11 April 2014
Earliest roots of psychiatric disorders traced to stress effects on single gene
by Will Parker
Babies whose mothers were exposed during pregnancy to stressors such as trauma, illness, alcohol, or drug abuse become susceptible to various psychiatric disorders later in life. Now, researchers think that it may be the stressor's effect on single gene that gives rise to conditions such as schizophrenia, PTSD, autism, and bipolar disorders.
The Yale University team behind the discovery say they have identified a single molecular mechanism in the developing brain that sheds light on how cells may go awry when exposed to a variety of different environmental insults. The findings, appearing in the journal Neuron, suggest that different types of stressors prenatally activate a single molecular trigger in brain cells that may make exposed individuals susceptible to neuropsychiatric disorders.
Specifically, the researchers found that mouse embryos exposed to alcohol, methyl-mercury, or maternal seizures all activate in the developing brain cells a single gene - HSF1- which protects and enables some of the brain cells to survive prenatal insult. Mice lacking the HSF1 gene showed structural brain abnormalities and were prone to seizures after birth, even after exposure to very low levels of the toxins.
In addition, the researchers created stem cells from biopsies of individuals diagnosed with schizophrenia. Genes from these "schizophrenic" stem cells responded more dramatically when exposed to environmental insults than stem cells obtained from non-schizophrenic individuals. The findings provide support to the notion that stress induces vulnerable cells to malfunction.
"It appears that different types of environmental stressors can trigger the same condition if they occur at the same period of prenatal development," said Yale's Pasko Rakic, senior author of the study. "Conversely, the same environmental stressor may cause different pathologies, if it occurs at different times during pregnancy."
Since HSF1 activation can potentially serve as a permanent marker of the stressed/damaged cell, it opens the possibility of identifying these cells in adults in order to explore the pathogenesis of postnatal disorders and how to protect vulnerable cells.
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Source: Yale University