Fit for life: Environmental risk factors and schizophrenia

Risk and resilience to mental disorders have been investigated in terms of both environmental and genetic factors. It is obviously much easier to modify a person’s environment than their genetics, so this has become a focus of attention for intervention before diseases develop.

The cost and burden of mental illnesses to individuals and society is very high. Any intervention in the development of these disorders, in terms of the risks to the individual or their resilience to the development of a disease, would therefore provide savings in terms of cost and in the overall burden of disease. Prof. Andreas Meyer-Lindenberg, Central Institute of Mental Health, Germany, discussed research into environmental risk factors for mental disease, and particularly schizophrenia, and how these have been shown to link to activity in specific areas of the brain.

Live well, live long

A range of lifestyle and clinical factors have long been associated with prolonging a person’s lifespan, in terms of sheer longevity but also in years of healthy life lived. Many of these are often the focus of healthcare interventions – such as body mass index, physical activity, tobacco and alcohol use. As noted by Prof. Meyer-Lindenberg, surprisingly, however, many of these have significant but relatively small effects on one’s overall mean lifespan. In contrast, some socioeconomic and sociocultural factors play a relatively large role in mediating lifespan and health.  In fact, the factors that have been shown to have the largest effects on lifespan and resilience to mental disorders have to do with having a supportive social environment – described by Prof Meyer-Lindberg as having people around you, who know you by name, and would do you a favor.

Factors shown to have the largest effects on lifespan and resilience to mental disorders have to do with having a supportive social environment

Another lifestyle factor that gained a great deal of attention in 2016 was financial income, which showed an extraordinarily linear relationship to expected lifespan in the USA. This effect appears not to depend on specific lifestyle factors, but rather on general socioeconomic status. Socioeconomic and sociocultural factors are, in turn, likely to be related to position in the social hierarchy. This, in turn, has been found to correspond to particular patterns of brain activation that also reflect risk for mental disorders. Modelling of a social hierarchy and social status using a computer game while undergoing functional neuroimaging demonstrated differential activation of two areas: the amygdala and an area of the anterior cingulate cortex (ACC) called the perigenual ACC (pACC). Activation in both of these areas was also reflective of actual social status in healthy individuals (as well as status in the artificial game).

Living in a big city has been shown to increase one’s risk for major depression or anxiety disorder by 20–40%. In addition, being born in the city triples one’s risk for schizophrenia

Life in the city may impact the risk of severe mental illness

Living in a big city has been shown to increase one’s risk for major depression or anxiety disorder by 20–40%. In addition, being born in the city triples one’s risk for schizophrenia compared with being born in the country. This is the strongest environmental risk factor that has been characterized for schizophrenia. It has been speculated that social stress in cities is a mechanism which plays a key role in increasing this risk to individuals.

In a social stress paradigm that activates  extended brain networks, these networks were found to be differentially activated, depending on whether the individual lived in a big city or in the country, and whether they were born in a big city. Activation of the amygdala in that paradigm was found to be related to the size of the person’s current environment in terms of its population. This makes intuitive sense, as the amygdala as a threat sensor could be seen as part of a final common pathophysiological pathway for stress, depression and anxiety.

Activation of the pACC was, likewise, related to current size of environment and to birth in a city. Moreover, the amygdala and pACC were found to have close functional connectivity, along with the prefrontal cortex (PFC) in a circuit proposed to mediate emotional effects. Finally, birth in the city has been shown to produce reductions in the size of the prefrontal cortex, and reductions in the size of the pACC (in men only). Consequently, urban birth and living may be associated with abnormalities in brain processing that could predispose an individual to the development of mental illness, including schizophrenia.

Urban birth and living may be associated with abnormalities in brain processing that could predispose an individual to the development of mental illness, including schizophrenia

Get out in nature, preferably with friends

More and more people are migrating to big cities globally. In fact, more people in the world now live in cities than in the countryside and these numbers are expected to grow in the next 30 years. It is therefore important to understand what features of cities have an impact on resilience to mental disorders, and what can potentially be done to combat negative effects.

Tracking people’s locations in cities and recording their reactions has illustrated many strong, positive effects of green spaces; subjective reporting that has also been validated using neuroimaging. Activity of the pACC also increases on exposure to green spaces, and being in nature appears to have a similar effect to the activity of the PFC in dampening the stress response.

Individuals who are at an increased risk for schizophrenia may benefit more from social interaction and may be at a reduced risk for the future development of the disease. Like the effects of city size, this ‘social gain’ for individuals at-risk maps onto changes in the activity of the amygdala and pACC.

Social interactions and being in green spaces may make the brain more resilient

Thus, the brain mechanisms for emotional resilience appear to converge on several brain structures, including the amygdala and pACC. Future research may focus on the pharmacology of that risk, and interventions that may help those at-risk.

Further reading

Tost H, Champagne FA, Meyer-Lindenberg A. Environmental influence in the brain, human welfare and mental health. Nat Neurosci 2015;18(10):1421-31. doi:10.1038/nn.410

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