The landscape of human society is changing drastically. In 1950, only 30% of the world's population lived in urban regions; today, more than 50% of us do so; by 2050, this figure is expected1 to have climbed to almost 70% (Fig. 1). And, just as social isolation is well known to have harmful effects2, so does the opposite extreme: overcrowding can induce stress and illness in species ranging from insects to rodents3 to primates, including humans4. In particular, mental illness in humans has been linked to the urban environment: living in a city increases the risk of depression and anxiety, and the rate of schizophrenia is markedly higher in people born and brought up in cities5. Writing on page 498 of this issue, Lederbogen et al.6 use functional magnetic resonance imaging to investigate for the first time the specific human brain structures that are affected by urban living.

Figure 1: The city allure.
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The percentage of the global population living in urban (blue) and rural (red) regions since 1950, with projected1 figures up to 2050.

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The study's participants lived or had lived in locations ranging from rural areas to large cities (Fig. 2). The authors measured regional brain activation while participants performed a social-stress test — solving hard arithmetic problems under time pressure and with negative feedback from the experimenter. This task not only increased the participants' heart rate, blood pressure and salivary levels of the stress-associated hormone cortisol, but also resulted in significant activity in brain structures known to be involved in emotion and stress.

Figure 2: Regional categories.
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PHOTOLIBRARY.COM; A, R. TOMLINSON; B, S. GRANDADAM; C, EYE UBIQUITOU

In their study6, Lederbogen et al. categorized living conditions as those asssociated with rural areas (a), towns with more than 10,000 inhabitants (b) and cities with more than 100,000 inhabitants (c). Their data suggest that city living affects the brain's response to stress.

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Of the activated brain regions, two were of particular interest: activation in the amygdala correlated with the size of the city in which an individual currently resided, and activation of the perigenual anterior cingulate cortex (pACC) correlated with how long a participant had lived in a large city during their childhood. Urban upbringing also affected the strength of the functional coupling between the amygdala and the pACC: those who had spent more time growing up in large cities had reduced functional connectivity between these two regions.

Intriguingly, a similar pattern of reduced amygdala–pACC coupling has previously been associated7 with genetic risk for psychiatric disorders, and the amygdala has recently been linked both to social-network size8 and to the sense of personal-space violation9. Taken together, the findings suggest that the cingulate–amygdala circuit is one on which genetic and environmental risks for mental illness may converge.

The sheer number and complexity of the factors involved in studies of real-world society raise concerns about both the reliability of effects and the possibility of confounding explanations. To address the first of these concerns, Lederbogen et al.6 replicated their findings in several separate samples, used two different stress-inducing tasks, and demonstrated that there were no effects of urbanicity on brain activation when participants performed a non-stressful cognitive task.

The second concern — that urbanicity may be confounded by other variables associated with but causally separable from it — is difficult to address, given the enormous number of such variables. To probe some of the possibilities, the authors examined participants' age, education, income, marital and family status, as well as aspects of their health, mood, personality and the amount of social support they had. None of these factors significantly influenced the effects of urbanicity, suggesting that living in a city environment changes brain response during a social stressor by a distinct, although mysterious, mechanism.

Given that Lederbogen and colleagues' study is purely correlational, an obvious next step will be to conduct larger-scale, longitudinal studies that measure more variables and that attempt to trace a causal factor linking brain activity to more fine-grained and individualized aspects of city living. Such studies could, for example, measure individuals' perceived position in a social hierarchy and frequency of encounter with strangers, as well as population density, amount of space and type of housing.

There are wide variations in individuals' preferences for, and ability to cope with, city life: some thrive in New York City; others would happily swap it for a desert island. Psychologists have found10 that a substantial factor accounting for this variability is the perceived degree of control that people have over their daily lives. Social threat, lack of control and subordination are all likely candidates for mediating the stressful effects of city life, and probably account for much of the individual differences seen.

But although the negative aspects of city living have been highlighted extensively, city life is by no means always bad. In many countries, for example, studies on the complex relationship between urbanicity and suicide show higher rates of suicide in rural areas than in cities11. Although there are a number of possible explanations for this observation, it could relate to cities' provision of a richer, more stimulating and more interactive social environment, a larger social-support network and easier access to medical care.

Future work complementary to Lederbogen and co-workers' study6 could investigate the positive effects of city living in more detail and begin to make recommendations for urban planning and architecture. Given the world's increasing population (estimated to hit 7 billion this autumn), the fact that we will be living mostly in cities seems inescapable. This highlights the importance of understanding the effects that such living conditions will have on human mental health.