Epigenetics and Mental Illness and You

Two posts ago, I took Robert Whitaker to task for misreporting an NIMH-funded study in order to advance his own idiosyncratic agenda. Whitaker reported the study as a garden variety postmortem exam of brains of those with schizophrenia vs controls. The study, in fact, involved epigenetics, which Whitaker both failed to mention and displayed no knowledge of.

I first came across the field in late 2003, which I reported soon after in an email newsletter and a month or two later in an article on mcmanweb. Last year, I folded the piece into a reworked article on genes. Back in 2003, like just about everyone else, I treated epigenetics as a sideshow - worth knowing about but not worth missing the latest American Idol over. Now, it is abundantly clear that epigenetics is emerging as the main event.

Lately, I've been running across reminders that I need to put a match to all my website content on genetics and start over, with epigenetics front-center. Great, a mammoth science project. In the meantime, here is my original piece ... 

The conventional wisdom on genes goes something like this: DNA is transcribed onto RNA, which form proteins, which are responsible for just about every process in the body, from eye color to ability to fight off illness. But even as the finishing touches were being applied to the sequencing of the human genome (completed in April 2003), unaccountable anomalies kept creeping in, strangely reminiscent of the quarks and dark matter and sundry weird forces that keep muddying the waters of theoretical physics.

Enter the science of epigenetics, which attempts to explain the mysterious inner layers of the genetic onion that may account for why identical twins aren't exactly identical and other conundrums, including why some people are predisposed to mental illness while others are not. Scientific American devoted a two-part article to the topic in its November and December 2003 issues. To summarize:

Only two percent of our DNA - via RNA - codes for proteins. Until very recently, the rest was considered "junk," the byproduct of millions of years of evolution. Now scientists are discovering that some of this junk DNA switches on RNA that may do the work of proteins and interact with other genetic material. "Malfunctions in RNA-only genes," explains Scientific American, "can inflict serious damage."

Epigenetics delves deeper into the onion, involving "information stored in the proteins and chemicals that surround and stick to DNA." Methylation is a chemical process that, among other things, aids in the transcription of DNA to RNA and is believed to defend the genome against parasitic genetic elements called transpons. A 2003 MIT study created mice with an inborn deficiency of a methylating enzyme. Eighty percent of these mice died of cancer within nine months.

A late 2003 PubMed search of epigenetics and bipolar disorder revealed but two articles. A Jan 16, 2011 search turned up 83. Arturas Petronis MD, PhD, of the University of Toronto authored both of the 2003 articles. In one of them, he filled in some of the blanks:

We know that there is a high concordance of identical twins with bipolar disorder, but epigenetics, he explains, may account for the 30 to 70 percent of cases where only one twin has the illness.

Identical twins share the same DNA, but their epigenetic material may be different. Moreover, whereas DNA variations are permanent, epigenetic changes are in a process of flux and generally accumulate over time. This may explain, Dr Petronis theorizes, why bipolar disorder tends to manifest at ages 20–30 and 45-50, which coincides with major hormonal changes, which may "substantially affect regulation of genes ... via their epigenetic modifications."

The dynamics of epigenetic changes may also account for the fluctuating course of bipolar, Dr Petronis speculates, perhaps more so than static DNA variations.

Finally, as Scientific American points out, the fact that epigenetic anomalies can be reversed makes them inviting targets for a new generation of meds.

In a 2003 pilot study, Dr Petronis and his colleagues investigated the epigenetic gene modification in a section of the dopamine 2 receptor genes in two pairs of identical twins, one pair with both partners having schizophrenia and the other having only one partner with the illness. What they discovered was that the partner with schizophrenia from the mixed pair had more in common, epigenetically, with the other set of twins than his own unaffected twin.

Check out this 2010 Time Magazine piece on epigenetics.