Is Lead Exposure Behind Cities’ Schizophrenia Problem?


In New York City, like in many other major metropolises, schizophrenia is a disease that can be more visible than most. In 1999, after a schizophrenic off his meds pushed a woman into the path of an oncoming N train, New York State even came up with a law to make the mentally ill seek compulsory treatment. Kendra’s Law, named after the woman who died on the tracks, sought to prevent violence by pushing schizophrenics with a potential for self-harm or violence into psychiatric care.

But for decades, researchers have been struggling with a bigger question about the nature of the relationship between schizophrenia and cities–and why, for example, growing up in a city makes you more vulnerable to developing schizophrenia as an adult.

A landmark study from Columbia’s Mailman School of Public Health and published last week in Schizophrenia Bulletin may shed new light on that connection–for the first time, animal models show that lead, along with other environmental toxins, could be a major contribution to the link.

Senior author Dr. Tomás Guilarte has been studying the effects of lead on cognitive function for more than two decades, but aside from two papers published in 2004 and 2008, he found that research on lead and schizophrenia didn’t really exist. Specifically, Guilarte was fascinated by how lead’s inhibition of something called the N-methyl-D-aspartate receptor (or NMDAR) in our brains might work in a person genetically predisposed to schizophrenia. Could an inhibited NMDAR, he wondered, which already affects learning development and memory, also trigger schizophrenia?

Guilarte’s department and a team from Johns Hopkins set up an experiment–they’d test pre and post-natal lead exposure on two groups of mice, both those engineered with DISC1, a gene proven to be a risk factor for schizophrenia in humans, and those without.

What they found confirmed Guilarte’s hypothesis: Mice with the genetic risk who were exposed to lead began to display signs of schizophrenia in humans–like brain imaging that mirrored the enlarged lateral ventricles of schizophrenia patients, an inability to suppress a startle response to sounds after being given a warning, and abnormally hyperactive behavior in response to stimulants like PCP, which can exacerbate similar symptoms in schizophrenics.

But lead isn’t the only NMDAR inhibitor out there. “There could be potentially tens of others, or hundreds, that we just don’t know about,” Guilarte told the Voice. Manganese, along with diesel-fume pollutant polycyclic aromatic hydrocarbons (PAHs), for example, are also NMDAR inhibitors.

New York City has historically struggled with childhood lead poisoning. While numbers have decreased sharply over the past decade, New York City Department of Mental Health and Hygiene numbers from 2005 show that lead poisoning has been concentrated in Brooklyn, the Bronx, and Queens, specifically neighborhoods like East Flatbush, West Queens, and Bed-Stuy–likely due to lead-based paint in old housing.

“We could just be scratching the surface,” Guilarte said. “Thousands and thousands of kids have been exposed to lead since the 1940s,” he added. “The amazing thing is that [the schizophrenia link] has never been studied.”

The major theory tying “urbanicity” to schizophrenia has centered on something called social fragmentation–Swedish researchers, for example, found that higher rates of schizophrenia occurred in neighborhoods marked by fear of crime, disorder, and victimization. Stress, Guilarte says, plays a major role in mental disorder.

“I think the social context is an important one,” Guilarte said. “You can take social stressors in combination with exposure to environmental toxicants, oftentimes in these neighborhoods are high-levels of exposure–and potentially with genetic susceptibility–you create conditions that are ripe for getting [this] disease.”


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