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Mental Health Information Centre - Southern Africa

Major New Study Rewrites the Nature v. Nurture Debate About Schizophrenia

One of the largest studies of postmortem human brain tissue found that environment affected brain changes associated with schizophrenia during early development but not during early adulthood when individuals appear to become ill

The Lieber Institute for Brain Development (LIBD) released today the results of a study that shed new insights on the nature versus nurture interplay in schizophrenia. Findings from one of the largest studies of postmortem human brain tissue suggest that environmental influences during the prenatal period cause brain changes associated with schizophrenia, but that environmental influences in early adulthood, when symptoms of the illness typically emerge, may not be as important as originally thought.

“Mapping DNA methylation across development, genotype and schizophrenia in the human frontal cortex”

The study and its relevant findings were published today in Nature Neuroscience. The published paper, titled “Mapping DNA methylation across development, genotype and schizophrenia in the human frontal cortex,” can be found online here.

Findings outlined in the paper shed new light on the potential role of environmental influences on an individual’s risk of developing schizophrenia. The role of the environment in causing schizophrenia is a hotly debated topic, with many theories focusing on the stressful environment around the early adult period that typically heralds the onset of clinical symptoms of schizophrenia. In the study, results suggest that the prenatal period, not early adulthood, is when environmental influences cause brain changes involving DNA methylation that are associated with a greater risk of schizophrenia.

The environment can affect human biology, e.g. how your brain responds to experience, or how your body responds to exercise, by influencing the mechanisms that turn genes on and off. One of these mechanisms is called “epigenetics,” which involves changes in the chemical structure of DNA without changes in the inherited genetic code itself. DNA methylation is an epigenetic change that signals an environmental effect.

Study investigators analyzed the brain tissue of 526 subjects, including 191 individuals with schizophrenia and 335 normal subjects, to determine how DNA methylation changes in the transition from prenatal to postnatal life and how it changes during early adult life. These time periods both involve profound environmental changes, both biological and experiential. These periods also involve major changes in DNA methylation.

Unexpectedly, investigators found that changes in DNA methylation that are associated with schizophrenia and observable in the brain tissue of patients with the illness had no observable relationship to the environmental effects that might have played on the brain at the time when individuals first require treatment in early adult life – for example, when they first seem to manifest the illness. Instead, the changes were strongly linked to the early development period.

“This is the first time we have been able to take a molecular snapshot of when the environment affects the brains of patients with schizophrenia,” said Andrew Jaffe, Ph.D., the study’s lead investigator.

The results suggest that the epigenetic changes that leave a lasting mark in the brains of patients with schizophrenia harken back to early brain development – long before the first symptoms of the illness are recognized. In other words, the building of the brain early in life is key to understanding schizophrenia, and the events around the apparent onset of the illness “may be a red herring,” said Dr. Jaffe.

“This conclusion, while perhaps not the final verdict on the subject, is hard to resist given this remarkable evidence,” said Daniel R. Weinberger, M.D., director and CEO of the Lieber Institute for Brain Development and co-leader of the research team with Joel Kleinman, M.D., Ph.D., the Lieber Institute’s associate director of clinical sciences. “These results have potentially far-reaching implications for how we understand schizophrenia, how we develop experimental models of this illness in scientific laboratories, how we search for new ways to prevent the disorder from happening, and how we treat it once it does.”

About the Lieber Institute for Brain Development

The mission of the Lieber Institute for Brain Development and the Maltz Research Laboratories is to translate the understanding of basic genetic and molecular mechanisms of schizophrenia and related developmental brain disorders into clinical advances that change the lives of affected individuals. LIBD is an independent, not-for-profit 501(c)(3) organization and a Maryland tax-exempt medical research institute affiliated with the Johns Hopkins University School of Medicine.


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In partnership with:

University of Stellenbosch
South African Medical Research Council
University of Cape Town