The Goldilocks Hormone: Oxytocin Keeps the Body Resilient

It’s a common saying that, in life, change is the only constant. From the shifting of the seasons to unexpected personal upheavals, the human body is in a perpetual face-off with its environment. The ability to stay steady through the storm is resilience—an essential mechanism that ensures survival. At the heart of resilience lies the body’s ability to regulate itself through two key processes: homeostasis and allostasis.¹

Consider the classic fairy tale “Goldilocks and the Three Bears.” A young golden-haired girl wandering through the forest chances upon an empty hut with three bowls of freshly prepared porridge. Hungry, Goldilocks enters the house and takes a spoonful out of all the bowls. The first one’s too hot, the next is too cold, but the last bowl is just right! That’s exactly the kind of balance the mammalian body works to maintain through homeostasis. Whether it’s temperature, blood pressure, or hydration, the body employs a Goldilocks approach all day long, adjusting and tweaking things to keep parameters just right despite changes in the environment. Hot weather induces sweating, a glucose spike prompts insulin release, and dehydration causes thirst.

But what if Goldilocks had a weather prediction app that warned her of an incoming cold spell? Anticipating the need for more warmth, she might have chosen to eat the bowl of hot porridge. That’s allostasis—not just reacting to change but preparing for it. It regulates the internal milieu of the body through gradual changes toward a new set point, expecting future shifts in the internal or external conditions. Some examples include an increase in muscle mass and lung capacity in response to exercise, callus formation due to repeated friction, and storage of fat in anticipation of hibernation. Together, homeostasis and allostasis enable long-term resilience.

At the heart of these adaptive mechanisms lies oxytocin, a small, nine-amino-acid-long neuropeptide that plays a pivotal role in maintaining physiological and psychological stability amid a changing environment.² Studies across species indicate that oxytocin contributes to both homeostasis and allostasis, helping organisms regulate internal processes in response to immediate challenges while also preparing for future demands. Understanding the hormone’s cornucopia of effects on the body is key to unlocking its potential in enhancing resilience and improving health outcomes.

Oxytocin Keeps the Balance

Oxytocin is produced in the hypothalamus region of the brain and transported to other brain areas and more distant organs. More than a century ago, researchers documented oxytocin’s role in stimulating uterine contractions and lactation.³ That was the molecule’s calling card for a long time.

In the 1970s, scientists injected oxytocin into virgin female rats and observed maternal behavior—nest building, pup grooming, and pup retrieval—establishing the hormone’s role in forging the mother-child bond.⁴ Decades later, researchers showed that higher oxytocin levels during pregnancy in humans predict stronger maternal bonding behaviors post-birth.⁵ Then came a breakthrough in the 1990s.

“The model for attachment at that time was based on steroids like estrogen and progesterone in females and androgens in males, but there seemed to be something missing. And I wandered around that construct for about a decade, feeling that I was not dealing with the full story,” said Sue Carter, a neurobiologist at Indiana University. Carter and her colleagues went on to explore the relationships of the monogamous prairie vole and discovered that oxytocin facilitates adult attachment, not just maternal behavior.⁶ “I just knew that I was on the track of something that was fundamental, going from prairie voles to humans,” Carter remarked. Eventually, the molecule earned the now disregarded title of the “love hormone.”

More Than Just a Love Hormone

Emerging research reveals oxytocin’s many non-social functions, such as its role in stress regulation, immune modulation, and non-social cognitive processes like attention and reasoning.⁷ Experiments in diverse species revealed a strong link between stressful situations like childbirth, trauma, grief, and physical exertion and high levels of blood oxytocin. “Oxytocin allows us to form social bonds and relationships, but that same hormone comes with a package of anti-inflammatory, antioxidant effects that protect us from just about everything,” Carter said.

Inga Neumann, a neurobiologist at the University of Regensburg, treated rats with an oxytocin antagonist and observed a marked increase in the activity of the hypothalamo-pituitary-adrenal (HPA) axis, a feedback loop that regulates the body’s stress response.⁸ In other studies, by Neumann, Carter, and their colleagues, the researchers demonstrated that administering oxytocin to anxious prairie voles who had experienced partner loss or repeated social defeat reduced their stress and normalized HPA axis activity.⁹ In humans, a dose of oxytocin can reduce pain, improve mood, and attenuate inflammation during infection.¹⁰

Despite its myriad roles, at its core, oxytocin is a neuromodulator. It can change neuronal activity by tuning up the strength of synapses and excitability of cells, potentially inducing long-term alterations to circuits. These findings prompted scientists to exploit the protective effects of oxytocin as a therapy for a host of disorders.

In Oxytocin-based Treatments, Context is Key

Intranasal oxytocin sprays have surfaced as treatments for various conditions where enhanced sociality could be beneficial: autism spectrum disorder, anxiety, depression, and post-traumatic stress disorder. But the results have been ambiguous. Carter said the discrepancies boil down to two explanations: not enough oxytocin reaches the brain and a failure to consider past experiences, which can color one’s perceptions and influence how the body reacts to oxytocin. Though oxytocin is essentially a pro-social hormone, there is nothing intrinsically social about it. Rather, the molecule makes the brain more sensitive to important sensory information, thus restructuring neuronal circuits and preparing the body for what’s to come later in life. Considering this, scientists have not been surprised that oxytocin treatment effects vary based on the context in which they’re given and on a patient’s experience, including a history of stress and trauma.

One of the most extensive efforts to use oxytocin-based therapeutics is in the context of autism spectrum disorders. Scientists hypothesized that the hormone could rescue social deficits in individuals but came up short. In a Phase 2 clinical trial in children with autism, intranasal administration of oxytocin had no effect.¹¹ “I’m not surprised,” said Neumann. “Very few autistic patients indeed have a lack of a functional oxytocin system.” She suggested a personalized approach to identify candidates who might benefit from the treatment. Asking individuals to perform activities that stimulate oxytocin release, such as exercise, and assessing oxytocin concentrations in their saliva could help researchers spot underlying problems. Even then, pairing the intervention with behavioral therapy is likely crucial to enhance social behavior.¹²

Context is also key to how oxytocin regulates bond formation. Robert Froemke, a neuroscientist at New York University Langone Health who has studied oxytocin’s role in maternal behavior for many years, reported that the hormone can make mouse moms more attuned to pup calls and in virgin female mice can even transform infant neglect behaviors into maternal care.¹³ “We all can hear baby cries. We all might have some kind of aversive reaction to that. But parenting is about working with your response to that cry and trying to make the child happy,” he said. However, just because the peptide enhances social behavior of moms, it does not indiscriminately do so in all situations. Previous studies have demonstrated that female hamster moms injected with oxytocin show more aggression towards a male intruder than those that were treated with an oxytocin antagonist.¹⁴ On the other hand, experiments done on prairie voles revealed that early life neglect can disrupt adult pair-bonds in animals with low oxytocin signaling, highlighting its influence on resilience.¹⁵

The context-based effects of oxytocin are starkly evident in clinical trials for treatment of mental health disorders. In a placebo-controlled experiment, scientists administered intranasal oxytocin to women with postpartum depression. While the treatment reduced depression symptoms in individuals with no early-life stress, it exacerbated symptoms in those with a history of stress.¹⁶ In some patients with major depressive disorder, the number of oxytocin-producing cells and the amount of released-oxytocin were higher, as compared to controls. When researchers tried treating major depressive disorder with intranasal oxytocin, they observed variation based on the patients’ past experiences.¹⁷ The treatment also led to diametrically opposite effects in relation to personality: Introverts showed significant improvement in depression symptoms, while extroverts deteriorated.¹⁸ Analysis of people with post-traumatic stress disorder revealed reduced levels of blood oxytocin. Additionally, scientists have observed that the genetic risk variation of the oxytocin receptor gene can predict resilience in children exposed to trauma.

But what about the hormone’s well-known roles in reproduction and lactation? Even there, oxytocin adjusts the body’s responses in accordance with changing conditions. Froemke and his team recently showed that the development of the pre-implantation embryo is paused in mouse mothers in response to nursing or optogenetic stimulation of oxytocin neurons simulating nursing patterns, highlighting an evolutionarily conserved mechanism to ensure successful reproduction.¹⁹ In lactating rodents, suckling stimuli from pups induces oxytocin release in the brain and increases the threshold for anxiety.²⁰

As this research shows, amid life’s constant changes, oxytocin is the body’s Goldilocks. It strives to strike a balance by regulating the response to stress while also preparing for future challenges. In a world of perpetual change, it serves as the body’s “just right” response to uncertainty.