-
Dialogues in Clinical Neuroscience Jun 2017Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive... (Review)
Review
Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive behavioral therapy, selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors, benzodiazepines) exist for social anxiety, they are effective for only 60% to 70% of patients. Thus, researchers have looked for other candidates for social anxiety treatment. Our review focuses on the peptide oxytocin as a potential therapeutic option for individuals with social anxiety. Animal research both in nonprimates and primates supports oxytocin's role in facilitation of prosocial behaviors and its anxiolytic effects. Human studies indicate significant associations between social anxiety and oxytocin receptor gene alleles, as well as social anxiety and oxytocin plasma levels. In addition, intranasal administration of oxytocin in humans has favorable effects on social anxiety symptomology. Other disorders, including autism, schizophrenia, and anorexia, have components of social anxiety in their pathophysiology. The therapeutic role of oxytocin for social dysfunction in these disorders is discussed.
Topics: Administration, Intranasal; Animals; Anti-Anxiety Agents; Fear; Humans; Oxytocin; Phobia, Social
PubMed: 28867943
DOI: 10.31887/DCNS.2017.19.2/cjones -
Pharmacology, Biochemistry, and Behavior Apr 2014The hypothalamic neuropeptide oxytocin has drawn the attention of scientists for more than a century. The understanding of the function of oxytocin has expanded... (Review)
Review
The hypothalamic neuropeptide oxytocin has drawn the attention of scientists for more than a century. The understanding of the function of oxytocin has expanded dramatically over the years from a simple peptide adept at inducing uterine contractions and milk ejection to a complex neuromodulator with a capacity to shape human social behavior. Decades of research have outlined oxytocin's ability to enhance intricate social activities ranging from pair bonding, sexual activity, affiliative preferences, and parental behaviors. The precise neural mechanisms underlying oxytocin's influence on such behaviors have just begun to be understood. Research suggests that oxytocin interacts closely with the neural pathways responsible for processing motivationally relevant stimuli. In particular, oxytocin appears to impact dopaminergic activity within the mesocorticolimbic dopamine system, which is crucial not only for reward and motivated behavior but also for the expression of affiliative behaviors. Though most of the work performed in this area has been done using animal models, several neuroimaging studies suggest similar relationships may be observed in humans. In order to introduce this topic further, this paper will review the recent evidence that oxytocin may exert some of its social-behavioral effects through its impact on motivational networks.
Topics: Animals; Behavior, Animal; Dopamine; Motivation; Oxytocin; Social Behavior
PubMed: 23850525
DOI: 10.1016/j.pbb.2013.06.011 -
Pharmacological Reviews Oct 2020Oxytocin is a pleiotropic, peptide hormone with broad implications for general health, adaptation, development, reproduction, and social behavior. Endogenous oxytocin... (Review)
Review
Oxytocin is a pleiotropic, peptide hormone with broad implications for general health, adaptation, development, reproduction, and social behavior. Endogenous oxytocin and stimulation of the oxytocin receptor support patterns of growth, resilience, and healing. Oxytocin can function as a stress-coping molecule, an anti-inflammatory, and an antioxidant, with protective effects especially in the face of adversity or trauma. Oxytocin influences the autonomic nervous system and the immune system. These properties of oxytocin may help explain the benefits of positive social experiences and have drawn attention to this molecule as a possible therapeutic in a host of disorders. However, as detailed here, the unique chemical properties of oxytocin, including active disulfide bonds, and its capacity to shift chemical forms and bind to other molecules make this molecule difficult to work with and to measure. The effects of oxytocin also are context-dependent, sexually dimorphic, and altered by experience. In part, this is because many of the actions of oxytocin rely on its capacity to interact with the more ancient peptide molecule, vasopressin, and the vasopressin receptors. In addition, oxytocin receptor(s) are epigenetically tuned by experience, especially in early life. Stimulation of G-protein-coupled receptors triggers subcellular cascades allowing these neuropeptides to have multiple functions. The adaptive properties of oxytocin make this ancient molecule of special importance to human evolution as well as modern medicine and health; these same characteristics also present challenges to the use of oxytocin-like molecules as drugs that are only now being recognized. SIGNIFICANCE STATEMENT: Oxytocin is an ancient molecule with a major role in mammalian behavior and health. Although oxytocin has the capacity to act as a "natural medicine" protecting against stress and illness, the unique characteristics of the oxytocin molecule and its receptors and its relationship to a related hormone, vasopressin, have created challenges for its use as a therapeutic drug.
Topics: Animals; Humans; Oxytocin
PubMed: 32912963
DOI: 10.1124/pr.120.019398 -
The Neuroscientist : a Review Journal... Dec 2021Humans are an unusually prosocial species, who engage in social behaviors that include altruism-whereby an individual engages in costly or risky acts to improve the... (Review)
Review
Humans are an unusually prosocial species, who engage in social behaviors that include altruism-whereby an individual engages in costly or risky acts to improve the welfare of another person-care, and cooperation. Current perspectives on the neurobiology of human prosociality suggest that it is deeply rooted in the neuroendocrine architecture of the social brain and emphasize the modulatory role of the neuropeptide hormone oxytocin. In this review, we provide a conceptual overview of the neurobiology of prosocial behavior with a focus on oxytocin's modulatory role in human prosociality. Specifically, we aim to encourage a better understanding of the peptide's susceptibility to diverse factors that produce heterogeneity in outcomes and the resulting methodological implications for measuring the behavioral effects of oxytocin in humans. After providing an overview of the state-of-the-art research on oxytocin's exogenous use, we elaborate on the peptide's modulatory role in the context of care-based altruism, cooperation, and conflict and discuss its potential for therapeutic interventions in psychiatric disorders characterized by social dysfunction.
Topics: Altruism; Humans; Mental Disorders; Oxytocin; Social Behavior
PubMed: 32981445
DOI: 10.1177/1073858420960111 -
The New England Journal of Medicine Oct 2021Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder.
METHODS
We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ.
RESULTS
Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups.
CONCLUSIONS
This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).
Topics: Administration, Intranasal; Adolescent; Autism Spectrum Disorder; Child; Child, Preschool; Double-Blind Method; Female; Humans; Least-Squares Analysis; Male; Oxytocin; Social Behavior; Social Skills; Treatment Failure
PubMed: 34644471
DOI: 10.1056/NEJMoa2103583 -
Science Translational Medicine Jan 2015Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of...
Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homolog of CNTNAP2 (contactin-associated protein-like 2), in which mutations cause cortical dysplasia and focal epilepsy (CDFE) syndrome, displays many features that parallel those of the human disorder. Because CDFE has high penetrance for autism spectrum disorder (ASD), we performed an in vivo screen for drugs that ameliorate abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment to rectify this deficit.
Topics: Animals; Animals, Newborn; Autistic Disorder; Behavior, Animal; Disease Models, Animal; Humans; Membrane Proteins; Mice, Knockout; Mice, Mutant Strains; Nerve Tissue Proteins; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Social Behavior
PubMed: 25609168
DOI: 10.1126/scitranslmed.3010257 -
Anaesthesia Oct 2019It is routine to give a uterotonic drug following delivery of the neonate during caesarean section. However, there is much heterogeneity in the relevant research, which...
It is routine to give a uterotonic drug following delivery of the neonate during caesarean section. However, there is much heterogeneity in the relevant research, which has largely been performed in low-risk elective cases or women with uncomplicated labour. This is reflected in considerable variation in clinical practice. There are significant differences between dose requirements during elective and intrapartum caesarean section. Standard recommended doses are higher than required, with the potential for acute cardiovascular adverse effects. We recommend a small initial bolus dose of oxytocin, followed by a titrated infusion. The recommended doses of oxytocin may have to be increased in women with risk factors for uterine atony. Carbetocin at equipotent doses to oxytocin has similar actions, while avoiding the requirement for a continuous infusion after the initial dose and reducing the need for additional uterotonics. As with oxytocin, carbetocin dose requirements are higher for intrapartum caesarean sections. A second-line agent should be considered early if oxytocin/carbetocin fails to produce good uterine tone. Women with cardiac disease may be very sensitive to the adverse effects of oxytocin and other uterotonics, and their management needs to be individualised.
Topics: Adult; Cesarean Section; Consensus; Female; Guidelines as Topic; Humans; Infant, Newborn; Oxytocics; Oxytocin; Pregnancy
PubMed: 31347151
DOI: 10.1111/anae.14757 -
Medicine Nov 2019To evaluate the efficacy and safety of carbetocin for prevention of postpartum hemorrhage in women undergoing vaginal delivery compared with oxytocin. (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of carbetocin for prevention of postpartum hemorrhage in women undergoing vaginal delivery compared with oxytocin.
METHODS
We conducted a systemic literature search in PubMed, the Cochrane Library, and Embase without language restrictions from inception of each of database to November 18th, 2018. Randomized controlled trials with outcome measure of blood loss ≥500 ml were eligible if they compared carbetocin with oxytocin to prevent postpartum hemorrhage during the third stage of labor in women undergoing vaginal delivery.
RESULTS
This meta-analysis of 5 randomized controlled trials (30,314 women) indicated that there was no significant difference between carbetocin and oxytocin in blood loss ≥500 ml in women undergoing vaginal delivery (relative risks (RRs), 0.52; 95% confidence intervals (CIs), 0.24 to 1.15; P = .11; I = 69%). Sensitivity analyses showed the same results. No significant differences were found in blood loss ≥1000 ml, use of additional uterotonic agents, blood transfusion, uterine massage, flushing, vomiting, abdominal pain, nausea, dizziness, headache, palpitation, itching, and shivering.
CONCLUSIONS
This meta-analysis showed that carbetocin was as effective and safe as oxytocin for prevention of postpartum hemorrhage in women undergoing vaginal delivery, and the choice of carbetocin for routine prophylaxis will depend on cost-effectiveness.
Topics: Delivery, Obstetric; Female; Humans; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31764790
DOI: 10.1097/MD.0000000000017911 -
Anaesthesia Aug 2022Carbetocin or oxytocin are given routinely as first-line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage....
Carbetocin or oxytocin are given routinely as first-line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage. Low doses may be as effective as high doses with a potential reduction in adverse effects. In this double-blind, randomised, controlled, non-inferiority trial, we assigned low-risk patients undergoing elective caesarean delivery under spinal anaesthesia to one of four groups: carbetocin 20 μg; carbetocin 100 μg; oxytocin 0.5 IU bolus + infusion; and oxytocin 5 IU bolus + infusion. The study drug was given intravenously after delivery of the neonate. Uterine tone was assessed by the obstetrician 2, 5 and 10 minutes after study drug administration according to an 11-point verbal numerical rating scale (0 = atonic, 10 = excellent tone). The primary outcome measure was uterine tone 2 min after study drug administration. The pre-specified non-inferiority margin was 1.2 points on the 11-point scale. Secondary outcomes included uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects. Data were available for 277 patients. Carbetocin 20 μg resulting in uterine tone of (median (IQR [range])) 8 (7-8 [1-10]) was non-inferior to carbetocin 100 μg with tone 8 (7-9 [3-10]), median (95%CI) difference 0 (-0.44-0.44). Similarly, oxytocin 0.5 IU with tone 7 (6-8 [3-10]) was non-inferior to oxytocin 5 IU with tone 8 (6-8 [2-10]), median (95%CI) difference 1 (0.11-1.89). Carbetocin 20 μg was also non-inferior to oxytocin 5 IU, and oxytocin 0.5 IU was non-inferior to carbetocin 100 μg. Uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects were similar in all groups.
Topics: Cesarean Section; Double-Blind Method; Female; Humans; Infant, Newborn; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy
PubMed: 35343585
DOI: 10.1111/anae.15714 -
Hormones and Behavior Mar 2012
Topics: Animals; Autistic Disorder; Biological Evolution; Brain Chemistry; Cognition; Humans; Maternal Behavior; Oxytocin; Receptor Cross-Talk; Receptors, Oxytocin; Receptors, Vasopressin; Social Behavior; Substance-Related Disorders; Vasopressins
PubMed: 22443808
DOI: 10.1016/j.yhbeh.2012.02.019