Showing posts with label neurobiology. Show all posts
Showing posts with label neurobiology. Show all posts

Friday, February 19, 2016

NEJM and the Neurobiology of Addiction

[Original Graphic removed due to license expiration]


There are numerous articles in the popular press that attack the disease concept of addiction as well as many that attack the idea that addiction may be a biological based problem,  Volkow, Koob and McLellan have an interesting article in a recent edition of the New England Journal of Medicine that discusses both the neurobiology and some of the biases involved in stating that addiction is neither neurobiologically based or a neurobiologically based disease.  The article is relatively low in the details that reductionists like myself like to read but it is well referenced and a good overview of what is known about the neurobiology of addiction.  It is also a discussion of failed theories and what is currently known.  There is only one graphic and it is the basic one shown at the top of this post.  It shows a basic mapping of typical behaviors associated with addiction and is an elaboration of George Koob's previous all-encompassing one liner that sought to capture the behavioral pharmacology of addiction in one sentence:

"Addiction is a chronic relapsing syndrome that moves from an impulse control disorder involving positive reinforcement to a compulsive disorder involving negative reinforcement."

In this review the authors describe three stages of addiction; binge and intoxication, withdrawal and negative affect, and preoccupation and anticipation.  They are located in the table immediately below the brain graphic in the above infographic.  They break it down at a neurobiological level.  For the binge and intoxication stage increased dopamine release at the reward centers occurs.  With repeated stimulation the dopamine release is attenuated in response to the reward and shifts to anticipation of the reward.  Most authors discuss the initial phase of this process as occurring on the ventral striatum, in dopaminergic neurons from the ventral tegmental area innervating the nucleus accumbens.  I had some initial difficulty seeing the nucleus accumbens but it is there.  The larger message  is that plastic or experience dependent changes occur in not only the nucleus accumbens but also the dorsal striatum, hippocampus, amygdala, and prefrontal cortex.  I also liked the authors' inclusion of the word salience defined as a property of the prefrontal cortex in assigning relative value to a stimulus.  It is common to attend addiction conferences and hear the term being bantered about without any clear reference to the prefrontal cortex attributing salience to a particular stimulus.

Their description of withdrawal and negative affect discusses how with repeated stimulation reward and motivational systems are focused on the more potent effects of addictive drugs rather than the usual correlates including food and fluids, social affiliation, sexual behavior, and even good decision making.  This used to be referred to as the Hijacked Brain Hypothesis which basically stated the same thing.  Any physician working in a large acute care hospital will see a significant number of patients admitted largely because they have been using intoxicants on a chronic basis and ignoring their basic need for food and fluids.  This behavior is consistent with a new set of priorities for the reward and motivational systems, that biases the system heavily in the direction of continued substance use.  The previous theory of increased sensitivity to dopamine and higher levels of dopamine in the dorsal and ventral striatum in persons with addiction was proven to be wrong.  In fact dopamine release is attenuated and the reward system becomes less sensitive to all activating stimuli.  This results in both the loss of drug-induced euphoria and the lack of reward effects for previous enjoyable and preferred activities.  Recovery of this effect takes a prolonged period of abstinence and a sustained effort to get back into previous activity patterns.  At the same time, the stress response mediated by corticotropin releasing factor and dynorphin are involved in further attenuation of reward system dopaminergic cells.  Combined with changes in the extended amygdala this results in a dysphoric state and decreased stress tolerance.  It is captured in the second part of Koob's sentence - addiction becomes "a compulsive disorder involving negative reinforcement."  At this point the person with an addiction is self administering a drug to "feel normal and function" rather than get high.

The preoccupation and  anticipation stage impaired dopaminergic and glutamatergic signalling in the prefrontal cortex inhibits more typical decision making and creates a bias in the direction of continued use.  Self monitoring processes that evaluate the decision, whether or not it was successful and whether or not it was adaptive are similarly affected by these systems.  The value of the reward is depicted in the graphic below from Fuster's text The Prefrontal Cortex:



           

 The authors clarify their use of the term addiction relative to the more commonly used DSM-5 terms. With the advent of DSM-5 the familiar definitions of use and abuse disappeared and there is a single use category.  Severe use disorder requires 6 or more of the 11 symptoms of the use disorder.  The authors equate severe use disorder with their use of the term addiction.  Thinking about the demographics of people with one or more severe use disorders fits their description of addiction.  It is also much more likely that this group of patients will have markers and behaviors that cannot be dismissed by those who criticize a neurobiological approach to addiction.

Apart from the neurobiology update, the other interesting aspect of this paper was the authors taking on critics of a neurobiological model of addiction.  They are generally the same crowd who is critical of the disease model of addiction.  This paper defines a more specific model of addiction and its features than the disease model, even though popular surveys illustrate that most people see addiction alcoholism, and severe psychiatric illnesses as diseases.  At some level the popular and medical definitions of disease encompass a diverse group of conditions and arbitrary definitions can be adopted to support and argument.  A favorite is always that there is no known observable lesion or pathology in conditions that are not diseases.  I have examined several of these arguments about addiction in a previous post.  The authors here include their examination of 7 arguments entitled:  Criticisms of the Brain Disease Model of Addiction and Counter‐ Arguments.  The only substantial way their differ from my examination of the criticisms of addiction being modulated by a distinct set of pathological neurobiological features is that they include two points about public policy specifically how research is funded and how patients have benefitted.  One of the most common misconceptions about psychiatric illness and addictions when they are approached from a neurobiological perspective is that critics seem to think that this is tantamount to the "medicalization" of a problem and that this means only a medical intervention or medication can be used to treat the disorder.  In the field of addiction, excellent work has been done showing a number of unique paths to recovery that may depend on speculative neurobiological mechanisms, but do not depend on the use of medications or contact with physicians.  Critics of neurobiology seem to see the brain as a turf war rather than a need for a deeper understanding of the most intricate organ in the body.

I encourage a careful reading of this paper, by anyone who wants a brief overview of how addiction may affect the brain.  This is not a comprehensive review by any means and at some point I will come back and point out some of the shortcomings.  If you are a psychiatrist or psychiatric resident - you need to know what is in this paper at the minimum.  That is true if you are involved in the diagnosis and treatment of addiction or not.  The systems discussed in this paper are involved in cognition and complex decision making.  Contrary to popular belief there are no decisions made that are devoid of an emotional component.  That fact does not come alive until you know the relationship between limbic structures and reward/motivational systems.  Thirty years ago, some of the free literature from pharmaceutical companies contained graphics highlighting some of these systems and how they may be affected in schizophrenia and psychosis.  In the intervening time period, the bulk of useful research in the area came from scientists and physicians doing research in addiction.

As the knowledge in this area increases, this neurobiology will have wider applicability across the entire spectrum of psychiatric disorders.  


George Dawson, MD, DLFAPA



References:

1: Volkow ND, Koob GF, McLellan AT. Neurobiologic Advances from the Brain DiseaseModel of Addiction. N Engl J Med. 2016 Jan 28;374(4):363-71. doi: 10.1056/NEJMra1511480. PubMed PMID: 26816013.


Attribution:

Graphic at the top is from reference 1, with permission from the Massachusetts Medical Society.  License date is Feb 1, 2016 - license number is 3801731329358 for 12 months from the date of the license.  According to the publisher I am classified as a free-lancer (not-for-profit publisher) and hence the change in my LinkedIn status to free-lance writer at Real Psychiatry.


Tuesday, July 15, 2014

Stigma Rhetoric

I have always been skeptical of the value of the stigma concept in advocating for the rights of people with mental illness.  It seems to imply that a person with a mental illness is obvious to everyone and nothing could be further from the truth.  The usual advocacy groups certainly jumped on it and it was later picked up by professional organizations.  My basic problem with the entire argument is that nobody should know that you have a mental health problem anymore than people should know that I have asthma.  It is a problem of medical confidentiality rather than a problem with stigma.  Anyone who thinks that is not the case just needs to consider what prospective employers think about hiring people with back pain, asthma, or any pre-existing condition that potentially impacts their group health insurance coverage.  Any confidential medical condition is potentially stigmatizing and it certainly is nobody else's business.  If people want to disclose that information that is certainly up to them and as I have posted here in many cases it can be a useful public service.  And I do realize that health insurance companies force you to disclose pre-existing conditions using various methods but that does not mean that your employer should know.

The other problem is that there has been broad and systematic discrimination against people with mental illness and addictions at all levels of government and the business community.  These are the people who have access to protected medical information and make decisions about health care based on it.  That discrimination occurs with full knowledge of a diagnosis and often a recommended treatment plan.  Multiple posts here document that problem and yet nobody comes right out and attacks that issue.  If anything social activism with a stigma focus seems to cast a wide discrimination net rather than focusing on the few people and agencies that can make a critical difference.  It  suggests that the general public is the problem and that educating the general public will solve the problem.

This morning a friend of mine posted this link on Facebook and asked me for my impressions of the argument that neuroscientific explanations potentially lead to more stigma.  That is probably what has me fired up.  If you are trained in science, you realize that there are  internal politics but in general that is not the same as the politics of the barbarians at the gate.  The problem is that all types of science from climate science to neuroscience gets co-opted and interpreted by people who don't know what they are talking about.  I think that is illustrated by one of the summary points in this article:

"As this revolution gathers force, we need to be mindful that biogenetic explanations for mental health problems can have troubling implications for the people who suffer them."

I think it should be obvious that there will be "troubling implications" for anyone who is ignorant on either end of a "biogenetic explanation".  Further, it is really impossible to separate allegedly biogenetic explanations from decades of conditioning by governments, businesses, and the media.  Troubling implications start when you realize that your employer's health plan does not have coverage for mental illnesses or addictions and you have a family member that needs that insurance.


What are the take home points about stigma in all of this?

1.  Businesses that discriminate against mental illness by rationing current services and destroying any infrastructure necessary to treat mental health are stigmatizing.  The message is clearly that they can't be bothered to treat these problems seriously by offering much of anything beyond a crisis stay in a hospital and a 10-20 minute "med check" by a "provider or prescriber" in an outpatient clinic every 3 - 6 months.   No research proven modalities to treat mental illness and a severe push to send people with addictions and serious mental illnesses to county detox, jail, or the street.

But even the businesses not involved can get into the act.  Practically every local market has a business some who is offering "crazy deals."  If you doubt it, Google "crazy deals" or the equivalent "insane deals" and see what you come up with.  Don't forget to look at some of the images.

2.  Governments that ration and destroy the mental health infrastructure and collude with rationing by businesses are stigmatizing.  Examples include empowering insurance companies to decide how they can deconstruct the billing and services of mental health providers and clinics to their advantage (the arbitrary insurance company audit),  empowering business to discount services, legitimizing utilization review and prior authorization (tools for arbitrary denials), and allowing for proprietary business guidelines to dictate who can receive treatment and who can not.  What could be more stigmatizing than to have a business suggest that a person is not "dangerous" enough to be treated and use that as a basis for medical decision making?  Why aren't there any rules about admitting only the "dangerous" myocardial infarctions and sending everybody else home?

3.  Court systems that treat the mentally ill like they are criminals are stigmatizing.  This includes practically all court systems because as any forensic psychiatrist will tell you, despite the myths about the so-called insanity defense - it is practically impossible for anyone to get off with that defense.  There are significant numbers of people who are incarcerated for minor nonviolent crimes that were the product of mental illness.  Ask yourself if it is more stigmatizing to have a confidential diagnosis of a mental illness or be listed in the paper as being incarcerated or having been convicted of a crime?

4.   The press has a very poor track record in the area of stigma.  It is well known that the press covers psychiatry more than other medical specialties and has a consistently negative view about the specialty.  How would you feel if you had an illness that resulted in you being seen by a physician whose specialty is consistently portrayed negatively in the media.   For the past two years the press has produced nonstop political arguments about a diagnostic manual that is practically little more than a guidebook for billing codes with many of the esoteric codes only of interest to researchers.  One of the main arguments in those articles was that the diagnostic manual led to arbitrary diagnosis and treatment for the benefit of the pharmaceutical industry.  For anyone with a serious mental illness, could there be a more stigmatizing argument?

5.  The entertainment industry never hesitates to make a buck off of mental illness.  The film Halloween is classic example of equating mental illness with an evil so unstoppable that the psychiatrist involved has to pack a .44 magnum.  That same message has been carried forward in recent television shows.  Some of the efforts in this area are so bad that it takes an incredible bias to justify the product as entertainment.

These are all much better examples than suggesting that science somehow stigmatizes people.  The associated problem is the misunderstanding of science.  We all understand that the media needs to sell stories and the truth about science is that it is a process and not the ultimate truth.  Every story about new fads based on an experimental finding that will never be replicated in the absence of a discussion of scientific method is corrosive to the public's confidence in science.  In this case using "chemical imbalance" as a scientific theory is about as ill informed as anyone could be about the neurobiology of mental illness or normal brain functioning.  At that level this story is more about press induced stigma than anything that neuroscience or neurobiology has to say.

The lesson for today is that the brain is not a sack full of neurotransmitters that is balanced or unbalanced.  If you believe that, you can either stay ignorant about the problem and talk about "chemical imbalance" as though it means something, educate yourself about neuroscience (there are many free sites on the Internet) or you can join any number of psychiatry bashing web sites that claim that psychiatrists believe there is a chemical imbalance.  Your first neuroscience assignment is to read about Eric Kandel and why he got the Nobel Prize.

And where does conflict of interest enter into the stigma equation?  In other words who benefits from mental health stigma as an operative social concept?  Advocacy organizations certainly do.  In many cases is it their raison d'ĂȘtre.  Interestingly concern over stigma has prevented some advocacy organizations from dealing effectively with the issue of people with mental illness who are violent.  They considered violence and aggression to be stigmatizing rather than a fact of some mental illnesses.  Professional organizations like the American Psychiatric Association benefit in that it enhances their credibility with the advocacy organizations but any counterattacks on the forces that ration and deny mental health services have been weak and ineffectual.  Those rationing entities including politicians, government agencies, pharmacy benefit managers and managed care companies benefit tremendously.  After all they have added hundreds of billions of dollars to their bottom lines by basically denying or rationing treatment and in many cases denying that there is any problem at all.

Stigma rhetoric makes it seem like this is a problem inherent in our society with no better solution than an enlightened public.  We will not be able to solve it until enough people are enlightened while the rationing schemes continue.

At that level you could say that stigma is a concept that can be spun for everyone, but let's agree that science has nothing to do with it.

George Dawson, MD, DFAPA



Supplementary 1:  I was asked by a reader to summarize the above post.  Here it is:

There are societal wide biases (business, government, legal, entertainment, etc) that stigmatize the mentally ill.  Some aspects of that process involve the distortion of science (e.g. "chemical imbalance theory").

Now what happens if I decide to run an experiment that asks people about how happy they would be if they had a biologically determined mental illness in that culture? Of course they would react strongly because:

a)  They are from a culture that stigmatizes people with significant mental illness.  They know how the various players would react if they found out that a person has a significant mental illness. Mental illness by itself does not produce a stigma. People are stigmatized by other people with biases and clear agendas.

b)  They really don't know what the scientific implications are because they have been hearing about false theories or reading overt propaganda or they don't know enough about the process or implications of science.