pituitrin and Autism-Spectrum-Disorder

Oxytocin and vasopressin are peptide hormones secreted from the pituitary that are well known for their peripheral endocrine effects on childbirth/nursing and blood pressure/urine concentration, respectively. However, both peptides are also released in the brain, where they modulate several aspects of social behaviors. Oxytocin promotes maternal nurturing and bonding, enhances social reward, and increases the salience of social stimuli. Vasopressin modulates social communication, social investigation, territorial behavior, and aggression, predominantly in males. Both peptides facilitate social memory and pair bonding behaviors in monogamous species. Here we review the latest research delineating the neural circuitry of the brain oxytocin and vasopressin systems and summarize recent investigations into the circuit-based mechanisms modulating social behaviors. We highlight research using modern molecular genetic technologies to map, monitor activity of, or manipulate neuropeptide circuits. Species diversity in oxytocin and vasopressin effects on social behaviors are also discussed. We conclude with a discussion of the translational implications of oxytocin and vasopressin for improving social functioning in disorders with social impairments, such as autism spectrum disorder.

Topics: Animals; Autism Spectrum Disorder; Humans; Male; Oxytocin; Pair Bond; Receptors, Oxytocin; Social Behavior; Vasopressins

Oxytocin and vasopressin systems have been studied separately in autism spectrum disorder (ASD). Here, we provide evidence from an evolutionary and neuroscience perspective about the shared mechanisms and the common roles in regulating social behaviors. We first discuss findings on the evolutionary history of oxytocin and vasopressin ligands and receptors that highlight their common origin and clarify the evolutionary background of the crosstalk between them. Second, we conducted a comprehensive review of the increasing evidence for the role of both neuropeptides in regulating social behaviors. Third, we reviewed the growing evidence on the associations between the oxytocin/vasopressin systems and ASD, which includes oxytocin and vasopressin dysfunction in animal models of autism and in human patients, and the impact of treatments targeting the oxytocin or the vasopressin systems in children and in adults. Here, we highlight the potential of targeting the oxytocin/vasopressin systems to improve social deficits observed in ASD and the need for further investigations on how to transfer these research innovations into clinical applications.

Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Humans; Oxytocin; Social Behavior; Vasopressins

Two clinical trials targeting the vasopressin pathway in autism highlight continuing challenges in outcome measures and statistical power.

Topics: Adaptation, Psychological; Autism Spectrum Disorder; Autistic Disorder; Humans; Male; Receptors, Vasopressin; Vasopressins

Although the neurohypophyseal hormones vasopressin (VP) and oxytocin (OT) are mostly known for their role respectively in antidiuresis, and in labour, lactation and maternal behavior, both might exert widespread influences either on emotion and cognition in healthy subjects, showing some gender-related differences. They interact with each other facilitating shifts between positive socially- oriented and defensive states. In fact, VP amplifies the reactivity to stressors showing also beneficial effects on attention, verbal learning as well as memory, whereas OT reduces the amplitude of the stress response, improves emotion processing, and can play a negative effect on memory and verbal learning in healthy individuals. Several data indicate the possible involvement of these neuropeptides in the pathophysiology of psychiatric conditions involving social interactions, such as autism, as well as in schizophrenia and depression. The aim of this paper is to review the literature relating to the role played by neurohypophyseal hormones in neuropsychiatric disorders.. We analyzed the best of published literature dealing with the relationships between neurohypophyseal hormones and neuropsychiatric conditions like autism (AD), major depressive disorder (MDD), bipolar disorder (BD) and schozophrenia, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on December 2017.. Several studies indicate a role played by OT and VP in AD, schizophrenia, MDD and BD. Even if conflicting data have been reported, several mechanisms may be involved in these behavioral diseases, such as differences in aminoacid sequence and peptide biological activity, neurotransmission and genetic disorders involving OT and VP receptors.. The involvment of VP and OT in neurpopsychiatric disorders can support a possible beneficial therapy with OT or with VP antagonists. The target may be obtained using effective drug delivery methods as well as the association with other drugs.

Topics: Affect; Animals; Autism Spectrum Disorder; Bipolar Disorder; Depressive Disorder, Major; Humans; Mental Disorders; Oxytocin; Pituitary Gland, Posterior; Schizophrenia; Schizophrenic Psychology; Signal Transduction; Vasopressins

Autism spectrum disorder is defined by two core symptoms: a deficit in social communication and the presence of repetitive behaviors and/or restricted interests. Currently, there is no US Food and Drug Administration-approved drug for these core symptoms. This article reviews the biological origins of the social function deficit associated with autism spectrum disorder and the drug therapies with the potential to treat this deficit. A review of the history of autism demonstrates that a deficit in social interaction has been the defining feature of the concept of autism from its conception. Abnormalities identified in early social skill development and an overview of the pathophysiology abnormalities associated with autism spectrum disorder are discussed as are the abnormalities in brain circuits associated with the social function deficit. Previous and ongoing clinical trials examining agents that have the potential to improve social deficits associated with autism spectrum disorder are discussed in detail. This discussion reveals that agents such as oxytocin and propranolol are particularly promising and undergoing active investigation, while other agents such as vasopressin agonists and antagonists are being activity investigated but have limited published evidence at this time. In addition, agents such as bumetanide and manipulation of the enteric microbiome using microbiota transfer therapy appear to have promising effects on core autism spectrum disorder symptoms including social function. Other pertinent issues associated with developing treatments in autism spectrum disorder, such as disease heterogeneity, high placebo response rates, trial design, and the most appropriate way of assessing effects on social skills (outcome measures), are also discussed.

Topics: Autism Spectrum Disorder; Bumetanide; Disease Progression; Fecal Microbiota Transplantation; Humans; Social Behavior Disorders; Social Skills; Sodium Potassium Chloride Symporter Inhibitors; Vasopressins

Autism Spectrum Disorders (ASD) are characterized by: social and communication impairments, and by restricted repetitive behaviors. The aim of the present paper is to review abnormalities of oxytocin (OXT) and related congenital malformations in ASD. A literature search was conducted in the PubMed database up to 2016 for articles related to the pathomechanism of ASD, abnormalities of OXT and the OXT polymorphism in ASD. The pathomechanism of ASD has yet to be. The development of ASD is suggested to be related to abnormalities of the oxytocin-arginin-vasopressin system. Previous results suggest that OXT and arginine vasopressin (AVP) may play a role in the etiopathogenesis of ASD.

Topics: Autism Spectrum Disorder; Female; Folic Acid; Humans; Infant, Low Birth Weight; Infant, Newborn; Male; Neurophysins; Polymorphism, Single Nucleotide; Pregnancy; Premature Birth; Prenatal Exposure Delayed Effects; Protein Precursors; Receptors, Oxytocin; Vasopressins

The motivation to engage in social behaviors is influenced by past experience and internal state, but also depends on the behavior of other animals. Across species, the oxytocin (Oxt) and vasopressin (Avp) systems have consistently been linked to the modulation of motivated social behaviors. However, how they interact with other systems, such as the mesolimbic dopamine system, remains understudied. Further, while the neurobiological mechanisms that regulate prosocial/cooperative behaviors have been extensively examined, far less is understood about competitive behaviors, particularly in females. In this chapter, we highlight the specific contributions of Oxt and Avp to several cooperative and competitive behaviors and discuss their relevance to the concept of social motivation across species, including humans. Further, we discuss the implications for neuropsychiatric diseases and suggest future areas of investigation.

Topics: Aggression; Animals; Autism Spectrum Disorder; Behavior, Animal; Brain; Competitive Behavior; Cooperative Behavior; Dopamine; Female; Humans; Mental Disorders; Motivation; Oxytocin; Pair Bond; Personality Disorders; Schizophrenia; Schizophrenic Psychology; Social Behavior; Stress Disorders, Post-Traumatic; Vasopressins

The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using a double-blind, randomized, placebo-controlled, parallel study design, we tested the efficacy and tolerability of a 4-week intranasal AVP daily treatment in 30 children with ASD. AVP-treated participants aged 6 to 9.5 years received the maximum daily target dose of 24 International Units (IU); participants aged 9.6 to 12.9 years received the maximum daily target dose of 32 IU. Intranasal AVP treatment compared to placebo enhanced social abilities as assessed by change from baseline in this phase 2 trial's primary outcome measure, the Social Responsiveness Scale, 2nd Edition total score (SRS-2

Topics: Administration, Intranasal; Autism Spectrum Disorder; Child; Female; Humans; Male; Pilot Projects; Placebos; Social Behavior; Treatment Outcome; Vasopressins

Joint attention (JA) is an important milestone in human infant development and is predictive of the onset of language later in life. Clinically, it has been reported that children at risk for or with a diagnosis of autism spectrum disorder (ASD) perform more poorly on measures of JA compared to neurotypical controls. JA is not unique to humans but has also been reported in great apes and to a lesser extent in more distantly related monkeys. Further, individual differences in JA among chimpanzees are associated with polymorphisms in the vasopressin and oxytocin genes, AVPR1A and OXTR. Here, we tested whether individual variation in DNA methylation of OXTR and AVPR1A were associated with performance on JA tasks in chimpanzees. We found that individual differences in JA performance was associated with AVPR1A methylation, but not OXTR methylation in the chimpanzees. The collective results provide further evidence of the role of AVPR1A in JA abilities in chimpanzees. The results further suggest that methylation values for AVPR1A may be useful biomarkers for identifying individuals at risk for ASD or related neurodevelopmental disorders associated with impairments in JA abilities.

Topics: Animals; Attention; Autism Spectrum Disorder; Child; Humans; Individuality; Methylation; Oxytocin; Pan troglodytes; Receptors, Vasopressin; Social Behavior; Vasopressins

Topics: Autism Spectrum Disorder; Humans; Vasopressins

Topics: Arginine Vasopressin; Autism Spectrum Disorder; Autistic Disorder; Biomarkers; Female; Humans; Infant; Infant, Newborn; Male; Medical Records; Neuropeptides; Neurophysins; Oxytocin; Prospective Studies; Protein Precursors; Social Behavior; Vasopressins

Evidence supports the notion that autistic symptoms and behaviors should be regarded as dimensional traits. The present study aimed to investigate the role of vasopressin (AVP), brain-derived neurotrophic factor (BDNF) and oxytocin (OXT) as potential biochemical correlates of subclinical autistic traits in a cohort of healthy young adults. One hundred and fifty-three subjects (80 males, 73 females) were recruited. Participants completed the Autism Spectrum Quotient (AQ), a widely used measure for the identification of autistic traits in the general population. Additionally, blood samples were obtained from all participants at the same time of the day to control for circadian variation. We conducted a multiple regression analysis using the AQ score as the dependent variable and age, sex, AVP, BDNF and OXT levels as the independent variables. The model explained approximately the 22% of the variance of the AQ score. Among the parameters included in the analysis, only BDNF levels were independent predictors of AQ score.

Topics: Adult; Autism Spectrum Disorder; Autistic Disorder; Biomarkers; Brain-Derived Neurotrophic Factor; Female; Humans; Male; Oxytocin; Regression Analysis; Vasopressins; Young Adult

Brain arginine vasopressin (AVP) critically regulates normative social behavior in mammals, and experimental disruption of the AVP signaling pathway produces social impairments in rodent models. We therefore hypothesized that AVP signaling deficits may contribute to social impairments in children with autism spectrum disorder (ASD). Since blood measures (which are far easier to obtain than brain measures) of AVP are most meaningful if they are related to brain AVP activity, Study 1 tested the relationship between AVP concentrations in concomitantly collected blood and CSF samples from children and adults (N = 28) undergoing clinical procedures. Study 2 tested whether blood AVP concentrations: 1) differed between children with ASD (N = 57), their ASD discordant siblings (N = 47), and neurotypical controls (N = 55); and 2) predicted social functioning (using the NEPSY-II Theory of Mind and Affect Recognition tasks and the Social Responsiveness Scale) in this large, well-characterized child cohort. Blood AVP concentrations significantly and positively predicted CSF AVP concentrations (F1,26 = 7.17, r = 0.46, p = 0.0127) in Study 1. In Study 2, blood AVP concentrations did not differ between groups or by sex, but significantly and positively predicted Theory of Mind performance, specifically in children with ASD, but not in non-ASD children (F1,144 = 5.83, p = 0.017). Blood AVP concentrations can be used: 1) as a surrogate for brain AVP activity in humans; and 2) as a robust biomarker of theory of mind ability in children with ASD. These findings also suggest that AVP biology may be a promising therapeutic target by which to improve social cognition in individuals with ASD.

Topics: Adolescent; Adult; Autism Spectrum Disorder; Biomarkers; Brain; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Neurophysins; Protein Precursors; Siblings; Social Behavior; Vasopressins; Young Adult