Human emotional behavioral systems – oxytocin
A study, published on June 12, 2012, in PLoS One, provides perhaps the first evidence that oxytocin and vasopressin are both dysregulated in Williams syndrome.
According to Li Dai et al., the authors of the PLoS One study:
Social and emotional responses are so fundamental to human behavior that they are often taken for granted.
The genetic and neurobiological bases of social behavior are largely unknown as are the mechanisms for disruptions in social behavior and emotional regulation that appear throughout the lifespan as features of mental illnesses.
Recent evidence indicates, however, that human emotion and social behavior are linked to neuroendocrine function, and two hypothalamic neuropeptides, oxytocin (OT) and arginine vasopressin (AVP) appear to regulate reproduction, social behaviors and emotionality in mammals.
Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Oxytocin is released into the bloodstream as a hormone in response to sexual activity and during labour. The uterine-contracting properties of the principle that would later be named oxytocin were discovered by British pharmacologist Sir Henry Dale in 1906, and is best known for its role in inducing labor and lactation. In the 1920s, oxytocin and vasopressin were isolated from pituitary tissue and given their current names.
Oxytocin both stimulates the muscles of the uterus to contract, and boosts the production of prostaglandins, which also increase uterine contractions. Women whose labor is slow to proceed are sometimes given oxytocin to speed the process. Once the baby is born, oxytocin helps to move milk from the ducts in the breast to the nipple, and foster a bond between mom and baby. Our bodies also produce oxytocin when we’re excited by our sexual partner, and when we fall in love. That’s why it has earned the nicknames, “love hormone” and “cuddle hormone.”
More recent research indicates that it is involved in a wide variety of physiological functions.
In humans, exposure to exogenous OT has been related to enhanced trust, emotional empathy, increased and direct eye gaze, maternal behavior, social recognition, social bonding and the establishment of early bonding, and increased generosity. Also low levels of oxytocin have been linked with anxiety in children and reported in women with depression.
Williams Syndrome (WS) is a neurodevelopmental disorder characterized by profound disturbances in social relationships. Resulting from a hemizygous deletion of ~25 genes on chromosome 7q11.23, a unique and robust behavioral characteristic of WS is an increased social drive particularly toward strangers, manifesting as a strength in processing social over non-social stimuli, engaging language, increased social gaze, and empathic, friendly, and emotional personality.
The strikingly gregarious personality and an increased approach to strangers is accompanied by enhanced emotional reactivity to music, high levels of generalized anxiety and poor social judgment. Music is known potent emotional stimulus, and interestingly, WS subjects show striking interest in and increased emotional and amygdalar responses to music.
One fascinating aspect of the WS social phenotype is that the haploinsufficiency resulting from the gene deletion leads to a profile characterized by intriguing dissociations, or strengths and weaknesses (e.g., overly-friendly with a difficulty in making friends; socially fearless but anxious; positive affect with maladaptive behaviors).
In the PLoS One study, Li Dai and colleagues from the Center for Integrated Neuroscience and Human Behavior, University of Utah, Salt Lake City, Utah, USA, studied blood levels of OT and AVP in WS and controls at baseline, and at multiple time-points following a positive emotional intervention (music), and to a well-characterized negative stressor, cold.
The authors found that the basal OT and to a lesser extent AVP, are elevated in WS, and are related to measures of WS social behavior. In addition, they report that emotional (music) and physically aversive (cold) stimuli caused an exaggerated release of OT and AVP. Of note, higher levels of basal OT were correlated with increased approach to strangers.
These results indicate that in WS, the neurobiological mechanisms that underlie intensified emotional responses to music and possibly social behavior, may in part involve the dysregulated synthesis or release of both OT and AVP from the hypothalamic neurohypophyseal system.
They may also indicate a paradigm shift toward understanding OT as an endogenous modulator of human behaviors that may not always be adaptive in daily life.
Source: PLoS One; June 12, 2012; http://dx.doi.org/10.1371/journal.pone.0038513
Read more: PLoS One
See also the BrainImmune’s commentary about this article by Vincent Geenen.
Updates
A 2015 perspective article Brian W. Haas and Alicia K. Smith presented a novel epigenetic model describing how DNA methylation may impact the expression of key genes within the OT and AVP systems, which may ultimately influence the social behavior observed in WS. This, according to these authors, was supported from data pooled from a prior empirical research study demonstrating that the oxytocin receptor gene (OXTR) is overexpressed in WS.
Background: Williams syndrome (WS) is a condition caused by a deletion of ∼26–28 genes on chromosome 7q11.23 often characterized by abnormal social behavior and disrupted oxytocin (OT) and vasopressin (AVP) functioning. Some genes that impact OT and AVP function include OXTR and AVPR1A, which encode the OT and AVP receptors, respectively, throughout the brain and body.
According to the authors, the pathophysiology underlying disrupted social-emotional processing in WS mirrors the pathophysiology often associated with other neurodevelopmental conditions such as autism. WS is characterized by an abnormally increased drive toward social interaction, while autism is characterized by a relative aversion toward social interaction.
Moreover, the authors discussed preliminary findings that have a clear and direct potential to improve treatment techniques for individuals with WS. For example, they called attention to the evidence that altering OT levels impacts sociability and communication in children and teens with autism. And the results of these clinical trials may also contribute to the design of treatment approaches that target the OT or AVP systems in WS.
A 2020 study by Ryo Kimura et al. revealed that the oxytocin receptor gene (OXTR) was down-regulated and hypermethylated in WS patients compared to controls.
Background: Williams syndrome (WS) is caused by a microdeletion of chromosome 7q11.23, and is characterized by various physical and cognitive symptoms. In particular, WS is characterized by hypersocial (overfriendly) behavior; WS has gained attention as aspects of the WS phenotype contrast with those of autism spectrum disorder (ASD). The oxytocin receptor gene (OXTR) contributes to social phenotypes in relation to regulation of oxytocin (OXT) secretion. Additionally, new evidence indicated that DNA methylation of OXTR is associated with human social behavior.
The study by Ryo Kimura et al. showed that three CpG sites around the TSS of OXTR demonstrated increased methylation levels in WS patients compared to controls, and these results were confirmed in different ethnic groups.
In addition, the study found that the identified hypermethylated CpG sites in WS patients were significantly correlated with the superior temporal gyrus and/or prefrontal cortex, both of which are known to mediate social function. These results may provide further support for the hypothesis that WS and ASD patients share common dysregulated pathways in the OXTR system.
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