The puzzling link between city living and schizophrenia

By Brendan Kelly

Published: Tuesday, 05 April 2022 at 12:00 am

In 1950, 746 million of us lived in urban areas. By 2014, that had increased to 3.9 billion, or 54 per cent of the world’s population. According to the UN, 66 per cent of all humans will live in cities by 2050.

There is much that is good about cities. They are highly efficient ways of focusing human activities such as business, education and research. Managed correctly, they offer substantial environmental advantages.

Cities bring us into closer routine contact with other humans, and most of us seem hardwired to seek out this enhanced level of contact: we like being in cities as much as we like being around people. But while we like cities, do our bodies and brains like them too?

Our beloved cities are associated with increased rates of childhood asthma, heart disease, diabetes and various cancers, as well as childhood psychiatric illnesses and adult mental health conditions such as depression and even schizophrenia.

Research into these disturbing statistics is best explored by looking at schizophrenia – surely the most enduring and mysterious malady in the history of medicine.

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What is schizophrenia?

Schizophrenia affects approximately 1 per cent of the world’s population at some point in life. Its causes are unknown and it is more common in men than women.

Symptoms start with subtle changes in childhood thinking and behaviour, but these are so vague that they are only recognisable in retrospect or in research studies.

The vast majority of such children do not develop psychological or psychiatric problems. Nonetheless, these subtle changes indicate that, for many people with schizophrenia, brain development takes a different pathway from an early stage, possibly even while still in the womb.

The first noticeable symptoms of schizophrenia emerge in the teenage years and include anxiety, low mood, social withdrawal or a preoccupation with odd beliefs. These symptoms are felt by most teenagers (and many adults) at some point so do not necessarily mean that the person is mentally ill.

However, if they are present to a substantial extent they might identify a young adult who is at high risk of psychological or psychiatric problems.

The classical symptoms of schizophrenia, when they eventually emerge, include delusions and hallucinations.

Other features include difficulties with clear thinking and a range of ‘negative’ symptoms similar to depression: low mood, loss of interest, depleted energy and persistent social withdrawal.

What causes schizophrenia?

While there has been much research into the biological underpinnings of schizophrenia, the disorder still remains one of the true enigmas of medicine.

This is partly because ‘schizophrenia’ is really a term used to denote a cluster of symptoms which tend to occur together, rather than a biologically defined entity.

This places schizophrenia in sharp contrast to conditions such as diabetes, which is biologically defined by measurement of blood glucose; or brain tumours, which are diagnosed with brain scans. There are no blood tests or brain scans for definitively diagnosing schizophrenia.

Nonetheless, there is growing evidence that dopamine, a key neurotransmitter in the brain, is abnormally regulated in schizophrenia. Given the highly interconnected nature of the brain, other neurotransmitters are sure to be involved too.

There is also a strong genetic element to schizophrenia, and there are likely to be multiple genes of moderate or small effect, which have yet to be fully understood.

Moreover, it remains stubbornly the case that most people with schizophrenia do not have a family history of the disorder, and most people with a family history do not develop schizophrenia.

Therefore, while family history and genes increase the risk of schizophrenia, environmental factors are critically important too. And this – finally – brings us to cities.

Schizophrenia and the urban effect

Studies of the distribution of schizophrenia around the world have long recognised that the condition is more prevalent in urban areas than rural ones.

Research that took place back in the 1960s and 1970s showed that the most obvious explanation for this turns out to be at least partly true: people who have pre-existing schizophrenia tend to move to urban areas to seek out assistance, accommodation and support, leading to a relative concentration of schizophrenia in cities as a result of the disorder.

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Young people born in a city environment have an increased risk of developing conditions such as schizophrenia. One factor that could contribute towards this is a higher baseline cortisol level in the body © Getty Images

It soon transpired, however, that this ‘urban drift’ effect was not of sufficient magnitude to entirely explain the association between schizophrenia and cities. Various other factors were at play.

Studies from the 1970s onwards shed further light by demonstrating repeatedly that, even after taking ‘urban drift’ into account, cities are associated with a substantially increased risk of people developing schizophrenia.

The more methodologically sound and larger the study, the greater the risk associated with cities.

All told, the scientific literature now definitively shows that urban birth, urban upbringing, and urban living are all associated with an increased risk of subsequent schizophrenia.

Just like having a family history of schizophrenia, exposure to urban environments appears neither necessary nor sufficient for developing the disorder, but it does increase the lifetime risk from 1 per cent to approximately 2 per cent, using the best available estimates.

This increase in risk is not nearly enough to advise against living in a city, even among those who have a family history or other risk factors for schizophrenia. So don’t move house – at least not yet.

But the fact that such a small risk is identified so consistently by different research groups, using different methodologies, in different locations, at different times, makes it unlikely that the finding is due to chance alone.

Moreover, in terms of causality, there is not only a strong correlation between cities and schizophrenia, but there is also evidence of a dose-response effect: the greater the degree of urbanicity at birth, the greater the risk of developing schizophrenia.

There is clearly something at work here, some unidentified biological or psychological factor associated with cities that alters brain development or function to increase the risk of schizophrenia. But what is it?

What’s the link between schizophrenia and cities?

There are multiple suggested explanations for the link between cities and schizophrenia.

For example, there is long-standing evidence that if a mother becomes unwell during pregnancy, such as coming down with influenza, then it might increase the baby’s risk of developing an illness or disorder as a young adult.

Another theory is that cities are associated with increased exposure to cats and, therefore, the risk of cat-borne infections such as toxoplasmosis.

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Increased exposure to cats leads to greater risk of cat-borne infections © Getty Images

It now appears that if there is an association between cats and schizophrenia (and that is not yet proven), it is independent of the link between cities and schizophrenia.

Other possible explanations for higher levels of schizophrenia in cities include increased exposure to air pollution and more incidences of vitamin D deficiency. But these, too, remain unproven.

As interest in this field soared during the 1990s, several possible explanations were ruled out. It is now clear that the increase in risk is not closely linked with socioeconomic group in childhood, household overcrowding, parental lower income, parental unemployment, increased cannabis use, or number of older siblings. So what theories are left?

Some of the most compelling schizophrenia research in recent years links increased risk of the disorder with ‘community disorganisation’ and its associated social, psychological and biological effects.

For example, it is known that migrants experience increased rates of many mental disorders, including schizophrenia. Why?

Psychiatrist Dr Jane Boydell and colleagues have shown that the smaller an ethnic minority group is, the greater its increase in risk. In other words, the size of any ethnic minority group operates as a buffer against the increased risk of schizophrenia: the larger the group, the lower the risk.

Are these social risk factors having a greater impact in cities than elsewhere, accounting for the link between urban living and schizophrenia? And, if so, what is the reason for this effect?

The effects of stress

Many psychiatric disorders, including schizophrenia, are associated with disturbances of the body’s stress responses. This is reflected in levels of cortisol, which is a steroid hormone that’s produced by the adrenal gland in stressful situations.

Chronic production of high levels of cortisol has a damaging effect on virtually all body systems, including the brain.

It is possible, and even probable, that belonging to a small migrant group is associated with a state of chronic stress, producing increased baseline cortisol and therefore increased risk of schizophrenia.

There are reasons to believe that this kind of ‘stress effect’ is more powerful in urban areas, because city living affects the brain’s response to stress. Baseline levels of crime, social fragmentation and urban decay are also important.

This model, linking community factors with effects on individual brains, receives strong support in a study by Duke University and King’s College London, published in Schizophrenia Bulletin in May in 2016.

The team analysed data from over 2,000 UK-born twins and found that reduced social cohesion and crime victimisation likely explain, at least in part, why children in cities have an increased risk of developing symptoms of disorders such as schizophrenia. It is not the cities themselves, then, but the way we live in them that likely matters most.

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Cortisol is produced by the adrenal gland in response to stressful situations © Getty Images

This is an exciting finding that is both consistent with previous studies and robust enough to add extra weight to the idea that community disorganisation is closely linked with whatever mysterious biological mechanism connects cities with schizophrenia.

So while research is clearly heading in the right direction, it still remains unclear what any of this will mean for the treatment and prevention of schizophrenia.

Treatments and risk factors

There are many pharmaceutical, psychological and social treatments for schizophrenia, and these help patients and families a great deal. It is critical that these treatments are delivered efficiently, effectively and with compassion, to heal and empower the mentally ill and their families.

But these treatments are deeply imperfect and are not cures for schizophrenia.

The prospects of better treatment would be much improved if we understood precisely what causes schizophrenia in the first place. But we do not.

In the search for answers, it is critical to develop a better understanding of urbanicity and – even more so – its relationship with other risk factors, such as genes, prenatal or birth injury, psychological trauma, cannabis, head trauma, migration, social adversity, chronic stress and others.

All are of these linked with schizophrenia to varying degrees, but none are fully understood.

Ultimately, research is hampered by the fact that schizophrenia is defined by symptoms rather than biological tests. ‘Schizophrenia’, like ‘fever’ or ‘headaches’, is almost certainly an umbrella term that covers a family of different but related ‘sub-disorders’, rather than a single, biologically distinct entity.

These sub-disorders, despite sharing many symptoms, might well have somewhat different origins in different groups or individuals. As a result, schizophrenia retains the ultimate mystery that is intrinsic to all true scientific enigmas: it might not exist as a definable entity.

The undeniable suffering of people diagnosed with schizophrenia may well reflect different combinations of risk factors producing similar – but not identical – collections of symptoms.

In this context, the link between schizophrenia and cities is, perhaps, not so surprising.

Cities are complex, intricate entities, difficult to define, challenging to explain, and yet remarkably enduring throughout recent human history. Cities, in other words, are a lot like schizophrenia.

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