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

That is the title of this article I am reviewing today. " 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. 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."This is very interesting and changes a lot of the thinking that environment is what causes this when you are reaching adulthood. A lot of changes could have happened when a person mother was pregnant.
The article goes on to say: "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." If your mother was sick with the flu or any changes could have happened.  That a person does not remember.
The article ends: "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." They do say this might not be the final word on this. It does make sense though would be glad when the final word about this comes out.

How Schizophrenia Affects the Brain

That’s the title of this article that I am writing about for this blog.  This is well studied article that starts off: “It’s hard to fully understand a mental disease like schizophrenia without peering into the human brain.  Now, a study by University of Iowa psychiatry professor Nancy Andreasen uses brain scans to document how schizophrenia impacts brain tissue as well as the effects of anti-psychotic drugs on those who have relapses.”  I only had a relapse once when my medication was to low that was a hard time because I had just started college and had to miss a week.  I had to change my Spanish class because he only allowed three missed days and I had already missed three.

How did they do this study? “Andreasen’s study, published in the American Journal of Psychiatry, documented brain changes in MRI scans from more than 200 patients beginning with their first episode and continuing with scans at regular intervals for up to 15 years.  The study is considered the largest longitudinal, brain-scan data set ever compiled, Andreasen says.  Schizophrenia affects roughly 3.5 million people, or about one percent of the U.S. population according to the National Institutes of Health.  Globally, some 24 million are affected, according to the World Health Organization.  That is a lot of people that have schizophrenia. She did this study for fifteen years.  That should have told a lot about the brain.
What did this study find? “The scans showed that people at their first episode had less brain tissue than healthy individuals.  The findings suggest that those who have schizophrenia are being affected by something before they show outward signs of the disease.  There are several studies, mine included, that show people with schizophrenia have smaller-than-average cranial size, explains Andreasen, whose appointment is in the Carver College of Medicine.  Since cranial development is completed within the first few years of life, there may be some aspect of earliest development—perhaps things such as pregnancy complications or exposure to viruses – that on the average, affected people with schizophrenia.  Andreasen’s team learned from the brain scans that those affected with schizophrenia suffered the most brain tissue loss in the two years after the first episode, but then the damage curiously plateaued—to the group’s surprise.  The findings may help doctors identify the most effective time periods to prevent tissue loss and other negative effects of the illness, Andreasen says.”  It is a drag not knowing why and how this happens.  All of us with schizophrenia would like solid answers.
The study also found: “The researchers also analyzed the effect of medication on the brain tissue.  Although results were not the same for every patient, the group found that in general, the higher the antipsychotic medication doses, the greater the loss of brain tissue.  This was a very upsetting finding, Andreasen says.  We spent a couple of years analyzing the data more or less hoping we had made a mistake.  But in the end, it was a solid finding that wasn’t going away, so we decided to go ahead and publish it.  The impact is painful because psychiatrists, patients, and family members don’t know how to interpret this finding.  Should we stop using antipsychotic medication? Should we be using less?”  It is hard not to take your medication because it makes a person almost normal.  I know when I was in jail for those months being psychotic just because the psychiatrist did not like me and told me that and would not put me on medication.  That was hard being punished because I was not liked.  At least the jail guard understood my position and helped me out. 
The study also studied relapses: “The group also examined how relapses could affect brain tissue, including whether long periods of psychosis could be toxic to the brain.  The results suggest that longer relapses were associated with brain tissue loss. The insight could change how physicians use antipsychotic drugs to treat schizophrenia, with the view that those with the disorder can lead productive lives with the right balance of care.  We used to have hundreds of thousands of people chronically hospitalized. Now, most are living in the community, and this is thanks, to the medications we have, Andreasen notes.  But antipsychotic treatment has a negative impact on the brain, so we must get the word out that they have fewer side effects than some of the other medications we use, they are certainly not trouble free and can have a lifelong consequences for the health and happiness of the people and families we serve.”  I could not live without my medication. I’ve been there.  Hopefully they put more into research for the future people who get schizophrenia so they can also lead productive lives and have medication that does not harm them.