Thursday, August 26, 2010

Tribute to Survival

This is dedicated to those who are surviving the Chemistry Experiment, and to those who hang in there with us.

Bring your courage and your hope, whatever you can manage.

And your helmet.



Thanks to Danny MacAskill and Band of Horses.

Thursday, August 19, 2010

Weighing the Costs and Benefits Part I -- What Counts?

Manifesto

If I am a lab rat, I will be a free-range lab rat.

There.  I feel better already.

To recap from last week:

You Have to Weigh The Costs and Benefits

That is what the doctor says.

Last week I promised I would develop a way to do that.  So this week we play math games.  For the next few weeks, actually.

Now, don't freak out.  I am not going to ask you to do math.  I am going to make up some rules.  You are along for the ride.  Though do feel free to suggest better rules.  Plus, I promise lots of pictures.  And a musical interlude.

I am a rat.  I live in a laboratory, where I participate in the Chemistry Experiment.  Along with other scientists, I am trying to find the chemicals that will make a dent in my mood disorder.  Not theirs.  Mine.  Which is how I got the rat end of this job.  But because I am a free-range rat, I get to decide which experiments I am willing to try.

I now insist that I contribute more to this enterprise than my body.

I have decided my contribution will be to develop the missing algorithm that lab rats of the species homo sapiens need to weigh our costs and benefits.  Something more scientific than our gut and desperation.

I call it an algorithm because that is what we scientists call it.

Algorithm:  A logical set of rules for solving a specific problem, which assumes that all of the data is objective, that there are a finite number of solutions to the problem, and that there are logical steps that must be performed to arrive at each of these solutions.

Remember the goal: logical rules applied to objective data to solve a problem.

The problem we want to solve is this:

Do I Want To Put These Chemicals Inside My Body?

Figuring out the rules is turning out to be quite a job, which might explain why nobody has done it so far, not even the FDA, who is supposed to decide whether a drug works well enough to warrant putting people through the consequences of taking it.  They don't have a formula.  They seem to decide on the basis of their own gut, just like us lab rats, plus lots of advice from the companies that want to sell the drugs, just like our doctors.  As it turns out, the FDA's standards are lower for meds used to treat mental illness than for meds used to treat other conditions.

But never mind.

I begin by defining the terms, the factors that I will use in my algorithm.  Factors is the scientific word for things you have to take into account, usually numbers.  There are a lot of factors.  The doctor will tell you, if you ask, 40% efficacy rate, 15% risk of insomnia, 15% mortality rate unless you take the meds for the rest of your life.

Now weigh your costs and benefits.

But there are lots and lots of these costs and benefits to weigh.  The numbers you get in your fifteen minute med check are abbreviated and oversimplified to the point of useless.  That is why this series will run over several weeks, so that I can weigh the costs and benefits that your fifteen minute med check skipped.

But remember, there will be a musical interlude.  Maybe two.

I have started several posts this week, and keep discovering I need to back up, start at an earlier point.  But for you, dear readers, I press on.  And for me.  And for science!  Not that I am expecting a Nobel Prize or anything.  I am not manic, after all.  Just excited.

Okay, so the best I can do this week is to list the factors.  Before you decide this is a measly week's work, wait until you read my list of factors.  40% efficacy, 15% insomnia, 15% mortality rate?  HAH!

Below are lists of the benefits, costs and considerations that will influence the odds.  Remember, it's all about the odds.  When you buy a Powerball ticket, the cost is $1.  The benefit is $97,000,000.  Now, weigh your costs and benefits.  It's a no-brainer.  Until you look at the odds.

A consideration in the case of Powerball might be whether you have enough money in your pocket for both the ticket and the milk.  Another consideration might be who is waiting at home for the milk.

BENEFITS OF THE CHEMICALS IN QUESTION:

Efficacy
   (LOTS of considerations to be factored here)
Shorter time to recovery or remission
   (I will explain the difference later)
Longer time to relapse
   (one number for recovery, another for remission)
Long term brain health
   (this may be indicated by time to relapse)
Lower mortality risk
   (needs to be weighted by other factors)

COSTS OF THE CHEMICALS IN QUESTION:

Side effects
   (tolerability is a consideration)
Down stream side effects
    (e.g., heart disease, liver disease, gum disease)
$$$$, both for medication and for med management
Risk of wrong diagnosis and inappropriate medication
   (may accelerate the course of real condition)

CONSIDERATIONS THAT INFLUENCE THE COSTS AND BENEFITS AND HENCE, YOUR DECISION

Severity of present condition
Number of previous trials
Spontaneous remission rate
Family health history
Factors specific to your own mortality risk
Family/job issues
What is your time frame?

See why this is going to take a while?  Are there other benefits, costs and considerations I have missed?  Ones that could be quantified, that is.  Not your favorite rant.  How about you put your favorite rant into you own blog and then link to mine?

Wish me luck.

All these images are Facebook Flair

Thursday, August 12, 2010

Manifesto of a Lab Rat -- Weighing the Costs and Benefits Part I

I Am A Lab Rat.  Yes, I am.

Here is the deal.  I was lucky enough, and you were lucky enough to be born after the discovery of penicillin (1928).  Well, I don't know when you were born.  But evidently penicillin was discovered before it became a life or death issue for either of us, or I wouldn't be writing and/or you wouldn't be reading Prozac Monologues.  This is good.

In another age, my ruptured appendix might have been treated with leeches.  That would not have been good.

As far as my more immediate health challenge goes, we are barely out of the leech stage.  Okay, that's a bummer, the timing of my life, that is.  But like I said, ruptured appendix, penicillin.  It could have been worse.

Research Into Mental Illness -- Rats

In the treatment of mental illness, they have figured out that leeches don't work.  They think chemicals might. They just haven't figured out which ones.  They are working on it.  They have lab rats, rattus norvegicus to be specific, who do the heavy lifting in this Chemistry Experiment.  Some people question the ethics of what gets done to these poor rattus norvegicuses who participate with not a single informed consent form in sight.  But that not only is another post, it is another blog.

Anyway, the rats can do just so much here.  It isn't their problem anyway.  The scientists have to figure out how to create something that approximates mental illness in rats before the scientists can try out the chemicals that might cure them.  After that homo sapiens have to pick up the load.  That seems only fair.

The Chemistry Experiment -- Human Beings

"I get good results from Effexor," my (previous) doctor said.  She didn't mean that she took it herself.

"Will it work for me?" I asked.

"We won't know until you try it," she said.

That, in a nut shell, is the Chemistry Experiment.

Then she told me to weigh my costs and benefits.

I have participated in a number of these personal test tube trials with mostly negative, but some positive results.  But any experiment is a success if it gives you information.  In that sense, the failed trials were not failed experiments.  Eventually the experiments led to a better diagnosis and subsequent treatment using a different class of chemicals.  Which is good, because we were running out of possible experiments with the previous class of chemicals and needed to expand our horizons.  Well, maybe this is good.

Today I have information that I did not have a week ago.  It will inform the next trial.

The Chemistry Experiment is not fun.  But there is no need to get pissy or throw a pity party or fantasize harm to myself and others.  I confess I have indulged in all of that behavior in the past.

Today I make another choice.  Today I woke up with a new thought.  What I need to do is reframe.

Manifesto

If I am a lab rat, then I will be a free-range lab rat.

There.  I feel better already.

Now that I am out of my cage and taking a look around this popsicle stand, I am looking for that scale where they weigh the costs and benefits.  You know what?  I can't find it.  It's not here.

They have all kinds of formulas around this place.  They call them algorithms.

Algorithm:  A logical set of rules for solving a specific problem, which assumes that all of the data is objective, that there are a finite number of solutions to the problem, and that there are logical steps that must be performed to arrive at each of those solutions.

Logical rules, objective data, finite solutions.  Yup.  This is a lab.

There are two algorithms most prominently displayed.  The first is a differential diagnostic tree.  It looks like those charts that the IRS has to help you figure out whether you can take the deduction.  If the answer to question #1 is yes, then go to question #2.  If no, then no deduction.  If answer #2 is yes, then go to question #3.  If no, then no deduction.  And so on.  It is really irritating when you answer yes to question after question, getting more and more excited as you approach the bottom of the page, and then get dumped out with a no at the very end.  No refund.  After all that work.

But I digress.

The differential diagnostic algorithm is more complicated than that.  You have to say yes to one out of this column, and four out of that column, factor in a time frame, ask about current events, past history, and so on.  When you get to the bottom of the diagnostic tree, you find -- an insurance reimbursement code.

Well, I am glad that I have an insurance reimbursement code.  But I was expecting a little something more from a laboratory full of scientists.

The other algorithm, like the first, takes input of the various symptoms, but includes more information about physical state, age, blood pressure, liver status, other chemicals already on board.  Stuff like that.  It yields a list of medications.  That is more like what I expected.

But still, there is something missing.  Where is that scale?

You Have to Weigh The Costs and Benefits

That is what the doctor said.  The thing is, you don't know what the costs and benefits are.  The doctor knows some of them.

The doctor knows the odds, some of the odds, and may or may not share them with you.  For just about any antidepressant, you might hear, if you ask, something like: 40% efficacy, 15% insomnia, 15% mortality rate if you don't take the meds for the rest of your life.  The doctor does not mention sexual side effects, unless the medication in question is that one with lower risk of sexual side effects.  It still has a risk of sexual side effects.  You just won't hear the odds.

So will it work for me? -- We won't know until you try it.  Again with the Chemistry Experiment!

But now that I am a free range lab rat, I am supposed to give consent to the experiment.  On what basis????  Weigh the costs and benefits, in the absence of any meaningful scale, means nothing more than, It's your body, not mine.  You're on your own.

The Problem: Do I Want To Participate In This Chemistry Experiment?

I know, I know.  Sometimes we are so desperate, we don't even want to know the costs and benefits.  We just pop the chemicals in our mouths and hope for the best.  That would be me last week.  It didn't work out well, which is why last week's post was a rerun.  But no permanent damage done.

If you want to skip all the numbers and this weighing without a scale and go by your gut, here is how my gut makes the calculation.  I call it the hundred years principle.  Today we say, concerning certain medical procedures of the past, What were they thinking?!?  For example, and it took less than a hundred years to get to What were they thinking: LOBOTOMY.  Enough said.

But I am a scientist.  It is true that I am a lab rat, but a free range one.  So I have scientific standards to uphold.  And the hundred years principle is not scientific.

It is time.  It is long past time for a new algorithm, a logical set of rules for processing objective data that will give me a scientific way to weigh my costs and benefits.  These other guys keep telling us lab rats that it is our job.  They won't do it.

So that, my friends, is what I am developing for your reading pleasure next week.

Assuming that we don't start another chemistry experiment and turn my brain to mush again.

Thursday, August 5, 2010

Nonsense and the Anterior Cingulate Cortex -- Redux


This traffic monitor should read YOUR SPEED 60 MPH.  But I couldn't find that image.  I suppose creating it would not be a good idea.  So this image will have to do.

If you are traveling too fast when you hit the pothole, you break your suspension.

So I am taking a break while we try to balance the GAMA and glutamate in my synapses.  Here is a slightly modified rerun of an oldie but a goodie.  I think it addresses the current phenomena of the Tea Party, the growing rigidity of those whom it threatens, and the retreat of the rest into reality tv.  If I didn't make so many connections like that, my brain wouldn't hurt so much.  Then again, Prozac Monologues wouldn't exist.

Nonsense and the Anterior Cingulate Cortex -- November 7, 2009 

John McNamany put the thought into my head, the New York Times tickled my fancy and a blog new to me gave me the art work.

Function of the Anterior Cingulate Cortex

Finally, it's Anterior Cingulate Cortex Week!  This lovely portion of the brain is found in the limbic system, located just above the center, about where Iowa would be and extending into western Pennsylvania, if you flip the image so that it faces right, as I did here.  Like a true Midwesterner, the ACC modulates emotional response.  A hard-working manager, the ACC handles motivation to solve problems and anticipation of tasks and rewards.  It also monitors for conflict, things that don't make sense.  The brain is unhappy when it cannot detect a pattern.  Confronted with anomaly, the ACC goes to work.

The Absurd Stimulates Pattern Finding Behavior

"Researchers have long known that people cling to personal biases when confronted with death... In a series of new papers, Dr. Travis Proulx of University of California Santa Barbara and Steven J. Heine, a professor of psychology at the University of British Columbia, argue that these findings are variations on the same process: maintaining meaning, or coherence. The brain evolved to predict, and it does so by identifying patterns.

"When those patterns break down — as when a hiker stumbles across an easy chair sitting deep in the woods, as if dropped from the sky — the brain gropes for something, anything that makes sense. It may retreat to a familiar ritual, like checking equipment. But it may also turn its attention outward, the researchers argue, and notice, say, a pattern in animal tracks that was previously hidden. The urge to find a coherent pattern makes it more likely that the brain will find one." [Benedict Carey, New York Times, October 5, 2009]

To test whether confronting the absurd leads to pattern-searching behavior, they had twenty college students read Kafka, The Country Doctor, a story that is urgent, vivid and nonsensical.  Does anybody who is not in college ever read Kafka?  Anyway, after reading the story, they were given a task, to study strings of letters that did not form words.  They were then shown a longer list, and asked to find the strings they had seen before.  The letters did have patterns, very subtle patterns.  And the students who had read Kafka did better at this task than another twenty who had not been exposed to the absurd, 30% better.  With a Kafka-stimulated ACC, they were primed to find the patterns.

I wonder if that explains the college student's propensity to read Kafka in the first place.  Not to mention all those posters by Salvador Dali on dorm room walls.  The college student is at a crossroads, and has to puzzle through the animal tracks of his/her life, to discern the pattern, the call, the next direction.  These representations of the absurd stimulate the part of the brain needed at this developmental moment, just as caffeine stimulates the system before the exam.

I graduated from college at loose ends, with the Episcopal Church still discerning the patterns that would allow for the ordination of women.  That was a few years off, and I wasn't ready to commit to a vocation that might not be received.  But I didn't read Kafka.  Instead, I decided to read everything that Kurt Vonnegut had written up to that point, a modern day Kafka.  Kafka-lite, if you will.  Today, as I fill out disability applications, I am again at a crossroads, and again instinctively, am drawn to Vonnegut, whose body of work has grown since 1975.  Evidently I am stimulating my ACC and boosting my pattern/meaning/coherence finding abilities, priming myself to discern my next direction.

Patterns and the fMRI

Oh boy, I found another fMRI experiment!  There is a study in the Journal of Pain (what a title!) that discovered, when people were prompted by pain-related words to remember painful autobiographical episodes, the fMRI machines showed that it was -- you guessed it?! -- the anterior cingulate cortex that lit up.

Dialectical Thinking -- On Not Blowing Out Your ACC

This person loved me; this same person abused me -- two memories in conflict, absurd.  Put them together, they cause pain. They call it dialectical thinking when you hold two seemingly contradictory ideas in the same head at the same time.  But dialectical thinking is a highly developed skill.  Before anybody ever suggested to me that I could employ it to reduce my pain, I spent (and still do spend) enormous amounts of energy trying to make sense of events that were absurd.

Some of us had Kafka-esque childhoods.  I wonder, does the ACC become quiet if we engage in dialectical thinking?  I wonder, does it blow a fuse if we don't?

If you are searching for Christmas gift ideas for the Prozac Monologues blogger, an fMRI machine would certainly be well received. 

photo of traffic sign by Richard Drdul, Creative Commons  

image of brain from NIMH 

Obama inauguration photo taken by
 Petty Officer 1st Class Chad J. McNeeley, USN 
and in the public domain