After nine years writing Slate’s “Dear Prudence” advice column, Emily Yoffe has noticed some recurring themes: “Mothers in law, husbands addicted to porn, impossible officemates, crazy brides.”

Sometimes, Yoffe says, letter-writers say they’re prepared to abide by her advice, whatever it is. “I have people writing to me, saying ‘I thought we wanted three children, but I realized I’m happy with two. My spouse wants another. What do you think?’ What do I think? You know this is not an issue for me to decide, right?”

But decide she does, and people keep asking her to weigh in on their anxiety-inducing decisions, big and small, from planning for the end of life, to when to let a daughter shave her legs.

The advice-seekers want a neutral third-party, one they trust, to arbitrate the conflicts of their lives. The letters often end with questions—how can I get over this? What should I tell her? Am I making the right choice?—that boil down to the universal “What should I do?”

Once they have an answer, they can act, see what happens, and stop living in anxious anticipation. Because it’s often the not-knowing that’s the worst.

One of the downsides of the mostly awesome phenomenon of human consciousness is the ability to worry about the future. We know the future exists, but we don’t know what’s going to happen in it. “In other animals, unpredictability or uncertainty can lead to heightened vigilance, but I think what’s unique about humans is the ability to reflect on the fact that these future events are unknown or unpredictable,” says Dan Grupe, a postdoctoral research associate at the University of Wisconsin-Madison’s Center for Investigating Healthy Minds. “Uncertainty itself can lead to a lot of distress for humans in particular.”

As a rule, humans prefer certainty to uncertainty. Studies have shown that people would rather definitely get an electric shock now than maybe be shocked later, and show greater nervous-system activation when waiting for an unpredictable shock (or other unpleasant stimulus) than an expected one. Where people differ is in the degree to which uncertainty bothers them.

This is what the Intolerance of Uncertainty Scale (IUS) measures. Developed in 1994 by a team of researchers in Quebec, the scale assesses how much people desire and seek out predictability, and how they react in ambiguous situations. A higher level of intolerance of uncertainty, or IU, is a “cognitive vulnerability,” according to Michel Dugas, a professor of psychology at the University of Quebec in Outaouais, and one of the architects of the IUS. He and his fellow researchers have linked high IU to several anxiety disorders as well as (less strongly) to eating disorders and depression. Much of his research has been done on generalized anxiety disorder (GAD), for which he says IU seems to be a causal risk factor—meaning it’s not just linked to GAD, but that higher IU has actually been shown through experimental manipulation to lead to more worry.

This is true not just of clinical anxiety, but everyday worries as well.  In fact, both Dugas and Grupe tell me that uncertainty seems to be a necessary condition for anxiety of any kind.

There’s a little bit of semantics involved in spelling out just what scientists mean by “worry” and “anxiety.” “Worrying” generally means thinking about possible future threats, accompanied by the emotion and bodily sensation of anxiety. If the object of worry was completely predictable, or currently happening (so there’s no more ambiguity), you wouldn’t be anxious about it, you would fear it. And if you’re just thinking about potential future bad stuff, but feeling pretty chill, “you’re probably not worrying,” Dugas says. “You’re probably planning, or preparing.”

So not knowing what to do, not knowing what’s going to happen, not knowing what other people are thinking and feeling—these situations are ripe to breed anxiety in anyone, depending on how well they’re able to tolerate uncertainty.

“I’m kind of a believer that there aren’t any clear-cut points between subclinical and diagnosed anxiety,” Grupe says. “It’s a continuous spectrum where uncertainty plays an increasing role, increasing the suckiness of unpredictability.”

Dugas agrees, saying, “It’s on a continuum. People with GAD are on the extreme end of worry, but that worry is not different from your worry or my worry. There’s just a lot more of it.”

He compares extreme intolerance of uncertainty to an allergic reaction. “If you’re allergic to nuts, and you have a piece of birthday cake that has a drop of almonds in it, you have a violent physical reaction to it,” he says. “A small amount of a substance that’s not harmful to most people provokes a violent reaction in you. It’s like a psychological allergy.”

Grupe and Jack Nitschke, also of the University of Wisconsin-Madison, have developed a theory of what brain mechanisms might be at play in this psychological allergy, which they laid out in Nature Reviews Neuroscience in 2013. It’s complicated—“There’s not a part of your brain that’s the IU part,” Grupe says. Rather, intolerance of uncertainty is likely linked to several different brain processes, including, Grupe suspects, emotional regulation, threat detection, and safety detection (the last two of which are distinct, separate processes).

In an ambiguous or unpredictable situation, the brain is going to look for clues in the environment, things it knows from past experience are associated with threat or safety. If this is unsuccessful, and the brain can’t tell what is dangerous and what isn’t, then anything could seem like a threat. Threat and safety detection has been linked to the amygdala, and emotion regulation seems to be the domain of the prefrontal cortex. Grupe also thinks the insula could play a role in processing information about the body and its environment to help create internal, subjective feelings.

“These processes are so intertwined,” Grupe says. “There’s a silly figure at the end of the paper with arrows pointing in every direction.”

Interactions between psychological processes that could lead to higher threat perception. (Nature Reviews Neuroscience)

To add another arrow into the mix, despite a general human preference for certainty, the unknown isn’t always anxiety-inducing. “Uncertainty has its upside, especially regarding temporary uncertainties or unknowns,” Michael Smithson, a professor at the Australian National University’s College of Medicine, Biology, and Environment, wrote in an email. “We don’t want to know right now the endings of all the books we’re going to read, [all] the movies we’ll ever watch, or the contents of all our future Christmas presents … We also like a sense of freedom and autonomy, of having options.”

There are circumstances under which uncertainty can be exciting and motivating, rather than worrisome. In her research, Ayelet Fishbach, a professor of behavioral science and marketing at the University of Chicago, has found that people feel more excited and work harder during tasks where the size of the reward is uncertain.

But, she clarifies, “it’s exciting when the stakes are not huge. We try to keep the stakes small enough so excitement doesn’t at any point turn into some terror. We don’t assume people would like their salary to be uncertain. It’s the small uncertainties.”

If the suspense of not-knowing is too much for someone, she’ll typically use one of two strategies: approach or avoid. Take the (unfortunately) classic advice-column scenario: Is my spouse cheating on me? The suspicious partner will either try to dispel the uncertainty by becoming certain—snooping around, asking outright—or will avoid thinking about or dealing with the situation at all. (Not surprisingly, IU has been linked to indecisiveness as well.)

People high in IU are more likely to compare themselves to others, research shows—another approach tactic. It stands to reason. If you’re not sure how successful you are, or how good your relationship is, you might gain clarity by figuring out how you’re doing relative to others.

Or, if you’re in avoidance mode, you might just ask someone else to tell you the answer. This is a large part of the appeal of advice columns.

“I’ve thought about this so many times,” Yoffe says. “Why would you reach out by email to a total stranger? ... There’s something about the form. You’ve got to shove it into a paragraph, and I’m answering in a paragraph. We’re stripping away the complexities, we’re boiling it down. The form requires you to make it as clear as possible so I can give as clear an answer as possible.”

To a degree, almost everyone employs these strategies sometimes. “We all have crutches,” Dugas says. But if someone is “allergic to uncertainty,” as some GAD patients are, they might, for example, become suspicious of their partner much more easily. They might see threats where there are none. “You might ask your spouse four times a day if they still love you, just in case they changed their mind,” Dugas says. “That would be a certainty-seeking behavior.” And a detrimental one.

On the flip side, Dugas says, avoidance taken too far could manifest itself in something like turning down a promotion at work, because you aren’t sure what the new job will be like, and you know you can do the one you have now. Grupe points out that avoiding unpredictable situations might rob people of opportunities to disprove their own worries. “With something like a party, you think, ‘I could be embarrassed, people might look at me,’ these kinds of worries. If you actually went to that party, you might have disconfirmed these fears, and reduced your anxiety,” he says.

If an aversion to uncertainty starts to negatively affect someone’s life like this, it can help to actively practice a third strategy: just living with it.

Dugas and his colleagues have developed a type of cognitive behavioral therapy based on this concept that has proved to be very effective for patients with GAD. Some people are more prone to the approach strategy, some to avoidance, some are a bit of both in different situations. And individuals also differ on what types of uncertainty bother them most. For a businesswoman who can’t stop checking the stock market, Dugas says he might have her start checking just once a day, then every other day, and so on. For parents who worry over the uncertainty of their kids’ grades, he’d have them slowly back off double-checking homework.

“The goal is always the same,” Dugas says. “To get them to experience uncertainty and learn “this isn’t fun, but I can tolerate this.”

Yoffe also advises people to accept life’s uncertainties sometimes. She recalls a recent Dear Prudie letter from a woman who didn’t meet her husband’s parents until shortly before they were married, and realized upon seeing them that they looked nothing like her husband. He did, however, resemble his maternal aunt and her husband.

“She’s like, ‘It’s pretty obvious the aunt and uncle had him and gave him to the people he thinks are his parents. Should I bring this up or explain it to him?’ No!” Yoffe says.

While in this case, she told the letter-writer, “Cut off this speculation,” she says, “I don’t think there’s a rule … The answer is the totality of the circumstances of the evidence, and your mental state.”

Ultimately there’s no escape from living with uncertainty, for anyone. No matter how often you compare yourself to others, or check your email, or read the news, no matter how much you worry, you’ll never know what happens after you die, or what other people really think of you, or what your life will be like in five years. So it helps to get comfortable with the small uncertainties, too. Then, at least, you’re used to it.