The role of father-daughter relationships in mediating behavioral, physiological, and neural mechanisms underlying attachment in female titi monkeys (Plecturocebus cupreus)
Social interactions regulate our behavior and physiology (Uchino, 2006), and connections between social well-being and health may be one reason why individuals who are happy with their relationships live longer (Diener & Chan, 2011). A pair bond is a selective, enduring, relationship that is regulated by physiology and behavior (Bales et al., 2021). Understanding mechanisms underlying social bonds is especially critical now because the COVID-19 pandemic has detrimentally impacted human social relationships (Evans et al., 2020; Luetke et al., 2020), which may result in adverse health outcomes (Saggiorio de Figueiredo et al., 2021). Despite the importance of social bonds for well-being, little is known about their underlying neurobiology. Much of what we know about the neurobiology of attachment comes from research conducted on males (Bales et al., 2017), despite studies finding opposite behavioral responses to neuroendocrine manipulations in males and females (Carter et al., 2008). Women are more likely to develop affective disorders like depression, which may be linked to social risk factors. Research on female attachment, particularly studies on daughters’ relationships with fathers, is incredibly limited and therefore warrants further investigation. Nonhuman primates are excellent models for understanding the effects of social bonds on human health due to their similar social dynamics, cognitive functioning, and immune systems (Phillips et al., 2014). Coppery titi monkeys (Plecturocebus cupreus) are socially monogamous South American monkeys that live in small family groups. They display classic attachment behaviors (Fuentes, 1998), including proximity maintenance with (Carp & Rothwell et al., 2015), distress upon separation from (Mendoza & Mason, 1986a), and stress buffering by (Mendoza et al., 2000) the attachment figure. Partners are each other’s primary attachment figures, while infants form selective bonds with their fathers (Mendoza & Mason, 1986a,b), making them ideal for studying father-daughter bonds. Methods: Our main objectives were to 1) identify foundational neurobiological and behavioral mechanisms underlying female attachment relationships and 2) determine how relationship quality affects bonding mechanisms. We established a novel method for measuring relationship quality in titi monkeys by quantifying degree of proximity maintenance and separation distress exhibited during infancy and adolescence in females. Given the importance of oxytocin (OT) and arginine-vasopressin (AVP) in pair bonds (Lim & Young, 2006), we also investigated how manipulations of these neuropeptides influenced juvenile attachment. Subjects received acute intranasal treatments of saline, low/medium/high OT, low/high AVP, or OT antagonist (OTA) prior to a social separation or parent preference test (Carp & Rothwell et al., 2015). These same females were then paired as adults and underwent preference tests and Positron Emission Tomography (PET) scans to determine how father-daughter bonds impact adult attachment. We used stepwise regression to determine which measures of infant and juvenile attachment best explained variability in responses to our social challenges. We then investigated the effects of predictors of relationship quality and neuropeptide treatments using general linear mixed-effects models and zero-inflated mixed-effects models with Poisson distributions. Chapter 1 Results: Fathers were significant behavioral and physiological stress buffers for their daughters as evidenced by fewer distress vocalizations (p < .001), less locomotion (p < .001), and lower plasma cortisol (p < .001) during social separation testing. Daughter’s quality of relationship with their fathers significantly explained variability in subjects’ separation distress. For example, females produced fewer distress vocalizations if they spent more time in proximity to their fathers as infants (p = .03), and this stress buffering effect remains even when the daughter is separated from the father (p < .001). While treatments did not alter separation distress behaviors, blockade of OT receptors with OTA resulted in the largest rise in plasma cortisol (p < .001), suggesting OTA is able to block the stress-buffering effects fathers have on daughters. Remarkably, if females have a high-quality father-daughter relationship, they exhibit an overall reduced physiological response to social separation (p = .04). Chapter 2 Results: Across all parent preference tests, females spent more time in proximity to their parents than the strangers or in the neutral preference zone; however, females exhibited a large degree of individual variation. Manipulations of the OT and AVP systems drove increased proximity maintenance with parents for females that exhibit behaviors indicative of a higher-quality relationship with their fathers. For example, females that spent more time in proximity to their fathers as infants also spent more time in proximity to their parents when treated with Medium OT (p = .007) and High AVP (p = .002). Females with higher quality father-daughter relationships also spent less time in proximity to strangers when treated with High OT (p = .003) and Low OT (p = .007), but more time near the strangers when treated with High AVP (p = .007), Low AVP (p = .009), and OTA (p = .001). These findings suggest that when females exhibit behaviors indicative of a high-quality relationship with their fathers, activation of the OT system reduced willingness to interact with strangers, while blockade of OT receptors and activation of the AVP system dysregulated species-typical proximity behaviors. While OT and AVP treatments did not impact the separation distress behaviors measured, the father-daughter relationship quality did. Females locomoted more during testing if they spent more time in proximity to their fathers as infants (p < .001) and juveniles (p = .03) and exhibited more distress upon separation as juveniles (p < .001). These findings suggest other neuroendocrine systems may be driving separation distress behaviors. Chapter 3 Results: Across our two experiments for Chapter 3, we found evidence to suggest that measures of relationship quality significantly explain variability in behavioral and neural correlates of adult social bonds in female titi monkeys. In particular, a higher-quality relationships with the father established a stronger foundation for forming and maintaining an adult pair bond. We also found evidence to suggest that females are capable of maintaining a relationship with their father at least 6-months post pairing, as evidenced by females spending a greater percentage of time in proximity to their fathers during testing if they exhibit higher-quality relationships with their fathers. Our examination of neural activity pre- and post-pairing suggests a high degree of overlap between circuitry driving filial attachment and adult pair bonding, as patterns of activity were similar across the two time points, despite overall activity being lower post-pairing (p < .001). It is likely that differences in OT, AVP, dopamine, and opioid activity underlie the differences observed in neural activity based on daughter’s relationship with their fathers. Conclusions: Overall, variability in the quality of father-daughter relationships significantly predicted patterns of stress buffering, separation distress, and proximity maintenance, while manipulations of the OT and AVP systems specifically impacted physiological separation distress and proximity maintenance. While blockade of OT receptors increased plasma cortisol, females with higher-quality father-daughter relationships exhibited reduced physiological and behavioral separation distress responses. Because our manipulations of the OT and AVP systems did not significantly affect separation distress behaviors, it is possible that other neuroendocrine systems, such as dopamine and opioids, influence female separation distress. Activation of the OT system increased time females spent in proximity to their parents during preference testing, but only if females also exhibited behavioral indicators of high-quality father-daughter relationships. Interestingly, activation of the AVP system and blockade of OT receptors resulted in dysregulated species-typical behavior, where females were more willing to interact with strangers. Females’ responses to treatments were mediated by their relationships with their fathers, suggesting differences in relationship quality may alter OT and AVP receptor distributions. For example, females with a higher-quality father-daughter relationship may have a higher density of OT receptors, which may make them more sensitive to activation of the OT system. Females with a higher-quality relationship with their father also exhibited a stronger foundational framework for forming and maintaining adult pair bonds. We also found evidence to suggest that daughters’ preference for their fathers are somewhat maintained as far as 6-months post-pairing, suggesting females may be capable of maintaining more than one relationship simultaneously. Indeed, patterns of neural activity underlying filial attachment and adult pair bonds was highly overlapping in the present study. It is likely that variation in relationship quality with the father alters neural activity in such a way that makes females more responsive to activation of the OT, AVP, dopamine, and opioid systems. Significance: We used behavioral, pharmacological, and neuroimaging techniques to address current gaps in knowledge of female social bonding and father-daughter relationships, as well as to elucidate the fundamental behavioral, physiological, and neural correlates of female attachment. OT and AVP were more strongly involved in proximity maintenance behaviors, and these neuropeptide systems were affected by the quality of relationship between fathers and daughters. While relationship quality significantly affected separation distress and stress buffering, it is likely that other neuroendocrine systems underlie separation distress. Results from our neuroimaging study suggest it would be beneficial to examine the role of dopamine and opioid systems in separation distress behaviors in addition to OT and AVP systems. We established a new method for quantifying relationship quality in titi monkeys and demonstrated the importance of accounting for relationship quality when interpreting responses to social challenges. More broadly, findings from the present studies advance current knowledge of the neurobiological mechanisms foundational to female attachment relationships, and help inform how social disruptions caused by the global pandemic may differently impact humans based on the quality of their social bonds.