Wednesday, February 1, 2012

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.

20 comments:

40 below said...

I lived with depression that resulted from thinking negatively about my environment and others. I made a fictional feature length movie about the experience:

http://www.openfilm.com/videos/of-games-and-escapes

Bevan.

Addy Bell said...

I'm glad I'm not the only one who thinks Whittaker's agenda as "idiosyncratic". He writes like he's got a horse in this race, but I haven't heard what is is -- does he have a friend or family member who suffered ill effects from brain meds? Or was it him?

John McManamy said...

Hey, Addy Bell. Very interesting observation of yours: "He writes like he's got a horse in this race." My response to that, he hasn't revealed his horse. In his 1998 book Mad in America - I'm citing this from memory here - he reveals that he got interested in mental health and psychiatry through the Mindfreedom people. Prior to that he was writing about shady ethics involved in drug trials (I think psych meds were only a small part of his beat). Before that, I think he worked various beats on a newspaper.

So basically, Whitaker is a journalist who found something interesting to write about - which is great. Fantastic, even. We need more journalists who find us interesting. And Whitaker certainly brings enviable skills to his reporting. Many a time, I've read his stuff and said to myself, "I wish I had written that," or "I wish I had had the skills or perseverance to dig that out."

But there are considerable downsides to journalists who find us interesting. This is nothing personal about Whitaker. This applies across the board. It also applies in other professions, including research and psychiatry. You probably know it already:

You become heavily invested in your own work. That is essentially the horse you have in the race. And you keep riding the same horse, no matter what.

In the recovery movement, we constantly have to remind those who purport to help us or speak on our behalf that their interests are not the same as ours. When our interests intersect, great partnerships result. When they conflict we need to be very aggressive in standing up for ourselves. This applies whether it is psychiatrist or a research or a drug company or someone pushing a herbal remedy we are talking about - or a journalist.

It's not just Whitaker. I need to be held accountable, as well.

And we're not always going to agree on what we see. Nevertheless, we need to bringing what we see to people's attention. Right now, I am having serious issues involving Whitaker's idiosyncratic agenda. Let's see where the conversation leads.

Again, many thanks for posting. :)

Anonymous said...

On more than one occasion, Whitaker has alluded to the premature death (from the metabolic consequences of the atypical antipsychotics)of a high school friend.

Tony Previte said...

ubtabJohn, I'm a little surprised at what amounts to an attack on Robert Whittaker. I know both of you beyond just being "fans" of your work and have had personal conversations with both of you. YES, I know this isn't personal to Robert... but it certainly doesn't appear that way to a more casual observer now does it?

John McManamy said...

Hey, Tony. Whitaker's spouting nonsense about the NIMH being tainted by eugenics and we're supposed to ...?

Tony Previte said...

.... Question it, for sure. But attack him?

Look, we've all been sold a bill of goods on many fronts when it comes to the field of Mental Health. It's not just a question of meds. Stories like mine are getting out there and yes... it's a little ugly for some people to accept. You mentioned in an earlier post that "This job sucks". You're right, it does!! Because nobody wants to pay for it, therefore it's not a job... you're volunteering. I've been volunteering in the hopes of landing a position as a peer support specialist in some kind of capacity for OVER a year, yet nobody hires me. My own success has cast me out as an outsider, much like groups like DMDA & DBSA did years ago.

I guess my point is while Robert may not have given the proper context for some NIMH studies and glossed over some stuff and spun it in a way that may seem disingenuous, in the broad view, there's a lot of truth in there. My own life is the proof I need of that.

So while the emerging new science of the brain will yield some amazing new discoveries, those of us that have "busted" our own labels will continue to be VERY critical of who is doing what to whom because the very agencies that we've entrusted to come up with answers have FAILED us in epic fashion for many years.

I know that you, me and Robert would probably agree about that!

Anonymous said...

Whitaker's treatment of Insel is mild compared to that of the retired psychiatrist who blogs at oneboringoldman.com. The truth is that psychiatry does have a very checkered past and a coercive present (depot injections, anyone?)
The epigenetic studies you cite are consistent with an interpretation that the long term use of antipsychotics can alter gene expression - frequently to the detriment of the patient.

John McManamy said...

Hey, Anonymous. I definitely agree. This blog has been very critical of psychiatry, past and present. My website urges readers to be skeptical of psychiatrists, rather than trusting. I also agree that if various environments can alter gene expression then obviously psychiatric meds are prime suspects.

Whitaker and others have made me realize I need to prioritize my research into epigenetics. It's also clear that we need a lot more funding for epigenetic research into mental illness (including new epigenetics meds research and how our current meds mess with gene expression).

Let's keep the conversation clear and focussed. Wild accusations about the NIMH with some kind of eugenics agenda does not help our cause.

Re 1boringoldman - many thanks for bringing him to my attention. I only had a chance to very quickly skim his stuff, but first impression he comes across as very informed and very informative. I will go back and read him in more detail.

John McManamy said...

Hey, Tony. Yep, we have been sold a huge bill of goods and this is a fact that unites us all. Psychiatry has been corrupted behind repair - I'm on record in a bunch of pieces on that proposition. You also know that I believe that 2/3 of pdocs are incompetent.

For years, I have been writing that it's the brain science and the recovery movement that is driving the future. The brain science is blowing old psychiatric notions right out of the water. It's really exciting stuff and it's validating the work of the recovery movement.

Not only that, we can apply brain science RIGHT NOW in our recovery. Never mind that we haven't had any new drugs since the 1960s - in the last decade the brain science has cracked the stress-anxiety/depression/other stuff connection.

This is major. Work on our stress, we start to get our lives back. We can cut back on our meds or maybe go off of them.

Right now, I can approach any psychiatrist in the world, look him or her right in the eye and say: The scientific evidence is absolutely solid for lifestyle change, yoga, meditation, etc etc while the evidence for meds is highly suspect.

In other words - our evidence is better than yours.

Six years ago, I don't think I could have said that - that's how fast the brain science is advancing. I say increase the funding for the brain science. Lots more money. Also, if we do the advocating for this - guess what? - we get to set a piece of the agenda.

I'm going on and on, but I think you see the point.

As for Thomas Insel - he may have an MD, but he thinks like a brain scientist. Indeed, he is a leading brain scientist, with pioneering research to his credit. (Google "Insel prairie vole"). The NIMH research on his watch has been nothing short of amazing. As well as opening new horizons, it has shown the limits of meds and psychiatry. Insel himself is a strong critic of psychiatry.

I'll shut up now ...

Amy Karon said...

Hi, John. I really like your overview of epigenetics. I read it without knowing much about the link between epigenetics and mental illness, and found it gave me a solid introduction. And thanks for reiterating the importance of emerging research on how stress can trigger or worsen symptoms of mental illness. I think this connection can't be overstated, given the data that's now out there.

John McManamy said...

Many thanks, Amy. I'm looking forward to publishing a lot more on epigenetics. Right now, I'm working my way through a 25-part lecture series by Robert Sapolosky. Dr Sapolsky, I'm sure you are aware, is a pioneer in the field of stress-human behavior research. So stay tuned for a whole host of blogs on stress.

You're absolutely right. This stuff is extremely important. :)

John McManamy said...

Hey, Corinna. I neglected to get back to you on your piece on genes you posted on WordWorks. I generally agree, but with this proviso. The gene research is coming in loud and clear on our vulnerability to stress. It's all about the environment. Our genes influence how we react to the stuff around us.

So the traditional gene research looking for mental illness genes is highly suspect. But stress is complicit in depression, anxiety, psychosis, etc.

Also, epigenetics - which is all about switching on and off genes in reaction to environmental influences - now appears to be the main event (till we find another main event).

Take home message - yours is the same as mine: Work on our stress. Think of ourselves as being vulnerable to stress rather than simply having mental illness. Work on our vulnerability with every recovery tool we can, with all we've got, and maybe we start turning our lives around.

I'm really glad you're getting the word out ...

Lauren Liefland PhD said...

There is "good stress" like positive excitement elicited by music, theater, exercise, dance and creative pursuitsisdat and "bad" stress like interpersonal conflicts and unhealthy lifestyles. Yoga is wonderful, John, but there are also exciting ways to get involved and engaged in stimulating activities and outlets that do not focus on withdrawal from the world. It is great to include the Hindu and Buddhist paths to serenity but it is also valuable to celebrate the active indulgences in healthy pleasures that spark the imagination and laughter.

John McManamy said...

Hey, Lauren. I do get my "good stress." I was out and about this weekend doing my didge-drumming thing. Last week I was with friends in LA - we witnessed Dude conducting my favorite Mahler symphony.

And I also experience the good stress of pushing myself, which includes the thrill of discovery in breakthroughs at work and play.

Re Buddhism - I see it as way more than serenity. It is a great psychology for keeping me engaged in the present and with the people around me. Throw in loving kindness and it is a great social-enhancer.

We have to worry about life overtaking us in two different directions. On one end, we are overstimulated, so finding sanctuary, asylum, is vital. On the other, we too easily get isolated, so we need to get out and connect. Finding the sweet spot is never easy. I'm getting better at it, but I don't always get it right.

Becky said...

a horse in the race---could be that Bob Whitaker just might give a flying fuck about humanity...just maybe. Or do y'all think only the biomedical believers are 'caring'????

truly sad how invested some of us can get in owning defects that are based on eugenic notions of inferiority...
Of course, once I started realizing that if I wasn't genetically defective or diseased; I should probably become accountable for my behavior, my thoughts and my emotions---and stop being a victim of a disease that there is no evidence exists...it does relieve a person of some responsibility to believe in the bullshit, which is why I stayed stuck in the role of being a victim of 'my mental illness'---as long as I bought into the bullshit, I lowered my expectations of myself, and so did everyone else...

Smitty said...

Whoa, epigenetics is about brain plasticity, isn't it?

If it leads us to natural methods of encouraging resiliency, like healthy diet, lifestyle changes, medications without side effects... meditation, THEN I am all for it. But if it leads us to more pills, and doctors just diagnosing more and more people without using good common sense, I don't want to pursue that line of research spending.

John McManamy said...

Hey, Smitty. Great minds think alike. I've been arguing for years now that brain science validates recovery. I'm way too jaded to believe that great new meds will come out of it, though I hope I'm wrong.

The big story is our recovery, things we can do RIGHT NOW for ourselves based on our new insights into how the brain works. We're not stuck with the same software for life - we can change it. And if genes are all about how we react to our environment - guess what? - we can change our environment.

You picked it up - the epigenetics looks like it is bringing the environment into sharp relief. It looks like there could be things we can do for ourselves to make sure we don't switch on the wrong genes. I need to do more research, but the recovery implications look enormous.

Again, I'm too jaded to think that good meds will come out of this, though never say never. It is natural for researcher to mention the possibility of new meds - that's how they get grants to keep researching. I say keep them researching for the sake of research. We're smart enough to their insights to our recovery.

herb said...

Re 1boringoldman

Yes John, he does come across “very informed and very informative” but what bothers me is the fact that I posted several times to his forum all of which for some strange reason never made it to his comment section. As you know I come from a different perspective that being a very, very long-time support person.

I asked the retired psychiatrist (1boringoldman) why is it that he sat by all these years that he practiced his profession without voicing or objecting to the practices, KOL, pharmaceutical industry etc., etc. that he is now so vociferously expounding publicly on his blog site as I would tend to now call “coming out of the closet”.

He never responded to me nor has he really addressed the question and issues of his silence although he does seem to favor those like-minded individuals stroking him who comment to his forum.

Maybe one day you or one of your readers might ask of him the same questions and hopefully get a public response.

Please don’t miss understand me, I do appreciate reading his thoughts and analysis but I certainly would have felt more comforted in his revelations during our 5 decade odyssey although we were fortunate in having caring and knowledgeable physicians attending to my spouse willing to share their knowledge with us and answering our questions as best they could.

As always, I wish you and yours wellness and all the good you’d wish for yourselves.

Warmly,
Herb
vnsdepression@gmail.com
http://www.vnstherapy-herb.blogspot.com

John McManamy said...

Hey, Herb. I, too, have issues with bloggers who claim to be doctors but don't reveal their names or personal information. Their professional credibility goes right out the window. Readers can not check up on them, see where their money is coming from, etc. As a journalist, I can't quote these people as MDs.

This applies to anyone writing blogs. We are entitled to disclosure. Professional credentials, patient credentials, family credentials, funding, life experience.

This is obviously important to 1boringoldman, too. He attacks Nemeroff and Biederman based on their ties to the drug industry. Fair enough. Those two deserve to be pilloried and their entire body of work deserves to be discredited as a result of the payola they received and failed to disclose.

What's good for the goose is good for the gander.

There are exceptions. A while back, a doctoral student with schizophrenia was posting a very informative blog. Obviously, we are not going to ask this person to commit social and professional hara kiri by revealing his or her identity.

There is also scope for patients and family members to blog anonymously. Their narratives either resonate or they don't.

In the "About" section, 1boringoldman does not claim to be a doctor. He's just some old retired guy. But this is disingenuous. Start reading his blogs and he starts referring to things he came across while practicing as a clinician.

Okay, so who is this guy?

I will acknowledge he posts some very good stuff, though it is basic psychiatry-bashing. Much better than your generic psychiatry-bashing, which makes the blog worth reading. Still, if this guy is a retired pdoc, I would be very much more interested in his clinical insights. For instance:

What qualities separated out patients who got better and those who didn't? Did he come across any predictors of successful outcomes?

What therapies, treatments, etc got the best results for his patients? On and on.

I'm guessing 1boringoldman comes from a psychodynamic background. Okay - does psychodynamics work? If not, can he justify why he used psychodynamics anyway and still got paid? If it does work, can he please educate us? Tell us why he believes psychiatry needs to return to his roots?

Admittedly, I have only sampled his blog. But those kind of insights did not turn up in my samples.

There is no point in personally challenging him on all this. This is what he does.

Hopefully, we will have more retired pdocs blogging and they will tell us more. We can certainly use their wisdom.