A Psychiatrist at Large

Polypharmacy for Schizophrenia

2011-08-04T10:54:00.000-07:00

This is what people out there have been doing for a long time. However, the evidence base of this type of practice is not substantial. A new paper published by Essock and colleagues in the July 2011 issue of the green journal tries to answer the question. Contrary to expectations, polypharmacy, while not as well tolerated as monotherapy, seems to be preferred. Due to lack of blinding, it is not clear though, if this is due to the patient's or provider's preferences (or biases) or both.

Still, a good beginning.

Can you change memories?

2011-05-05T17:26:00.000-07:00

Maybe, according to a new study that has just been published in the Journal of Neuroscience. Apparently a group of scientists at UCLA were able to do just so by "erasing" a traumatic memory in a marine snail by inhibiting PKM - a protein kinase associated with memory. This feast was in part possible because the researchers were able to target a single synapse - which is impressive but might be a bit hard to replicate in humans.

However, assuming that somehow a technique could be developed, the possibility of erasing memories raises a number of difficult ethical questions. We are our memories, with the good, the bad, and the ugly. Erasing a part of who we are might have unintended consequences - changing our view of the world, others and ourselves.

Traumatic memories, as painful as they might be, served a role in the individual's make-up. Let's assume that somehow they resulted in a cautious, think before you commit, double check everything modus operandi. Let further assume that at the push of a button the traumatic memory miraculously evaporates. But then what? Should one continue to erase (e.g. suspiciousness, double checking etc.)? If so, when will one stop - as in all likelihood there are consequences to consequences?

At some point the process could result into a significant erasure of one's persona, and a decision will need to be made about stopping and integrating whatever it might be left (consequences wise).

The idea is that integration is necessary regardless of what and how much one erases. But then, why take the risk of unforeseen and possibly dangerous changes, instead of targeting integration for whatever is traumatic from the beginning of the process?

Cognitive Remediation in Schizophrenia

2011-04-13T14:19:00.000-07:00

My Faculty of 1000 review of Wikes and collegues recently published meta-analysis:
http://f1000.com/9528958

I am glad to see that there is some signal for a non-pharmacological intervention who can move us more in the direction of adressing functional deficits.

The Gift of a Sound Mind

2011-04-12T12:09:00.000-07:00

As a non-native English speaker I always wonder about the English words and phrases roots. One such phrase is "sound mind".

Well, surprise, surprise! From the field of neuroplasticity here it is an interesting paper showing how sound, when wisely put to work, can work its way into a "sound mind".

International Congress of Schizophrenia Research

2011-04-12T12:04:00.000-07:00

Just came back from ICOSR. A brilliant meeting where great minds get together to solve the mystery of schizophrenia. I thought it would be interesting to see how the themes of the meeting inform about the current view of schizophrenia.
And here they are:
1. Biology continues to have the upper hand. The vast majority of the communications (oral and posters) were from the biological camp.
2. Fundamental research (or basic science) has the upper hand. Clinical research is playing catch up.
3. Psycho-social research is making a comeback by changing its theoretical allegiance from a psychological to a biological perspective. In other words psychosocical research appears to regain status while conceding to the view that the mind is a brain epiphenomenon. Thus, the gold standard psycho-social assessments and interventions are to be measured against is their ability to measure/change brain states, rather then mind states or social functioning.
4. Cognition in schizophrenia is on the rise. It has been steadily consolidating prior gains and is now rubbing elbows with the major league players (genetics and functional imaging). In fact cognition might end up stealing the show as it is ideally positioned at a crossroad between biological, psychological and social theories as applied to both assessment and intervention research.

Local Brain Inefficiency

2010-10-28T12:31:00.000-07:00

An interesting paper further advancing the idea that we are looking at “local” rather than “global” brain deficits in schizophrenia.

In the Sept issue of the J Neurosci Wang et al. have a new take on what might be wrong with the brain in schizophrenia: they are proposing that the we are looking at small-world (rather than global) cortical network deficits.

What does this all mean? While the global functional brain network architecture is okay (consistent with a plethora of studies reporting “diffuse” brain changes in schizophrenia) the problem is that that the network local units are performing suboptimally.

Think about it this way. FedEx global infrastructure is up and running: the planes and trucks and trains and ships are all on schedule, doing a fine job. But if the local FedEx man chooses to spend some extra 10 minutes on his latte instead of picking up your package and, due to those few extra minutes, the plane leaves on schedule without your package – well, then the package will not get delivered in time, will it?

Local Hubs Differences

Another intriguing finding here is the local network hubs in healthy controls (HC) and schizophrenia were in different locations. The equivalent regions of HC hubs had decreased gray matter in patients; AND the local network hubs in SCZ were in completely different locations than in HC.

Here is the $546 question: Are these hub location changes primary or secondary?

Primary: the wrong placement might be responsible for the local network inefficiency. The hubs “form” in all the wrong places, then there is subsequent gray matter decrease at other locations, due to these regions relative lack of use and subsequent disconnection (in line with Hebb’s principle).
OR
Secondary: due to a primary deficit in the “optimal” hubs regions, the brain accommodates and develops secondary hubs at some other locations. A good compensatory move maybe, but different than standard. Survival is ensured but you could get either (too) creative or psychotic (hence the overlapping creativity/SCZ)

A lot of speculation here-but I find this whole small-network inefficiency story pretty intriguing.

2010-04-19T13:22:00.000-07:00

Why do I post a video about the domino effect of CDOs on the financial markets?
1. Because it's smart.
2. Because it's a simple and clear explanation of something that is very complex.
3. Because it nicely demonstrates two things that I think are relevant to psychiatry:
Context matters!
Look for the complexity behind apparent simplicity!

Crisis explainer: Uncorking CDOs from Marketplace on Vimeo.

Tripping for the Evidence

2010-04-16T11:32:00.000-07:00

You search Trip Database for "schizophrenia and asenapine".

One of the nice things about Trip is its color-coding of what it finds based on the quality of the evidence.

Green is best. This includes evidence based synopses, guidelines and systematic reviews. Why is this best? Because people who know what they do already reviewed the available evidence, graded it and summarized it - all in all, less work for you!

Blue is for original research, i.e. research that you need to directly review and asses according to "best evidence" criteria.

Red and brown is for textbook based evidence (otherwise known as background evidence), news etc. - evidence that maybe informative but it's harder to asses in terms of validity and bias.

You would hope that you will find evidence clustering towards blue. In this instance though Trip doesn't find any "best evidence". You find only 3 articles, all original research. From those there is only one clinical trial comparing asenapine (Saphris) with risperidone (Risperdal) in schizophrenia (1).

Good try but you need to move to step 2: SUMSearch.

N.B. In the future, if you want to try your own "trips" from this blog, you can go under the "search this" box and simply click on Trip Database.

1. Potkin et al: Efficacy and tolerability of asenapine in acute schizophrenia: a placebo- and risperidone-controlled trial. J Clin Psychiatry. 2007 Oct;68(10):1492-500.

Finding the Best Evidence

2010-04-16T10:42:00.000-07:00

Everybody is using PubMed.

Not a bad choice but not necessarily the place where you would want to start. PubMed is the search engine for Medline, an indexed bibliographic database curated by the U.S. National Library of Medicine. Which means that the amount of evidence is, at the same time, impressive and overwhelming. You need to know how to find what you are looking for when faced with such an enormous amount of data.

So, given the choice, why not making it easier on yourself? How about getting some help, i.e. letting someone else do some of the tedious work of filtering and grading the evidence before you try your hand at it.

Suppose that you just saw a patient with a diagnosis of schizophrenia, suffering of chronic auditory hallucinations on his current regimen of ziprasidone (Geodon) and divalproex (Depakote). You have tried all the others second generation antipsychotics and a few of the first generation - they were either only partially effective or poorly tolerated. The patient tells you he's heard of asenapine (Saphris), a new drug that has been recently approved for the treatment of schizophrenia. He asks if you would consider switching him to this new drug.

You've read the news about asenapine but didn't get a change to review the litterature. You tell him you will look it up and then discuss the options.

Before searching Medline, which you know will bring uo quite a few articles, you decide to call in your helpers. Their names are Trip Database and SUMSearch.

What do you find?

RSS Joy

2010-04-15T18:13:00.000-07:00

Moving toward Web 2.0. It's difficult nowadays to keep abreast with all the new medical info. The world wide dimension of the web is no longer a metaphor.

To help myself (and others who might be interested in this) I am adding two customized PubMed RSS feeds to my blog. Both targeting schizophrenia focused research. The first brings in research about the cingulate gyrus functioning and structure, the second meta-analysis studies.

For those of you who are curious about the search strategy:
1. PubMed MESH "gyrus cinguli" AND "schizophrenia".
2. PubMed MESH "schizophrenia". Limits: meta-analysis, English and human.

Enjoy!

Calling A Name

2010-02-25T15:51:00.000-08:00

You and I are different
We enjoy each other
We live together
Making fun of how different we are
To make fun is good
We are good to each other
They come
And tell us that
Poking fun at differences is
Insensitive
Inappropriate
Racist or sexist
In short
Bad
They label is “bad”
People doing bad things are bad people
Here we are now
Making fun is no longer
Fun and good
But
Mean and bad
Angry labelers pointing their fat fingers
Label us as bad
And before you know it
Before I know it
Here we are pointing fingers at each other
Mean
Bad
Mad.

Adrian Preda

2009-01-02T18:35:00.001-08:00

Well, it is a New Year. I debated about the many different topics of interest and after a lot of going back and forth – between such topics as the brain effects of optimism, physical exercise, yoga, meditation or just contemplative techniques in the broadest sense, I decided I will focus on love and wisdom. Love is commonly seen as both a process and an outcome. Wisdom is mostly seen as an outcome. They are both good states of mind and, I would further argue, good states for the brain. The question is: are there proven techniques to cultivate – teach one how to love and become wiser? If so, how do they work? What are their effects? And specifically, are there psychological versus physiological benefits? Are there any counter-indications? We will try to answer as many of these questions as possible in the posts to come.

Positive Psychology

2008-03-20T12:11:00.000-07:00

As an eternally optimistic medical student one of the reasons for which I was interested in psychiatry was that I wanted to figure out what are the mechanisms underlying happiness and personal growth. But that is not the traditional focus for either psychiatry or western psychology. When it comes to the mind or the brain our scientific interest has been in studying the abnormal and pathological with the idea that is the way to learn and understand what normal is. This is a logically valid approach if normal and abnormal would be parts of the same continuum - in other words, qualitatively equivalent states that are mainly differentiated through quantitative differences. But is this the case? What if we are in fact looking at discrete, qualitatively different states? Or, to put it differently: how much can we learn about happiness by looking at unhappiness and misery? Can we understand serenity by studying anxiety or creativity by dissecting psychosis?

All these are questions that are still unanswered.

The reality is that we are just coming our of a century dominated by the Freudian (mis)conception that the goal of our interventions should be to help patients transform their “misery into common unhappiness” and, at the best, provide them “with a mental life that has been restored to health [so they] will be better armed against that unhappiness” (Breuer & Freud, 1895/1955, p. 305). So, it's so much more refreshing to see that there is a new school of thinking proposing that happiness is common and achievable, while unhappiness is neither common nor normal.

This might seem like a purely academical point but is it really? Consider this question: while agreeing that depression equals unhappiness what is the best intervention?
A. An intervention that would "fix" unhappiness?
B. An intervention that would promote happiness?
My answer would actually be C. Both.

We now know that the brain circuits responsible for feeling unhappy are not the same with the brain circuits responsible for feeling happy. If that is the case then A and B interventions actually engage different brain circuits and by using both we are pulling in more resources that the brain can use.

While this is true most of our present day interventions, including both psychotherapy and medications, fall under the A category.

Here is where I see that value of positive psychology. Building on the shoulders of Maslow's self actualization theory, positive psychology finally got it right: when it comes to happiness learning how to be happy might just be a better strategy than learning how not to be unhappy.

2008-03-19T23:53:00.001-07:00

Introducing Snap Shots from Snap.com

I just installed a nice little tool on this site called Snap Shots that enhances links with visual previews of the destination site, interactive excerpts of Wikipedia articles, MySpace profiles, IMDb profiles and Amazon products, display inline videos, RSS, MP3s, photos, stock charts and more.

Sometimes Snap Shots bring you the information you need, without your having to leave the site, while other times it lets you "look ahead," before deciding if you want to follow a link or not.

Should you decide this is not for you, just click the Options icon in the upper right corner of the Snap Shot and opt-out.

Exercise Those Brain Genes

2008-03-12T14:38:00.000-07:00

So, how does exercise work in changing the brain? Is it only an indirect effect of a better brain "environment"? Of course, the brain loves to be in a "healthy" environment. In fact, the healthier the better - and physical exercise (PE) and its effects on controlling the fats and the sugars and optimizing brain oxygenation through good blood flow and pressure - would clearly have a major role in "optimizing" the environment.

But is this the whole story? Here is the great news: maybe not. One of the most exciting hypotheses is that PE might have a direct effect on the brain. My colleagues at Yale University (1) have shown that mice spending their time running on training wheels turn on brain genes that are responsible for the production of a number of neurotrophic and growth factors, including VGF, a neuropeptide precursor involved in energy balance, and neuritin, an immediate early gene involved in neuroplasticity. These are all proteins that keep the brain going and possibly also growing. Same genes were simply silent in the comparator group of sedentary mice. Moreover, the action of one gene in particular - VGF - while greatly enhanced by exercise, has also been shown to have a powerful anti-depressant effect, while blocking VGF inhibited the effects of exercise and induced depressive-like behavior in the mice.

A few important take home points: the mice joggers were not joking around - they were really running, covering an average of 4-6 miles (10 km) a day. The genetic effects were reported after about 4 weeks of such - rather intense (at least by human standards) - exercise, which is consistent with other studies. We know that mice, given on opportunity, love to run, and these mice were indeed given the opportunity (i.e. unrestricted access to a running wheel that they can us as much or as little as they wanted). Also, they were doing it because they wanted to (i.e. they were not forced to exercise)!

Now, any such study raises a number of "human comparisons" questions. For us humans 6 miles a day might be a lot, but is that true when it comes to mice? In a cat running after a mouse world is 6 miles a day a lot or just what's expected? Also, is that what a mouse would do anyway, even in their wild, natural environment or running all day long only happens when they live in a cage, bored to death, with nothing else to do? And, more importantly, how does 6 mice miles compare with human miles? Finally, is it really that PE is the proximal cause or is PE just one event from a cascade (e.g. an "intellectual gratification" activity) of events that eventually results in the reported effects?

My two cents: while these are important questions this landmark study suggests that when it comes to PE and the brain, while the old claim that "what's good for the body is also good for the mind" is true, there is so much more to the story. Now, when someone says "exercise that brain" you actually have a reason to exercise it as hard as you can as in "Aaah, what do you mean, really?"

(1) http://www.nature.com/nm/journal/v13/n12/pdf/nm1669.pdf

Exercising Your Brain

2008-03-11T13:30:00.000-07:00

Latest news: I am going to start posting on brain - related subjects on SharpBrains - you can now see my first post, on physical exercise and the brain @... well, just click on the title of this entry...

Physical exercise effects on the brain is an interesting subject in general but even more so when it comes to the American culture. A culture that seems to be caught in a perpetual ambivalence between two extremes: the fitness obsession on one hand and "the forget how to walk as you can always drive instead" culture. In other cultures a daily dose of physical exercise in embedded in the daily routine of walking places (work, grocery stores, etc.), talking the stairs up and down, going up and down steep streets, running after the bus or metro etc. In the US that is rarely the case. And then is it really a surprise when we find out the obesity and metabolic problems are endemic? These, as we are now learning, are not stand alone problems, but come with a plethora of other issues: last but not least a not so great prognosis for a brain that is drowning in fats and sugars.

Looking forward to comments on the post.

From Columbine to Virginia Tech

2007-04-19T02:36:00.000-07:00

Here is a disturbing time line of school killings in America put together by Times On Line(1):April 2007: A student goes on the rampage at the campus of Virginia Tech killing 32 people before killing himself.October 2006: A 32-year-old gunman goes on the rampage at an Amish school in Pennsylvania, shooting dead at least three girls before killing himself. September 2006: A gunman in Colorado shoots and fatally wounds a teenage schoolgirl, and then kills himself. September 2006: A teenager kills the head-teacher of a school in Cazenovia, Wisconsin. November 2005: A student in Tennessee shoots dead an assistant principal and wounds two other administrators. March 2005: A schoolboy in Minnesota kills nine, and then shoots himself. May 2004: Four people are injured in a shooting at a school in Maryland.April 2003: A teenager shoots dead a head-teacher at a Pennsylvania school, and then kills himself. January 2002: A student who had been dismissed from the Appalachian School of Law in Grundy, Virginia, kills the dean, a professor and a student, and wounds three others. March 2001: A pupil kills two students after opening fire at a school in California February 2000: A classmate shoots dead a six-year-old girl in Michigan. November 1999: A 13-year-old girl is shot dead by a classmate in New Mexico. May 1999: Six are injured by a student in a shoot-out in Georgia. April 1999: Two teenagers shoot dead 12 students and a teacher before killing themselves at Columbine School in Colorado.

What are we to make out of this? Clearly, we are no longer looking at isolated events, the sort of things that, as disturbing as they might be, we can easily file away as “accidents”, before turning on the other side and falling asleep. We know now that we are looking at a pattern. A horrific pattern of children killing children in schools. Children, a symbol of live before anything else, killing? And where? At school. I am not sure what frightens me more. Is it that children kill children? Or is it that schools are now places where one can kill and be killed? The school, a place that is supposed to evoke feelings of safety and joy and respect is redefining itself as the new human jungle, a place that starts to feel as unsafe as a run down, drug and crime infested neighborhood. When above all, a school is supposed to be both a sacred and safe place for our children. How can one teach and how can one learn when one worries about one’s safety?

My fear is that schools’ violence will effectively condemn our children to perpetual inadequacy and fear. My fear is that our scared and scarred children will grow up into fearful adults who will become used to think that violence is normal and to kill and be killed is a fact of life. This is one frightening prospect.

What are we to do? The easy answer is to do whatever it takes to establish safety. Easy, as it does define what safety is. And where the problem is coming from? Does establishing safety mean beefed up barbwire fences, and metal detectors, and paratroopers-like, around the clock, security guards carrying assault weapons and bullet proof jackets marching down the schools hallways? Or does rather mean an open school, without isolating fences, where students are connected to each other, respectful of their teachers and excited to learn?

As a psychiatrist, I know that fear begets fear and violence begets violence. More of the same begets sameness. When I see violence I first look for the violence that preceded it. As in my book understanding is at the root of healing. As more of the same begets sameness, I also know that violently curbing violence, as appealing as that might be on the short run, will certainly bring not less, but more violence in the future. I believe that the way to peace is through peace, and only understanding can mend misunderstanding.

What is preceding our school violence? Can it have anything to do with the fact that violence is prevalent in America, starting with the often decried media fatal attraction to juicy, violent subjects, and ending with the much less publicized fact that the US is possibly the only country that has been almost continuously at war for more than a century(2)?

Can it be related to the fact that our society values individualism above all? Our heroes are outcasts and pioneers settling on the FAR border, creating places for themselves in the mists of nowhere as FAR as possible from any other humans.

Should we then be surprised when centuries later, which is now, feeling isolated and disconnected is commonplace for our suburbia generations? When our cities are spreading out instead of coming together and distance rather than closeness is a common trait of the American urban landscape, should we really be surprised if people feel lonely even when they are in a middle of a crowd,and constantly alienated from not only the others but themselves as well? And if that is so, what is it left? The way of a Reservoir Dog, of a natural born killer, always ready to kill the common bill, in an impeccably told pulp fiction: and that is, sadly enough, our daily bread!

(1) www.timesonline.co.uk/tol/news/world/us_and_americas/article1662373.ece

(2) http://academic.evergreen.edu/g/grossmaz/interventions.html

Ticut Follies (documentary)

2007-04-11T02:26:00.000-07:00

A 1966 film about the realities of a Massachusetts state institution for criminally insane.

Haunting cinematography in black and white, without any commentary, as the images are powerful enough in themselves. It is deeply unsettling to see the overlapping delusional universes - the patients' and the staff's views of the world, each one right in their own eyes, and at the same time utterly unable to see the reality through the eyes of the other. It is also unnerving to see how the professionals end up harming those they genuinely want to help. Schizophrenia is projected into the very system that is supposed to break it. The movie clearly demonstrates the system's fundamental flaw, which is its attempt to cure splitting by further splitting it (away from the world). Which may be why instead of mending those who suffer "the system" not only perpetuates sufferance but ends up breaking itself.

Available for download at http://www.libertv.com/.

Do (not) ask why

2007-02-13T11:15:00.000-08:00

One of the characteristics of my psychotherapy class was its close parallel with a therapy session. Routine, as an indication of stability, with all its "safe haven" connotation, was strongly encouraged. Our instructor, a venerable and distinguished training analyst, was a staunch proponent of experiential teaching methods, a fervent advocate of the view that a professor's role is to facilitate his students' discoveries through exploration and relentless questioning, rather than by feeding them prepared lectures. His idea was that the teaching process was to be similar to the therapist's guiding his patient's exploration of his issues.

So the one day when instead of his usual sitting down Dr. E stood up and announced that, only for that class, he was actually going to lecture us, was bound to make a strong impression on us. The lecture, he said, was going to likely surprise us; as it was doing to be not in favor, but rather against one prevalent question. We were going to hear about the traps and promises of the "why question".

This was one significant event for a professor who at the beginning of his class stated in unambiguous terms that for he saw no difference between the more traditional ex cathera teaching and preaching. Yet, there he was, ready to "preach"to us. And preached he did, painting a dark picture where "why" was shown as a metaphorical spear unforgivably piercing through the carefully constructed armor of one's defenses and coping skills, shattering it all, to prematurely free painfully contained anxieties and fears and guilt.

Our distinguished lecturer concluded his passionate discourse by approaching each of us with a question: "Why... (did you chose psychiatry, are you here today, etc.)?". Such an elegant demonstration of how suddenly "why" can stir a most extreme self closing protective reflex! No less miraculous was the transformation that our teacher seemed to suffer as he was gradually entering deeper and deeper in the "why" country. It did not take long to see how the repeated question of "why" has metamorphosed him, symbolically, from a trusted adviser and teacher in a cruel interrogator-executioner. Thus we learned the important lesson that self-reflexion, as good as it might be, is not to be forced at the speedy rates of the "why" method.

Years after the "do not why others" lesson, I discovered that is also a good idea to try not to abuse "whying oneself". To a "why" question, from others or myself, I learned to answer "why not"?

How liberating that is. Thus, "why not" rather than "why" is the justification of this blog.

I am an academic psychiatrist who chooses to believe in potential rather than deficits, strength rather than weakness, unity rather than split, sense rather than chaos. Not because these choices are "right", or "better", or even justifiable. I am the first to agree that the opposite of my choices are equally right and tenable. As above all, I also believe in dialectics and relativity and complementarity. The light shines in darkness, lies can save lives, and yin requires yang. Yet, we are bound to make choices, and those are my choices.

In the spirit of "why not" my goal is to have this blog as an instrument to explore beliefs and evidence, lore and folklore about the wonders of the brain and the mind. This is not a place for preconceived ideas or predetermined agendas, a cathedra for "preaching" about only half known truths. First and foremost, as our knowledge is unfolding, this is a place for questions. The great thing about "why not" is that it is all inclusive.

And then, contrary, yet at the same time in the spirit of a very distinguished analyst who was once my teacher, as "why not" is my guide, this is a place, maybe one of the few, where"why" will also be welcome.