oxytocin and Phobic-Disorders

The neuropeptide oxytocin (OXT) has been revealed as a profound anxiolytic and antistress factor of the brain, besides its many prosocial and reproductive effects. Therefore, there is substantial scientific and medical interest in its potential therapeutic use for the treatment of psychopathologies associated with anxiety, fear, and social dysfunctions, such as generalized anxiety disorder, posttraumatic stress disorder, and social anxiety disorder, as well as autism and schizophrenia, among others. Focusing on preclinical studies, we review the existing evidence for the regulatory capacity of OXT to fine-tune general and social anxiety-related behaviors, as well as cued and social fear conditioning from a translational perspective. The available evidence from animal and human studies substantiates the hypothesis of an imbalance of the endogenous brain OXT system in the etiology of anxiety disorders, particularly those with a social component such as social anxiety disorder. In addition, such an imbalance of the OXT system is also likely to be the consequence of chronic OXT treatment resulting in a dose-dependent reduction in OXT receptor availability and increased anxiety.

Topics: Anxiety; Fear; Humans; Oxytocin; Phobic Disorders; Social Behavior

The popularity of oxytocin (OT) has grown exponentially during the past decade, and so has the number of OT trials in healthy and clinical groups. We take stock of the evidence from these studies to explore potentials and limitations of pharmacotherapeutic applications. In healthy participants, intranasally administered OT leads to better emotion recognition and more trust in conspecifics, but the effects appear to be moderated by context (perceived threat of the 'out-group'), personality and childhood experiences. In individuals with untoward childhood experiences, positive behavioral or neurobiological effects seem lowered or absent. In 19 clinical trials, covering autism, social anxiety, postnatal depression, obsessive-compulsive problems, schizophrenia, borderline personality disorder and post-traumatic stress, the effects of OT administration were tested, with doses ranging from 15 IU to more than 7000 IU. The combined effect size was d=0.32 (N=304; 95% confidence interval (CI): 0.18-0.47; P<0.01). However, of all disorders, only studies on autism spectrum disorder showed a significant combined effect size (d=0.57; N=68; 95% CI: 0.15-0.99; P<0.01). We hypothesize that for some of the other disorders, etiological factors rooted in negative childhood experiences may also have a role in the diminished effectiveness of treatment with OT.

Topics: Administration, Intranasal; Anti-Anxiety Agents; Anxiety; Child; Child Development Disorders, Pervasive; Depression; Humans; Mental Disorders; Oxytocin; Personality Disorders; Phobic Disorders; Schizophrenia; Stress Disorders, Post-Traumatic; Trust

Oxytocin and vasopressin are regulators of anxiety, stress-coping, and sociality. They are released within hypothalamic and limbic areas from dendrites, axons, and perikarya independently of, or coordinated with, secretion from neurohypophysial terminals. Central oxytocin exerts anxiolytic and antidepressive effects, whereas vasopressin tends to show anxiogenic and depressive actions. Evidence from pharmacological and genetic association studies confirms their involvement in individual variation of emotional traits extending to psychopathology. Based on their opposing effects on emotional behaviors, we propose that a balanced activity of both brain neuropeptide systems is important for appropriate emotional behaviors. Shifting the balance between the neuropeptide systems towards oxytocin, by positive social stimuli and/or psychopharmacotherapy, may help to improve emotional behaviors and reinstate mental health.

Topics: Adaptation, Psychological; Administration, Intranasal; Animals; Anxiety; Brain Chemistry; Depression; Emotions; Female; Homeostasis; Humans; Hypothalamus; Lactation; Limbic System; Male; Models, Biological; Oxytocin; Phobic Disorders; Polymorphism, Single Nucleotide; Pregnancy; Receptors, Oxytocin; Receptors, Vasopressin; Reproduction; Rodentia; Social Behavior; Vasopressins

Animal studies point to the role of two neuropeptides-oxytocin and vasopressin-in the regulation of affiliative behaviors including mating, pair-bond formation, maternal/parenting behavior, and attachment. These findings may have important implications for understanding and treating clinical disorders marked by social deficits and/or disrupted attachment. This review focuses on advances made to date in the effort to forge links between basic and clinical research in the area of neuropeptides and social behavior. The literature on oxytocin and its involvement in stress response, affiliation, and prosocial behavior is reviewed, and the implications of these findings for such disorders as autism as well as other social and stress-related disorders including social phobia, post-traumatic stress disorder, and some personality disorders are considered. Finally, unresolved issues and directions for future research are discussed.

Topics: Animals; Autistic Disorder; Humans; Oxytocin; Personality Disorders; Phobic Disorders; Social Behavior; Stress Disorders, Post-Traumatic; Stress, Psychological; Vasopressins

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.. 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 randomized, double-blind, and placebo controlled (n = 13 placebo, 11 females; n = 10 OT, 8 females) with 1-week and 1-month follow-up assessments. Dependent measures attended to arachnophobia symptoms (self-report), phobic behavior (behavioral avoidance of spider task), and treatment credibility/therapeutic alliance.. 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.. These results suggest that OT administration effects on extinction may vary depending on conditions and population.

Topics: Administration, Intranasal; Adult; Animals; Combined Modality Therapy; Double-Blind Method; Fear; Female; Humans; Implosive Therapy; Male; Mental Processes; Middle Aged; Oxytocin; Phobic Disorders; Premedication; Spiders; Treatment Outcome

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 randomized, double-blind, crossover trial, we gave male psychiatric outpatients 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 populations and contexts, 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.

Topics: Adult; Affect; Antidepressive Agents; Anxiety; Behavior; Cognition; Depressive Disorder; Double-Blind Method; Humans; Hydrocortisone; Interview, Psychological; Male; Middle Aged; Neuropsychological Tests; Oxytocin; Phobic Disorders; Psychotherapy; Saliva; Social Behavior; Surveys and Questionnaires; Theory of Mind; Young Adult

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 randomized, 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.

Topics: Administration, Intranasal; Adult; Aged; Anxiety; Desensitization, Psychologic; Humans; Male; Middle Aged; Oxytocin; Phobic Disorders; Placebos; Psychological Distance; Social Behavior Disorders; Speech; Task Performance and Analysis

Social soft robotics may provide a new solution for alleviating human pain and fear. Here, we introduce a hand-held soft robot that can be clenched by the wearer. The robot comprises small airbags that can be inflated to provide the wearer with a feeling of being clenched. We then conducted an in-depth study of 66 adults who participated in a pain research protocol using thermal stimulation to investigate the effect of wearing the robot on pain perception and fear of injections. Pain assessment scale scores for perceived pain decreased significantly [Formula: see text] when participants wore the robot compared with the baseline condition in which the robot was not worn. In addition, the saliva test results showed a downward trend in oxytocin level when the robot provided the wearer with haptic feedback via the inflation of the internal airbags in response to the wearer's clench. Furthermore, the negative psychological state of participants, as measured using the positive and negative affect scale, improved significantly when wearing the robot. We also revealed that the salivary cortisol level, an indicator of stress, decreased significantly across all participants at the end of the experiment. In addition, participants' fear of injections was significantly improved after participation in the experiment. These results suggest that the wearable soft robot may alleviate the human perception of pain and fear in during medical treatments, such as vaccinations.

Topics: Adult; Fear; Humans; Hydrocortisone; Oxytocin; Pain; Phobic Disorders; Robotics; Wearable Electronic Devices

The neuropeptides oxytocin (OT) and arginine-vasopressin (AVP) have been implicated in modulating sex-specific responses to offspring in a variety of uniparental and biparental rodent species. Despite the large body of research in rodents, the effects of these hormones in biparental primates are less understood. Marmoset monkeys (Callithrix jacchus) belong to a clade of primates with a high incidence of biparental care and also synthesize a structurally distinct variant of OT (proline instead of leucine at the 8th amino acid position; Pro(8)-OT). We examined the roles of the OT and AVP systems in the control of responses to infant stimuli in marmoset monkeys. We administered neuropeptide receptor agonists and antagonists to male and female marmosets, and then exposed them to visual and auditory infant-related and control stimuli. Intranasal Pro(8)-OT decreased latencies to respond to infant stimuli in males, and intranasal AVP decreased latencies to respond to infant stimuli in females. Our study is the first to demonstrate that Pro(8)-OT and AVP alter responsiveness to infant stimuli in a biparental New World monkey. Across species, the effects of OT and AVP on parental behavior appear to vary by species-typical caregiving responsibilities in males and females.

Topics: Acoustic Stimulation; Animals; Arginine Vasopressin; Callithrix; Female; Male; Maternal Behavior; Motor Activity; Oxytocin; Paternal Behavior; Phobic Disorders; Social Behavior; Stress, Psychological; Vocalization, Animal

Oxytocin, an octapeptide synthesized in the hypothalamus, stimulates milk election and uterine contractions. In the brain this hormone acts as a neuropeptide. It could inhibit through the GABAergic system the activity of limbic amygdala, which is involved in the response to fear. Oxytocin could also induce the protective behaviour of the mother towards its offspring through the dopaminergic system. In mankind, oxytocin plays a role in trust, empathy, generosity, stress and sexuality. Clinical studies are testing potential benefits of oxytocin administration in autism, depression and social phobia. Results are still preliminary.

Topics: Autistic Disorder; Humans; Love; Mental Disorders; Object Attachment; Oxytocics; Oxytocin; Phobic Disorders

Generalized Social Anxiety Disorder (GSAD) is characterized by excessive fear and avoidance of several types of social and performance situations. The pathophysiology is not well understood, but research in animals and humans has provided evidence that oxytocin helps regulate normal social affiliative behavior. Previous work in healthy male subjects demonstrated a rise in plasma oxytocin after receiving a high trust signal. To examine the oxytocin system in GSAD, we measured plasma oxytocin in GSAD patients and controls, before and after the social "Trust Game," a neuroeconomic test examining trust behavior and reaction to trust using real monetary incentives.. Thirty-nine subjects with GSAD and 28 healthy controls provided three blood samples for oxytocin measurement before the Trust Game, and one sample after the game. Plasma estradiol was also measured at baseline. The Trust Game protocol version prioritized the sending of a signal of high cooperation and trust to all participants. All analyses controlled for gender and estradiol levels.. Mean oxytocin levels post-Trust Game (P = .025), and overall (area under the curve, P = .011) were lower in GSADpatients compared to controls, after controlling for sex and estradiol. There was no significant change in oxytocin levels after the game in either group.. We report low plasma oxytocin levels in patients with GSAD during a prosocial laboratory task paradigm. Additional research will be important to further examine the relationship between oxytocin and social behavior in GSAD.

Topics: Adult; Case-Control Studies; Cooperative Behavior; Estradiol; Female; Humans; Interpersonal Relations; Male; Middle Aged; Oxytocin; Phobic Disorders; Social Behavior; Trust

Oxytocin is a neuropeptide recently associated with social behavior in animals and humans, but the study of its function in populations with social deficits such as autism, schizophrenia, and social anxiety disorder has only recently begun. We measured plasma oxytocin in 24 patients with Generalized Social Anxiety Disorder (GSAD) and 22 healthy controls using an enzyme-linked immunosorbent assay. There were no significant differences in oxytocin level (pg/mL) between patients (M=163.0, SD=109.4) and controls (M=145.0, SD=52.9, z=0.21, P=0.8). Within the GSAD sample, however, higher social anxiety symptom severity adjusted for age and gender was associated with higher oxytocin level (R2=0.21, beta=0.014, SE=0.006, t=2.18, P=0.04). In addition, dissatisfaction with social relationships was associated with higher oxytocin levels (R2=0.18, beta=-0.20, SE=0.10, t=-2.01, P=0.05). Our data provide preliminary support for a link between social anxiety severity and plasma oxytocin. These findings may suggest a possible role for oxytocin as a facilitator of social behavior, an effect which may not be fully utilized in individuals with severe social anxiety.

Topics: Adult; Age Factors; Case-Control Studies; Female; Humans; Male; Middle Aged; Oxytocin; Phobic Disorders; Reference Values; Severity of Illness Index; Sex Factors; Social Behavior; Social Environment

Topics: Amygdala; Fear; Humans; Oxytocin; Phobic Disorders