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Mice Study Suggests Lead Exposure Linked to Schizophrenia

Mice Study Suggests Lead Exposure Linked to Schizophrenia New research proposes early lead exposure can alter a human gene that leads to brain changes associated with schizophrenia.

Investigators discovered that mice engineered with a human gene for schizophrenia, then exposed to lead during early life, presented behaviors and structural changes in their brains consistent with schizophrenia.

Researchers from Columbia University’s Mailman School of Public Health and the Johns Hopkins University School of Medicine believe this finding suggests a synergistic effect between lead exposure and a genetic risk factor.

Experts say this discovery will help them better understand the complex gene-environment interactions that put people at risk for schizophrenia and other mental disorders.

The link between prenatal lead exposure and schizophrenia has been proposed for nearly a decade.

But a big question remained: How could lead trigger the disease? Based on his own research, Tomas R. Guilarte, Ph.D., senior author of the new study, believed the answer was in the direct inhibitory effect of lead on the N-methyl-D-aspartate receptor (NMDAR), a synaptic connection point important to brain development, learning, and memory.

His research in rodents found that exposure to lead blunted the function of the NMDAR. The glutamate hypothesis of schizophrenia postulates that a deficit in glutamate neurotransmission and specifically hypoactivity of the NMDAR can explain a significant portion of the dysfunction in schizophrenia.

In the new study, Guilarte and his co-investigators focused on mice engineered to carry the mutant form of Disrupted-in-Schizophrenia-1 (DISC1), a gene that is a risk factor for the disease in humans.

Beginning before birth, half of the mutant DISC1 mice were fed a diet with lead, and half were given a normal diet. A second group of normal mice not expressing the mutant DISC1 gene were also split into the two feeding groups. All mice were put through a battery of behavioral tests and their brains were examined using MRI.

Mutant mice exposed to lead and given a psychostimulant exhibited elevated levels of hyperactivity and were less able to suppress a startle in response to a loud noise after being given an acoustic warning. Their brains also had markedly larger lateral ventricles—empty spaces containing cerebrospinal fluid — compared with other mice.

These results mirror what is known about schizophrenia in humans.

While the role of genes in schizophrenia and mental disorders is well established, the effect of toxic chemicals in the environment is only just beginning to emerge. The study’s results focus on schizophrenia, but implications could be broader.

“We’re just scratching the surface,” said Guilarte. “We used lead in this study, but there are other environmental toxins that disrupt the function of the NMDAR.”

“Similarly, any number of genes could be in play,” added Guilarte, noting that DISC1 is among many implicated in schizophrenia.

Research in the future will seek to determine the extent by which schizophrenia is determined by environmental versus genetic factors or their interactions — and, what other mental problems might be in the mix.

One ongoing study by Guilarte is looking at whether lead exposure alone can contribute to deficits of one specialized type of neuron called parvalbumin-positive GABAergic interneuron that is known to be affected in the brain of schizophrenia patients.

Scientists are also interested to establish the critical window for exposure—whether in utero or postnatal, or both.

“The animal model provides a way forward to answer important questions about the physiological processes underlying schizophrenia,” Guilarte said.

Source: Columbia University’s Mailman School of Public Health

Word collage of schizophrenia photo by shutterstock.

Mice Study Suggests Lead Exposure Linked to Schizophrenia

Rick Nauert PhD

Rick Nauert, PhDDr. Rick Nauert has over 25 years experience in clinical, administrative and academic healthcare. He is currently an associate professor for Rocky Mountain University of Health Professionals doctoral program in health promotion and wellness. Dr. Nauert began his career as a clinical physical therapist and served as a regional manager for a publicly traded multidisciplinary rehabilitation agency for 12 years. He has masters degrees in health-fitness management and healthcare administration and a doctoral degree from The University of Texas at Austin focused on health care informatics, health administration, health education and health policy. His research efforts included the area of telehealth with a specialty in disease management.

APA Reference
Nauert PhD, R. (2018). Mice Study Suggests Lead Exposure Linked to Schizophrenia. Psych Central. Retrieved on November 28, 2020, from
Scientifically Reviewed
Last updated: 8 Aug 2018 (Originally: 3 Jun 2013)
Last reviewed: By a member of our scientific advisory board on 8 Aug 2018
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