The curious psychiatric state of Robert F Kennedy Jr

Robert F Kennedy Jr showed up in a scrum of pro-measles whackos recently. It  me wonder how he got so nuts.

There’s an extensive wikipedia page for him, starting with a time I remember:

He was 9 years old when his uncle, President John F. Kennedy, was assassinated during a political trip to Dallas, and 14 years old when his father was assassinated…

Despite childhood tragedy he was a successful academic and he’s done some decent work legally and for the environment. He seems to have started off the rails in the 80s:

In 1983, at age 29, Kennedy was arrested in a Rapid City, South Dakota airport for heroin possession after a search of his carry-on bag uncovered the drug, following a near overdose in flight.

By 1989 he’d started on vaccines — but not with autism … 

His son Conor suffers from anaphylaxis peanut allergies. Kennedy wrote the foreword to The Peanut Allergy Epidemic, in which he and the authors link increasing food allergies in children to certain vaccines that were approved beginning in 1989

By 2000s he’d jumped from immunizations causing his son’s anaphylactic disorder to immunization causing autism. He became "chairman of “World Mercury Project” (WMP), an advocacy group that focuses on the perceived issue of mercury, in industry and medicine, especially the ethylmercury compound thimerosal in vaccines”. It was a downward spiral from there.

Despite his vaccine delusions and troubled marriages he seems to have maintained a fairly active wealthy person life. He’s said to be a good whitewater kayaker.

Psychiatrically it’s curious. He combines fixed irrational beliefs (the definition of delusions) with relatively high functioning in other domains. He reminds me of L Ron Hubbard, founder of Scientology. 

We need to keep him far from the political world.

High functioning schizophrenia: an academic's story.

"THIRTY years ago, I was given a diagnosis of schizophrenia."

That's a helluva way to start one of the most important NYT OpEd's of 2013 ...

Successful and Schizophrenic - ELYN R. SAKS NYTimes.com 

... I made a decision. I would write the narrative of my life. Today I am a chaired professor at the University of Southern California Gould School of Law... 

... Although I fought my diagnosis for many years, I came to accept that I have schizophrenia and will be in treatment the rest of my life. Indeed, excellent psychoanalytic treatment and medication have been critical to my success... 

... Over the last few years, my colleagues, including Stephen Marder, Alison Hamilton and Amy Cohen, and I have gathered 20 research subjects with high-functioning schizophrenia in Los Angeles.. 

... At the same time, most were unmarried and childless, which is consistent with their diagnoses. 

... in addition to medication and therapy, all the participants had developed techniques to keep their schizophrenia at bay. For some, these techniques were cognitive... 

... One of the most frequently mentioned techniques that helped our research participants manage their symptoms was work... 

... Personally, I reach out to my doctors, friends and family whenever I start slipping, and I get great support from them. I eat comfort food (for me, cereal) and listen to quiet music. I minimize all stimulation. Usually these techniques, combined with more medication and therapy, will make the symptoms pass. But the work piece — using my mind — is my best defense. It keeps me focused, it keeps the demons at bay. My mind, I have come to say, is both my worst enemy and my best friend... 

Elyn R. Saks is a law professor at the University of Southern California and the author of the memoir “The Center Cannot Hold: My Journey Through Madness.”

My freshman roommate developed what I believe was schizophrenia. He dropped out for years, then one day returned to school, completed a PhD and started working. I suspect he was not "cured", just as Elyn Sanks is not cured.

Whatever the limitations of the "schizophrenia" as a diagnostic label (they are many), we now know that a few people are able to manage around a grievous and terrible disability. They have shown that it can be done.

That's important. Remember Roger Bannister? He was one of the first Europeans to officially run a 4 minute mile (I suspect other humans had done it before). Before he did it, few tried. Now many men have done it, including one runner in his 40s. It's still hard to do, but it's not news any more.

Succeeding with schizophrenia is the psychic equivalent of running the four minute mile. Terribly hard to do, but once done methods can be refined, goals set, support provided, lessons learned.

Lessons that I suspect will be of value to many persons, not just schizophrenic and autistic adults, but also all inheritors of the 150,000 year old human mind; hacked together in a blink of Darwin's eye. The techniques used to manage severe psychic turmoil can also be used to manage the lesser afflictions we all experience.

Elyn Saks and fellow champions, we salute you.

See also:

• Who were the crazy genius scientists? 5/2012

Tax bullets to pay for better mental health care

We tax cigarettes to offset some of the social costs of tobacco use. This is type of Pigovian Tax.

We could tax bullets to offset the direct costs of America's weapons glut, but it's hard to make up for murder. 

Better to prevent the murders.

So tax bullets to pay for better mental health care.

All psychiatrists, social workers and primary care physicians know what a train wreck American psychiatry mental health care is. Rich state, poor state, it's a train wreck everywhere. Families don't know what to do for impaired loved ones - because, often, there's nothing available.

There are many things that could be done. We lack will, and we lack money.

The money problem is easy to solve.

Tax the bullets.

See also:

• Be the Best You can Be: Violence and the natural history of Autism - so what do we know? 3/2009: We known almost nothing. Looking at this case history, I suspect "Andrew" had a childhood history of Asperger's followed by late adolescent onset of schizophrenia; atypical because of his preexisting connectopathy. In truth, however, our 21st century psychiatric classifications are the equivalent of 19th century medical classification.
• Gordon's Notes: Aurora - the rational response is better schizophrenia management 7/2012: Ebert and Collins links are, of course, just as relevant today. Same with my 7/12 posts.
• NRA Sets 1,000 Killed In School Shooting As Amount It Would Take For Them To Reconsider Much Of Anything | The Onion - America's Finest News Source 5/2012. Yep.
• When My Crazy Father Actually Lost His Mind - NYTimes.com 6/2012. A typical tour of American mental health. Nothing unusual about it.
• App.net thread on this topic, with appreciation to Clark G.

Aurora - the rational response is better schizophrenia management

Robert Ebert:  "Here is a record of mass shootings in the United States since 2005. It is 62 pages long ... The hell with it. I'm tired of repeating the obvious."

Gail Collins: "Did you catch the one last week in Tuscaloosa? Seventeen people at a bar, hit by a gunman with an assault weapon."

Well said, but both Collins and Ebert know we're not going to get meaningful gun control in the United States any time in the next twenty years. We'll get a Carbon Tax long before we'll get weapon management.

American gun control died when the NRA pushed Bush to a statistical tie with Gore, and brought us the torture presidency.

In any case, it's not clear even strict gun control would be more successful than the American War on Drugs. There are vast numbers of inexpensive and effective weapons of mass murder in the US. The cost of havoc is low.

As a nation, we've gone a long way down a rough road.

That doesn't mean we can't do anything. It's almost certain that the latest killer is mentally ill, probably paranoid schizophrenic. As a nation, our care of the mentally ill is abysmal in blue and red states alike. Physicians have fled the specialty of psychiatry and we're dramatically short of the family physicians who might fill the gap.

If we're going to get anything of value from this soon-to-be forgotten nightmare, it won't be from some incremental and soon eroded change to Colorado's gun control laws. It will come from leveraging Obamney Care's new financing for mental illness. We need to make it much easier for friends, family, and teachers to get help for paranoid schizophrenics, and we need to provide support for treated schizophrenics to stay well.

Update 7/22/2012: A slightly different take from a Columbine book author:

The Unknown Why in the Aurora Killings - David Cullen - NYTimes.com

... Dylan Klebold was an extreme and rare case. A vast majority of depressives are a danger only to themselves. But it is equally true that of the tiny fraction of people who commit mass murder, most are not psychopaths like Eric Harris or deeply mentally ill like Seung-Hui Cho at Virginia Tech. Far more often, they are suicidal and deeply depressed. The Secret Service’s landmark study of school shooters in 2002 determined that 78 percent of those shooters had experienced suicidal thoughts or attempts before mass murder...

It's a bit odd to say that someone who is suicidal and has delusional symptoms of major depression is not "deeply mentally ill", but Cullen is not a physician.

I think what he's trying to say is that most shooters are mentally ill, but that psychotic or severe depression is more common than schizophrenia.

I haven't been able to find any public health literature, but it's important to note that many shooters don't survive to get to a full psychiatric evaluation. One of the best responses to the Aurora shooting would be to fund a review of psychiatric issues in shooters and identify intervention opportunities.

Who were the crazy genius scientists?

Which famous scientists and/or mathematicians were also "crazy" (e.g. - far outside behavioral "norms") during their adult productive lives (excluding those, like Pauling, who became eccentric at an age where dementia is common)?

My current list is ...

1. Newton: Perhaps autism spectrum, but he was so brilliant, and so bizarre, that he's untypable. He's outside of the human range. He may have hard mercury poisoning late in life, or perhaps a late-onset schizophrenia-like psychosis.
2. John Nash: paranoid schizophrenic, though somewhat late-onset. His recovery is remarkable, as was Newton's -- but he was psychotic for a longer time period.
3. Kurt Godel: schizotypal, later in life delusional beliefs with paranoid features.
4. Nikolai Tesla: OCD, Autism spectrum?
5. Henry Cavendish: social phobia, anxiety disorder.
6. Boltzmann: bipolar disorder (classic)

Our classifications of mental illness are pretty weak even in normal IQ adults; this group is probably unclassifiable. Who else should be on the list?

Update: Philip K Dick wasn't quite in this group, but his late-onset pyschosis experience resembles Tesla's. Matt suggested Godel and Boltzmann. The pattern of schizotypal personality disorder behaviors with late-onset deterioration or psychosis might apply to Tesla, Newton and Godel. Botlzmann and Nash had more classic neurospychiatric disorders.

These are most extraordinary minds. It would not be surprising if they had extraordinary dysfunctions.

Update 6/7/2012: An academic opinion.

Rule 34 by Charlie Stross - my review

I read Charlie Stross's Rule 34. Here's my 5 star Amazon review (slightly modified as I thought of a few more things):

Rule 34 is brilliant work.

If Stross had written a novel placed in 2010, it would have been a top notch crime and suspense novel. Charlie's portrayal of the criminal mind, from silence-of-the-lambs psychopath (sociopath in UK speak, though that US/UK distinction is blurring) to every day petty crook, is top notch.

Stross puts us into the minds of his villains, heroes, and fools, using a curious 2nd person pronoun style that has a surprising significance. I loved how so many of his villains felt they were players, while others knew they were pawns. Only the most insightful know they're a cog in the machine.

A cog in a corporate machine that is. Whether cop or criminal or other, whether gay or straight, everyone is a component of a corporation. Not the megacorp of Gibson and Blade Runner, but the ubiquitous corporate meme that we also live in. The corporate meme has metastasized. It is invisible, it is everywhere, and it makes use of all material. Minds of all kinds, from Aspergerish to sociopath, for better and for worse, find a home in this ecosystem. The language of today's sycophantic guides to business is mainstream here.

Stross manages the suspense and twists of the thriller, and explores emerging sociology as he goes. The man has clearly done his homework on the entangled worlds of spam and netporn -- and I'm looking forward to the interviewers who ask him what that research was like. In other works Stross has written about the spamularity, and in Rule 34 he lays it out. He should give some credit to the spambots that constantly attack his personal blog.

Rule 34 stands on its own as a thriller/crime/character novel, but it doesn't take place in 2010. It takes place sometime in the 2020-2030s (at one point in the novel Stross gives us a date but I can't remember it exactly). A lot of the best science fiction features fully imagined worlds, and this world is complete. He's hit every current day extrapolation I've ever thought of, and many more besides. From the macroeconomics of middle Asia, to honey pots with honey pots, to amplified 00s style investment scams to home foundries to spamfested networked worlds to a carbon-priced economy to mass disability to cyberfraud of the vulnerable to ubiquitous surveillance to the bursting of the higher education bubble, to exploding jurisprudence creating universal crime … Phew. There's a lot more besides. I should have been making a list as I read.

Yes, Rule 34 is definitely a "hard" science fiction novel -- though it's easy to skip over the mind-bending parts if you're not a genre fan. You can't, however, completely avoid Stross's explorations of the nature of consciousness, and his take on the "Singularity" (aka rapture of the nerds). It's not giving away too much to say there's no rapture here. As to whether this is a Rainbow's End pre-Singular world … well, you'll have to read the novel and make your own decision. I'm not sure I'd take Stross's opinion on where this world of his is going - at least not at face value.

Oh, and if you squint a certain way, you can see a sort-of Batman in there too. I think that was deliberate; someone needs to ask Charlie about that.

Great stuff, and a Hugo contender for sure.

If you've read my blog you know I'm fond of extrapolating to the near future. Walking down my blog's tag list I see I'm keen on the nature and evolution of the Corporation, mind and consciousness, economics, today's history, emergence, carbon taxes, fraud and "the weak", the Great Recession (Lesser Depression), alternative minds (I live with 2 non-neurotypicals), corruption, politics, governance, the higher eduction and the education  bubble, natural selection, identity, libertarianism (as a bad thing), memes, memory management, poverty (and mass disability), reputation management, schizophrenia and mental illness, security, technology, and the whitewater world. Not to mention the Singularity/Fermi Paradox (for me they're entangled -- I'm not a Happy Singularity sort of guy).

Well, Stross has, I dare to say, some of the same interests. Ok, so I'm not in much doubt of that. I read the guy religiously, and I'm sure I've reprocessed everything he's written. In Rule 34 he's hit all of these bases and more. Most impressively, if you're not looking for it, you could miss almost all of it. Stross weaves it in, just as he does a slow reveal of the nature of his characters, including the nature of the character you don't know about until the end.

Update: In one of those weird synchronicity things, Stross has his 2032 and 2092 predictions out this morning. Read 'em.

Neither Loughner, Palin, Beck nor Limbaugh are responsible. Who is?

Jared Loughner is a paranoid schizophrenic.

Loughner a "textbook" case paranoid schizophrenic - Jared Loughner - Salon.com

... He's a textbook case. Most psychiatrists will tell you they need to examine a patient before diagnosing him, but this guy has all of the symptoms. He has the right age of onset. He has a deteriorating social course, as they say in the [DSM], social and occupational dysfunction...

This is not a hard diagnosis. This is like diagnosing rain by looking at the splashing drops. In any sane society, Loughner would not be considered responsible for his actions. He is not the "face of evil" dammit, he is a victim of one of the most terrible diseases in the vast array of terrible diseases.

Nor are Palin, Beck or Limbaugh responsible. Yes, paranoid schizophrenics do listen to talk radio, and, yes, it does influence them. Palin and Limbaugh, at least, are sane enough to bear some responsibility for their rhetoric. The voices in Loughner's own head, however, would be stronger than their rants.

If I were a theist I would blame this one on God, but I'm not. There are, however, some close human substitutes. They would be NRA supporters and GOP voters.

If the 2004 assault weapons ban were still in place Loughner would still have shot Giffords, but his kill count would be much lower. If Arizona had a robust mental health care system nobody might have died.

People who support the GOP and the NRA are responsible both for the failure to renew the assault weapons ban and for the miserable state of Arizona (and America's) mental health care.

If you are looking for an intelligent and thoughtful response to this tragedy, forget Loughner. Forget (please) Palin, Beck and Limbaugh. Forget gun control, that won't happen in America. Instead, focus on the identification and management of major psychiatric disorders.

A quiet revolution in naming and framing disorders of the mind

Victory: The war against 20th century psychiatric diagnoses is all but won. It's been a long time coming, this rebellion has roots going back to the 1970s (not all of them equally evidence based). Things have really picked up over the past decade.

Our misclassification of disorders of the mind has led psychiatry, and neuropsychiatry, into a frustrating blind alley. Now that we're realizing our mistakes, we can start to make real progress.

There are significant implications for our understanding of disability in a technocentric society, and for our glacial rethinking of the meaning of responsibility. Those memes are still baking ...

Wetware routers and intermittent consciousness

Today's Carl Zimmer article gives new insight into the nature of consciousness. Even in neurotypical brains decision tasks create a psychic bottleneck, which is also a sort of perceptual blindspot. Our consciousness goes "offline", very briefly, when we make choices (emphases mine) ...

The Brain: The "Router" in Your Head—a Bottleneck of Processing | Carl Zimmer | DISCOVER Magazine:

... The brain is, in the words of neuroscientist Floyd Bloom, “the most complex [jg: known] structure that exists in the universe.” Its trillions of connections let it carry out all sorts of sophisticated computations in very little time. You can scan a crowded lobby and pick out a familiar face in a fraction of a second, a task that pushes even today’s best computers to their limit. Yet multiplying 357 by 289, a task that demands a puny amount of processing, leaves most of us struggling.

... The fact that we struggle with certain simple tasks speaks volumes about how we are wired. It turns out the evolution of our complex brain has come at a price: Sometimes we end up with a mental traffic jam in there...

... If we don’t have enough time between two tasks, we slow down on the second one—a lag known as the “psychological refractory period.”...

... Psychologists have long been puzzled by the psychological refractory period because it doesn’t fit with other things we know about how the brain works. We are very good at doing many things at once... Yet there are simple jobs—like math problems—that our brains can handle only one at a time. It is as if signals were flying down a 20-lane superhighway, and then the road narrowed to a single lane...

Each time we perform a task we perform it in three steps. Step 1: Take in information from the senses. Step 2: Figure out what to do in response. Step 3: Carry out that plan by moving muscles...

...  scientists varied one of the three steps of the thought process to see if they could change the length of the psychological refractory period. Only when they tinkered with step 2—figuring out what response to make—could they produce a change...

... when we have any two simple decisions to make, we must wait for the first task to move through a bottleneck before taking on the second. That is what makes mental multiplication so hard. Instead of carrying out many steps simultaneously, we have to do them one at a time.

... In 2008 the scientists reported that during the psychological refractory period, a network of brain regions are consistently active, some near the front of the brain and some near the back...

... these regions appear to be part of a network that is important for our awareness of our own experiences. This helps explain why we are oblivious to our mental traffic jams.

.. The brain began measuring how long a task took only after the previous task moved out of the bottleneck. Whenever a perception of a sound or a letter got stuck in the mental traffic jam, the subjects were not aware of it...

... The neurons that take in sensory information send it to a neural network that he and his colleagues call the "router." Like the router in a computer network, the brain’s version can be reconfigured to send signals to different locations. Depending on the task at hand, it can direct signals to the parts of the brain that produce speech, for instance, or to the parts that can make a foot push down on a brake pedal. Each time the router switches to a new configuration, however, it experiences a slight delay...

The "router" theory is very much an unproven model. If something like it holds up, however, we will find variations in router performance. There may be advantages and costs to different router algorithms. There will be articles on router performance in autism and schizophrenia and in disorders of consciousness (coma, etc). Perhaps we will discover ways  to train and retrain our internal routers for different settings.

It wasn't the primary emphasis of the article, but I'm struck again by the contingent and intermittent nature of our consciousness. Continuity of consciousness is very much an illusion. We are offline, briefly, thousands of times a day.

How quickly can humans evolve?

Even fifteen years ago cognitive science courses taught that the human mind was frozen in the Paleolithic Pleistocene. Humans didn’t evolve any more

Now we wonder how fast can humans evolve ...

Scientists Cite Fastest Case of Human Evolution – Nicholas Wade - NYTimes.com

…. Comparing the genomes of Tibetans and Han Chinese, the majority ethnic group in China, the biologists found that at least 30 genes had undergone evolutionary change in the Tibetans as they adapted to life on the high plateau. Tibetans and Han Chinese split apart as recently as 3,000 years ago, say the biologists, a group at the Beijing Genomics Institute led by Xin Yi and Jian Wang. The report appears in Friday’s issue of Science.

If confirmed, this would be the most recent known example of human evolutionary change. Until now, the most recent such change was the spread of lactose tolerance — the ability to digest milk in adulthood — among northern Europeans about 7,500 years ago. But archaeologists say that the Tibetan plateau was inhabited much earlier than 3,000 years ago and that the geneticists’ date is incorrect.

When lowlanders try to live at high altitudes, their blood thickens as the body tries to counteract the low oxygen levels by churning out more red blood cells. This overproduction of red blood cells leads to chronic mountain sickness and to lesser fertility — Han Chinese living in Tibet have three times the infant mortality of Tibetans…

This is vicious selection; in pre-technological times the infant mortality gap was probably even greater.

Which reminds me of something I wrote two months ago …

… Even after the development of agriculture and writing we see thousand year intervals of relative stasis in China, Egypt and Mesopotamia. How could this be when our fundamental technologies change in decades. Are the minds of modern Egyptians radically different from the minds of only 6,000 years ago? Why? Why do we see this graph at this time in human history?

What did humans do in Georgian caves for 30,000 years? Thirty thousand years of waving and sewing and nothing changes?! They could not have had the same brains we have. They seem more … Neandertal…

Six thousand years is twice the time it took humans to adapt to the Tibetan plateaus. So that’s plenty of time for brains to change.

Except brains are qualitatively different from red cells. Brains are a platform for minds. Left handed people flip hemispheric specializations, and yet seem to think very much like right handed people.

Think about that. Mutations that flip cardiac orientation are 100% lethal. Flipping hemispheres though – the mind adapts. People born with half a brain can function in human society. Five percent of the population have big ugly looking mutations in brain development systems – yet they seem fine.

The human mind can run similarly on a diverse infrastructure. The software analogy is irresistible. A browser running on an iPhone can look and act a lot like one running on a Win 7 box – but the two systems are very different.

This gives a lot more leeway to evolution. It means that the ‘variation controls’ on the genetic programs for neural development can be “set” (by evolution) to “high variation” – and we can still turn out functioning humans minds. It means that brains may be evolving very quickly – over the course of a thousands of years.

It will be interesting to compare the DNA of Homo sapiens 2000 BCE with Homo sapiens 2010 ACE.

See also

• The evolution of the human brain- ASPM, microcephalin and FOXP2 (2005)
• Human evolution- a pillar falls (2007)
• The evolutionary wonder of reading – hints from intracranial electrophysiology (2009)
• Is schizophrenia the price we pay for an evolving brain? (2007)
• Schizophrenia and autism- evolutionary disorders? (2007)
• Structural variation in the human genome and its r... [Annu Rev Med. 2010]
• The new history is deep history (2010)
• What if we could see the diversity of minds? (2008)
• What is schizophrenia- Not what we thought (2008)

Update 7/20/2010: John Hawks reviews the evidence for active selection. I think when he talks about "demographics" he might be talking about how the unification of dispersed human populations causes new phenotypes to emerge -- but he's tip-toeing around something and is being cryptic.

What gene studies reveal about the diversity and resilience of mind, and the limitations of psychiatric disease classification

This research further confirms results first published in Science three months ago. The continued blurring of the diagnostic boundaries between manic-depression and schizophrenia is significant, as is the relationship to control of the immune system. It has always been interesting to contemplate similarities between the immune and nervous systems …

BBC NEWS | Health | Gene clues to schizophrenia risk

Scientists have identified thousands of tiny genetic variations which together could account for more than a third of the inherited risk of schizophrenia…

… The findings came from work by three separate teams, who analysed DNA from thousands of people.

The studies - the biggest ever into the genetics of schizophrenia - appear in the journal Nature.

The findings suggest that schizophrenia is much more complex than previously thought, and can arise not only from rare genetic variants, but common ones as well…

… The researchers say that individually many of the genetic variations they have identified play only a tiny role in raising the risk of passing schizophrenia down the generations … "Cumulatively, they play a major role, accounting for at least one-third - and probably much more - of disease risk."

All three studies highlight genes found on Chromosome 6 in area known as the Major Histocompatibility Complex, which plays a role in the immune system, and in controlling when other genes are switched on and off.

The researchers believe this might help explain why environmental factors also seem to affect risk for schizophrenia…. For example, there is evidence that children whose mothers contract flu while pregnant have a higher risk.

In total the researchers identified 30,000 tiny genetic variants more common in people with schizophrenia.

A similar pattern was found in people with bipolar disorder…

… Dr Thomas Insel, of the US National Institute of Mental Health, said: "These new results recommend a fresh look at our diagnostic categories.

… "If some of the same genetic risks underlie schizophrenia and bipolar disorder, perhaps these disorders originate from some common vulnerability in brain development." …

It feels like we’re making a genuine leap forward in our understanding of the what some call the “connectopathies”. One of the more immediate implications is that we’re driving another nail into the increasingly problematic classificationd (nosologies, as in DSM IV) (see – psychiatric diagnoses, 200 years behind) of disturbances of the mind.

The BBC article claims that this is a new discovery of similarities between schizophrenia and bipolar disorder, but I posted on that in 2003 …

BBC NEWS | Health | Mental illnesses share gene flaw (September 2003)

… Sabine Bahn, who led the research, published in The Lancet, said: "We believe that our results provide strong evidence for oligodendrocyte and myelin dysfunction in schizophrenia and bipolar disorder.

"The high degree of correlation between the expression changes in schizophrenia and bipolar disorder provide compelling evidence for common pathophysiological pathways that may govern the disease phenotypes of schizophrenia and bipolar disorder." …

In particular childhood onset “bipolar disorder” seems to have a great deal in common with early onset schizophrenia.

In a more abstract direction this research provides some tantalizing hints about the diversity of mind/brain, and the emergent resilience of the brain/mind. Thousands of gene variants all affecting minds in unpredictable ways.

By comparison we can see the diversity of our bodies, but they’re really all somewhat familiar. From a distance a parade of human forms is not that interesting. Four feet to seven feet tall, a bit of pigment variation, some muscular variability – but really, not so different. Dogs are much more diverse.

I suspect though, that a parade of minds would be far more interesting. Minds twenty feet tall and 6 inches tall, minds wide and minds narrow …

The resilience of the mind is also reinforced by this study and the earlier Science article. One in twenty people have big, ugly, mutations that ought to mess their minds completely – and yet they function very well (at least in mid-life, who knows about senescence). Somehow our minds are able to construct themselves from a very diverse and often severely flawed substrate.

That last point is what I find most interesting …

For further reading, see also the links associated with this 2008 post of mine.

More evidence that schizophrenia is an evolutionary disorders

A year ago I coined the term "evolutionary disorders" for diseases arising from malfunctions of rapidly evolving organs -- like the human brain.

Today comes news that the vast spectrum of disorders we lump together as "schizophrenia" arise from a very diverse array of unrelated mutations.

Sounds like a disorder of evolution.

See also:

•  What is schizophrenia? Not what we though
  
•  Is schizophrenia the price we pay for an evolving brain?
  

An astounding series on mental health disorders

I'm visiting family in Montreal, and the Globe and Mail came with the room today.

I've read the G&M before. It's a duller version of the Wall Street Journal, without the journalism. I didn't expect anything.

So I really was astounded by their special series on mental health: Breakdown: Canada's Mental Health Crisis.

The title is misleading, there's nothing particularly Canadian about the stories. The portrayal of schizophrenia (let us honor the Bigelow family) and David Golbloom's review of the mission of the Mental Health Commission of Canada are among the best writings on mental health I've seen anywhere.

The G&M has excellent journalists. I never suspected.

Canada's imperfect health care system gets knocked by people who don't read outcomes research, but it's vastly better than the America's non-system when it comes to delivering services to the underclass*. Canada is also quite good at "commissions"; Canada evolved the endless commission as an alternative to civil war. So the Mental Health commission may have an impact both in Canada and the US:

...People living with mental illness have the right to obtain the services and supports they need. They have the right to be treated with the same dignity and respect as we accord everyone struggling to recover from any form of illness.

The goal of the Mental Health Commission of Canada is to help bring into being an integrated mental health system that places people living with mental illness at its centre.

To this end, the Commission encourages cooperation and collaboration among governments, mental health service providers, employers, the scientific and research communities, as well as Canadians living with mental illness, their families and caregivers...

The world changes in the strangest ways. Decades of slow progress, regression and failure, then suddenly the world flips about. And that's just "gay marriage".

Progress does happen. We may be entering a new cultural model of cognition, cognitive disability, and cognitive variability.

* In defense of America, Canada has nothing like the Americans with Disabilities Act. There are things Canada could learn from the US.

What if we could see the diversity of minds?

Humans, to the eye, are not so diverse.

The vast majority have, or once had, four limbs, two eyes, one head. Most rely heavily on vision. Some are faster, some slimmer, some taller -- but not so much. They all have similar genetic aging rates, from old at 50 to old at 80.

But what if you could see minds instead of forms?

Would the average street look something like this?

(MIT geo-biology, burgess shale)

Ok, so pre-Cambrian diversity was pretty extreme. But human brains are actively evolving now. To quote Hawks (via Marginal Revolution):

We are more different genetically from people living 5,000 years ago than they were different from Neanderthals...

Active brain evolution means lots of variation. Most of the variations are mostly marginally harmful, some quite disabling, some both advantageous and problematic. They all mean that brains are less alike than the bodies we see.

The variation doesn't end there. Brains, among other things, run minds. Minds, among other things, run memes.

Brain, mind and meme give three platforms for variation and selection to play on. It's a recipe for combinatorial variation.

So it's plausible, that if we were able to see minds the way we see bodies, we'd find a very entertaining sidewalk. Some pedestrians would be twenty feet all and thin as posts, others ten feet wide with an extra limb and a tail. Some covered in fur, others green and yellow with antennae.

Perhaps, as some of my favorite writers have speculated, one day we'll remake our bodies to fit our minds, and the streets will make today's San Francisco seem quietly uniform.

That's a long way away, and perhaps unlikely. In the meantime, however, we can start imaging minds instead of seeing bodies. With a dash of enlightenment 2.0, we may see the aliens among us, and sense a deeper truth beneath what vision alone can show.

See also: neurodiversity 2004.

Network biology and the holographic resilience of biological function - lessons from E. coli

A recent groundbreaking study on the genetics of schizophrenia found a varied pattern of large scale "sledgehammer" (as in whack the genes) mutations in many persons with schizophrenia. These are thought to affect varying stages of brain development.

Curiously, the researchers found the same problems in a minority of the "control" group of "normal" people:

Gordon's Notes: schizophrenia

One in twenty seemingly normal people have big, ugly looking mutations that ought to be messing up their brain development. Yet they seem "normal"...

Now another big study explains this strange normality (emphasis mine) ...

Zimmer - Wired 04.18.08

.... In the latest issue of Nature, scientists reported an experiment in which they wreaked havoc with E. coli's network. They randomly added new links between the transcription factors at the top of the microbe's hierarchy. Now a transcription factor could turn on another one that it never had before. The scientists randomly rewired the network in 598 different ways and then stepped back to see what happened to the bacteria.

You might expect that they all died. After all, if you were to pop open the back of an iPod and start linking its components together in random ways, you'd expect it to crash. But that's not what happened.

About 95 percent of the rewired bacteria did just fine with their new networks. They went on with their lives, feeding, growing and dividing. Some even performed better than microbes with the original wiring, under some conditions.

The tolerance these bacteria showed reveals something important about how evolution works. Humans can randomly rewire cells, and so can mutations. There's something about gene networks that allow them to thrive despite these mutations, and, in some cases, to even gain an edge in the evolutionary race.

But scientists don't quite know why a network like the one in E. coli can handle this rewiring so well. The source of their strength lies not in a single molecule -- DNA -- but in a complicated web of relationships. The network itself is the mystery for biologists in the 21st century...

This is of a piece with the discovery that DNA control system have complex topological components, my June 2007 essay on evolved circuits. and reading I've done over the past year on bioinformatics (systems biology) and the modeling of interacting protein networks (interactome) (example).

The blueprint for an organism is emergent. It "appears" through the interaction of the storage elements in DNA and DNA associated packaging, but, like a holographic image, it can "appear" even when pieces of the storage structure are absent or reorganized. This is a shared characteristic of evolved systems on every scale, we see hints of this even in evolved mechanical systems such as the freight train pneumatic braking system. Bacteria, of course, are the most "evolved" of all systems -- far more evolved than mere humans.

That's why major "controllers" of brain development can be disrupted, but, in many cases, the brain can still develop -- differently perhaps. In some settings, the differences might even be advantageous.

How will we understand this emergent control system? We will not be able to do perceive it directly. We will need computational systems to discern the emergent controllers, and to be able to relate a network level "control element" to the set of physical manifestations of the abstract control element in real-world DNA.

Sigh. It all looked so simple in the days of 'one gene, one protein' ...

Update 4/19/08: There's an obvious metaphor for the type of emergence we see here. An example that makes the problem transparently obvious for all of us.

Imagine that I want you to meet me by the science museum at 11:30 am. I could use English or French or draw a picture. In any spoken or written language I could use an enormous variety of words and word order and still communicate my meaning.

If we think of "the meaning" in cellular biology as that which arises from interacting protein networks, then by analogy we can understand that many different gene arrangements and even several somewhat different proteins could produce similar protein network interactions.

What is schizophrenia? Not what we thought.

Some recent results for a study of the genetics of schizophrenia got a lot of press attention. Among other things, the studies are one more indication that the term "schizophrenia", like the term "autism", is obsolete.

First, here's the best of the coverage I read. One came from a blog, the other from the Washington Post. The rest of the coverage, including the NYT and Scientific American, was pretty bad. (Unfortunately Science does not allow public access to articles, I really wish they'd go out of business):

Schizophrenia involves an increased rate of mutations (Ars Technica)

... schizophrenics displayed a high rate (three times the expected level) of genetic mutations at the chromosomal level, where individual genes were either absent, or present multiple times, leading to over-representation. In patients with early-onset schizophrenia, this rate of mutation was four times the expected level.

The genes involved turned out to be important in brain development including neuregulin and glutamatergic signalling, along with ERK/MAPK signaling and genes that are involved in adhesion and synaptic plasticity. Interestingly, the mutations were not common across the schizophrenic patients, instead differing along familial lines...

Schizophrenia Linked to Rare, Often Unique Genetic Glitches (Rick Weiss, Washington Post)

Patients with schizophrenia are three to four times as likely as healthy people to harbor large mutations in genes that control brain development, and many of those glitches are unique to each patient, researchers reported yesterday.

The findings are forcing scientists to rethink the reigning model of how genes and environment conspire to cause the debilitating disease, which affects about 1 percent of the population worldwide.

In part, scientists said, the new view is daunting because it suggests that many people with schizophrenia have their own particular genetic underpinnings.

At the same time, the study shows that new screening techniques can find and differentiate among those various mutations. In the long run that could help doctors choose the best medications for individual schizophrenics and speed the development of drugs tailored to certain patients' needs.

"If the genetics tells us that schizophrenia is really 10 different disorders, then let's have 10 treatments that optimize the outcomes for everyone and not just use the same drugs for everybody," said Thomas Insel, director of the National Institute of Mental Health, which helped fund and conduct the study.

The work also offers evidence that autism shares some genetic roots with schizophrenia.

"Take away schizophrenia's hallucinations and delusions," said Jon McClellan, a child psychiatrist at the University of Washington and a leader of the study, published in yesterday's online issue of the journal Science, "and the symptoms that remain, the lack of social interest and withdrawal, are what we call autism. There is clearly an intersection of the brain systems involved."

... scientists [had concluded] that the mutations contributing to schizophrenia are probably common in the population but have little impact individually, and that only when several occur together is a critical mass of neurological trouble achieved.

The model emerging from the new study is quite different. It says most cases of schizophrenia may be caused by rare genetic glitches that are individually potent.

The turnaround is the result of sophisticated gene scans conducted on 233 schizophrenics, including 83 who got the disease in childhood, a more serious condition. The scans looked for rare stretches of DNA where more than 100,000 "letters" of genetic code were either missing or mistakenly present in duplicate.

About 15 percent of schizophrenics, and 20 percent of those affected in childhood, had such glitches, compared with 5 percent of healthy individuals who were also studied. Yet the glitches, including one previously associated with autism, were different in each person.

Unlike previous scans based on older technology, which could at best find general genomic "neighborhoods" where mutations associated with schizophrenia are present, the new scans pinpointed the individual genes affected...

...The genes implicated are diverse, but many are known to play crucial roles in how the brain gets wired early in life. Normally that process starts with a huge overproduction of neurons, followed by a controlled winnowing that leaves only those that have made proper connections.

"Changes in these genes could bias the way circuits get sculpted out and could perhaps lead to a brain in which signals that would normally get filtered out don't get filtered out," which could interfere with thinking and prompt hallucinations, Insel said.

The delayed onset of the disease can be explained by the fact that some genes and brain connections do not take on central roles until young adulthood, said Jonathan Sebat of Cold Spring Harbor Laboratory, one of the study leaders...

Rick Weiss of the Post did a far better job than anyone else on summarizing these results. The NYT coverage, in particular, was disappointing.

This feels big, but note that that only 15% percent of "schizophrenics" fit this pattern. This is not the whole story, but it's the biggest piece we've gotten so far.

I'll summarize the key implications:

• Schizophrenia is not a disease. It's the name given a fairly large number of unique disorders of brain development that have, among their endpoints, social withdrawal, hallucinations, and fixed beliefs.
• A good number of cases of "autism" and "schizophrenia" are different manifestations of overlapping sets of mutations.
• There may be"no genes for most instances autism and schizophrenia". There are sets of large scale mutations that are similar between close genetic relatives, but similar appearances are resulting from disorders of quite different components of brain development.
• One in twenty seemingly normal people have big, ugly looking mutations that ought to be messing up their brain development. Yet they seem "normal". Seventeen in twenty persons with "schizophrenia" do NOT have these nasty scattered "sledgehammer" mutations. (So called because it's as though something took a sledgehammer to the genome.)
• The age onset of schizophrenia is determined by when the disordered developmental genes are activated. There's a lot of this going on in late teen years. The implication is that the same thing explains why "autism" presents around ages 2-3, and why it can seem to appear fairly suddenly. This may also explain why some conditions seem to improve at other ages. Schizophrenia syndromes often improves in middle age, for example.
• If every person with autism has a somewhat unique disorder, then treatments and prognosis are also unique. This validates the age old practice of asking someone with a cognitive/psychiatric disorder what treatments have worked for relatives.

The puzzle is far from complete, but one part of it has been filled out. We don't know what's causing these scattershot mutations, though a viral infection in very early development is one obvious possibility. I think this picture is also consistent with my earlier speculation that schizophrenia and autism are evolutionary disorders (see also).

Incidentally, Emily reminds me that autism was once considered a childhood variety of schizophrenia.

To me one of the most amazing results of the study is that 1/20 randomly selected health individuals have major derangements of genes responsible for brain development -- yet their brains still work. That's a group I'd really like to study!

See also:

• A mouse model for calcineurin-type Schizophrenia: exciting news indeed

• Regions of rapidly evolving genes: evidence of genetic control of the rate of adaptation and disorders of evolution

• Schizophrenia and Bipolar disorder both have shared pathophysiology?

• Reversing a severe brain disorder in adult mice

• Neuregulin: Monster gene of madness

• Is schizophrenia the price we pay for an evolving brain?

• Schizophrenia and autism: evolutionary disorders?

• Myelin disorders underlie schizophrenia?

• More evidence of hacked wetware: the DARPP-32 gene and schizophrenia

• Schizophrenia and the increased attractiveness of the non-conformist

• The extraordinarily rapid selection and evolution of the human brain

• Autism-like findings in relatives of autistic children and the evolutionary biology of autism

• A mouse model for schizophrenia

• Redefining mental retardation and autism - the revolution ahead

• Very annoying: the diagnostic criteria for Asperger's are not all that useful

To sleep, perchance to run lossy compression algorithms

Another NYT article on theories about why humans sleep:

Sleep - Brain - Neurons - New York Times:

...So Dr. Tononi and a colleague, Chiara Cirelli, have hypothesized that during sleep, the synapses weaken. The downscaling is across the board, so that the synapses’ relative strength is maintained. Those that have been used (those involved in learning) stay stronger than those that haven’t....

Both autism and schizophrenia have, at various times, been connected with disorders of pruning neuronal networks. (Errors both ways -- too much and too little.)

Neural gardening is hard to get right, and, in fact, there can't be a "right" answer. The "right" answer will depend on environment, which is fungible.

I do wonder sometimes if the alleged benefit of exercise for dementia prevention is entirely related to the benefit exercise has for sleeping.

Incidentally, my recollection is that this original theory was found to be too simplistic. I recall that studies published @ 2011 showed that what's occuring in sleep is a refactoring of memories into a compressed formthat sacrifices accuracy for retrieval speed and lesser storage demands. I think the researchers found a curious correspondence to lossy fractal-based compression algorithms used in early 21st century computing ... [1]

[1] Sorry, sometimes it's hard for me to forget I'm not supposed to remember the future. I think I need more sleep.

Schizophrenia and autism: evolutionary disorders?

I was thinking this morning, as I often do, of brain and mind, evolution, schizophrenia, and autism (more autism related posts), particularly in the context of a recent post about the perplexing prevalence of schizophrenia and a model of autism genetics involving spontaneous mutation, female non-expression, and inheritance in the male.

The pieces of the puzzle seem to fit together. If I were to read the minds of the researchers in these domains, I suspect they're beginning to think of autism and schizophrenia as examples of an entirely new class of illness - "evolutionary disorders". These are a class of disorders that arise in an organ, in this case the brain, that is undergoing rapid evolutionary change with a high mutation rate and a lot of suboptimal experiments.

I used to think that human evolution more or less ended with the invention of fire, at least that's what I recall from my high school essays [1]. Now we know that the human brain and human gut (they're very closely related systems) have undergone major adaptive changes within the past 15,000 years. It's increasingly plausible, but I don't think it's been proven, that these are systems predisposed to high mutation rates [2].

Systems predisposed to high mutation rates are going to produce a lot of "suboptimal" results, and a few significant improvements. This is what may account for the perplexing prevalence of two syndromes, autism and schizophrenia, that share similar traits:

• no obvious adaptive advantages
• common
• ill-defined and probably multiple underlying pathophysiologies
• complex genetic variability -- many different identified mutations and a suspicion that the disorders may arise from interacting protein networks.
  

I wonder if, should we look for them, we would identify similar "evolutionary disorders" in other animals undergoing rapid adaptive changes in some phenotype. Maybe that would explain all those odd-colored squirrels we see ...

[1] I've been fascinated by human evolution forever. Even as a child I didn't care for the traditional eugenics that is increasingly commonplace today, so I then advocated the encouragement of inter-ethnic marriage to dilute "bad" genes -- until we could directly engineer germ cell lines. Hey, it was a long time ago ...

[2] I think the theory here is that mutation rates can be selected for, so when "rapid change" is advantageous there is selection for "genomic creativity" over "genomic conservation". I think that's the mechanism that's supposed to underlie "punctuated equilibrium", but I'm not a biologist. I just write to learn ...

Update 5/6/2010: Yes, they're evolutionary disorders. In 2010 the term "evolutionary disorder" has a lot of hits, but I may have been one of the first users of it in this context.

Is schizophrenia the price we pay for an evolving brain?

Schizophrenia is pretty darned common, and it's a terrible disorder with clear inherited roots. So why is it so common?

Scientific American 9/6/07: It's No Delusion: Evolution May Favor Schizophrenia Genes

New research reveals that genes related to the debilitating disorder may also provide developmental advantages..

...Dorus co-authored a report, appearing in this week's Proceedings of the Royal Society B, about the evolution of genes linked to schizophrenia. After analyzing human DNA from several populations around the world and examining primate genomes dating back to the shared ancestor of both humans and chimpanzees, researchers reached a striking conclusion that several gene variants linked to schizophrenia were actually positively selected and remained largely unchanged over time, suggesting that there was some advantage to having them.

"Schizophrenia can be explained by a lot of individual alleles (variations of genes)," Dorus notes. "There are many different loci that impact the actual manifestation of the disease." Over the past decade, several dozen genes have been identified as potential culprits, and scientists believe that several genes cause disruptions in protein formations predisposing a person to schizophrenia.

...the team ... focused on 76 gene variations most strongly related to schizophrenia. By comparing these combinations with the evolution of other genes known to affect neuronal processes, the researchers determined that 28 of the schizophrenia-associated genes have been evolutionarily preferred in recent years by either Caucasian, Asian or African populations.

"Because it's a such a complex genetic trait … you actually expect there to be some variability from population to population, in terms of what genes are playing a role in the disorder," Dorus says. He notes that he was surprised that the study turned up a positive selection for some of the genes most closely associated to the disease, including DISC1 (disrupted in schizophrenia 1), which is involved in the transport of proteins along the relatively lengthy cell bodies of neurons, among them. "The most important thing is we don't really know what the basis of the selection has been," he says. "It could be due to an entire range of neurodevelopmental processes."

Co-author Crespi says that a number of theories have been floating around regarding the persistence of schizophrenia's genetic underpinnings. One holds that schizophrenia is a "disorder of language" and that the illness is an unfortunate consequence of the development of human speech, expression and creativity. "Whenever you get strong selection, it's like a big plus, and you can drag along a lot of minuses," he says. "You can think of schizophrenics as paying the price of all the cognitive and language skills that humans have—they have too many of the alleles that taken individually…might have positive effect, but together they are bad."

Dorus says the team will now home in on the 28 genes fingered in positive selection in the hope of finding new treatments for the mysterious disorder.

The explanation seems to be that it's very hard to construct a functioning human brain, and that the brain is still actively evolving. So in this case there's not necessarily an advantage to a schizophrenia gene, but rather that the diffuse set of disorders we label as "schizophrenia" arise because the human brain is very much a work in progress, one with a high defect rate ...

Update 7/2/2010: Structural variation in the human genome and its r... [Annu Rev Med. 2010]...

... The discovery of submicroscopic copy-number variations (CNVs) present in our genomes has changed dramatically our perspective on DNA structural variation and disease. ... CNVs, to a larger extent than SNPs, have been shown to be responsible for human evolution, genetic diversity between individuals, and a rapidly increasing number of traits or susceptibility to traits; such conditions have been referred to as genomic disorders. In addition to well-known sporadic chromosomal microdeletion syndromes and Mendelian diseases, many common complex traits including autism and schizophrenia can result from CNVs. Both recombination- and replication-based mechanisms for CNV formation have been described.

How long to make the Blacksburg schizophrenia connection?

I've been curious how long it would take the media to make the obvious connection between the Blacksburg disaster and schizophrenia.

As of today, a Google news search has five hits.

If I were running the planet (be afraid), I'd assemble a group to review what policy, educational, and legal changes should be made to improve the recognition and management of psychotic disorders (schizophrenia, major depression, mania, etc) in young adults. The group would be asked to consider management in the context of families, tribes, and cultures that deny the biological reality of psychiatric disorders. The denial group is large, and it includes most American social conservatives.

As ruler of earth, I'd also ask my science czar (I'd have a large science department) to review research on the prevention and management of schizophrenia, and to review the relationships between autism-spectrum disorders and schizophrenia.

I can only hope the worldmind will see things my way, and that the hit count will be higher a week from now.

Update 4/21/07: There's been much more discussion about the schizophrenia (and even autism) connection, including a Slate article that linked to an FBI analysis of the Columbine murders. That's a link worth following, btw.