks measuring attention , perception and memory . Twenty-nine male healthy volunteers were r and omly allocated to receive a single dose of oxytocin nasal spray ( 24 UI ) or placebo . 50 min later , participants completed a battery of psychological tests measuring emotional processing . A single dose of intranasally administered oxytocin slowed reaction time to correctly identify fearful facial expressions and reduced the misclassification of positive emotions as negative ones . These effects occurred in the absence of significant differences in subjective ratings of mood and anxiety . These results suggest that oxytocin modulates emotion processing in healthy male volunteers . This action may contribute to the emerging role of the neuropeptide in promoting affiliative and approach behaviours by reducing the salience of potentially ambiguous and threatening social stimuli 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 Generalized social anxiety disorder ( GSAD ) is characterized by aberrant patterns of amygdala-frontal connectivity to social signals of threat and at rest . The neuropeptide oxytocin ( OXT ) modulates anxiety , stress , and social behaviors . Recent functional neuroimaging studies suggest that these effects are mediated through OXT ’s effects on amygdala reactivity and /or amygdala-frontal connectivity . The aim of the current study was to examine OXT ’s effects on amygdala-frontal resting-state functional connectivity ( rsFC ) in GSAD patients and healthy controls ( HCs ) . In a r and omized , double-blind , cross-over design , 18 GSAD and 18 HC participants received intranasal OXT ( 24 IU or 40.32 μg ) or placebo ( PBO ) before resting-state functional magnetic resonance imaging . In individuals with GSAD , OXT enhanced rsFC of the left and right amygdala with rostral anterior cingulate cortex (ACC)/medial prefrontal cortex ( mPFC ) , and in doing so , reversed ( ie , ‘ normalized ’ ) the reduced amygdala-frontal connectivity observed relative to HCs evident on PBO . Higher social anxiety severity in GSAD subjects correlated with lower amygdala-ACC/mPFC connectivity on PBO and higher social anxiety also correlated with greater enhancement in amygdala-frontal connectivity induced by OXT . These findings show that OXT modulates a neural circuit known for social threat processing and emotion regulation , suggesting a neural mechanism by which OXT may have a role in the pathophysiology and treatment of social anxiety disorder Ostracism is such a widely used and powerful tactic that the authors tested whether people would be affected by it even under remote and artificial circumstances . In Study 1 , 1,486 participants from 62 countries accessed the authors ' on-line experiment on the Internet . They were asked to use  mental visualization while playing a virtual tossing game with two others ( who were actually computer generated and controlled ) . Despite the minimal nature of their experience , the more participants were ostracized , the more they reported feeling bad , having less control , and losing a sense of belonging . In Study 2 , ostracized participants were more likely to conform on a subsequent task . The results are discussed in terms of supporting K. D. Williams 's ( 1997 ) need threat theory of ostracism The Fear of Spiders Question naire ( FSQ ) , an 18-item self-report question naire assessing spider phobia , was developed in an attempt to complement the information provided by the Spider Phobia Question naire ( SPQ ) . Data obtained from 338 undergraduates revealed that the FSQ was able to discriminate phobics from nonphobics , and indicated decrements in phobic responding from pretest to posttest following cognitive therapy . Test-retest data , obtained from non-treatment control groups , indicated that scores on the FSQ are stable over a one month period . The FSQ also demonstrated adequate convergent validity due to its significant correlations with the SPQ and a behavioral avoidance test . Finally , a factor analysis revealed two factors accounting for 55 % of the variance . It is argued that , compared to the SPQ , items on the FSQ are more explicit regarding the time period to be assessed , and may be more sensitive to differences between phobics and nonphobics and decrements in phobic responding following treatment BACKGROUND A diagnostic hallmark of autism spectrum disorders is a qualitative impairment in social communication and interaction . Deficits in the ability to recognize the emotions of others are believed to contribute to this . There is currently no effective treatment for these problems . METHODS In a double-blind , r and omized , placebo-controlled , crossover design , we administered oxytocin nasal spray ( 18 or 24 IU ) or a placebo to 16 male youth aged 12 to 19 who were diagnosed with Autistic or Asperger 's Disorder . Participants then completed the Reading the Mind in the Eyes Task , a widely used and reliable test of emotion recognition . RESULTS In comparison with placebo , oxytocin administration improved performance on the Reading the Mind in the Eyes Task . This effect was also shown when analysis was restricted to the younger participants aged 12 to 15 who received the lower dose . CONCLUSIONS This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders . Findings suggest the potential of earlier intervention and further evaluation of oxytocin nasal spray as a treatment to improve social communication and interaction in young people with autism spectrum disorders In humans , oxytocin nasal administration reduces social-threat perception and improves processes involved in communication and the encoding of positive social cues . The aim of this study was to determine whether oxytocin given as an adjunct to exposure therapy improves treatment for  social anxiety disorder ( SAD ) as indicated by a comprehensive set of symptom outcome measures . In a r and omized , double-blind , placebo-controlled trial , we administered 24 IU of oxytocin or a placebo in combination with exposure therapy to twenty-five participants who met primary diagnosis for SAD . Participants administered with oxytocin showed improved positive evaluations of appearance and speech performance as exposure treatment sessions progressed . These effects did not generalize to improve overall treatment outcome from exposure therapy . Participants who received oxytocin or placebo reported similar levels of symptom reduction following treatment across symptom severity , dysfunctional cognition , and life-impairment measures . This study shows that the administration of oxytocin improves mental representations of self , following exposure therapy . These effects may be either short term or situation specific . Future research is now needed to determine whether oxytocin can enhance treatment outcomes for SAD when used with greater frequency , with a wider variety of social learning experiences , and in conjunction with interventions that more specifically target change in broader dysfunctional cognitions BACKGROUND Postnatal depression is common and negatively affects the mother-baby relationship ; oxytocin has been found to have positive effects on parenting behavior . We hypothesize that intranasal administration of oxytocin to mothers with depression will influence their parenting related expressed emotion , creating a better basis for sensitive parenting . METHODS Twenty-five postnatally depressed mothers with infants less than one year participated in a r and omized , double-blind , placebo controlled within-subject clinical study in 2011 . Mothers attended an out-patient perinatal psychiatry setting in NSW , Australia . They received 24 IU of oxytocin alternating with placebo approximately one week apart in r and om order , prior to completing outcome measures . The outcome measures were the Five Minute Speech Sample , the Self- Assessment Manikin and the Controlled Oral Word Association Test . RESULTS In the oxytocin condition mothers were sadder ( p=.01 ) , and they more often initially described their babies as difficult ( p=.038 ) , but they reported that the quality of their relationship with their infant was more positive ( p=.036 ) . LIMITATIONS Despite an adequate sample size to answer our central hypothesis , a larger sample may have eluci date d a moderating effect of childhood trauma . CONCLUSION Oxytocin did not make depressed mothers  happier but their perception of the relationship with their baby improved . Treatment with intranasal oxytocin might show some unwanted side-effects in depressed individuals
target: 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 .
background: 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 .