Abstract
Personal social network size exhibits considerable variation in the human population and is associated with both physical and mental health status. Much of this inter-individual variation in human sociality remains unexplained from a biological perspective. According to the brain opioid theory of social attachment, binding of the neuropeptide β-endorphin to μ-opioid receptors in the central nervous system (CNS) is a key neurochemical mechanism involved in social bonding, particularly amongst primates. We hypothesise that a positive association exists between activity of the μ-opioid system and the number of social relationships that an individual maintains. Given the powerful analgesic properties of β-endorphin, we tested this hypothesis using pain tolerance as an assay for activation of the endogenous μ-opioid system. We show that a simple measure of pain tolerance correlates with social network size in humans. Our results are in line with previous studies suggesting that μ-opioid receptor signalling has been elaborated beyond its basic function of pain modulation to play an important role in managing our social encounters. The neuroplasticity of the μ-opioid system is of future research interest, especially with respect to psychiatric disorders associated with symptoms of social withdrawal and anhedonia, both of which are strongly modulated by endogenous opioids.
Introduction
The origin of societies is considered one of the major evolutionary transitions. This has been accomplished by numerous species but arguably no society is as widespread, complex and technologically advanced as our own. The human brain has evolved to thrive in social environments, providing us with the cognitive processing power to deal with our dynamic and intricate personal relationships. However, there is limited understanding of the neurobiological processes underpinning human sociality. A growing number of studies highlight the important role played by endogenous opioid peptides, most notably β-endorphin, in affiliation and bonding in social animals such as rodents and primates, including humans. This neuropeptide is released from the CNS and has the highest binding affinity for μ-opioid receptors, which are widely distributed in the brain. Upon binding, β-endorphin induces analgesia and a sense of well-being. The brain opioid theory of social attachment postulates that the endogenous μ-opioid system is fundamental to the establishment and maintenance of social bonds. Indeed, μ-opioid neurotransmission has been shown to modulate social motivation and plays a key role in attributing positive value to social interactions. Specifically, the close relationship between the opioid and dopamine systems is integral to the rewarding nature of social interactions.
Until relatively recently, experimental evidence supporting the role of the endogenous opioid system in modulating social behaviour mainly derived from the administration of opioids and opioid blockers. For instance, humans given the μ-opioid antagonist naltrexone experience feelings of reduced social connection. With advances in genetics, knockout technology has revealed that mice lacking the μ-opioid receptor gene show severe deficits in numerous facets of social behaviour, including interactions with conspecifics, communication and infant attachment. Furthermore, there is increasing interest in the use of positron emission tomography (PET) scanning to measure activity of the μ-opioid system in relation to differences in social behaviour, both within individuals (Manninen et al. in prep) and between individuals.
Since β-endorphin is a potent analgesic, indeed more so than the pain-relieving opiate drug morphine, the primary hypothesis tested here was whether pain tolerance (as a proxy for activation of the μ-opioid system) predicts social network size. We tested this hypothesis in a population of healthy young adults (n = 101). The study involved a questionnaire relating to the two innermost social network layers (approximately corresponding to those individuals contacted at least once a week and once a month respectively), as well as collecting information on personality, sociodemographics and lifestyle. Since the blood-brain barrier is impermeable to β-endorphin, CNS endorphin levels can only be accurately determined by sampling cerebrospinal fluid via lumbar puncture, whilst measuring the μ-opioid system directly requires the use of PET scanning. Instead, pain tolerance was assessed by means of a non-invasive, physical pain test (see Methods). (...)
Discussion
Our results show that pain tolerance positively predicts social network size. This therefore supports our hypothesis that variation in the μ-opioid system underlies individual differences in sociality. These results are consistent with a recent PET imaging experiment demonstrating a correlation between μ-opioid receptor availability and attachment style, such that individuals showing greater avoidance of social attachment exhibit lower receptor densities. Our findings are also in agreement with previous pain tolerance studies indirectly implicating the endogenous opioid system in human social bonding activities such as music-making, dancing and laughter. In addition, laughter has since been shown to correlate with elevated μ-opioid activity, as measured by PET scanning (Manninen et al. in prep). This suggests that tests of pain tolerance like that used in our study may indeed serve as a useful proxy for assessing activation of the μ-opioid system.
Variation in μ-opioid receptor signalling may be due to underlying differences in both endogenous opioid release and receptor density, though their relative contribution is yet to be fully determined. However, studies of oxytocin and vasopressin signalling in rodents have shown that CNS receptor densities strongly modulate the influence of these neuropeptides, irrespective of neuropeptide abundance. In fact, analyses of post-mortem brain tissue and in vivo PET studies in humans have revealed a broad range of μ-opioid receptor densities within the population, differing by at least 30–50% (...)
Personal social network size exhibits considerable variation in the human population and is associated with both physical and mental health status. Much of this inter-individual variation in human sociality remains unexplained from a biological perspective. According to the brain opioid theory of social attachment, binding of the neuropeptide β-endorphin to μ-opioid receptors in the central nervous system (CNS) is a key neurochemical mechanism involved in social bonding, particularly amongst primates. We hypothesise that a positive association exists between activity of the μ-opioid system and the number of social relationships that an individual maintains. Given the powerful analgesic properties of β-endorphin, we tested this hypothesis using pain tolerance as an assay for activation of the endogenous μ-opioid system. We show that a simple measure of pain tolerance correlates with social network size in humans. Our results are in line with previous studies suggesting that μ-opioid receptor signalling has been elaborated beyond its basic function of pain modulation to play an important role in managing our social encounters. The neuroplasticity of the μ-opioid system is of future research interest, especially with respect to psychiatric disorders associated with symptoms of social withdrawal and anhedonia, both of which are strongly modulated by endogenous opioids.
Introduction
The origin of societies is considered one of the major evolutionary transitions. This has been accomplished by numerous species but arguably no society is as widespread, complex and technologically advanced as our own. The human brain has evolved to thrive in social environments, providing us with the cognitive processing power to deal with our dynamic and intricate personal relationships. However, there is limited understanding of the neurobiological processes underpinning human sociality. A growing number of studies highlight the important role played by endogenous opioid peptides, most notably β-endorphin, in affiliation and bonding in social animals such as rodents and primates, including humans. This neuropeptide is released from the CNS and has the highest binding affinity for μ-opioid receptors, which are widely distributed in the brain. Upon binding, β-endorphin induces analgesia and a sense of well-being. The brain opioid theory of social attachment postulates that the endogenous μ-opioid system is fundamental to the establishment and maintenance of social bonds. Indeed, μ-opioid neurotransmission has been shown to modulate social motivation and plays a key role in attributing positive value to social interactions. Specifically, the close relationship between the opioid and dopamine systems is integral to the rewarding nature of social interactions.
Until relatively recently, experimental evidence supporting the role of the endogenous opioid system in modulating social behaviour mainly derived from the administration of opioids and opioid blockers. For instance, humans given the μ-opioid antagonist naltrexone experience feelings of reduced social connection. With advances in genetics, knockout technology has revealed that mice lacking the μ-opioid receptor gene show severe deficits in numerous facets of social behaviour, including interactions with conspecifics, communication and infant attachment. Furthermore, there is increasing interest in the use of positron emission tomography (PET) scanning to measure activity of the μ-opioid system in relation to differences in social behaviour, both within individuals (Manninen et al. in prep) and between individuals.
Since β-endorphin is a potent analgesic, indeed more so than the pain-relieving opiate drug morphine, the primary hypothesis tested here was whether pain tolerance (as a proxy for activation of the μ-opioid system) predicts social network size. We tested this hypothesis in a population of healthy young adults (n = 101). The study involved a questionnaire relating to the two innermost social network layers (approximately corresponding to those individuals contacted at least once a week and once a month respectively), as well as collecting information on personality, sociodemographics and lifestyle. Since the blood-brain barrier is impermeable to β-endorphin, CNS endorphin levels can only be accurately determined by sampling cerebrospinal fluid via lumbar puncture, whilst measuring the μ-opioid system directly requires the use of PET scanning. Instead, pain tolerance was assessed by means of a non-invasive, physical pain test (see Methods). (...)
Discussion
Our results show that pain tolerance positively predicts social network size. This therefore supports our hypothesis that variation in the μ-opioid system underlies individual differences in sociality. These results are consistent with a recent PET imaging experiment demonstrating a correlation between μ-opioid receptor availability and attachment style, such that individuals showing greater avoidance of social attachment exhibit lower receptor densities. Our findings are also in agreement with previous pain tolerance studies indirectly implicating the endogenous opioid system in human social bonding activities such as music-making, dancing and laughter. In addition, laughter has since been shown to correlate with elevated μ-opioid activity, as measured by PET scanning (Manninen et al. in prep). This suggests that tests of pain tolerance like that used in our study may indeed serve as a useful proxy for assessing activation of the μ-opioid system.
Variation in μ-opioid receptor signalling may be due to underlying differences in both endogenous opioid release and receptor density, though their relative contribution is yet to be fully determined. However, studies of oxytocin and vasopressin signalling in rodents have shown that CNS receptor densities strongly modulate the influence of these neuropeptides, irrespective of neuropeptide abundance. In fact, analyses of post-mortem brain tissue and in vivo PET studies in humans have revealed a broad range of μ-opioid receptor densities within the population, differing by at least 30–50% (...)
Further research is required to understand the causality of this relationship between pain tolerance and network size. It may be that individuals with genetic variants conferring enhanced μ-opioid neurotransmission derive greater reward from social interactions, thereby seeking more company. An alternative, though not mutually exclusive, explanation is that individuals leading lives rich in social interactions may release higher levels of endogenous opioids and/or have elevated receptor expression. However, we currently lack knowledge regarding the neuroplasticity exhibited by the μ-opioid system. This is of particular interest in relation to psychiatric disorders. Indeed, healthy females asked to sustain a sad mood for only 30 minutes show a reduction in μ-opioid receptor activation. Thus prolonged sadness, as experienced by those suffering from depression, may over time lead to a significant fall in opioidergic signalling. We hypothesise that reduced μ-opioid activity may characterise the onset of conditions such as depression and schizophrenia, resulting in the common symptoms of anhedonia and social withdrawal. Indeed, endogenous opioids mediate hedonic experiences and are integral to our feelings of social connection. In support of this, there is evidence of compromised μ-opioid receptor signalling in patients suffering from depression and schizophrenia and studies using rodent models of depression also implicate the μ-opioid system. (...)
Understanding the biological causes of variation in social network size is of particular interest given the robust association between an individual’s social support and their health, ranging from functioning of their immune, endocrine and cardiovascular systems to myelin integrity. Interestingly, it is an individual’s perceived level of social support that may often be a more reliable indicator of their health status. Compared to other lifestyle factors, we have limited understanding of the mechanisms via which sociality influences morbidity and mortality risk, though reduced activation of the neuroendocrine stress response likely plays a significant role in both humans and animals. Since β-endorphin is known to alleviate the stress response and protect against inflammation and cancer, the activity of an individual’s endogenous μ-opioid system may have important consequences for their health. However, such a direct interaction between social and somatic health is yet to be explored.
In summary, there is substantial evidence that μ-opioid neurotransmission influences sensitivity not only to our physical environment but also our social one. This study adds to previous research implicating the μ-opioid system as a key neural substrate upon which human sociality has evolved.
by Katerina V.-A. Johnson and Robin I. M. Dunbar, Nature | Read more:
Understanding the biological causes of variation in social network size is of particular interest given the robust association between an individual’s social support and their health, ranging from functioning of their immune, endocrine and cardiovascular systems to myelin integrity. Interestingly, it is an individual’s perceived level of social support that may often be a more reliable indicator of their health status. Compared to other lifestyle factors, we have limited understanding of the mechanisms via which sociality influences morbidity and mortality risk, though reduced activation of the neuroendocrine stress response likely plays a significant role in both humans and animals. Since β-endorphin is known to alleviate the stress response and protect against inflammation and cancer, the activity of an individual’s endogenous μ-opioid system may have important consequences for their health. However, such a direct interaction between social and somatic health is yet to be explored.
In summary, there is substantial evidence that μ-opioid neurotransmission influences sensitivity not only to our physical environment but also our social one. This study adds to previous research implicating the μ-opioid system as a key neural substrate upon which human sociality has evolved.
by Katerina V.-A. Johnson and Robin I. M. Dunbar, Nature | Read more:
[ed. Wow, μ-opioid receptor densities among individuals can vary up to 30-50 percent, further discrediting the "chemical imbalance" theory of depression. More to the point (of this study), now I know why I quit Facebook - low tolerance to pain.]
