Tuesday, March 31, 2009

Figuring Out Schizophrenia - Part II

Another full day at the International Congress on Schizophrenia Research, here in San Diego. To recap:

Breakfast: Beatriz Luna of the University of Pittsburgh tells me she isn't a schizophrenia researcher. Rather, she's into something called "development." I'm thinking development, as in a child psychologist.

No, she tells me. This is about brain development, as in the child brain maturing into the adult brain. She will be one of the speakers at a two-hour symposium later in the morning. (That's her in the photo.) Curious, I check it out:

Think of research into normal brain development shedding valuable light on schizophrenia, and, by extension, all of mental illness. The first speaker, Patricio O'Donnell of the University of Maryland, talks about cortical microcircuits and the balance between excitation and inhibition. Dopamine, he says, plays a large role in the modulation of circuits in the prefrontal cortex. During adolescence, he explains, these circuits experience dramatic connecting changes.

For instance, "phasic dopamine" (firing in bursts) gets dialed in, with improved signal to noise ratios.

But suppose the brain doesn't mature? Are we then looking at an approximation of schizophrenia?

David Lewis of the University of Pittsburgh shows slides that highlight the neuron's "dendritic spines." These spines play a major role in brain cells talking to one another. We know that people with schizophrenia are not favorably endowed in this category, but what does it mean?

In normal brain development, he explains, there is an early dramatic increase in spine density followed by a dropping off in adolescence and leveling out in adulthood. But are we talking about a drop-off in "functionally mature" or "functionally immature" connections? In other words, when the brain experiences structural changes, are the right chemical messages crossing the dendritic divide or the wrong ones?

Early intervention, he says, might be directed at enhancing the normal development of these synapses.

Dr Luna informs the audience that adolescence involves major risk of mental illness. As she explained to me over breakfast, this is when the brain changes gears. But what if something goes wrong in the transition? Might this underlie the pathology of mental illness?

During adolescence, the brain undergoes "synaptic pruning," along with axonal "myelination." In essence, brain function becomes more equally distributed, with less reliance on impulses from the basal ganglia and other more primitive regions of the brain.

But what if something goes wrong? Normal child brain function is suddenly not so normal, not in an adult brain anyway. You can kind of see this with the current economic meltdown, Dr Luna explains. It's a new world. AIG and GM and the rest can't behave the way they used to. The failure in executive behavior in this new context, she concludes, now becomes obvious.

Lunch time posters: This is where I get to ask all my stupid questions. For instance, over the past two days, the area of the brain I've been hearing most about is the dorsolateral prefrontal cortex, the brain function I've been hearing the most about is working memory, and the researcher I have been hearing most about is Joseph Callicot of the NIMH.

"Allelic Variation in KCNH2 is Associated with Dorsolateral Prefrontal Cortex Activation During Working Memory," reads the poster.

The name tag on the man standing in front of the poster reads Joseph Callicot.

Knock me over with a feather. Fire away with all your stupid questions, says the look on his face.

I love this job ...

Monday, March 30, 2009

Figuring Out Schizophrenia

I'm back home after an exhilarating and exhausting day at the International Congress on Schizophrenia Research in San Diego, 40 miles "down the hill" from where I live. To briefly recap:

Early morning: I'm up at 5 AM and out the door an hour later. Shortly after seven, I announce myself to a small breakfast gathering of brain researchers as, "The only C student at this table."

The line works so well I use it the rest of the day. It doesn't take me long to get into the spirit of the conference. I start referring to my coffee as my "neuro-cognitive starter." I find myself talking to a woman who is not a brain scientist. Her doctorate is in education, and she is involved in changing behavior in patients that just about everyone else has given up on.

"You can change the brain by changing behavior," she lets me know. Little steps at a time. You will probably hearing a lot more about her, if for no other reason than I plan to be writing more about her.

Late morning: I arrive at my appointed symposium for two hours of dopamine. These are brain scientists talking to brain scientists. To give you some perspective: When brain scientists talk to psychiatrists, they dumb down their talks. That way, I can almost understand their presentations.

Not the case here. Daniel Weinberger of the NIMH is one of the presenters. A couple of years ago, at the American Psychiatric Association annual meeting, I heard him explain to his audience the val-met COMT variation. Today, he just assumes that the people in the audience understood. Then he gets really technical.

Just over the aisle, in the same row where I am sitting is Arvid Carlsson, recipient of the 2000 Nobel Prize in Medicine (with Paul Greengard and Eric Kandel). Dr Carlsson received his Nobel for his work into dopamine. Let's put it this way: BC (Before Carlsson), dopamine had minor chemical status. Then Dr Carlsson started investigating and suddenly dopamine was a major neurotransmitter. (That's Dr Carlsson's photo to this blog post.)

In order to appreciate the environment Dr Carlsson was working in at the time, science only had theories about how brain cells communicated. Chemical? Electrical? Dr Carlsson and his contemporaries resolved that debate, but not without bucking a lot of the conventional wisdom of the day. In addition, Dr Carlsson connected dopamine deficiency to Parkinson's, which in turn led to L-DOPA for treating the illness, thus benefiting untold millions.

So here's Dr Carlsson listening to a younger generation of scientists carry on his work. Immediately after the session, I walk over and ask for his autograph. (I was a C student, remember? I can get away with this behavior.) He graciously signs the inside back cover of my conference booklet. My son-in-law is a neurosurgeon in New Zealand and a great guy. He's gonna be thrilled when this autograph arrives in the mail.

Don't tell - it's a surprise.

Early afternoon: Over lunch and at the poster session, I get to talk to the researchers one on one. First, let me make a confession - the technical stuff is way over my head. I'm here to simply get a feel for things, develop an appreciation. One of the things I notice is that the posters on the cognitive aspects of schizophrenia outnumber the psychosis side of the illness by a ratio of at least three to one.

Was it this way ten years ago? I wonder. I'll have to ask. Antipsychotics work very well against psychosis, but when your basic thinking is messed up - never mind the psychosis - your life is going to involve smoking cigarettes in front of TV in some dreary day room someplace.

No wonder the people I'm talking to are telling me that doctors and patients and family members got oversold on the new generation of antipsychotics. From what I can gather, certain systems in the brain go down. Systems we are only just finding out about. Systems we haven't even discovered yet. Systems all over the brain, interdependent, so when one system goes down, different parts of the brain all over fail to talk to one another.

Some of it is genetic. Some of the genetic mischief occurs during fetal development, other mischief further on in the life span. There may be direct genetic impact, or it may be like billiard balls caroming off one another. Or it may have something to do with a new area of gene research called epigenetics (which has something to do with why identical twins aren't really identical).

And forget about finding schizophrenia genes. These guys seem to be concentrating on "endophenotypes," symptoms common to the general population, as well, say, delayed reaction time to an event. If, say, we find a delayed reaction time gene and connect it to neurons and connect the neurons to brain systems and connect the brain systems to behavior, and connect the behavior to schizophrenia, maybe then we can really start connecting some dots.

Then there's environmental factors. The brain is shaped by literally everything, such as the way a mother holds her baby. African-Caribbean immigrants in the UK, for instance, have a nine-fold higher schizophrenia risk than the rest of the population there. What is going on?

Later afternoon: My brain is on overload. I leave the conference at four and am home at five. Twenty minutes later, I'm crashing in my own bed.

Evening: Dinner, chill time, and this blog post. Time to kick the cat off the prime spot on my bed. Up at five again tomorrow. I love my job ...

Sunday, March 29, 2009

Reporting on Schizophrenia Research

My annual conference season unexpectedly began three weeks early today, when I attended what I thought would be an afternoon local family forum on schizophrenia. I turned up at the Grand Hyatt on San Diego's waterfront only discover the forum was a satellite to a four-day major world conference: The International Conference on Schizophrenia Research, held every two years.

So that explained the star-studded list of speakers at our local family forum.

(Small sound-bite from that forum: According to John McGrath MD, PhD of the University of Queensland, hallucinations and delusions are "very very common" in the general population. Four percent of the US population hears voices.)

As soon as the forum ended, I headed over to the registration area of the main conference to secure media credentials. Mind you, here I was, a mental health journalist feeling obliged to explain why I knew nothing about a major world schizophrenia conference in my own backyard until today.

"Bipolar," I said to someone behind the desk, pointing to a copy of my book I happened to have in my bag, as if that explained everything. Another person was called over to assist.

"Tamminga," said the name on her tag.

She caught the look on my face. "It looks like you're familiar with the name," she said. "I'm her daughter." As in daughter of Carol Tamminga MD of the University of Texas Southwestern Medical Center, first rank researcher and one of the conference organizers. In addition, Dr Tamminga is very generous in giving her time to NAMI and other causes. (That's Dr Tamminga's photo on this blog post.)

Nearly two years ago I happened to sit next to Dr Tamminga over dinner in Pittsburgh at a closed function at the Seventh International Conference on Bipolar Disorder. (I was a special guest by virtue of a public service award I would receive two nights later.) Just to show you what a thoroughly gracious person Dr Tamminga is, our section of the table also included Thomas Insel MD, head of the NIMH, and Darrel Regier MD, co-chair of the DSM-V task force, but Dr Tamminga talked to me as if the other two weren't there.

"I was about to use your mother as a reference," I joked, then I briefly explained the connection.

Ten minutes later, I was at a patio table, poring over my conference materials. A brain scientist from Australia sat down, and for the next hour we talked about the brain, the metric system, politics, the environment, Einstein, and autism (she has a son with autism). Ninety percent of marriages involving an autistic child end in divorce, she informed me.

Tomorrow, I will be waking up before dawn to catch Dr Insel at a plenary session, then over to a morning symposium on "Dopamine Signaling in the Era of Molecular and Genetic Pathways." I'll hit the research poster sessions over lunch, then take in an afternoon of "Aberrant Functional Connectivity in Schizophrenia: Changes in Frequency, Symptoms, Drugs, and Genes."

Tuesday and Wednesday will be more of the same.

What is a depression and bipolar writer doing at a schizophrenia conference? From a recent blog post:

Back in 2003, I had one of those breakthrough moments, the type you associate with light bulbs switching on. I was at the American Psychiatric Association's annual meeting attending a symposium on genetics. Robert Freedman MD of the University of Colorado started explaining his research into schizophrenia.

"The DSM-IV was not designed with human gene function in mind and genes do not encode for psychopathology," he said. Instead, "genes encode simple molecules in cells that alter cell function and brain information processing."

I had kind of been aware of this, but this time I went, "Aha!" ... The upshot of my Aha! moment was the realization that to better understand my own illness (bipolar) I needed to research other illnesses as well, such as schizophrenia. The brain, after all, doesn't organize itself according to the DSM.

Listening to the schizophrenia people, in effect, gives me insights into my illness that I would never get from limiting my enquiry to the mood disorders experts. Take my word for it, I'm like a kid in a candy store at these events. The only thing about my job that I love more than listening to super-smart people who have dedicated their lives to improving yours and mine is writing about it.

Stay tuned ...

Friday, March 27, 2009

What's Wrong with Pharma? They Don't Listen to Their Customers

In my last blog piece, I presented a simplified overview of the appalling Pharma management practices that have resulted in no truly new psychiatric meds on the market in more than 50 years, with no replacement drugs on tap that they can even pretend to call new.

What went wrong? Lots of things. But it all boils down to this one cardinal sin: Pharma never listened to its customers.

My background as a finance/business journalist has given me considerable insight into this. Back in the late eighties, when I lived in Australia, I co-wrote a book with a prominent businessperson there, entitled "The Customer," which went to number two on the best-seller list.

It's all about organizing your business around the customer. If management isn't directly serving the customer, then they need to be serving the people serving the customer. It's amazing how entire industries get this principle wrong. Detroit, for instance, has always dictated the terms of the customer relationship. Marketing, to them, is about conditioning us into acceptance rather than finding out what we want.

Look at where Detroit is now.

Detroit, at least, pretends to listen to the customer. Pharma? Let me tell you a story:

Two years ago, I was at a book launch on the east coast. I grabbed some finger food and started up a conversation with a pharmacology expert from Bristol-Myers Squibb.

"Maybe you can enlighten me," I opened. I had been doing some research into dopamine and had pretty well concluded that stimulants and antipsychotics amounted to "dumb" dopamine meds.

We needed "smart" dopamine meds. Surely, Bristol-Myers Squibb was aware of the situation. Surely, such a drug was at least on their radar screens, if not their drawing boards.

(For background on the issue, please see For Discussion: Dopamine Cocktail.)

We actually have a smart dopamine med, the man informed me. "Aripiprozole."

Surely, he misunderstood. Nothing against Aripiprozole (Abilify), but it's been on the market for years. I was looking into the future. I realized he wasn't in a position to disclose any company trade secrets, but he could at least fill me in on some general principles, namely: Where were the next new meds going to come from?

I'm a customer. I have a right to ask.

It was if the man hadn't heard me. Once again, he started talking about aripiprozole, undoubtedly the exact same pitch he gives to psychiatrists. For years, BMS has been telling doctors that aripiprozole is a "Goldilocks" drug - not too much dopamine, not too little, just right.

Stop trying to sell me something. I'm a journalist. I've heard it all before.

Again, I tried to get the conversation back on track. Again, the man tied to shove his stupid drug down my throat. It never occurred to him to ask me why I was so interested in a "smart" dopamine med in the first place.

Were there special challenges I faced that a smart dopamine med might address? he could have asked.

Was there anything about my illness that he needed to know, that he wasn't finding out about from psychiatrists? If a "magic bullet" were to come on the market tomorrow, how would this affect my life? What impact would a safer and more effective med have on my compliance?

Believe it or not, this man could have learned a lot from me. So could BMS and their competitors. Let me assure you, no one in the entire drug industry has even bothered to ask. I'm a patient author and advocate, so if they're not interested in me then I know they are not interested in you, either.

Actually, BMS did bring a patient author on board, Andy Behrman, author of "Electroboy," but in the capacity as a spokesperson - a grateful patient - for Abilify. The arrangement worked fine until the drug pooped out and Andy went public. Then all hell broke loose. (Never piss off a writer: Andy has a tell-all book coming out.)

So what happens to companies not interested in listening to their customers? We know the answer. The evidence is there. Detroit, Wall Street, Pharma ...

"How deserted lies the city," says Lamentations, "once so full of people!"

It's tempting to say, "good riddance," but if Pharma goes down, what becomes of us?

Big Pharma: Dumber Than Detroit

More than a year ago, I wrote that Big Pharma may go the way of Detroit. Detroit, I wrote, won't be around 10 years from now. Little did I realize how prescient I was.

An opinion piece in the LA Times by author Greg Critser neatly encapsulates things the patient community has been discussing over the past 10 years:

First of all, Mr Critser notes, the meds don't work well. (Assuming the drug is reasonably safe, 50 percent of patients getting 50 percent better is all that is required for an FDA indication.) Nevertheless, even badly flawed meds have amounted to licenses to print money. Think Prozac. Think Zyprexa.

But these drugs have now ridden off into the sunset - gone generic - and there is nothing to replace them.

No new drugs. How stupid is this? Imagine if the movie industry were to announce that there were no new films in production, that holiday movie-goers were going to have to make do with the likes of "Parent Trap I."

According to the LA Times piece:

"As Bloomberg News Service recently reported, the world's pharmaceutical firms need to find replacements for $84 billion in sales now generated by products ending their patent life."

Sounds like appallingly bad management, right? No, it's always someone else's fault:

"If you ask the typical Pharma executive why sales are down, you get an alternative reality. The devil isn't in their drugs, it's in - surprise - onerous government regulation, penny-pinching insurers and, of course, that perennial boogeyman: healthcare reform."

Here's my very simplified take on what happened: In the eighties and nineties, Big Pharma got lucky with a new generation of antidepressants and antipsychotics. The drugs were hardly new - they were based on the same technology as the old ones - but they were promoted as new.

Psychiatry and patients' groups bought into the hype and the result was easy money.

As any business textbook will teach you, easy money is the greatest disincentive to sound management. Bad decisions and waste do not get penalized. Innovation and efficiency do not get rewarded. Necessary course corrections are not made.

During the easy times, the drug companies got out of the drug development business. Research went into "me-too" drugs - different versions of Prozac and Zyprexa. Corporate attention was devoted to lobbying the government (Big Pharma has way more lobbyists than any other industry) and wooing doctors (typically with drug reps who look like Heidi Klum and Russell Crowe).

The easy money, of course, ran out, but we're still stuck with the same bad management, ingrained in their easy money bad habits.

So, when, if ever, will we get meds that are a real improvement on the old ones?

Short answer: Never. Not with the current managers in place. Take my word for it - these guys are dumber than Detroit.

Much more to come ...

Further reading from mcmanweb

Blue Moon Musings

I'm not through: I'm strongly getting the impression you guys are like the auto industry. Same old engines, new fins. In case you haven't noticed, Detroit probably won’t be around ten years from now.

You are the only industry that doesn’t talk to its customers, the end users of your products, and it shows. You certainly haven't sent any Heidi Klum look-alikes to my door. ..

Wednesday, March 25, 2009

Trick Question: Lamictal for Bipolar Depression

GSK manufactures Lamictal (lamotrigine), used for treating bipolar depression. Which drug company sponsored the one unambiguous clinical trial showing that Lamictal is effective for this use?

Answer: Eli Lilly. Here's the story, which I reported in full in my Newsletter in early 2007:

In 1999, GSK published a study showing that Lamictal was effective for treating bipolar depression in its acute (initial) phase. The finding was at best ambiguous, as the study failed on its primary endpoint.

GSK spent the next six years working to come up with a study that would impress the FDA. (The FDA looks for at least two successful trials.) In all, GSK sponsored seven more acute phase trials testing Lamictal for unipolar and bipolar depression. In each of these studies, Lamictal failed to beat the placebo. Predictably, none of these studies was published.

But GSK did come up lucky in two long-term studies showing that, compared to lithium, Lamictal worked better at delaying relapses into bipolar depression. These studies had a major flaw in that the long-term phase only included patients who had responded to lithium or Lamictal during the initial phase of the study. In other words, "non-responders" likely to fail had been weeded out.

Nevertheless, on the strength of these two studies, in 2003 Lamictal received an FDA indication for "bipolar maintenance."

The news was interpreted as an FDA indication for treating bipolar depression, which was clearly not the case. Predictably, GSK did nothing to disabuse patients and clinicians of the notion. Quite the contrary, GSK launched an aggressive advertising and marketing campaign targeted specifically at bipolar depression.

Four North American treatment guidelines, including one put out by the American Psychiatric Association, bought into the hype and came out recommending Lamictal as a first option for treating acute bipolar depression. Ironically, treatment guidelines are supposed to be "evidence-based."

One beneficial result of GSK's efforts was that bipolar depression - which is more prevalent and destructive than mania, not to mention much harder to treat - began receiving the attention it deserved. Lamictal's flavor-of-the-month status also drew long-overdue attention to bipolar II and "soft" bipolar.

Here's where Eli Lilly comes in. In late 2003, the company received a true FDA indication for its combo Prozac-Zyprexa pill, "Symbyax," to treat bipolar depression. Confident its own med would crush the competition, Eli Lilly sponsored a head-to-head trial (with no placebo group) pitting Symbyax against Lamictal under conditions that gave its own drug considerable home field advantage.

Get ready for this: On the important measure for bipolar depression, Lamictal and Symbyax ended up in a virtual dead heat. Not only that, those on Lamictal had way fewer side effects.

Here's how Eli Lilly spun the study (published in 2006):

"[Symbyax]-treated patients had significantly greater improvement than lamotrigine-treated patients in change from baseline across the 7-week treatment period on the Clinical Global Impressions-Severity of Illness scale ..."

The best way to explain the spin is this: If Eli Lilly were AIG, they would be reporting record profits.

So, there you have it: The story of how Eli Lilly came to sponsor the one unambiguous trial showing that GSK's Lamictal works against bipolar depression.

A couple of follow-ups:

Following the revelation of the unpublished GSK studies, in its new bipolar treatment guideline due out next month, the American Psychiatric Association will no longer be recommending Lamictal as a first treatment option for acute bipolar depression.

In the wake of Lamictal going generic last year, GSK no longer heavily markets the drug.

Further reading from mcmanweb:

Treating Bipolar Depression

At the 2008 APA symposium, Robert Post MD of Penn State advised: "We have to change the way we practice this illness."

Back in 2001, in a survey by the Stanley Foundation Bipolar Network, Dr Post and his colleagues did some counting of their own. Their tally revealed that, despite the fact that mania gets virtually all the attention, bipolar patients are depressed three times more than they are manic or hypomanic.

Knock me over with a feather. Now if we only knew how to treat bipolar depression. ...

Tuesday, March 24, 2009

Desert Wildflowers Photos

Anza-Borrego Desert, March 23. Enjoy ...

Desert Wildflowers! - The Sequel

The desert wildflowers are probably in their last week, here in southern CA. On Monday, four of us piled into a friend's vehicle and drove to the nearest corner of the Anza-Borrego Desert. Naturally, I had my video camera with me. This is the "sequel." You can check out my original desert wildflowers video here.

Enjoy ...

The Onion: 98% Of Babies Bipolar

According to a Science and Technology news brief in yesterday's The Onion:

"A new study published in The Journal Of Pediatric Medicine found that a shocking 98 percent of all infants suffer from bipolar disorder."

According to The Onion:

"'The majority of our subjects, regardless of size, sex, or race, exhibited extreme mood swings, often crying one minute and then giggling playfully the next,' the study's author Dr. Steven Gregory told reporters."

Additionally ...

"'We found that most babies had trouble concentrating during the day, often struggled to sleep at night, and could not be counted on to take care of themselves—all classic symptoms of manic depression.'"

Not only that ...

"Gregory added that nearly 100 percent of infants appear to suffer from the poor motor skills and impaired speech associated with Parkinson's disease."

Readers may recall that in May 2001, The Onion broke the story, "God Diagnosed with Bipolar Disorder," noting that:

"In a diagnosis that helps explain the confusing and contradictory aspects of the cosmos that have baffled philosophers, theologians, and other students of the human condition for millennia, God, creator of the universe and longtime deity to billions of followers, was found Monday to suffer from bipolar disorder."

Monday, March 23, 2009

Nicholas Hughes and Sylvia Plath: Suicide Family Curse?

On March 16, marine biologist and outdoor adventurer Nicholas Hughes hanged himself at his home in Fairbanks, Alaska. According to his sister, Frieda, "he had been battling depression for some time." He was 47.

According to an account in the Fairbanks Daily News-Miner:

"He made lasting friendships in Fairbanks with those who shared his inventive interests in such varied pursuits as stream ecology, pottery, woodworking, boating, bicycling, gardening and cooking the perfect pecan pie. Nick guided many people in the winter to spots along the Tanana to savor the art of burbot fishing through the ice."

Nick Hughes was one-year-old when his mother, the celebrated poet Sylvia Plath, on a bitter cold London day in 1963, turned on the gas. Ms Plath's work reveals a lust for life. In a poem, she boasted:

"I rise with my red hair
And I eat men like air"

But her dark side gets nearly all the attention. This from a 1952 journal entry:

"God, if ever I have come close to wanting to commit suicide, it is now, with the groggy sleepless blood dragging through my veins ... "

Is suicide a family curse? Consider Ernest Hemingway, another literary lion with a lust for life: On a summer Idaho day in 1961, he aimed his favorite shotgun at his head and pulled the trigger. His father, Clarence, shot himself when the author was 29. His sister Ursala died of a drug overdose in 1966. His brother Leicester shot himself with a pistol in 1982, and his granddaughter Margaux took a drug overdose in 1996.

A University of Pittsburgh study, published in the Sept 2007 American Journal of Psychiatry, tracked 365 offspring of 203 parents with mood disorders over six years. The average age of the offspring at the beginning of the study was 20. Among other things, the study found that the offspring of those who had made suicide attempt had a six times higher risk of suicidal behavior than the offspring of those who had not made attempts.

The study corroborates findings from a 2002 study by the same group of reseachers.

The authors of the study make it clear that familial transmission "is not the same as demonstration of a genetic etiology," as family environmental factors also come into play.

Prevention of depression, the authors observe, may reduce risk, but they are quick to point out that a lot more may be going on. Impulsive behavior and parental history of sexual abuse also loom large. Therefore, preventive measures that only target depression may not be adequate.

The following is worth quoting in full:

"These findings suggest that clinicians treating adult depressed suicide attempters should assess for a history of abuse and review the home environment to ensure that risk of exposure to domestic violence and abuse is minimized for the patient and the patient’s children. Similarly, clinicians who treat adolescent suicide attempters should inquire about family history of depression, since maternal depression has been linked in several studies to an adverse response to treatment. Moreover, recent evidence shows that treatment of maternal depression results in improved psychiatric and functional outcomes for children."

Further reading from mcmanweb:

Sylvia Plath - In Her Own Words

That such a vital force was struck down by depression perhaps makes her short life all the more tragic. But her own words also portray triumph, of a woman who overcame tremendous odds just to find some joy in her life, a joy she was able to manifest in full measure. This is the side to Sylvia Plath we have tended to overlook. Her Journals will hopefully, if belatedly, rectify that oversight.

Sunday, March 22, 2009

Judi Chamberlin: Still Going Strong

Judi Chamberlin's Wikipedia entry describes her as an "anti-psychiatry activist." If so, hers is a voice of conscience, an influential one that has helped shape both the mental health and disabilities conversations over the last three decades.

Judi was hospitalized against her will in 1966. In her own words, from an article on the National Empowerment Center website:

"Being a patient was the most devastating experience of my life. ... It was clear that my thoughts, feelings, and opinions counted for little. I was presumed not to be able to take care of myself, not to be able to make decisions in my own best interest, and to need mental health professionals to run my life for me. For this total disregard of my wishes and feelings, I was expected to be appreciative and grateful. ..."

Her initial activism focused on the rights of inpatients, but, as hospitals closed, her focus shifted to the needs of outpatients, then she expanded her reach to those with physical disabilities. She has frequently crossed swords with psychiatry, but out of concern for keeping psychiatry honest.

In a debate with E Fuller Torrey MD over the controversial issue of compelling patients with severe mental illness to take meds in certain situations, Ms Chamberlin noted that many people do not choose to be patients and that:

"With regard to outcome, there is little objective evidence that [schizophrenia] is improved by neuroleptic drugs. In fact, there has been little change in outcomes of people diagnosed with serious mental illness over the past 100 years, despite claims that neuroleptic drugs are specific treatments."

In a piece for the blog, Voices of Recovery, she wrote:

"I really believe that it's those of us who were considered the most ill, the most non-compliant, the most trouble, we're the ones who have the fastest track on getting better, because there's always that part of us saying, 'No, no, no. I'm not going to take your vision of what my life is going to be. I'm going to stick to my own vision of what my life is going to be.'"

In 1992, she received the National Council on Disability's Distinguished Service Award of the President of the United States, and helped push a treaty on disability rights that the UN passed in 2006.

Now, at age 64, Judi is in hospice care. She is dying of obstructive pulmonary disease, an incurable lung disease, most commonly caused by cigarettes (she never smoked). For someone largely confined to bed and reliant on oxygen, Judi is amazingly active. In a March 14 blog entry, she chronicled a day spent with fellow advocates and a radio show she participated in, observing that:

"I really enjoyed talking about the issues that I have worked on for so many years, and using the model I have been developing linking how hospice services are delivered with the kind of mental health system we envision."

Hospice care has imbued Judi with new insights, and she's wasting no time in getting out her message. In another blog entry, she notes:

"Again, I can't help contrasting this with the mental health system, where often what people want is very practical stuff, like finding a place to live, and instead they have to jump through all kinds of hoops because someone else decides what's most important. That approach makes the person feel even less in charge of his or her own life."

And in an interview in today's Boston Globe:

"The hospice model puts the patient in the center. What matters is what the patient wants. And then the various people who are the staff - the nurses and social workers and others - are there to support their choices. They're not there to impose their ideas."

In a blog entry from yesterday, Judi observed:

"I don't believe in an afterlife; I think when I die it will just be a return to the same nothingness as before my birth. I believe that the only 'afterlife' is the way one lives on in people's memories, and it has been so gratifying to me to hear from so many people who appreciate the work I've done and the positive effect I've had on their lives. So I feel confident that I will live on in the memories of many, many people, and that thought gives me great comfort."

In the meantime, life goes on. From today's blog entry:

"Ted really enjoyed the casserole, which was as good as I remember. ..."

Check out Judi's blog: Life as a Hospice Patient

Friday, March 20, 2009

Depression - Are We All Alone?

Trying to tell someone who has never experienced depression what depression is like is like trying to describe a headache to someone who has never had a headache. People just don't get it, and they never will.

No one writes about this better than Therese Borchard of Beyond Blue. Here's the last three paragraphs from a blog post from yesterday:

"The pain of severe depression is quite unimaginable to those who have not suffered it," Styron wrote. "To the tragic legion who are compelled to destroy themselves there should be no more reproof attached than to the victims of terminal cancer."

Like Styron, I was both enraged and saddened that friends and family were shocked to hear that two doctors sliced me open--before full anesthesia kicked in--to save little David's life in an emergency C-section. Yet when I voiced the desperation of depression--which made the knife cut feel like a knee scratch--they often brushed it off, as if I were whining to win some undeserved sympathy votes.

But I should know better. Most people don't get it. And the day I get that through my head I'll be less disappointed.

Obviously, Therese touched a raw nerve. Her blog post (as of right now) drew an incredible 209 comments, nearly all of it along the lines of "my friends and family don't get it, either."

So, are we on our own? No, not really. Way too many of us, unfortunately, get depressed. Between those with major unipolar depression and those with bipolar depression, not to mention those with depression as a symptom of another illness, we are talking in the neighborhood of one in five Americans who experience major depression over the course of their lifetimes.

So, if your family and friends are deaf to you, all you have to do is reach out a little further. Literally, throw a stone out the window. It is bound to land on someone who has been through depression. You will have someone to talk to. Keep in mind that Bill Styron, cited by Therese, cultivated friendships with fellow depressives Mike Wallace and Art Buchwald.

Also, keep in mind that although most people don't get depression, they are not exactly hostile, either. Chances are, depression has touched their lives in some way. They may not understand what is going on, but a good many are truly moved by the suffering they have witnessed close-up.

Finally, be mindful of the fact that depression affects our capacity to process positive news. Friends and family may be more supportive than you give them credit for.

Thursday, March 19, 2009

Of Mice and Neurons - Brain Cell Growth, the Hippocampus, Depression, and Other Cool Stuff

I simply love reporting on brain science. Perhaps it's because the degree of difficulty is so high that nailing the landing, so to speak, has a way of setting off my dopamine in a highly pleasurable way.

Or maybe it's simply the fact that I love dealing with smart people working on really cool stuff.

About eight or nine years ago, I came across a journal article about how a research team led by Ron Duman PhD at Yale found that antidepressants caused brain cells to grow in the hippocampus.

Brain cells can actually grow? I thought. Then I asked: What the hell's a hippocampus?

We need to go back a year or two earlier when Fred Gage PhD of the Salk Institute discovered that we are not, in fact, stuck with the brain cells we are born with, that new brain cell growth takes place in an area of the brain known as the hippocampus.

The hippocampus is a tiny region in the limbic system of the brain that is involved in learning and memory, as well as complicit in regulating the stress response and in modulating dopamine's reward and motivation systems. New brain cell growth and regeneration is called "neurogenesis."

Around the same time, Husseini Manji MD and his team at the NIMH found that lithium increased brain cell growth. At first, I thought the fact that psychiatric meds could act as brain fertilizer was the story.

No, Dr Manji told me. Sure, the fact that the brain could grow new cells was important, but the real story, he said, was in how these new and regenerated brain cells connected to other brain cells. Let's return to Dr Duman's research:

In his experiments, Dr Duman and his team exposed lab rats to repeated foot shocks to induce behavioral helplessness equating to depression. When the rats were "depressed," neurogenesis was virtually shut down. But when the animals were treated with different classes of antidepressants, the process was reversed. Neurogenesis cranked up and the little guys were happy again.

Subsequent studies found these new cells and restored older cells established connections with existing neuronal systems. In other words, weakened brain pathways became stronger. The brain functioned better.

I had the pleasure of hearing both Dr Duman and Dr Gage talk about their research in two separate lectures two years ago at the American Psychiatric Association annual meeting in San Diego.

Think of it this way: Under the old way of thinking, psychiatry assumed that all we had to do was squirt serotonin or other neurotransmitters at a neuron and - poof! - no more depression. They even had a name for this: the monoamine hypothesis.

But suppose whole brain systems are off-line, that brain cells aren't talking to one another. That vital "be happy" and "get excited" messages get lost in the mail. What then?

Well, the serotonin may work, but it's going to take time. First, the individual brain cells need to boot up. Both Drs Manji and Duman have been pioneering in figuring out which "signal transduction pathways" and their constituent proteins inside the neuron play key roles in the booting up and other processes.

I have heard Dr Manji at numerous conferences explain that if we can develop treatments that directly target the proteins in these specific pathways we may be able to, in effect, get atrophied neurons booting up much quicker, and thus expeditiously bring entire brain systems back online.

This would translate into quick and safe and effective treatments for depression and bipolar and other mental illnesses.

Today I came across an article in the March 1 Biological Psychiatry that illustrated how Dr Duman's team has been dialing in their research. Their latest study used the same foot shock techniques as their earlier ones. This time, postmortem examination (that's right, they killed the poor guys after torturing them) using electron microscopy in the brain tissue revealed loss in the hippocampal neuron spines.

These dendritic spines play a key role in neurotransmitter traffic, that is in neurons connecting to other neurons.

The study also found that six days of antidepressant treatment reversed the process. In other words, the spines grew back.

Thus, in the entire depression-recovery cycle, we are beginning to see - actually see - the structural changes taking place in the brain and understand the significance of these changes. This particular study represents but a jigsaw puzzle piece in the overall scheme of things, but a picture is forming, one that is changing how we think about mental illness.

Further reading from mcmanweb:

Inside the Neuron

Dr Manji explained how for the last three decades, neurotransmitters have been the focus of mental health research. But recently, he went on to say, we have been learning that mental illness is much more complicated than that. Nerve cells communicate with each other through neurotransmitters, but do not actually go inside the nerve cell. Rather, they are merely the keys that unlock what is going on inside the neuron, "where all the action is." ...


Last night, I dreamed I was in an episode of "Lost." This may have had something to do with the fact that shortly before bedtime last night I was watching an episode that aired on ABC. Let's see if I can bring you up to date:

Last night's episode opens with a plane containing "The Oceanic Six" crash-landing on the same mysterious uncharted island a second time. To any follower of "Lost," this is the logical explanation to Sawyer's amazement at seeing his old friends alight from a vintage 70s Volkswagen van that ended last week's episode.

Sawyer, of course, is stuck on the Island in the year 1977. So - presumably - the plane carrying the Oceanic Six took off in the present and crashed-landed three decades in the past, when Jimmy Carter was President.

Sawyer is now (or then) going by the name of Jim La Fleur, and is living off his wits pretending to be a member of the Dharma Initiative. As you will recall, when the original "Lost" crew crashed on the island back in the present, the Dharma Initiative was no more. So now Sawyer has to figure out a way to get his friends accepted into the doomed Dharma Initiative community without them being mistaken for "Hostiles," which we know is not a pleasant fate.

The crash survivors inform Sawyer AKA La Fleur that Locke is dead, but, this being "Lost," we know that dead really doesn't mean dead. Complicating matters is that one of the crash survivors - Sayid - has already been captured by the Dharma Initiative and another two, including the evil genius who killed Locke (who, as we know, can't possibly be dead), are running loose.

Oh, yeh, there is also a brief appearance by a character from 1954, when there was the small matter of a lost (and now found) atomic bomb that needed dismantling. Or maybe that was last week.

Anyway, here I am in my dream with Jim La Fleur, living off my wits pretending to be part of the Dharma Initiative. One mistake, one slip of the tongue, and I'm going to have to explain myself to a bunch of people with absolutely no sense of humor about Dharma impersonators.

Out of nowhere, in my dream, Sean Connery picks up a telephone pole and throws it, which, I take it, is perfectly normal for "Lost." By now, the Dharma people are on to me, and I find myself talking like I've never talked before to a highly-skeptical woman in a nun's habit.

Thankfully, just when I'm about to irredeemably incriminate myself, I woke up. My cat, Bullwinkle, was reassuringly snoozing across my chest. Whew! It is the present, the year 2015. Rush Limbaugh is President and everything is going to be alright ...

Wednesday, March 18, 2009

For Discussion: The Dopamine Cocktail

In response to a blog post from two days ago on meds compliance, Cretin, who is on Zyprexa, commented:

"After a neurological test implicated working memory as the problem, my doctor had me try adding dextroamphetamine (Dexadrine). In essence we are adding in more dopamine to the system while blocking enough D2 receptors with olanzapine (Zyprexa) to avoid any psychotic symptoms. So far that has worked. It would be interesting to see if this combination would lead to greater compliance with medications."

Funny you should raise that, Cretin. I've been on a kick about "smart" dopamine meds for some time now. The ones we're working with are pretty dumb. Here's the situation:

Working one side of the street are antipsychotics, which block dopamine. Too much dopamine tends to result in over-excitement and psychosis. Antipsychotics such as Zyprexa work well against psychosis, but often at the expense of cognitive function, awareness, and motivation, not to mention pleasure and reward, which tends to involve instant eunuch-hood.

In addition, shortage of dopamine can result in temporary and permanent Parkinson's-like tremors known respectively as EPS and tardive dyskinesia.

Working the other side of the street, for lack of a better term, are "dopamine enhancers." These include anti-Parkinson's agents, ADD meds such as Ritalin, and the wakefulness agent Provigil. In addition, MAOI antidepressants and the antidepressant Wellbutrin have a modest dopamine effect.

Last but not least, we have methamphetamines, which tend to get abused as street drugs, plus street drugs with no medicinal value. For the sake of extreme over-simplicity, think of ADD meds and Provigil as methamphetamines with brakes.

A "smart" dopamine med would restore dopamine balance without over-shooting the mark in one direction or the other. It would also dispatch dopamine to certain parts of the brain where more is needed and slow it down in other areas where less is needed.

The problem is, a smart dopamine med doesn't exist. But we can still come up with smart strategies based on the meds we have. Cretin and her doctor did just that. Think "dopamine cocktail."

I stumbled upon this by accident about four years ago when someone I know raised with her psychiatrist the idea of Wellbutrin to deal with a particular side effect of the antipsychotic she was on. The Wellbutrin turned out to be a dud in this regard, but unexpectedly her head cleared up. She could "think" again.

Thinking - something people with no mental illness or who have never been on a psychiatric med take for granted.

Two-and-half years ago, I began researching dopamine in earnest. Soon after, a friend landed a part-time research position, which represented a major step in his recovery - if he could hold onto the job.

My friend has a masters degree and teaching experience, but his previous employment was parking cars, and even that was a struggle for him. Between his illness and the antipsychotic he was on, his brain had a hell of a time booting up.

I suggested he ask his psychiatrist about Provigil. In essence, something to counteract the antipsychotic. A dopamine cocktail, if you like. I won't say the med brought his brain completely back online, but what he reported was a miracle. He could function. No longer was he overwhelmed by work and the people around him. He credits the Provigil with saving his job.

There is a twist to this. Thanks to our system of mangled care, my friend was deprived his Provigil. His psychiatrist was smart enough to substitute an ADD med, which didn't work as well, but nevertheless got the job done until my friend managed to get back on the Provigil.

Clearly, psychiatrists are willing to give dopamine cocktails a try, but the fact we don't hear more from people such as Cretin indicates this is clearly not widespread practice. What gives?

For one, there is no evidence base to go on, much less any CME courses to educate physicians, much less FDA indications for using meds in this capacity. In short, the only thing guiding psychiatrists is their own clinical wisdom.

For another, there is legitimate fear of abuse and addiction (a small study that just came out in JAMA found potential for addiction in Provigil).

Add to that my own strong belief that doctors tend to err on the side of overmedicating and over-sedating us. The thought of us cracking jokes and solving differential equations while we dance with the stars seems to set off a primal reaction in just about every card-carrying psychiatrist I have known.

Finally, there may be other and possibly safer alternatives to dopamine-enhancers, such as meds that work on the cholinergic system (for instance, Alzheimer's meds). A good psychiatrist will take these and other matters into consideration.

Obviously, this is an extremely complex issue. Any decision needs to be an informed one between you and your psychiatrist. By all means, let's get a conversation going, but until we learn more, let's not jump to any premature conclusions.

More to come in future blogs ...

From mcmanweb:

Dopamine - Serotonin's Secret Weapon

The April 2007 American Journal of Psychiatry features an editorial by Bruce Cohen MD, PhD and William Carlezon PhD, both of Harvard, entitled "Can’t Get Enough of That Dopamine." As the authors point out, "through their many connections, dopamine neurons participate in the modulation of expectation, reward, memory, activity, attention, drives, and mood - the very substrates of psychiatric illness." ...

Tuesday, March 17, 2009

Bob Ashburn: Hero

Dateline - Two and a bit years ago: I was new to water volleyball. I was serving. For a change the ball cooperated with me and took off like a rocket on its mission of doom. I was already warming up for my end zone dance when the water immediately on the other side of the net erupted in swirling white foam.

Was it a shark? A porpoise?

Suddenly, ten feet above the surface appeared a muscular guy with a friendly killer grin. He brought his right arm around like a windmill blade and literally hammered my deadly serve back over the net into the water and through the bottom of the pool and the center of the earth clear to China.

He vanished as mysteriously as he appeared.

"You ruined my self-confidence!" I shouted in high dudgeon in the direction of the miraculous visitation, or words to that effect. The nerve!

A few days later, I had my revenge. The perpetrator of my humiliation - Bob Ashburn - showed up at my place to install a satellite dish. He was up on the roof when a freak Southern California hailstorm let loose.

I couldn't resist. I ran out into the hail, totally impervious to the ice pellets bouncing off my skull, jumping up and down as I pointed to him on the roof and shouted ten dozen times, with full trash talk effect, "Aha! That'll show you!"

Fortunately, I live in a rural environment, so there weren't any neighbors to call the police.

Bob and his wife Linda are two of the most gracious people I've ever met, and many times I have enjoyed their hospitality. The two went out of their way to welcome me to water volleyball and to the resort community where we play the game. Bob and Linda have an RV residence at the resort (80 miles in the desert east of San Diego), and also live in an RV park in San Jacinto, closer to LA.

It was at San Jacinto last weekend that Bob did something amazing.

An RV residence there caught fire. Bob arrived on the scene and asked the park manager if there was anyone inside. When the manager replied, "I think so," Bob did not hesitate. In he went. He fought his way through the smoke. A man - Tom - was inside, in shock, in flames.

Bob literally dragged him out, then neighbors put out the flames with a hose.

According to a local news account: "[The manager] recalls Ashburn running in and pulling out the man without any hesitation and 'no regard for his own life when he went in to look for him.'

"'Tom was still on fire, his head was aflame,' [the manager] said. 'If not for Bob, he would have been a goner - bar none.'"

The news account reports that Tom is currently in critical condition, with third degree burns covering 50 percent of his body and damage inside his lungs.

So there you have it - restored faith in the goodness of man, a person to look up to, someone I'm proud to have as a friend.

Bob, I promise - next water volleyball game I'll go easy on you.

Monday, March 16, 2009

Trick Question: Meds Compliance

What is the one drug taken by 85 percent of those with schizophrenia and two in three with bipolar that they are 100 percent compliant with?

Answer: Nicotine.

I posed this question last year to 50 or 60 clinicians at a grand rounds lecture I presented at a psychiatric facility in Princeton. Just prior to asking the question, I cited a 2006 study in which four in five patients on Zyprexa dropped out of the long-term phase of the trial.

This is not an isolated finding. The drop-out rate figure fluctuates between 40-to-100 percent over the long term across a broad range of psychiatric meds and diagnoses.

What's different about nicotine? In my talk, I showed a slide citing the research of Robert Freedman MD of the University of Colorado that connected "auditory gating" disturbance to nicotine craving. Apparently, individuals with schizophrenia have trouble screening out the second of two repetitive sounds, which does hell to their concentration.

This gating response is mediated by - drum roll, please - the alpha-7 nicotinic receptor.

Nicotine works. With nicotine, patients actually get their brains back - even if just for a precious few seconds. Apparently, in the brief time a cloud is in the patients' lungs, a cloud clears from the brain.

The only thing that is wrong is the delivery system, but in the drug development pipeline are nicotinic agonists.

Here's where I won over my audience: "So, if you prescribe cigarettes," I said, "you will get much better compliance than if you prescribe an atypical antipsychotic."

(Clinicians like to show their appreciation by looking like they're holding in their lower intestinal tract versions of auditory gating.)

"Now, compare that with an atypical antipsychotic," I went on to say. "Rather than clearing the brain, these meds actually take major parts of the brain off-line."

For support, my slide quoted a 2007 editorial in the American Journal of Psychiatry:

"Without adequate dopamine signaling, our patients do not feel 'well.' When dopamine systems are dysfunctional, patients seek a change. This may involve stopping taking a medication, such as antipsychotic drugs that block dopamine."

Then I quoted John Krystal MD of Yale from a lecture he gave to the American Psychiatric Association the year before:

"Our medications are least effective for the most disabling symptoms of schizophrenia," namely, "the cognitive dysfunctions ..."

Cognitive dysfunction also looms large in bipolar.

Let's start connecting the dots: We have psychiatrists prescribing patients a class of drugs that work well against psychosis at the expense of worsening the most pronounced feature of schizophrenia and a significant feature of bipolar. No surprise - low compliance rates.

Meanwhile, we have a drug that doctors try to ban that actually helps bring patients' brains back online for a few precious seconds. Surprise, surprise - high compliance.

You tell me: Who are the smart people in this equation?

"Far from lacking insight into their illness, from refusing to put up with side effects," I said, "patients are willing to put up with a drug with one of the worst side effects profiles in the world. Why? Because it works. It works where they want it to work."

I was just getting warmed up:

"Let's face it," I said, "we've all been badly oversold on the new generation antipsychotics - you, me, family members. When all is said and done, these new generation atypicals are basically Thorazine with the tires rotated."

I wasn't through:

"The CATIE studies brought this out loud and clear. My question for you is why did it take you so long to figure this out? The same info was in the journals you subscribe to, on the labeling of the meds you prescribe. More important, your patients have been telling you this for years.

"Why haven't you been paying attention?"

This part of my talk was interrupted by a spontaneous display of stony cold silence. The temperature in the room literally dropped ten degrees.

What were they expecting? A CME lecture sponsored by Eli Lilly with free "Zyprexa" pens and coffee mugs?

Remembering Pearl Harbor

This weekend, a bunch of us drove out to Yuma, AZ to view an airshow at the Marine Corps Air Station there. The highlight was a re-enactment of Pearl Harbor staged by a group known as the Commemorative Air Force. I remembered to pack my videocam. Following is their tribute (and mine) to the greatest generation.

Enjoy ...

Friday, March 13, 2009

Happy Anniversary, Emily!

A year ago, I was in New Zealand to attend my daughter's wedding. Her first anniversary is in two days, technically tomorrow factoring in the International Date Line.

I lived in New Zealand for eleven years, back in the 70s and 80s. I met Gail, my first wife, in San Francisco. Gail is a Kiwi, and 18 months later we were in New Zealand. We settled in Dunedin, at the bottom of the South Island, and both of us enrolled in law school (law is an undergraduate degree there).

In our second year of law school, we had Emily. We spent the rest of law school handing off Emily like a football to each other between classes. Since males don't have breast milk, I had to be especially inventive in keeping Emily happy.

After graduation, we moved to Wellington, New Zealand's capital. Gail went into law and I found my way into financial journalism. A year and a bit later, our marriage broke up, and five years later I headed to Melbourne, Australia to take up a post as feature writer for the business section of a daily newspaper.

Six months later, thanks to a mixed manic episode, I found myself a stranger in a strange land, broke and friendless and unemployed. I managed to scrape by for the next five years, then returned to the east coast of the States just in time for a crushing depression and more lost years than I would care to admit.

Those lost years involved missing out on a lot of my daughter's growing up. Her mother did a great job raising her. Emily wound up getting a law degree from the same place her mother and I did, plus a marketing degree, then went to work in New Zealand's wine industry.

Fathers, of course, always ask questions they shouldn't. On the phone, I got Emily to own up to the fact she was dating. "Is he a keeper?" I asked. Let's put it this way - it was the kind of "yes" every father wants to hear.

I later met Hamish when he and Emily were visiting the States. I couldn't have picked out a better mate for her, myself. Her mother says the same thing.

I hadn't been to New Zealand since the early nineties. In many ways, it was the same country. In so many other ways, though, it had transformed itself. Back when I was living there, New Zealand was full of smart and sophisticated people working to fashion a society in their image. By the time I returned, they had largely succeeded.

I harbored a bit of regret that I wasn't part of that. Indeed, I spent a lot of time facing down - and ultimately exorcising - ghosts from my past. I was a different person now, but this distant place in a distant time shaped me, gave me an education, got me started on a career. And, of course, gave me Emily.

Funny thing about Emily's wedding day, the thing I recall most vividly is chatting with the taxi driver on the way back from the reception. He was from Somalia. Here he was, an immigrant, in a new country. A new start, a young man with a future. That's how I felt when I arrived on this distant shore more than 30 years before.

Now, here I was, looking back at my past. But also into a future that involves a wonderful daughter and her fine husband.

Happy first anniversary, Emily and Hamish!

Wednesday, March 11, 2009

Madness and Creativity - What's the Connection?

Back in 2003, I had one of those breakthrough moments, the type you associate with light bulbs switching on. I was at the American Psychiatric Association's annual meeting attending a symposium on genetics. Robert Freedman MD of the University of Colorado started explaining his research into schizophrenia.

"The DSM-IV was not designed with human gene function in mind and genes do not encode for psychopathology," he said. Instead, "genes encode simple molecules in cells that alter cell function and brain information processing."

I had kind of been aware of this, but this time I went, "Aha!"

Dr Freedman had been exploring the link between "sensory gating disturbance" and why people with schizophrenia crave nicotine. A normal person, for instance, can tune out the second of two repetitive sounds. Many people with schizophrenia, however, cannot, and so have great trouble concentrating.

It turns out that the alpha7 nicotinic receptor mediates sensory gating, and thanks to the work of Dr Freedman and others, drug manufacturers have a nicotinic agonist in development.

The upshot of my Aha! moment was the realization that to better understand my own illness (bipolar) I needed to research other illnesses as well, such as schizophrenia. The brain, after all, doesn't organize itself according to the DSM.

A couple of years ago, at the APA, I listened to various schizophrenia researchers talk about the thinking processes of the brain. To vastly oversimplify, individuals with schizophrenia have trouble tuning out distractions from competing neurons; yet what is also in play is the potential for novel neuronal alignments to generate novel thoughts.

At the same APA meeting, Nancy Andreasen MD, PhD of the University of Iowa discussed her research into creativity, which began with a hunch based on schizophrenia.

What we seem to be looking at is that fine edge where productive novel thinking ventures close to the precipice of pathologically delusional thinking. I raised this issue in an earlier blog about John Nash and in another blog about evolutionary psychiatry.

The other day, I came across a blog post on Psychology Today by author Scott Barry Kaufman PhD, entitled Schizophrenic Thought: Madness or Potential for Genius?

Eureka! Cue up the light bulbs.

Dr Kaufman talks about "latent inhibition" (LI), the brain's ability to unconsciously filter out information. High latent inhibition is conducive to rational thought. Low latent inhibition is associated with psychosis and schizophrenia.

But can there be an upside to low latent inhibition? Writes Dr Kaufman:

"Recently researchers have wondered whether a reduced latent inhibition can actually be beneficial for creativity. After all, decreased LI may make an individual more likely to see connections that others may not notice."

In support of this, Dr Kaufman cites research by Shelley Carson PhD of Harvard showing that those with a high IQ and decreased LI reported increased creative achievement. The key here appears to be adequate levels of executive function to ride herd on the stampede of incoming information. The catch is people with schizophrenia tend to score very low on measures of executive function.

Another point that Dr Kaufman raises is that people with schizophrenia have difficulty sorting out their emotions. Again, they are overwhelmed. Here's where it gets interesting: A lot of these emotions may be intuitions that are accurate, thus enhancing the potential for making a creative connection.

Dr Kaufman is engaged in research on subjects with normal levels of executive function. This involves measuring LI. In the first part of the task, subjects need to screen out certain irrelevant input to achieve success; in the second part, processing that same irrelevant information is vital to arriving at the right answer.

According to Dr Kaufman:

"I found that those who reported a higher faith in intuition displayed decreased latent inhibition. In other words, those who reported higher faith in their intuitions allowed the information that was tagged as irrelevant in the first phase to be treated as novel and interesting in the second phase, and by doing so were faster at figuring out the answer."

Alas, it seems, those with schizophrenia lack the necessary executive function to cope. Way too much information. "Indeed," says Dr Kaufman, "this idea of 'sensory gating' has been quite influential in the literature on schizophrenia."

Sensory gating! Where have I heard that before?

Much more research is needed, Dr Kaufman acknowledges. "Nonetheless, an understanding of the biological basis of individual differences in different forms of implicit processing and their relationship to openness to experience and intuition will surely increase our understanding of how certain individuals attain the highest levels of creative accomplishment."

And in conclusion: "Perhaps such research will even allow us to stop rehashing old ideas about the potential links between madness and creativity and re-conceptualize the thought processes that are prone to psychosis not as madness at all but as potential for creative greatness."

Further reading from mcmanweb:

The Thought Spectrum

If all that sounds way too simple, Dr Krystal rolled out a far more complicated scenario involving glutamate’s tag team partner, GABA (the main inhibitory neurotransmitter), in particular a group of GABA neurons referred to as chandelier cells. In this context, GABA helps prevent glutamate from running wild. When involved in working memory, GABA tunes out distractions from competing neurons, allowing the brain to focus. But a deficit in NMDA glutamate receptor function effectively disables GABA chandelier cells. ...

Monday, March 9, 2009

Industrial Disease: What Are We Doing To Ourselves?


The average working couple in America spends 20 minutes a day together.

"Family time" has become a goal, an achievement, rather than a natural consequence of being a family.

Most Americans are trapped in a vicious cycle of overwork and over-consumption.

Dropping in on a neighbor is practically nonexistent.

Keeping busy and multitasking are praised, while slowing down is frowned upon.

This from Therese Borchard, writing on the Huffington Post. She was drawing from a book by Abby Sexias, "Finding the Deep River Within."

"The disease of a-thousand-things-to-do," is how Ms Seixas describes it. I would give it another name: industrial disease.

In 2004, a major World Health Organization survey of 14 countries and two Chinese cities found Nigeria and Shanghai with the lowest prevalence of mental illness, way lower than the US and Europeans. In mood disorders, the Nigerians were at the very bottom (less than one percent over 12 months compared to nearly 10 percent in the US).

Maybe Nigerians are too worried about where their next meal is coming from to ruminate on the things we do. But I have a strong suspicion that they have something we haven't got, things we lost a long time ago, things our kids will never know about.

The beginning of the industrial revolution in the mid-eighteenth century coincided with a sudden explosion in mental illness. It didn't take people long to finger the stresses of urban life as the culprit. The asylums - literally sanctuaries - that sprang up in nineteenth century were beautiful country estates with farms attached. They were the product of the various reform movements of the age that included abolition, self-improvement, and enlightened Christianity.

In other words, way back when, people actually recognized that if you treated the mentally ill with compassion, took them away from stressful environments, and gave them opportunities to take pride in their work then their condition might actually improve.

The inaugural 1844 issue of the American Journal of Psychiatry (then called The American Journal of Insanity) reported on an institution in Utica, then in operation for 18 months. According to the report, of 433 patients admitted, 123 had recovered.

It was only later that these same institutions became the chambers of horrors that shame us as humans.

So, have we learned anything over the intervening years?

Yes. If we place families under impossible financial obligations with absurd expectations, force both partners to labor late into the night in high pressure corporate sweat shops devoid of fresh air and natural light, sleep-deprived and alienated from nurturing communities, sooner or later they will go crazy and drive other people crazy.

Not only that, see what happens when we over-school and over-regiment their kids.

Our brains simply weren't built for this.

If you scroll back to some of my recent blogs, you will note a number of short home-made nature videos. They are there for a reason. Since moving to a rural environment more than two years ago, I noticed something astonishing - my mental health improved, dramatically so. I work from home. I keep my own schedule. When I need a mental health break, I take it. All I have to do is step outdoors.

Welcome to my world.

Your world - and your responsibilities - are certainly a lot different. But your brain undoubtedly has the same limited warranty as mine. This is a tough world, growing tougher by the day. Survival depends on your creativity in carving out sanctuary - asylum.

It's a principle as old as the hills. Our ancestors understood it. Nigerians and other societies probably still do. We are incredibly slow learners in a painful process of relearning.

My Good Friend Kevin - Six Months Later

Yesterday, my former wife Susan reminded me that it is coming up to six months from when a very good friend of ours, Kevin, threw himself in front of a train. He was 28.

Four and a half years ago, when I was in my second marriage, I was facilitating a DBSA support group in Princeton, NJ. In walked Kevin, exuding a goofy charm, baseball cap on backward. But there was something about his presence that indicated he was no mere goofball. The others in the room felt it, too.

Over the weeks, I couldn't help but be impressed by the way Kevin carried himself. He would walk up to newcomers and introduce himself and start up a conversation. In the group, he was a great listener, dispensing the wisdom of a sage, leavened by a keen sense of humor.

It was amazing to observe him with people much older. At once, he was deferential, compassionate, and exuding great authority. You simply forgot you were talking to someone much younger. You simply wanted to be around him, laugh with him, seek advice from him.

He had his setbacks, his dark moments. Yet, over time - in group, over coffee, over sandwiches, hanging out - I watched him blossom. With his extraordinary people skills, the sky was the limit.

In late 2006, my marriage broke up. Kevin was the first to offer me support. He also reached out to Susan.

Suddenly, I had my life in seven or eight FedEx cartons and a one-way ticket to San Diego. I popped into the DBSA group one last time. Kevin was facilitating. He gave me a heartfelt tribute. I felt the goodness in the man. Goodness, true goodness. That was the last time I saw him alive.

He had so much to live for, so much to offer. Yet, on a miserable muggy New Jersey morning, his brain tricked him into believing otherwise. Six months later, Susan and I, plus all those he left behind, are still dealing with it.

I've been suicidal. So has Susan. We fully understand, yet - we totally don't understand.

My way of coping was this suicide prevention video, "The Road to Nowhere." The message is simple: Don't be fooled. You are really somewhere. I shot it two or three weeks after the horrible news.

Kevin, you still shine a light on the world. Nothing - nothing - is ever going to extinguish it.

Sunday, March 8, 2009

More Desert Wildflowers

Desert Wildflowers!

On Friday, I drove two hours from my home 40 miles east of San Diego to meet up with a good friend of mine from LA in the middle of the desert. The Anza-Borrego Desert has a subtle stark beauty all its own. But this time of year, thanks to winter rains, the desert floor and slopes are loud with wildflowers.

This is a year that seasoned observers are describing as "good to very good."

Enjoy ...

Thursday, March 5, 2009

Rush Limbaugh, Nihilism, and Antipsychiatry - Where is the Off-Button?

Only in America:

Yesterday, right-wing radio blabbermouth Rush Limbaugh challenged President Obama to a debate. From the transcript of his March 4 show:

"Why doesn't President Obama come on my show? We will do a one-on-one debate of ideas and policies. ... I am offering President Obama to come on this program - without staffers, without a teleprompter, without note cards - to debate me on the issues. Let's talk about free markets versus government control. Let's talk about nationalizing health care and raising taxes on small business."

Do the words grandiose and delusional come to mind?

And didn't Limbaugh earlier say he hopes the President will fail?

How about nihilist to describe the guy?

Funny thing - call it my own internal Rorschach test - when I think nihilist I think antipsychiatrist. In his blog on Psychology Today, Nassir Ghaemi MD of Tufts University writes:

"I suggested that many critics of academic psychiatry, especially those who attack links to the pharmaceutical industry, suffer from postmodern nihilism. They do not believe in any truths; thus they see the manipulative interests of private enterprise and the greedy search for wealth behind everything."

Wait, here's the kicker: "Scientologists cannot be accused of that motivation. If anything, they are true believers ..." Say whatever you want about Scientologists, at least they stand for something.

So, is it possible to be in sync with antipsychiatry and not be an antipsychiatrist? Yes, as long as you don't let "anti" define you. Let me give you an example:

Back in 2003, I attended a two-day Non-Pharmaceutical Approaches to Mental Disorders conference in Pasadena, sponsored by Safe Harbor, which is the best source of non-meds info on the web. Founder Dan Stradford has connections with Scientology, which I'm only bringing up before someone else does in a negative guilt-by-association way. When you hear Dan speak you can't help but be moved by his story about his late father.

At the conference, I heard Lewis Mehl-Madrona, MD, PhD discus integrative psychiatry and Native American healing, Julie Ross on natural supplements, William Walsh PhD on methylation and metal poisoning, Doris Rapp MD on toxins, Kathleen Crowley on procovery, and much much more

I love Ms Crowley's advice, by the way: "Just start anywhere."

Intriguingly, a panel of parents of bipolar kids testified on the progress of their kids on natural regimens. Mind you, we didn't hear any failure stories, but in strong contrast to the antipsychiatry party line we did hear explicit recognition that bipolar in kids is horrific and real.

Naturally, I was interested in what the people who paid to attend thought of the proceedings. It's fair to say they were not exactly bullish on psychiatry, but neither did they identify themselves by what they were against. Instead, they were hopeful that people could live better lives, and to a person they wanted to be part of that process. One group of very pleasant women was interested in forming a "NAMI Natural" branch to their local NAMI.

Clearly, these people weren't antipsychiatrists. Far from it. And because they actually had something to say, not to mention showing an interest in where I was coming from, I was all ears. With antipsychiatrists, take my word for it, you wish you had a button to turn the audio off. Ah - so that's why they remind me of Rush Limbaugh.