City living and urban upbringing affect neural social stress processing in humans

Journal name:
Nature
Volume:
474,
Pages:
498–501
Date published:
DOI:
doi:10.1038/nature10190
Received
Accepted
Published online

More than half of the world’s population now lives in cities, making the creation of a healthy urban environment a major policy priority1. Cities have both health risks and benefits1, but mental health is negatively affected: mood and anxiety disorders are more prevalent in city dwellers2 and the incidence of schizophrenia is strongly increased in people born and raised in cities3, 4, 5, 6. Although these findings have been widely attributed to the urban social environment2, 3, 7, 8, the neural processes that could mediate such associations are unknown. Here we show, using functional magnetic resonance imaging in three independent experiments, that urban upbringing and city living have dissociable impacts on social evaluative stress processing in humans. Current city living was associated with increased amygdala activity, whereas urban upbringing affected the perigenual anterior cingulate cortex, a key region for regulation of amygdala activity, negative affect9 and stress10. These findings were regionally and behaviourally specific, as no other brain structures were affected and no urbanicity effect was seen during control experiments invoking cognitive processing without stress. Our results identify distinct neural mechanisms for an established environmental risk factor, link the urban environment for the first time to social stress processing, suggest that brain regions differ in vulnerability to this risk factor across the lifespan, and indicate that experimental interrogation of epidemiological associations is a promising strategy in social neuroscience.

At a glance

Figures

  1. Relationship between current urbanicity and amygdala activation.
    Figure 1: Relationship between current urbanicity and amygdala activation.

    a, Discovery study (N = 32): T map of significant correlations between stress-related activations (in the experimental versus control contrast) and current urbanicity scores shown at a threshold of P<0.005, uncorrected. b, Discovery study: contrast estimates at the most significantly correlated voxel in the amygdala (located at x = 21, y = −9, z = −15) for the experimental compared to control contrast for the three current urbanicity groups (*P<0.05; error bars indicate s.e.m.). c, Replication study (N = 23): T map of significant correlations between activations in the experimental compared to control contrast and current urbanicity scores (shown at P<0.05, FWE corrected for the right amygdala as region of interest (ROI)). d, Replication study: contrast estimates at the most significantly correlated voxel in the amygdala (located at x = 24, y = 2, z = −18) for the experimental compared to control contrast for the three current urbanicity groups (*P<0.05, error bars indicate s.e.m.).

  2. Relationship between early life urbanicity scores and pACC activation.
    Figure 2: Relationship between early life urbanicity scores and pACC activation.

    a, Discovery study (N = 32): T map of significant correlations between stress-related activations (in the experimental versus control contrast) correlating with urbanicity scores shown at a threshold of P<0.005, uncorrected. b, Discovery study: scatterplot of urbanicity scores and mean contrast estimates of the significantly (at P<0.005) correlating voxels within the ACC in the experimental compared to control contrast. Results indicate a linear relationship between these two variables (r = 0.56, P = 0.001). c, Replication study (N = 23): T map of significant correlations between activations (in the experimental compared to control contrast) and urbanicity scores (shown at P<0.05, FWE corrected for the rostral ACC as ROI). d, Replication study: scatterplot between contrast estimates for the stress compared to control contrast and the urbanicity score shown for the mean of all significantly (P<0.005) correlated voxels (r = 0.64, P<0.001).

References

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Author information

  1. These authors contributed equally to this work.

    • Florian Lederbogen,
    • Peter Kirsch &
    • Leila Haddad

Affiliations

  1. Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, 68159 Mannheim, Germany

    • Florian Lederbogen,
    • Peter Kirsch,
    • Leila Haddad,
    • Fabian Streit,
    • Heike Tost,
    • Philipp Schuch,
    • Stefan Wüst,
    • Marcella Rietschel,
    • Michael Deuschle &
    • Andreas Meyer-Lindenberg
  2. Douglas Mental Health University Institute, McGill University, Montreal, Quebec H4H 1R3, Canada

    • Jens C. Pruessner

Contributions

F.L., P.K and L.H. designed and performed experiments, analysed data and wrote the paper; F.S., P.S. and S.W. designed and performed experiments, analysed data and reviewed the manuscript; H.T. analysed data and reviewed the manuscript; M.D. and M.R. designed experiments and reviewed the manuscript; J.C.P. developed the MIST paradigm and reviewed the manuscript. A.M.-L. obtained funding, designed the study and experiments and wrote the paper.

Competing financial interests

The authors declare no competing financial interests.

Corresponding author

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Supplementary information

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  1. Supplementary Information (766K)

    This file contains Supplementary Methods, with additional references, Supplementary Tables 1-3 and Supplementary Figures 1-3 with legends.

Comments

  1. Report this comment #24487

    oliver elbs said:

    5 years ago, I once read a paper (in PNAS, I think) that showed that the ubiquitous cars coming out from all streets in cities have replaced the old sabretooth tigers lurking in the bush.
    In fact, the reaction of the brain toward a car is exactly the same as the reaction of the brain toward a sabretooth tiger.

    Ironically, in Switzerland, the last wild bear was shot in 1906 --- exactly when the first cars arrived in the streets.

    No wonder, that I am under constant stress (from cars) while living in Switzerland with its high density of cars everywhere.

    When I am dead, I will have seen and avoided billions of cars, but I will have seen and encountered no single intelligent being...

    Please, could somebody find my old reference above (PNAS, I think).

  2. Report this comment #24511

    James Kirkbride said:

    Mannheim, Germany, has long-played a pivotal role in unearthing links between the environment and schizophrenia.1 Using administrative incidence data from Mannheim in 1965, Hafner and colleagues were amongst the first groups to independently verify Faris and Dunham?s seminal work from Chicago in the 1920s, which showed that hospitalised admission rates of schizophrenia increased in progressively more urban areas of the city.2 Now, almost 50 years later, Mannheim?s historical pedigree in this area looks set to endure, following the publication of Lederbogen et al.?s landmark study in Nature this week,3 which reported for the first time an association between urban living and upbringing and increased brain activity amongst health volunteers in two regions involved in determining environmental threat and processing stress responses.

    Tantalisingly, their work bridges epidemiology and neuroscience and provides some of the first empirical data to directly implicate alterations in stress processing associated with living in urban environments. One important step will now be to discover whether such neural changes (following exposure to urban environments) are associated with clinical phenotypes, such as schizophrenia. This would support long-speculated social stress paradigms4 as an important mechanism in a causal pathway between the environment and psychosis, although alternative environmental exposures in urban areas, including viral hypotheses and vitamin D should not yet be excluded.

    Lederbogen et al.3?s work opens up many future avenues for possible study, including replication of their findings in clinical samples (via case-control designs) and using population-based rather than convenience samples. One of the greatest challenges in the social epidemiology of psychiatric disorders is our ability to identify the specific suite of factors which underpin associations between the urban environment and risk of clinical disorder. While subject to the same caveat, the work of Lederbogen et al.3 also informs this search, because it suggests that focussing on factors likely to which induce (or protect against) social stress would be potentially fruitful. To this end, their work should pave the way for mimetic studies, in both non-clinical and clinical populations, which investigate neural processing in response to a range of candidate social risk factors for psychiatric illness established in previous epidemiological studies.5-6 This list may include the effect of migration or minority group membership,7 childhood traumas and other major life events,8-9 neighbourhood socioeconomic deprivation,10 income inequality^11^ and both individual-level social networks and neighbourhood-level social cohesion and ethnic density,12 which may serve to mitigate the effects of social stress.

    The interface between social epidemiology and social neuroscience will also potentially provide new avenues to develop public health interventions. Presently, universal prevention strategies which focus on community-based interventions to prevent mental illness are not readily viable,13 given both the absolute rarity of psychotic disorder and the relative ubiquity of broadly-defined exposures such as urban living (many people live in urban environments, but only a handful of them will ever develop a psychotic illness). However, social neuroscience breakthroughs such as those reported here increase the viability of community-based public health initiatives because it may become possible to move the focus of the intervention from the prevention of the clinical phenotype to the prevention of neural changes associated with social stress processing. Because this intermediate phenotype may be associated with a range of neuropsychiatric and somatic disorders, public health strategies which target reductions in social stress rather than any single outcome may lead to significant improvements in population health across a range of morbidities, as well as associated fiscal incentives through gains in economies of scope.

    References

    1. Hafner H, Reimann H, Immich H, Martini H. Inzidenz seelischer Erkrankungen in Mannheim 1965. Soc Psychiatr. 1969;4:127-135.

    2. Faris REL, Dunham HW. Mental disorders in urban areas. Chicago: University of Chicago Press; 1939.

    3. Lederbogen F, Kirsch P, Haddad L, et al. City living and urban upbringing affect neural social stress processing in humans. Nature. 2011;474(7352):498-501.

    4. Selten JP, Cantor-Graae E. Social defeat: risk factor for schizophrenia? Br J Psychiatry. August 1, 2005 2005;187(2):101-102.

    5. Cantor-Graae E, Selten J-P. Schizophrenia and Migration: A Meta-Analysis and Review. Am J Psychiatry. January 1, 2005 2005;162(1):12-24.

    6. March D, Hatch SL, Morgan C, et al. Psychosis and Place. Epidemiol Rev. July 30, 2008 2008;30:84-100.

    7. Coid JW, Kirkbride JB, Barker D, et al. Raised incidence rates of all psychoses among migrant groups: findings from the East London first episode psychosis study. Arch Gen Psych. 2008;65(11):1250-1258.

    8. Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ. Childhood parental loss and adult psychopathology in women. A twin study perspective. Archives of General Psychiatry. Feb 1992;49(2):109-116.

    9. Morgan C, Kirkbride JB, Leff J, et al. Parental separation, loss and psychosis in different ethnic groups: a case-control study. Psychological Medicine. 2007;37(4):495-503.

    10. Croudace TJ, Kayne R, Jones PB, Harrison GL. Non-linear relationship between an index of social deprivation, psychiatric admission prevalence and the incidence of psychosis. Psychological Medicine. Jan 2000;30(1):177-185.

    11. Boydell J, van Os J, McKenzie K, Murray RM. The association of inequality with the incidence of schizophrenia--an ecological study. Soc Psychiatry Psychiatr Epidemiol. Aug 2004;39(8):597-599.

    12. Kirkbride J, Boydell J, Ploubidis G, et al. Testing the association between the incidence of schizophrenia and social capital in an urban area. Psychological Medicine. 2008;38(8):1083-1094.

    13. Kirkbride JB, Coid JW, Morgan C, et al. Translating the epidemiology of psychosis into public mental health: evidence, challenges and future prospects. Journal of Public Mental Health. 2010;9(2):4-14.

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