Introduction to Oxytocin 

Switching brain serotonin with oxytocin.

Abstract

Serotonin (5-HT) and oxytocin (OXT) are two neuromodulators involved in human affect and sociality and in disorders like depression and autism. We asked whether these chemical messengers interact in the regulation of emotion-based behavior by administering OXT or placebo to 24 healthy subjects and mapping cerebral 5-HT system by using 2′-methoxyphenyl-(N-2′-pyridinyl)-p-[(18)F]fluoro-benzamidoethylpiperazine ([(18)F]MPPF), an antagonist of 5-HT1A receptors. OXT increased [(18)F]MPPF nondisplaceable binding potential (BPND) in the dorsal raphe nucleus (DRN), the core area of 5-HT synthesis, and in the amygdala/hippocampal complex, insula, and orbitofrontal cortex. Importantly, the amygdala appears central in the regulation of 5-HT by OXT: [(18)F]MPPF BPND changes in the DRN correlated with changes in right amygdala, which were in turn correlated with changes in hippocampus, insula, subgenual, and orbitofrontal cortex, a circuit implicated in the control of stress, mood, and social behaviors. OXT administration is known to inhibit amygdala activity and results in a decrease of anxiety, whereas high amygdala activity and 5-HT dysregulation have been associated with increased anxiety. The present study reveals a previously unidentified form of interaction between these two systems in the human brain, i.e., the role of OXT in the inhibitory regulation of 5-HT signaling, which could lead to novel therapeutic strategies for mental disorders.

Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8637-42. doi: 10.1073/pnas.1319810111. Epub 2014 May 27.

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Effect of intranasal oxytocin administration on psychiatric symptoms: A meta-analysis of placebo-controlled studies.

Abstract 

Clinical trials of intranasal administration of oxytocin for treating psychiatric problems have yielded mixed results. To conduct a quantitative review of placebo-controlled clinical trials of intranasally-administered oxytocin (OT) for psychiatric symptoms, manual and electronic searches using PubMed and PsycINFO were conducted. Of 1828 entries, 16 placebo-controlled studies totaling 330 participants were included in the analysis. The overall placebo-controlled effect size was moderately strong (Hedges’ g=0.67) and robust as suggested by the fail-safe N and funnel plot analysis. OT reduced symptoms of depression, anxiety, autism/repetitive behaviors, psychotic symptoms, and general psychopathology. In the combined sample, symptom reduction was moderated by frequency of administration. Publication year and diagnostic category did not moderate the effect of OT on the clinical outcome measures. We conclude that intranasal administration of OT is a potentially useful intervention for reducing psychiatric symptoms. However, more studies are needed to determine the best treatment target and to identify the mechanism of treatment change. http://www.ncbi.nlm.nih.gov/pubmed/26094200

Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans.

Abstract 

There has been an unprecedented interest in the modulatory effects of intranasal oxytocin on human social cognition and behaviour, however as yet no study has actually demonstrated that this modality of administration increases concentrations of the peptide in the brain as well as blood in humans. Here using combined blood and cerebrospinal fluid (CSF) sampling in subjects receiving either 24 IU of oxytocin (n = 11) or placebo (n = 4) we have shown that oxytocin levels significantly increased in both plasma and CSF. However, whereas oxytocin plasma concentrations peaked at 15 min after intranasal administration and decreased after 75 min, CSF concentrations took up to 75 min to reach a significant level. Moreover, there was no correlation (r = <0.10) between oxytocin plasma and CSF concentrations. Together, these data provide crucial insights into the plasma and CSF kinetics of intranasally administered oxytocin.

Reference: Striepens N, Kendrick KM, Hanking V, Landgraf R, Wüllner U, Maier W, Hurlemann R. Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans. Sci Rep. 2013 Dec 6;3:3440. doi: 10.1038/srep03440. PubMed PMID: 24310737; PubMed Central PMCID: PMC3853684.

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853684/

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Anxiety Disorders

Generalized Anxiety Disorder (GAD), Social Anxiety Disorder, Post Traumatic Stress Disorder

Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder.

Abstract 

Patients with generalized social anxiety disorder (GSAD) exhibit heightened activation of the amygdala in response to social cues conveying threat (eg, fearful/angry faces). The neuropeptide oxytocin (OXT) decreases anxiety and stress, facilitates social encounters, and attenuates amygdala reactivity to threatening faces in healthy subjects. The goal of this study was to examine the effects of OXT on fear-related amygdala reactivity in GSAD and matched healthy control (CON) subjects. In a functional magnetic resonance imaging study utilizing a double-blind placebo-controlled within-subjects design, we measured amygdala activation to an emotional face matching task of fearful, angry, and happy faces following acute intranasal administration of OXT (24 IU or 40.32 μg) and placebo in 18 GSAD and 18 CON subjects. Both the CON and GSAD groups activated bilateral amygdala to all emotional faces during placebo, with the GSAD group exhibiting hyperactivity specifically to fearful faces in bilateral amygdala compared with the CON group. OXT had no effect on amygdala activity to emotional faces in the CON group, but attenuated the heightened amygdala reactivity to fearful faces in the GSAD group, such that the hyperactivity observed during the placebo session was no longer evident following OXT (ie, normalization). These findings suggest that OXT has a specific effect on fear-related amygdala activity, particularly when the amygdala is hyperactive, such as in GSAD, thereby providing a brain-based mechanism of the impact of OXT in modulating the exaggerated processing of social signals of threat in patients with pathological anxiety.

Neuropsychopharmacology. 2010 Nov;35(12):2403-13. doi: 10.1038/npp.2010.123. Epub 2010 Aug 18.

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Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder.

Abstract 

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 randomized, double-blind, placebo (PBO)-controlled, within-subjects design, 18 HCs and 17 GSAD subjects performed a functional magnetic resonance imaging task designed 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 implications such as enhancing the integration and modulation of social responses.
Neuropsychopharmacology. 2015 Jan;40(2):278-86. doi: 10.1038/npp.2014.168. Epub 2014 Jul 7.
http://www.ncbi.nlm.nih.gov/pubmed/24998619

Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial.

BACKGROUND

Currently few evidence based interventions are available for the prevention of PTSD within the first weeks after trauma. Increased risk for PTSD development is associated with dysregulated fear and stress responses prior to and shortly after trauma, as well as with a lack of perceived social support early after trauma. Oxytocin is a potent regulator of these processes. Therefore, we propose that oxytocin may be important in reducing adverse consequences of trauma. The ‘BONDS’ study is conducted in order to assess the efficacy of an early intervention with intranasal oxytocin for the prevention of PTSD.

METHODS/DESIGN

In this multicenter double-blind randomized placebo-controlled trial we will recruit 220 Emergency Department patients at increased risk of PTSD. Trauma-exposed patients are screened for increased PTSD risk with questionnaires assessing peri-traumatic distress and acute PTSD symptoms within 7 days after trauma. Baseline PTSD symptom severity scores and neuroendocrine and psychophysiological measures will be collected within 10 days after trauma. Participants will be randomized to 7.5 days of intranasal oxytocin (40 IU) or placebo twice a day. Follow-up measurements at 1.5, 3 and 6 months post-trauma are collected to assess PTSD symptom severity (the primary outcome measure). Other measures of symptoms of psychopathology, and neuroendocrine and psychophysiological disorders are secondary outcome measures.

DISCUSSION

We hypothesize that intranasal oxytocin administered early after trauma is an effective pharmacological strategy to prevent PTSD in individuals at increased risk, which is both safe and easily applicable. Interindividual and contextual factors that may influence the effects of oxytocin treatment will be considered in the analysis of the results. http://www.ncbi.nlm.nih.gov/pubmed/24485496

Intranasal oxytocin as strategy for medication-enhanced psychotherapy of PTSD: salience processing and fear inhibition processes.

About ten percent of people experiencing a traumatic event will subsequently develop post-traumatic stress disorder (PTSD). PTSD is characterized by an exaggerated fear response which fails to extinguish over time and cannot be inhibited in safe contexts. The neurobiological correlates of PTSD involve enhanced salience processing (i.e. amygdala, dorsal anterior cingulate cortex (dACC) and anterior insula (AI) hyperactivity), and reduced top-down inhibitory control over this fear response (i.e. dorsal and ventromedial prefrontal cortex (vmPFC) hypoactivity and diminished structural and functional connectivity between the vmPFC, hippocampus and amygdala). Therefore, dampening the exaggerated fear response (i.e. by reducing amygdala hyperactivity) and enhancing top-down inhibitory control (i.e. by promoting prefrontal control over the amygdala) during psychotherapy is an important target for medication-enhanced psychotherapy (MEP) in PTSD patients. Since the neuropeptide oxytocin (OT) has been found to act on these two processes, we propose that OT is a promising pharmacological agent to boost treatment response in PTSD. Human fMRI studies indicate that intranasal OT attenuates amygdala (hyper)activity and enhances connectivity of the amygdala with the vmPFC and hippocampus, resulting in increased top-down control over the fear response. In addition, intranasal OT was found to attenuate amygdala-brainstem connectivity and to change activity and connectivity in nodes of the salience network (i.e. AI and dACC). Furthermore, OT administration may modulate hypothalamus-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) function and may enhance social behaviour, which could be beneficial in the therapeutic alliance. We also discuss contextual and interindividual factors (e.g. gender and social context) which may influence the effectiveness of OT in MEP. In all, we propose that intranasal OT given prior to each psychotherapy session may be an effective additive treatment to boost treatment response in PTSD. http://www.ncbi.nlm.nih.gov/pubmed/24485496

Autism Spectrum Disorders (ASD)

Oxytocin and autism: a systematic review of randomized controlled trials.

Abstract

OBJECTIVE

Little is known about the effectiveness of pharmacological interventions on autism spectrum disorder (ASD). This is a systematic review of the randomized controlled trials (RCTs) of oxytocin interventions in autism, made from January 1990 to September 2013.

METHOD

A search of computerized databases was supplemented by manual search in the bibliographies of key publications. The methodological quality of the studies included in the review was evaluated independently by two researchers, according to a set of formal criteria. Discrepancies in scoring were resolved through discussion.

RESULTS

The review yielded seven RCTs, including 101 subjects with ASD (males=95) and 8 males with Fragile X syndrome. The main categories of target symptoms tested in the studies were repetitive behaviors, eye gaze, and emotion recognition. The studies had a medium to high risk of bias. Most studies had small samples (median=15). All the studies but one reported statistically significant between-group differences on at least one outcome variable. Most findings were characterized by medium effect size. Only one study had evidence that the improvement in emotion recognition was maintained after 6 weeks of treatment with intranasal oxytocin. Overall, oxytocin was well tolerated and side effects, when present, were generally rated as mild; however, restlessness, increased irritability, and increased energy occurred more often under oxytocin.

CONCLUSIONS

RCTs of oxytocin interventions in autism yielded potentially promising findings in measures of emotion recognition and eye gaze, which are impaired early in the course of the ASD condition and might disrupt social skills learning in developing children. There is a need for larger, more methodologically rigorous RCTs in this area. Future studies should be better powered to estimate outcomes with medium to low effect size, and should try to enroll female participants, who were rarely considered in previous studies. Risk of bias should be minimized. Human long-term administration studies are necessary before clinical recommendations can be made.

Reference: Preti A, Melis M, Siddi S, Vellante M, Doneddu G, Fadda R. Oxytocin and autism: a systematic review of randomized controlled trials. J Child Adolesc Psychopharmacol. 2014 Mar;24(2):54-68. doi: 10.1089/cap.2013.0040. Review. PubMed PMID: 24679173.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24679173

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Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger’s Disorders

Autism is a neurodevelopmental disorder characterized by dysfunction in three core behavioral domains: repetitive behaviors, social  deficits, and language abnormalities. There is evidence that abnormalities exist in peptide systems, particularly the oxytocin system, in  autism spectrum patients. Furthermore, oxytocin and the closely related peptide vasopressin are known to play a role in social and  repetitive behaviors. This study examined the impact of oxytocin on repetitive behaviors in 15 adults with autism or Asperger’s disorder  via randomized double-blind oxytocin and placebo challenges. The primary outcome measure was an instrument rating six repetitive  behaviors: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a  significant reduction in repetitive behaviors following oxytocin infusion in comparison to placebo infusion. Repetitive behavior in autism spectrum.

Reference: Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR, Mosovich S. Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology. 2003 Jan;28(1):193-8. PubMed PMID: 12496956.

Source:https://www.researchgate.net/profile/Eric_Hollander/publication/10978075_Oxytocin_Infusion_Reduces_Repetitive_Behaviors_in_Adults_with_Autistic_and_Asperger’s_Disorders/links/0c96053550b56e0e0d000000.pdf

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Promoting social behavior with oxytocin in high-functioning autism spectrum disorders

Abstract 

Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients’ gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.

Reference: Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4389-94. doi: 10.1073/pnas.0910249107. Epub 2010 Feb 16. PubMed PMID: 20160081; PubMed Central PMCID: PMC2840168.

Source: http://www.pnas.org/content/107/9/4389.short

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Oxytocin increases retention of social cognition in autism.

Abstract

BACKGROUND

Oxytocin dysfunction might contribute to the development of social deficits in autism, a core symptom domain and potential target for intervention. This study explored the effect of intravenous oxytocin administration on the retention of social information in autism.

METHODS

Oxytocin and placebo challenges were administered to 15 adult subjects diagnosed with autism or Asperger’s disorder, and comprehension of affective speech (happy, indifferent, angry, and sad) in neutral content sentences was tested.

RESULTS

All subjects showed improvements in affective speech comprehension from pre- to post-infusion; however, whereas those who received placebo first tended to revert to baseline after a delay, those who received oxytocin first retained the ability to accurately assign emotional significance to speech intonation on the speech comprehension task.

CONCLUSIONS

These results are consistent with studies linking oxytocin to social recognition in rodents as well as studies linking oxytocin to prosocial behavior in humans and suggest that oxytocin might facilitate social information processing in those with autism. These findings also provide preliminary support for the use of oxytocin in the treatment of autism.

Reference: Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L, Anagnostou E, Wasserman S. Oxytocin increases retention of social cognition in autism. Biol Psychiatry. 2007 Feb 15;61(4):498-503. Epub 2006 Aug 14. PubMed PMID: 16904652.

Source: http://www.ncbi.nlm.nih.gov/pubmed/?term=Oxytocin+Increases+Retention+of+Social+Cognition+in+Autism

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Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders.

Abstract 

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, randomized, 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.

Source: http://www.ncbi.nlm.nih.gov/pubmed?cmd=historysearch&querykey=36

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Oxytocin Serum Levels in ASD

Plasma oxytocin levels in autistic children.

Background

Social impairments are central to the syndrome of autism. The neuropeptide oxytocin (OT) has been implicated in the regulation of social behavior in animals but has not yet been examined in autistic subjects.

Methods

To determine whether autistic children have abnormalities in OT, midday plasma samples from 29 autistic and 30 age-matched normal children, all prepubertal, were analyzed by radioimmunoassay for levels of OT.

Results

Despite individual variability and overlapping group distributions, the autistic group mad significantly lower plasma OT levels than the normal group. OT increased with age in the normal but not the autistic children. Elevated OT was associated with higher scores on social and developmental measures for the normal children, but was associated with lower scores for the autistic children. These relationships were strongest in a subset of autistic children identified as aloof.

Conclusions

Although making inferences to central OT functioning from peripheral measurement is difficult, the data suggest that OT abnormalities may exist in autism, and that more direct investigation of central nervous system OT function is warranted.

Reference: Modahl, Charlotte et al., Plasma oxytocin levels in autistic children. Biological Psychiatry, Volume 43, Issue 4, 270 – 277

Source: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(97)00439-3/abstract?cc=y=

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Oxytocin and autistic disorder: alterations in peptide forms

Abstract

Background

Oxytocin (OT) is synthesized as a prohormone that is sequentially processed to peptides. These peptides are the bioactive amidated form (OT) and the C-terminal extended peptides, OT-Gly, OT-Gly-Lys and OT-Gly-Lys-Arg, which are designated together as OT-X. As an extension of our previous study finding decreased plasma OT in autism, studies were conducted to determine whether there were changes in OT peptide forms in autistic children.

Methods

Twenty eight male subjects (97 ± 20 months; range, 70–139 months), diagnosed with DSM-IV autistic disorder through observation and semi-structured interview, were compared with 31 age-matched nonpsychiatric control subjects (106 ± 22 months; range, 74–140 months). Using OT antisera with different specificity for the peptide forms, we measured plasma OT and OT-X in each group.

Results

T tests showed that there was a decrease in plasma OT (t = 4.4, p < .0001), an increase in OT-X (t = 2.3, p < .03) and an increase in the ratio of OT-X/OT (t = 4.5, p < .0001) in the autistic sample, compared with control subjects.

Conclusions

The results suggest that children with autistic disorder show alterations in the endocrine OT system. Deficits in OT peptide processing in children with autism may be important in the development of this syndrome.

Reference: Green L, Fein D, Modahl C, Feinstein C, Waterhouse L, Morris M. Oxytocin and autistic disorder: alterations in peptide forms. Biol Psychiatry. 2001 Oct 15;50(8):609-13. PubMed PMID: 11690596.

Source: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(01)01139-8/abstract

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Oxytocin Receptor Gene (OXTR) and ASD

Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition

Abstract 

Evidence both from animal and human studies suggests that common polymorphisms in the oxytocin receptor (OXTR) gene are likely candidates to confer risk for autism spectrum disorders (ASD). In lower mammals, oxytocin is important in a wide range of social behaviors, and recent human studies have shown that administration of oxytocin modulates behavior in both clinical and non-clinical groups. Additionally, two linkage studies and two recent association investigations also underscore a possible role for the OXTR gene in predisposing to ASD. We undertook a comprehensive study of all 18 tagged SNPs across the entire OXTR gene region identified using HapMap data and the Haploview algorithm. Altogether 152 subjects diagnosed with ASDs (that is, DSM IV autistic disorder or pervasive developmental disorder—NOS) from 133 families were genotyped (parents and affected siblings). Both individual SNPs and haplotypes were tested for association using family-based association tests as provided in the UNPHASED set of programs. Significant association with single SNPs and haplotypes (global P-values <0.05, following permutation test adjustment) were observed with ASD. Association was also observed with IQ and the Vineland Adaptive Behavior Scales (VABS). In particular, a five-locus haplotype block (rs237897-rs13316193-rs237889-rs2254298-rs2268494) was significantly associated with ASD (nominal global P=0.000019; adjusted global P=0.009) and a single haplotype (carried by 7% of the population) within that block showed highly significant association (P=0.00005). This is the third association study, in a third ethnic group, showing that SNPs and haplotypes in the OXTR gene confer risk for ASD. The current investigation also shows association with IQ and total VABS scores (as well as the communication, daily living skills and socialization subdomains), suggesting that this gene shapes both cognition and daily living skills that may cross diagnostic boundaries.

Reference: Lerer E, Levi S, Salomon S, Darvasi A, Yirmiya N, Ebstein RP. Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition. Mol Psychiatry. 2008 Oct;13(10):980-8. Epub 2007 Sep 25. PubMed PMID: 17893705.

Source: http://www.nature.com/mp/journal/v13/n10/abs/4002087a.html

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Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism

Abstract 

The oxytocin receptor gene (OXTR) has been studied in autism because of the role of oxytocin (OT) in social cognition. Linkage has also been demonstrated to the region of OXTR in a large sample. Two single nucleotide polymorphisms (SNPs) and a haplotype constructed from them in OXTR have been associated with autism in the Chinese Han population. We tested whether these associations replicated in a Caucasian sample with strictly defined autistic disorder. We genotyped the two previously associated SNPs (rs2254298, rs53576) in 57 Caucasian autism trios. Probands met clinical, ADI-R, and ADOS criteria for autistic disorder. Significant association was detected at rs2254298 (p = 0.03) but not rs53576. For rs2254298, overtransmission of the G allele to probands with autistic disorder was found which contrasts with the overtransmission of A previously reported in the Chinese Han sample. In both samples, G was more frequent than A. However, in our Caucasian autism trios and the CEU Caucasian HapMap samples the frequency of A was less than that reported in the Chinese Han and Chinese in Bejing HapMap samples. The haplotype test of association did not reveal excess transmission from parents to affected offspring. These findings provide support for association of OXTR with autism in a Caucasian population. Overtransmission of different alleles in different populations may be due to a different pattern of linkage disequilibrium between the marker rs2254298 and an as yet undetermined susceptibility variant in OXTR.

Reference: Jacob S, Brune CW, Carter CS, Leventhal BL, Lord C, Cook EH Jr. Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett. 2007 Apr 24;417(1):6-9. Epub 2007 Feb 3. PubMed PMID: 17383819; PubMed Central PMCID: PMC2705963.

Source: http://www.ncbi.nlm.nih.gov/pubmed/17383819

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Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level.

Abstract 

An increasing number of animal studies advert to a substantial role of the neuropeptide oxytocin in the regulation of social attachment and affiliation. Furthermore, animal studies showed anxiety and stress-reduced effects of oxytocin. First human studies confirm these findings in animal studies and implicate a crucial role of oxytocin in human social attachment behavior and in social interactions. Thus, the oxytocin system might be involved in the impairment of social interaction and attachment in autism spectrum disorders (ASD). The human oxytocin receptor gene (OXTR) represents a plausible candidate gene for the etiology of ASD. To analyze whether genetic variants in the OXTR gene are associated with ASD we performed family-based single-marker and haplotype association analyses with 22 single nucleotide polymorphisms (SNPs) in the OXTR and its 5′ region in 100 families with autistic disorders on high-functioning level (Asperger syndrome (AS), high-functioning autism (HFA), and atypical autism (AA)). Single-marker and haplotype association analyses revealed nominally significant associations of one single SNP and one haplotype with autism, respectively. Furthermore, employing a “reverse phenotyping” approach, patients carrying the haplotype associated with autism showed nominally significant impairments in comparison to noncarriers of the haplotype in items of the Autism Diagnostic Interview-Revised algorithm describing aspects of social interaction and communication. In conclusion, our results implicate that genetic variation in the OXTR gene might be relevant in the etiology of autism on high-functioning level.

Reference: Wermter AK, Kamp-Becker I, Hesse P, Schulte-Körne G, Strauch K, Remschmidt H. Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level. Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):629-39. doi: 10.1002/ajmg.b.31032. PubMed PMID: 19777562.

Source:http://www.ncbi.nlm.nih.gov/pubmed/term=Evidence+for+the+involvement+of+genetic+variation+in+the+oxytocin+receptor+gene+(OXTR)+in+the+etiology+of+autistic+disorders+on+high-functioning+level†

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Schizophrenia 

Intranasal oxytocin as an adjunct to risperidone in patients with schizophrenia : an 8-week, randomized, double-blind, placebo-controlled study.

Abstract

BACKGROUND

Impairment of oxytocinergic function and/or oxytocin receptor genetic abnormalities has been demonstrated in patients with schizophrenia. Oxytocin reverses emotional recognition deficit and might restore sense of trust in patients with schizophrenia. Some short-term studies have shown efficacy and tolerability of oxytocin in patients with schizophrenia. However, there is a lack of evidence on the efficacy and tolerability of oxytocin in patients with schizophrenia beyond 3 weeks.

OBJECTIVE

The objective of this study was to assess the efficacy and tolerability of oxytocin intranasal spray (given as an adjuvant to risperidone) in patients with schizophrenia.

STUDY DESIGN

]This was an 8-week, randomized, double-blind, placebo-controlled study.

STUDY SETTING

Inpatients of two large referral psychiatric hospitals in Iran were recruited for the study.

PATIENTS

Forty patients (male and female gender) aged 18-50 years with a diagnosis of schizophrenia (DSM-IV-TR) who were on a stable dose of risperidone for a minimum of 1 month and who were chronically partially responsive to antipsychotic monotherapy were included in the study. INTERVENTIONS: The patients were randomly assigned to oxytocin intranasal spray (Syntocinon(®); Novartis, Basel, Switzerland) or placebo intranasal spray containing normal saline (ACER, Tehran, Iran) for 8 weeks. Oxytocin spray was administered as 20 IU (five sprays) twice a day for the first week followed by 40 IU (ten sprays) twice a day for the following 7 weeks. Placebo spray was administered at the same dose as the oxytocin spray. In addition, participants were on a stable dose of risperidone (5 or 6 mg/day). OUTCOMES: The patients were assessed using Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 0, 2, 4, 6 and 8. Primary outcomes were the differences in the PANSS scores between the two groups at the end of the trial. Adverse effects were recorded using a checklist and the Extrapyramidal Symptom Rating Scale (ESRS) at baseline and at weeks 1, 2, 4, 6 and 8. RESULTS: All patients had at least one post-baseline measurement and 37 patients (19 in the oxytocin and 18 in the placebo group) completed the study. Repeated measure analysis of variance showed significant effect for time X treatment interaction on the PANSS total [F(2.291,87.065) = 22.124, p < 0.001], positive [F(1.285,48.825) = 11.655, p = 0.001], negative [F(2.754,104.649) = 11.818, p < 0.001] and general psychopathology [F(1.627,61.839) = 4.022, p = 0.03] subscale scores. By week 8, patients in the oxytocin group showed significantly greater improvement on the positive (Cohen’s d = 1.2, 20 % vs. 4 % reduction in score, p < 0.001), negative (Cohen’s d = 1.4, 7 % vs. 2 % reduction in score, p < 0.001) and general psychopathology (Cohen’s d = 0.8, 8 % vs. 2 % reduction in score, p = 0.021) subscales and total (Cohen’s d = 1.9, 11 % vs. 2 % reduction in score, p < 0.001) PANSS scores than the placebo group. Adverse effects including the sodium concentration change were similar between the two groups.

CONCLUSION: 

Oxytocin as an adjunct to risperidone tolerably and efficaciously improves positive symptoms of schizophrenia. In addition, effects on negative and total psychopathology scores were statistically significant, but likely to be clinically insignificant. The interesting findings from the present pilot study need further replication in a larger population of patients.

CNS Drugs. 2013 Jan;27(1):57-65. doi: 10.1007/s40263-012-0022-1.

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Intranasal oxytocin as an adjunct to risperidone in patients with schizophrenia : an 8-week, randomized, double-blind, placebo-controlled study.

Abstract 

BACKGROUND

Impairment of oxytocinergic function and/or oxytocin receptor genetic abnormalities has been demonstrated in patients with schizophrenia. Oxytocin reverses emotional recognition deficit and might restore sense of trust in patients with schizophrenia. Some short-term studies have shown efficacy and tolerability of oxytocin in patients with schizophrenia. However, there is a lack of evidence on the efficacy and tolerability of oxytocin in patients with schizophrenia beyond 3 weeks.

OBJECTIVE

The objective of this study was to assess the efficacy and tolerability of oxytocin intranasal spray (given as an adjuvant to risperidone) in patients with schizophrenia.

STUDY DESIGN

This was an 8-week, randomized, double-blind, placebo-controlled study.

STUDY SETTING

Inpatients of two large referral psychiatric hospitals in Iran were recruited for the study.

PATIENTS

Forty patients (male and female gender) aged 18-50 years with a diagnosis of schizophrenia (DSM-IV-TR) who were on a stable dose of risperidone for a minimum of 1 month and who were chronically partially responsive to antipsychotic monotherapy were included in the study.

INTERVENTIONS

The patients were randomly assigned to oxytocin intranasal spray (Syntocinon(®); Novartis, Basel, Switzerland) or placebo intranasal spray containing normal saline (ACER, Tehran, Iran) for 8 weeks. Oxytocin spray was administered as 20 IU (five sprays) twice a day for the first week followed by 40 IU (ten sprays) twice a day for the following 7 weeks. Placebo spray was administered at the same dose as the oxytocin spray. In addition, participants were on a stable dose of risperidone (5 or 6 mg/day).

OUTCOMES

The patients were assessed using Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 0, 2, 4, 6 and 8. Primary outcomes were the differences in the PANSS scores between the two groups at the end of the trial. Adverse effects were recorded using a checklist and the Extrapyramidal Symptom Rating Scale (ESRS) at baseline and at weeks 1, 2, 4, 6 and 8. RESULTS: All patients had at least one post-baseline measurement and 37 patients (19 in the oxytocin and 18 in the placebo group) completed the study. Repeated measure analysis of variance showed significant effect for time X treatment interaction on the PANSS total [F(2.291,87.065) = 22.124, p < 0.001], positive [F(1.285,48.825) = 11.655, p = 0.001], negative [F(2.754,104.649) = 11.818, p < 0.001] and general psychopathology [F(1.627,61.839) = 4.022, p = 0.03] subscale scores. By week 8, patients in the oxytocin group showed significantly greater improvement on the positive (Cohen’s d = 1.2, 20 % vs. 4 % reduction in score, p < 0.001), negative (Cohen’s d = 1.4, 7 % vs. 2 % reduction in score, p < 0.001) and general psychopathology (Cohen’s d = 0.8, 8 % vs. 2 % reduction in score, p = 0.021) subscales and total (Cohen’s d = 1.9, 11 % vs. 2 % reduction in score, p < 0.001) PANSS scores than the placebo group. Adverse effects including the sodium concentration change were similar between the two groups.

CONCLUSION

Oxytocin as an adjunct to risperidone tolerably and efficaciously improves positive symptoms of schizophrenia. In addition, effects on negative and total psychopathology scores were statistically significant, but likely to be clinically insignificant. The interesting findings from the present pilot study need further replication in a larger population of patients. http://www.ncbi.nlm.nih.gov/pubmed/23233269

Self-Perception of Personality 

Oxytocin and enhancement of the positive valence of social affiliation memories: an autobiographical memory study.

Abstract 

Intranasal oxytocin has been shown to alter self-perceptions of personality (e.g., more trusting, increased extraversion). To follow up these findings, we examined the acute effects of two doses of intranasal oxytocin (24 IU and 48 IU) on another form of self-referential cognition: autobiographical memory. Changes in autobiographical memory (personal memories for the past) could conceivably effect change in self-perception and consequently alter social behaviors. We predicted that oxytocin would increase the number of specific personal memories recalled, and promote the recall of positive social affiliation memories. (PSAM) Seventeen male participants self-administered a placebo or oxytocin (24 IU, 48 IU) using a nasal spray on three separate occasions in a placebo-controlled, double-blind, and within-subject experiment. Participants completed the Autobiographical Memory Test (AMT) 110 minutes later. Analyses revealed a quadratic dose-response curve for the effects of intranasal oxytocin on autobiographical memory recall. The 24 IU dose, relative to the 48 IU dose and placebo, increased the number of specific personal memories recalled and promoted the recall of social affiliation memories that were rated more positively. The lack of effect with the 48 IU dose could be due to saturation of the oxytocin receptors at higher doses. Changes in autobiographical memory may be one mechanism by which oxytocin alters prosocial worldviews. http://www.ncbi.nlm.nih.gov/pubmed/24387003

Acute intranasal oxytocin improves positive self-perceptions of personality.

Abstract

RATIONALE

Research suggests the experimental manipulation of oxytocin facilitates positive interactions, cooperation, and trust. The mechanism by which oxytocin influences social behavior is not well understood.

OBJECTIVE

We explored the hypothesis that oxytocin alters how people perceive themselves, which could be one mechanism by which oxytocin promotes prosocial behavior.

METHOD

In a between-subject, randomized, and double-blind experiment, 100 university students received a 24 i.u. dose of intranasal oxytocin or placebo, and then completed the revised neo personality inventory (neo-pi-r) and other self-report measures 90 min later.

RESULTS

Intranasal oxytocin increased ratings of neo-pi-r extraversion and openness to experiences [f(1,98) = 4.910, p = .025, partial η (2) = .05; f(1,98) = 6.021, p = .016, partial η (2) = .06], particularly for the following facets: positive emotions (d = 0.48, p < .05), warmth (d = 0.47, p < .05), openness to values (d = 0.45, p < .05) and ideas (d = 0.40, p < .05), trust (d = 0.44, p < .05), and altruism (d = 0.40, p < .05). Oxytocin had no influence on ratings of negative emotionality, conscientiousness, rejection sensitivity, depression, worry, self-esteem, and perceived social support.

CONCLUSION

The administration of oxytocin improved participants’ self-perceptions of their personality, at least for certain traits important for social affiliation. Increased positive self-referential processing may be one mechanism by which oxytocin promotes positive social behaviors.

http://www.ncbi.nlm.nih.gov/pubmed/22012170#

Sports Performance

Oxytocin and the biopsychology of performance in team sports.

Abstract 

Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is related to biopsychological processes aimed at convergence of emotions and moods between people, and in doing so it is a critical neuropeptide involved in the shaping of important team processes in sport such as trust, generosity, altruism, cohesion, cooperation, and social motivation, and also envy and gloating. Future research should examine the role of oxytocin in these essential components of sport performance. In particular, the link between oxytocin, emotional contagion and the cultivation of experiences of positive emotions is a worthwhile line of investigation for sport participation and development as well as high performance in sports.

http://www.ncbi.nlm.nih.gov/pubmed/22997498