Over the last few years, I’ve had several friends begin their battles with mental illness. For some it was a short lived depressive episode, for others it has been much more serious with chronic depression and even schizophrenia. All this begs the question: are these battles the result of nature or nurture?
The public as a whole seems to be very torn on whether mental illness is the result of a person’s genetics or if it is due to their environment. Back in the 1960’s and 1970’s it was commonly believed that mental illness was caused by bad parenting and “the refrigerator mother.” By the late 1990’s it was still widely believed that a current stressful environment and neglectful upbringing was the major cause; but it also became more popular to cite a “chemical imbalance” as the cause of mental illness (though the public never seemed to know what these “chemicals” were). Even now, when searching through literature, it is equally as common to find journal articles that claim genetic factors are the major cause as it is to find articles claiming societal or environmental factors are the major cause. So if both the “experts” and the public at large are so confused about the cause of mental illnesses, how are we supposed to know how to prevent it? Are we all just ticking time bombs?
|Where is adult-onset mental illness on this spectrum?|
It turns out, the answer to the question of the cause of mental illness being nature or nurture may be as simple as: both. This year an article was published in Science about epigenetic causes of adult-onset psychiatric disorders. Now, most of the time when you tell someone that something is caused by epigenetics, they will respond with “eh-pee-jah-what?” So when you go and tell all your friends about this article, you can just tell them that epigenetic changes are changes to how your cells read your DNA without changing the sequence of your DNA base-pairs. These researchers focused specifically on how environmental stressors in childhood and adolescence cause an epigenetic change, and it is this change that causes the adult onset mental illnesses that we have been talking about.
In this study, mouse models were used to emulate different possible causes of mental illness. These groups of mice received one of four different treatments: only genetic risk factors, only environmental stressors, no genetic risk factors or environmental stressors, or both genetic risk factors and environmental stressors. To create the genetic risk factor the researchers created a mutation in the gene for a protein called DISC1 (which stands for “Disrupted In Schizophrenia 1”) to alter the normal protein that is produced naturally by cells. In humans changes to the DISC1 gene is thought to cause a predisposition to disorders such as schizophrenia, clinical depression, and bipolar disorder. The environmental stressor was created by placing young mice in isolated cages for 3 weeks during brain development; since mice are social animals, this treatment is thought to mimic the stress of separation from parents and family in human children and adolescents.
The researchers found that only mice in the group that had both the genetic risk factor and the environmental stressor displayed behavioral symptoms that would indicate mental illness in humans. These behavioral symptoms included significant deficiencies in locomotor activity and swim tests. These symptoms were present in both males and females within this treatment group, but no observable physical changes (such as gain or loss of body weight) were initially found to explain them.
When the brains for each group were studied, there was no significant difference in the number of neurons or glial cells present indicating that these symptoms were not caused by an anatomical difference in the brain.
However, it was found that in mice that had the genetic factor and the environmental stressor there was a significant decrease in the amount of dopamine and tyrosine hydroxylase (a precursor for dopamine) present in the frontal cortex of the brain compared to all of the other treatment groups. Dopamine is one of the chemicals involved in communication between neurons, and is known to play a role in reward-driven learning. Highly addictive drugs such as methamphetamine cause the release of excessive amounts of dopamine, where diseases like Parkinson’s that are characterized by tremors and decreased motor function are caused by the degeneration of dopamine releasing neurons. So if a combination of genetic factors and environmental factors can cause a decrease in this chemical, it is unsurprising that these mice’s behavior shows a decrease in motor function.
|Dopamine Pathways in the Frontal Cortex of the Brain|
They were also able to show that the decrease in dopamine was related to the significant increase of corticosterone in these mice. The human equivalent of corticosterone is called cortisol, and has been shown to be significantly increased with stress. Humans with chronically high levels of stress will also have chronically high levels of cortisol. It has also been reported that cortisol can influence a type of epigenetic change called DNA methylation.
Finally, it was found that mice that had received both the genetic factor and the environmental stressor had a significant increase in the amount of DNA methylation on the gene for tyrosine hydroxylase (i.e. the gene that causes the production of dopamine). This increase in DNA methylation persisted even after the mice had been back in group housing for 12 weeks (a relatively large portion of a mouse’s life!).
|DNA Methylation, a Type of Epigenetic Change|
So let’s recap. We know that high levels of stress cause higher levels of cortisol. Cortisol can cause epigenetic changes known as DNA methylation to the gene that produces the precursor for dopamine. These epigenetic changes cause less dopamine to be produced. Less dopamine causes less motor function. Less motor function is an indicator of mental illness in mice.
But that leaves the question: how does this relate to us? If the decreased motor function in the mice in fact translates to mental illness in humans, then it means that genetic predisposition or environmental stressors during childhood alone will not cause adult-onset mental illness. Both must be present for one of these disorders to occur.
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Link, B.G., J.C. Phelan, M. Bresnahan, A. Stueve, and B.A. Pescocolido. 1999. Public Conceptions of Mental Illness: Labels, Causes, Dangerousness, and Social Distance. American Journal of Public Health 89:1328-1333.
Nestler, E.J., M. Barrot, R.J. DiLeone, and L.M. Monteggia. 2002. Neurobiology of Depression. Neuron 34:13-25.
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