Rerun - Remembering Pearl Harbor

My mind was on a lot of other matters today. A few minutes ago, as I was getting ready to crash on a friend's couch three time zones from home, I suddenly realized what day it was and what it means. I put this together back in March ...

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 ...

Considering Ethnic Perspectives

On Friday, I attended a one-day conference on ethnic diversity in the older mental health community, put on by the Senior Mental Health Partnership, which is a program of NAMI San Diego. The emphasis was on the special needs of the many and diverse ethnic groups that call San Diego county their home. These needs include cultural and language barriers that pose a challenge to treatment, as well as the psychic horrors from atrocities that many must contend with, particularly older generations.

My friend Sally Shepherd MN of UCSD , who organized the conference and set the scene in an opening presentation, provided this salient example:

According to one study, 70 percent of southeast Asian refugees receiving mental health care met diagnostic criteria for PTSD. In a study of Cambodian adolescents who survived Pol Pot’s concentration camps, nearly half experienced PTSD and 41 percent suffered from depression ten years after leaving Cambodia.

Meanwhile, demographics are dramatically shifting. Ms Shepherd noted that in a matter of years, latinos in California will outnumber whites. By 2020, whites will comprise 37 percent of the population while hispanics will make up 41 percent, almost an exact reversal on current figures. By 2050, this “minority” will be in a “majority” at more than 50 percent of the population, with whites at one in four.

As one commentator remarked: “Few of their children in the country learn English ... the signs in our streets have inscriptions in both languages ... unless the stream of their importation could be turned ... they will soon so outnumber us, that all the advantages we have will not in my opinion be able to preserve our language, and even our government will become precarious.”

Ben Franklin said that, back in 1753, not Lou Dobbs. Franklin was expressing his alarm over Germans settling in Pennsylvania. Some things, Ms Shepherd pointed out, apparently never change.

Concepcion Barrio PhD of the USC School of Social Work talked about mobilizing “culturally salient protective factors” in working with latinos. These include strong family attachments, supportive community networks, and deep spiritual/religious convictions. For instance, according to a 1998 study, of those with severe mental illness, 75 percent of latinos and 60 percent of African-Americans lived with their families, as opposed to just 30 percent of whites.

A 2006 meta-analysis of  56 studies found that interventions targeted to specific cultural groups were four times more effective than those non-targeted interventions and that those conducted in a client’s native language were twice as effective as those conducted in English.

Simply having providers employ ethnically-matched staff, along with other surface strategies, is only part of the picture, Dr Barrio argued. Deeper approaches incorporate the traditions of the ethnic group. She cited the well-known “Mexican Paradox,” which has to do with first-generation Mexican-Americans faring a lot better mentally than assimilated later generations.

In addition, Dr Barrio pointed out, families from third-world nations tend to manifest lower “expressed emotions,” such as hostilities. Acceptance and warmth in Mexican-American families, for instance, predict better outcomes from schizophrenia.

The catch, of course, is that mental health providers need to be making the effort. In this context, we hear terms such as “cultural competency,” which involves, among other things, not making false assumptions about others’ ways based on one’s own limited personal experience.

Not good in healthcare, Ms Shepherd concluded.

More later ...

A Sunday Drive

No fish tacos in Beantown! I had to settle for a lobster roll in Revere Beach, instead. That's snow where the sand should be. Thank you for the ambiance, Jonathan Livingston.

Boston from Nahant.

House of the Seven Gables, Salem.

Another view from Nahant.

iPhone Photo of the Day

As you can see, I ventured slightly out of my neighborhood. I'm in Lexington, MA, just in time for the first snowfall of the year here. I'll be back in southern CA in a few days. Ah, short winters. Love it.

Rerun - Of Mice and Neurons

Two of my recent blog pieces offered a "macro" systems view of the brain experiencing breakdown. Here's a complementary "micro" cellular view I first published in March ...

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." ...

Me, Apollo 15, and the Future

The following is a continuation of Me, Captain Ahab, and the Anterior Cingulate Cortex:

The year - 1971. Location - the moon. After 23 hours with no sleep, Apollo 15’s two moonwalkers were back in their command module in lunar orbit, preparing for their return home. Back in Houston 240,000 miles away, ground controllers picked up anomalous EKG readings from one of the astronauts. Jim Irwin’s heart was skipping a beat, then beating twice rapidly. After communicating with Irwin, the flight surgeon at Mission Control diagnosed a specific type of heart arrhythmia known as bigeminy.

Had Irwin been on the ground, doctors would have treated him for heart attack. But it turned out that the command module, with a 100 percent oxygen atmosphere and zero gravity, was better than any ICU he would have been placed in on earth. His heart soon settled back to normal, and Apollo 15 later successfully splashed down without incident. A few months later, Irwin had a heart attack. Twenty years later, yet another heart attack killed him.

Fast forward to the present. Location - earth. An individual very close to me was admitted to a psychiatric unit, and, after careful evaluation, was diagnosed with depression and given an antidepressant. Following a second hospitalization, he was put on different meds and released. Soon after, he was back in the hospital.

Basically, this individual has broken brain disease, and if we knew exactly what part of the brain was broken and could link the malfunction to the symptoms he was experiencing, we would have an exact term for it and perhaps have a clue of how to best treat it. But diagnostic psychiatry in 2009 is no match for the diagnostic cardiology of 1971 - at least not right now it isn’t.

Part of what is holding us back is that mental illness is far more complex than cardiac illness. What brain scans are showing is something akin to a total system collapse in the brain, involving many interconnected brain regions, rather than a specific fault. The brain science is beginning to tease out subtle structural and functional distinctions across a range of diagnoses. But this is hardly equivalent to taking an X-ray, finding a bone fracture, and knowing exactly how to set the break.

Nevertheless, brain scans are providing us with a sneak preview of the future. In a famous set of experiments performed two or so decades ago, OCD subjects (ones obsessed with cleanliness) shared a brain scan machine with a "dirty" sweat sock. Their respective brain loops lit up like a Christmas tree. When exposed to a "clean" sock, their brains quieted down.

The anterior cingulate cortex (ACC), part of the mid-brain, contains specialized neurons responsible for “gating.” which allows the brain to focus on certain incoming information (such as a conversation) while tuning out others (such as the background hum of an air conditioner). When things go wrong in the ACC, all manner of bad things can happen, such as OCD or schizophrenia or depression.

Thanks to this knowledge, doctors were able to adapt deep brain stimulation (DBS), used for Parkinsons, to experimental (and still extremely rare) psychiatric surgery. In Feb this year, the FDA approved DBS as a last resort treatment for OCD. The procedure also shows promise for depression. In DBS, a metal lead is inserted through folds in the brain. An electric pulse breaks up neuronal signals (such as those responsible for distracting thoughts and ruminations) in the ACC region. Unlike earlier generations of brain surgery (such as cingulotomies) no surgical lesions are involved. The surgery is reversible, but does involve risk.

Let’s be clear on this: This is not a piece extolling the virtues of psychiatric brain surgery. Indeed, it is difficult to imagine psychiatry headed in this direction. But what we are witnessing nonetheless presents us with a tantalizing peak at what tomorrow may involve, namely:

It is foreseeable that advances in technology will make MRI machines, or some other brain scan technology, convenient and affordable and routine, equating to advances in computer technology.

In the meantime, we already have the means to do gene scans - the chips are getting faster every year. Now imagine the software to interpret data coming from a whole ranges of sources - gene scans, brain scans, psychiatric evaluation, neurological testing, etc - to give the treating psychiatrist a range of options to consider.

The following is wild speculation: Keep in mind that the dominate operating paradigm for mental illness is system breakdown, a host of things going wrong seemingly all at once. But suppose we could get a bit closer to the source - say the hippocampus (involved in memory) failing to boot up, say key parts of the frontal lobes going off-line, say certain stress pathways overloading. Say we were able to pinpoint various signaling bottlenecks and hubs.

Thus, depression is no longer just depression. In fact, once we get a true read on what is going on, we may call its manifold variations something entirely different. All this would suggest targeted treatments and therapies, even with today’s highly imperfect remedies. Perhaps a dopamine enhancer to kickstart a certain brain system rather than an SSRI. Perhaps talking therapy focusing on past trauma rather than directed at here and now challenges.

The long-term pay-off would be that this kind of knowledge would spur future drug development (namely smart meds) and further refine talking therapies. It could also open the way for pinpoint electrical therapies and who knows what.

Private investors would need to see the solid science - a clear idea of how to get from A to B to C - before they were willing to put their money on the line. The catch is this type of science is dependent on the public sector. Basic research into mental illness is notoriously underfunded as it is. For lack of will, then, we may be unable to see our way to the future, much less realize it. The Apollo program was supposed to signal the beginning of manned space exploration. We haven’t been back to the moon since 1972, nor do we have the rockets for it.

The future - so near, yet so far ...

iPhone Photo of the Day

Another beautiful day 3,500 feet up in the mountains in southern CA. I took this a mile and a half from my home.