Prenatal Folic Acid and Schizophrenia Prevention

My group has been studying folic acid, which is B vitamin, and it's potential for neuroprotective effects in schizophrenia Given that schizophrenia is thought to be fundamentally an illness of disordered brain development, events in brain development that happen during pregnancy subsequently laying the foundation for risk later on in life, we were curious about whether folic acid exposure during pregnancy might have a stronger effect than what we see after the onset of illness and could even potentially prevent some cases of schizophrenia later in life

To understand this question, which is difficult to study given the delay of about 20 years between prenatal development and the onset of schizophrenia, we decided to leverage, as a natural experiment of sorts, the roll out of folic acid fortification of the grain supply, which was introduced in the late 1990s, in order to reduce risk of spina bifida and other neural tube disorders What we have found is that that intervention seems to be associated with changes in the trajectory of brain development, and specifically in the development of the cerebral cortex, that appear to be protective against risk for schizophrenia This data, really for the first time, links a brain-biology marker of schizophrenia risk, which is cortical thickness reduction, to an intervention that occurs during prenatal life that, indeed, in many cases, is already being given These relationships between folic acid exposure and brain development, subsequent risk of illness, appear to be strong, and at the same time, on the level of basic brain biology, we're not sure what the mechanisms are This would be really important to try to understand, because if we can pull out intermediate mechanisms on the level of cell biology, gene environment interactions, especially since what folic acid does is help to control gene expression through changes in methylation, this might identify some new bio-chemical, metabolic pathways that can be leveraged to develop even more specific treatments

And when I say treatment, that could either be in the realm of treatment after someone develops the illness or a preventative type of intervention On one level, we are interested in understanding more about the biology that drives these changes, so that we can harness that biology to get even more specific interventions On the other hand, there is an important public health issue here, which is that with the availability of folic acid and it's being recommended universally, in terms of supplements for women who are trying to become pregnant, and somewhat less universally in terms of fortification of the food supply, there is a real opportunity here to try and understand why it is that more women of child-bearing are not taking folic acid, either as a supplement or why certain governments have chosen not to fortify the food supply If we can understand those barriers, then potentially we can increase the adherence to something that really is already recommended, and not only see a benefit in terms of spina bifida, but also potentially in terms of risk for severe mental illness


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