Our protagonist moves to the big city, seeking a better life. It's a classic—and increasingly common—tale. More than half the world's population now lives in a metropolis, and by 2050 that figure will very likely jump to two thirds. China's megacities in particular are fueling the trend, with more than 10 million new residents every year. Historically, urbanization has brought about stupendous changes—the Renaissance, the industrial revolution, globalization. Yet this urban migration represents one of the most dramatic environmental shifts human beings have ever undertaken. So one might be tempted to ask: How are we adapting to our new digs?

At first glance, trading green fields for gray grids would seem to be a trade up. City slickers have, on average, more money, better food and greater access to health care than country folk. On the flip side, though, recent studies indicate that memory and attention can suffer in urban environments, and psychologists have long known that city life takes an emotional toll. Urbanites are more likely to suffer from anxiety and depression, and the risk of schizophrenia increases dramatically among people raised in a city. Some researchers have calculated that children born in cities face twice, if not three times, the risk of developing a serious emotional disorder as compared with their rural and suburban peers.

These statistics may not surprise harried rush-hour commuters, but they are also not easily explained. Epidemiologists have ruled out the most obvious answers—namely, that people at risk for developing emotional disorders are more drawn to urban areas. Instead certain aspects of metropolitan life appear to incline the brain toward mental illness. A number of possible culprits are now under investigation, among them noise, pollution and social pressure, in both the form of greater competition and weaker community ties.

Several inquiries suggest that this last factor, social stress, is especially harmful. Our work at the Central Institute of Mental Health in Mannheim, Germany, corroborates this view and provides the first neurobiological mechanism to explain it. In a series of studies, my colleagues and I have found evidence that the social strain of urban living engages specific stress circuits in the brain—circuits known to go awry in mood disorders and other mental illnesses. Perhaps by understanding this mechanism and its role in the etiology of psychiatric conditions, we can find ways to intervene and make cities more livable.

Stress in the City

Many studies have confirmed the link between social strain and mental illness. In 2010 Stanley Zammit and his colleagues at Cardiff University in Wales traced the origins of schizophrenia in 200,000 individuals in Sweden. They found an array of contributing factors, all of which were increasingly potent in more urban environments. In general, though, people who perceived themselves as isolated—immigrants, for example—were at significantly greater risk. Such research is invaluable but relies on a coarse metric: the frequency of clinically diagnosed psychiatric patients. To look for more subtle connections between the pressure of city life and emotional instability, my colleagues and I turned to functional magnetic resonance tomography, a means of monitoring brain activity by way of blood oxygenation levels.

In 2011 we recorded the brain activity of 32 German college students, who hailed from big cities, towns or countryside. As our recruits performed a series of brainteasers, we deliberately stressed them out. For example, while inside the scanner, each volunteer saw a phony performance meter, which indicated that they were doing poorly compared with everyone else. At the same time, one of us admonished them to try harder lest they ruin the experiment. Our ruse worked. Not only did we detect an elevated heart rate, blood pressure and level of stress hormones in our participants, but after the test—when we told them what we were up to—they confirmed that they had indeed felt pressured.

As expected, this stressful experience activated many areas in the brain. Astonishingly, though, we discovered one particular region, the amygdala, whose activity under pressure exactly matched the subjects’ address: the more urban their home environment, the more engaged their amygdala became. This cherry-size structure, deep within the temporal lobe, serves as a danger sensor of sorts, prompting the “fight or flight” response. It also modulates emotions such as fear. In our study, the amygdala seemed almost impervious to stress among villagers and was only moderately active among those from small towns. For big city residents, stress kicked it into overdrive.

We had not expected such a strong correlation, and so we repeated the experiment, placing 70 additional test subjects under slightly different stress conditions. Again, we saw the same pattern. In each experiment, we could readily identify city residents by brain scan alone: urban life had marked all of them with telltale hyperactivity in the amygdala. This finding revealed at least one way in which city stress can lead to mental illness. An amygdala in high gear is also observed in patients suffering from depression and anxiety. Not all urbanites succumb to mood disorders, of course, but we surmise that chronic overstimulation of this brain region puts some people at a higher risk.

The very same mechanism may play at least a small role in prompting violent behavior. Violence is not a psychiatric diagnosis per se; it results from an exceedingly complex interplay of factors. Even so, data from the U.S., Germany and elsewhere confirm that violence is a bigger problem in cities, and several lines of inquiry link violent behavior with overstimulation of the amygdala.

Urban Upbringing

We wanted to follow up on another important observation—namely, the increased risk for schizophrenia in people born and raised in cities. We analyzed the same subjects described above and quantified their early urban exposure using a simple score: we assigned three points for each year they resided in a city as a child, two for each year in a town and one for each year of country living. Again, we found one specific brain region—the perigenual anterior cingulate cortex (pACC)—whose activity levels under stress reflected the city score. Subjects who spent the most time growing up in cities showed the highest levels of pACC activity under pressure. Our second experimental group of 70 students showed the same correlation between pACC activation and urban upbringing.

This finding was not a total surprise. The pACC and the amygdala are closely interconnected. Studies indicate that the pACC serves to inhibit activity in the amygdala. If the pACC is damaged through chronic stimulation during a city upbringing, it might then fail to quell an overactive amygdala in an urban adult. If the same adult were sheltered from social strain, this deficit might never surface. Indeed, we gave brainteasers to a control group, without any pressure, and found no association between childhood environment and activity in the amygdala or pACC.

Additional research supports this idea. Various researchers—including Tsutomu Takahashi of Toyama University in Japan—have found structural changes in the pACC in patients with schizophrenia. Notably, these alterations also manifest among those who are at an increased genetic risk of the disease developing, before they exhibit any psychiatric symptoms. Similarly, working in conjunction with Daniel Weinberger and his colleagues at the National Institute of Mental Health, we have found dysfunctional feedback between the pACC and amygdala in people who are at an increased genetic risk for mood disorders but are not mentally ill.

Lean on Me

Our data reveal that the longer a person lives in a city, the less communication occurs between their amygdala and pACC. Genes and other factors then steer city dwellers closer to developing schizophrenia, anxiety, depression or violent tendencies. Fortunately, scientists have found mechanisms that strengthen feedback between these two brain regions. In 2011 Lisa Feldman Barrett and her colleagues at Massachusetts General Hospital reported that the volume of the amygdala increases with the size of a person's circle of friends. Our team has found that the hormone vasopressin—which, among other roles, is released during moments of bonding—reduces activity in areas of the cingulate cortex, including the pACC, and boosts feedback to the amygdala.

These studies highlight the well-documented fact that a close network of friends and family can insulate us from the most damaging effects of stress, but this is not the whole story. A lack of green space, noise and other environmental factors may also contribute to pACC and amygdala dysfunction, a possibility we plan to pursue in future imaging tests. Such research could have far-reaching consequences: Almost a third of schizophrenia cases might be avoided if more people were born in a rural setting. Herein lies a paradox: we cannot act on this insight without urbanizing the countryside. But we can try to design our cities so that they promote emotional well-being. In this way, we might take aim at the real goal of psychiatry, which is to prevent serious emotional disorders, not just treat them.