Rerun: Figuring Out Schizophrenia - Part II

Nothing like a three-part piece from March 2009 to rerun while I perform clean-up on the Augean Stables that is my website. Looking forward to being back live soon ...

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 ...

Rerun: Reporting on Schizophrenia

Until I get my website overhauled (a mammoth undertaking), I will be posting reruns. This three-parter (from March, 2009) will get me through most of this week. Looking forward to being back live very soon ...

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 ...

Skid Row, Schizophrenia,The Soloist

Last week, the LA Times reported that College Hospital in Costa Mesa, 40 miles south of LA, "dumped" Steven Davis, whom they had diagnosed with schizophrenia, bipolar, and schizoaffective, outside of Union Rescue Mission located along LA's infamous Skid Row.

Literally, the hospital loaded him into a van, drove him 40 miles north, and dropped him on the street. This is what they call a "dump." College Hospital dumped Steven Davis the way some people dump their excess garbage in shopping mall dumpsters - surreptitiously, with hopefully no one watching.

But the Union Rescue Mission was watching, and when they complained, the van returned - and dumped Steven outside another shelter.

The city attorney reported that College Hospital was responsible for dumping 150 mentally ill in this fashion over 2007-2008. Steven Davis was a key to the city attorney's office making its criminal case. As part of a settlement, the hospital will pay $1.6 million in penalties and charitable donations.The hospital denies any wrongdoing.

In case you are experiencing deja vu, Michael Moore's 2007 documentary, "Sicko," showed security cam footage of a 63-year-old homeless and disoriented woman, Carol Reyes, wearing only a thin hospital gown, dumped in front of the same Union Rescue Mission by Kaiser Permanente's Bellflower Hospital.

Criminal charges were filed against the hospital's officials, and Kaiser paid a large settlement. LA authorities have been cracking down on dumping.

Doing something about Skid Row is far more problematic, an approximate 4x4 square block area where 7,000 to 8,000 homeless - many of them with mental illness - sleep on filthy streets, conveniently out of sight and out of mind to the rest of the world.

On April 24, Hollywood will be giving the area a lot more visibility. That is the day of the much-anticipated release of "The Soloist," starring Jamie Foxx and Robert Downey Jr, based on a book of the same name by LA Times columnist Steven Lopez. The book and movie chronicle the unlikely friendship forged on Skid Row between Lopez and Nathaniel Ayers, a gifted cellist who lost his mind to schizophrenia while attending Julliard.

We see only the homeless. But Nathaniel's story is all too typical. Think of schizophrenia as a developmental disease. Kids are leading normal lives. Then - at say age 17 - something happens. One minute they're doing well in school and looking forward to college. Then they start acting a bit strange. Then - bam! - all at once, they are robbed of their minds, their humanity - everything.

Just like that it's over. The illness has a poor outcome, made much poorer by our appalling health care system and the unconscionable way our winner-take-all society turns its back on people they view as losers.

I'm sure "The Soloist" will bring this out loud and clear. I loved "Shine." I loved "A Beautiful Mind." I'm sure I will be profoundly moved by "The Soloist." But if nothing changes for the better in this country as a result, then there will be no feel-good ending.

The Soloist trailer.

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 ...

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 ...

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 ...