Tuesday, May 02, 2006

and with that let's end with

what is it. do we have it. and if so, can we change it.


Monday, May 01, 2006

Sin to Syndrome - Owen

In Sin to Syndrome, the basic question is are individuals responsibile for their actions or are they the victims of their biology and circumstances? The authors argue that Americans are "too nice" and have decided that individuals like Jeffrey Dahmer are to be pitied, not judged. "After all, it is an eating disorder..."

Though the authors assert that a political science professor, Alan Wolfe, has determined that Americans are "nonjudgmental" and "loath to make any meaningful moral judgment about any behavior, no matter how criminal or depraved" (p. 78; does he live in the same USA that I do?), no actual evidence for this claim is presented in this essay beyond four quotes from random Americans. Without evidence for this claim, it may be a little premature conclude that there is indeed a "new nonjudgmentalism" in America.

But putting this "Nice American" idea aside for the moment, the authors go on to cite the cases of sexual molestation by Catholic priests and crimes by violent criminals in which the defense of perpetrators centered around their uncontrollable problem that they should be held less responsible for. The authors touch on the classic philosophical debate of free will versus determinism (which is the essence of the question) and check in with Stephen Pinker who asserts that "personal responsibility has an eminently practical function: deterring harmful behavior" in a community (p.94). He goes on to say, "we are that community, and our major level of influence consists of appealing to that inhibitory brain system." That is, one assumes, by threatening or delivering punishment.

Almost anyone can agree with punishment as a general rule, but what about cases of mental illness? The question of mental illness is where the authors argument breaks down the most, in that they suggest that only two mental states are legitimate grounds for avoiding criminal responsibility, "madness and self-defense" (p.97). The problem lies in defining "madness." Do victims of abuse or those with addiction become severely distressed enough to be considered "mad?" The authors offer no helpful distinction or test of madness in order to determine who should benefit from an insanity defense.

At the end of the essay, the authors conclude that, in the interest of a workable society, we should punish those who commit acts unless they are mentally ill or acting in self-defense. I agree, but the authors have not provided any substantive evidence that helps clarify the most problematic question of who should or who should not be considered mentally ill. I think a reasonable test of this question may be possible someday, perhaps based on neuropsychological testing, but in the meantime preventing future harm via incarceration may be the only (unsatisfactory) answer for the borderline cases.

Lane - Miller responses

The Miller study really changed the way I look at alcoholism treatment. I think its great that Miller et al. emphasized the non-abstinence improvement of treated alcholics. After all, isn't a reduction in drinking and its negative consequences the goal of therapy in the first place? I think that setting up alcoholics with total abstinence as their only measure of success is a great way to really damage the self-esteem of the alcholic who slips once, and in turn push them back toward drinking as a coping strategy for poor self esteem. I am referring to the alcoholic who goes to AA unsure of anything but the fact that his drinking is causing a problem, is then told in AA that he is a "one drink drunk", slips up after a month of abstinence and gets drunk one night, then goes on a one week binder in response to his dissapointment in his self. Maybe if he didn't feel like such a failure for having one slip he would be more likely to go back to AA and try again, as opposed to slipping back into abuse.

However, anecdotal evidence against this point is suggested in our blog posts. Had the first who slipped (whoever they are), not done so, would the rest of us have been so likely to allow ourselves a slip and then get back on the wagon? Or in my case, allow myself a slip and then never get back on it at all? I know that AA is supportive toward members who slip and then come back with a renewed interest in quitting, but maybe if the standards for "sobriety" and "abstinence" were not one in the same, alcholics would be more likely to go from alcoholic to "sober user" (my term for the people who showed an 87% improvement in drinking), as opposed to going from alcholic to "AA failure".

In any case, quoting Josh, "Sommers and Satel also talk about how two people can use drugs, one who will use drugs, love it, and immediately want more, and one who will use, love it, and never use again. They say "this is not a matter of brain physiology". I understand the point they are trying to make, but there is nothing to say that the difference between someone who uses and wants more and someone who uses and does not is not related to some pre-existing brain difference." Right on Josh, who do they think they are? And how did this make it past a critically thinking reviewer?

Sunday, April 30, 2006

Taboo topics in addiction--Becky

I enjoyed the Chiauzzi & Liljegren paper on "Taboo Topics in Addiction Treatment" as it was an informative synthesis of the research on addiction. I thought it was great that they came right out and said, "this may be what's wrong with addiction research and we're not afraid to publish it!" Like Deb, though, I felt frustrated about a few of the topics. The authors point out that individualized treatment seems to be the best way to keep addicts clean and sober, yet insurance companies insist on cookie-cutter treatments that lump all addicts together without regard to what form of treatment may work best. It seems unfathomable to me, although I realize it must happen all the time, that insurance companies will support treatments that may simply be putting on a band-aid where stitches are necessary. A treatment designed to be widely used is likely the most cost-effective up front, but an individualized treatment that has a higher success rate will save money down the road. So why are we not following the advice of the researchers? The authors point out that insurance companies may be coming around (and this was in 1993) as they are becoming aware of the lack of empirical support for uniform treatments, but are responding by decreasing the amount of time allowed in inpatient services. One step forward, and three steps back?

I also thought the "cue exposure" topic was interesting and made an excellent point. Why not bring cues into therapy? It seems to me that having practice sitting in a room with an ashtray in a controlled therapeutic setting would be much easier to handle for a recently abstaining smoker than seeing an ashtray at a restaurant. This seems to me a bit like desensitization therapy for phobics. Exposing an addict to drug paraphernalia before sending him/her off into the real world allows them to experience several successful encounters, which may help bolster their resolve when away from therapy. This is similar to Tim Baker's research where subjects practice quitting over the course of treatment, prior to their actual quit date.

On a personal note...this whole caffeine abstention hasn't been working too well. The end of the semester is just not conducive to being tired OR getting much sleep. I needed my crutch. I used it. A lot. And it felt good. :)

Clinical Impliciations--Emily

I had a lot of the same reactions as Jess in reading this paper. I'm not sure how promising it is to show that this works as long as they are being overtly reinforced, the follow-up time periods aren't very significant. They offered reinforcement for three years to one group and found good results, but they were reinforcing this whole time. They did not speak very much to how to train yourself for self-reinforcement and the only nonsocial activities that they seemed to mention were outdoor activities like hiking. They said that abstinence was correlated with a higher frequency of nonsocial, drug-free activities, but again don't get into much detail. It seems to me that often, the suggestion of looking for "drug-free" activities is scoffed at when one looks at the offerings. I think that the idea of it is good, find something you enjoy doing on your own that does not require drugs, but moving from one life to another with that kind of guidance doesn't seem too easy.

I also had issues with the reinforcement of pregnant mothers. I was torn over this because it seemed like an immediate and short-term fix to a long-term problem. On one hand, getting the mothers to abstain for at least the term of the pregnancy gives the child a shot at least to be healthy from the start, but at the same time, not addressing the bigger problem of caring about the health of their child does not help the child at all in the long-term. They offered vocational training to the mothers, but no healthy baby or well-baby classes. Granted, the mothers may not have been so willing to attend something that didn't benefit them directly, so again, I'm not sure the advantage to something like that.

I thought the adolescent smoking reinforcement studies were interesting as well. I think this gets into somewhat dangerous territory in that it may recruit adolescents who do not smoke to start smoking and join the study to earn some money or earn whatever the reinforcement is. I expect that they have some sort of safeguard in place for this, but adolescents talk to their friends and I can imagine that it is a potential concern.

Overall, despite my skepticism, it seems to be fairly effective in getting people to abstain for awhile. As Jess mentioned, everyone would love to get paid to do nothing. I think it would be interesting to attach some more responsibility or contingency to this model and see what happens. I think some of the studies required some attendance at meeting, but maybe something more intensive. It doesn't seem as if natural reinforcers work that well, so options seem limited after that. As for now, I am still torn on the whole idea...

Ahhh, last confessions on addiction. I admit it. I lapsed after my brown bag in a wonderful frenzy of half price margaritas, I lapsed once again at the open bar at the symposium dinner, and I lapsed again to have wine at dinner on both Friday and Saturday. Suffice it to say, I believe that I have RElapsed. Oh yeah, and I plan on lapsing during class tomorrow as well : ) It's good to be off the wagon...


Yes I relapsed. I have been to McDonalds 3x. Yes I am sorry. Yes I liked it. Yes I will do it again, but I really, really am sorry.

"Taboo Topics in Addiction and Treatment" - Deb Kerr

In reading "Taboo Topics in Addiction and Treatment" I found that I really liked how it expeditiously and effectively covered such a wide variety of different topics. Also how it wasn’t focusing on what is correct and incorrect but “on the uneven flow of empirical information” in the American concept of Alcoholism. Which currently, is viewed as a disease model, even though the #1 treatment option that endorses this constitutes its largest hypocrisy.

In reading this I became extremely disenchanted with our nations populus, or at least our inflexibility and/or ignorance on this subject. I also became disenchanted with AA, or perhaps I garnered a more realistic view of it. Specifically, AA seems like a cult and not a self-help group. Are people who are more susceptible to conformity better suited to recovery via AA? I’ve love to see some data on this using The Conformity Scale developed by Mehrabian and Stefl (1995). http://www.kaaj.com/psych/scales/conform.html

There are the clear facts. AA says that is ascribes to a disease model of alcoholism but in reality it does not. Take AA’s mistrust of potentially helpful psychotropic medication. If alcoholism is a medical disease the definition in and of itself lends to medicine. Another hypocrisy is that AA states that God need not be the higher power that you have to surrender yourself too, but God is mentioned in 4 of the 12 steps. And the fact that is it ‘their way or the highway’ and that they neglect empirical evidence that may suggest change clearly is not in accordance with a disease model. As Chiauzzi pointed out, if AIDS or cancer research put up a barrier to empirical advancements, its likely that over half our population would be dead by now.

Something that we have forgotten about is self-responsibility. It may be of use to muse on this for a moment, esp. on the ‘internal’ versus ‘external’ attribution idea. If you are an addict and decide of your own accord to stop and do so successfully, i.e. natural recovery, the outcome of your recovery process is better than someone who recovered who actually received formal intervention. Is this because something innately about you made you more susceptible to a higher yield at the end of the process, or, because you specifically invested yourself in such an intense way? I speculate on the latter. Again and again psychological studies show that people who find something more rewarding and positive if they went through some sort of personal involvement process where they performed certain actions and took responsibility of them to gain the outcome. Conversely, people who once highly valued a hobby such as piano playing or painting ceased to do so after they began to be paid for it….i.e. when they could not attribute the joy they felt upon doing the activity to something internally within them but onto something externally like a job market or process. Bypassing AA and doing something on your own MAY result in a better benefit because those people are taking responsibility personally, decide to quite personally, decide to set up a treatment plan personally, and follow that plan personally. Everything is internal and there is no one else dictating what they need to believe or need to do. This speculation goes along well with the general sentiment of the one nation under therapy article.

Now I’ll lay off of AA. Things I liked about the article were its emphasis on individualism in acquisition, maintenance and treatment of alcoholism. Also, the description of natural recovery and resilience.

General conceptual questions: What is rational recovery? Is it the same as rational emotive therapy (p308)? Would this be along the lines of Frey’s usage of the Tau to mold new interpretations and pathways for his life?

Clinical Implications of Reinforcement... Kirkland

In the Clinical Implications paper, authors review evidence suggesting that reinforcers (most often vouchers redeemable for retail items) can be effective promoters of abstinence in alcohol and drug-dependent patients. I can see how these laboratory studies have worked, but I'm not convinced by this paper that these types of approaches are realistic for therapy in general.

First, different voucher values are going to be inherently more or less rewarding depending on the population of interest...With some populations probably requiring significant compensation to abstain.

Second, even small-monetary-value vouchers or programs that use the "fishbowl" method (where the reinforcer value varies widely and is most likely small) are not really sustainable for the long-term. Addicts will not be reinforced for abstinence forever. Should we really be promoting this "I'll pay you to stay clean" method? Especially if the issue is that addicts are less likely to have available "natural" reinforcer options? Might this leave addicts MORE likely to use when the money is gone?

Third, I would like to know how voucher programs compare at 12 months to the programs described in the Chiuzza paper. Do they follow this "rule of 1/3s"?

Finally, we know people will work for money. We also know that more money does not really equal more happiness. The only program described in this paper that really emphasizes healthy alternatives to drinking/drugs is the CRA model...but this model was not really fleshed out in the paper. How can we teach addicts to reward themselves? I'm not convinced this covers it. Also, I'm very surprised that this method works in homeless couples, and I would be interested to know what exactly the program suggested as alternative activities.

One Nation Under Therapy - Helen

Sin to Syndrome
Sommers & Satel

The finding of "nice Americans" and the new nonjudgmentalism quite pleased me. I hadn't realized that Americans were more nonjudgmental as they seem (although I still want to see the exact 8 cities where they conducted the study; Tipton, Iowa, still does not seem like the Bible Belt to me). I think the nonjudgmental approach is the first step towards rehabilitating or preventing development into criminals or addicts rather than simply punishing them. However, I like the point made that just because we understand some psychological or neural reasons that contribute to maladaptive behavior, does not excuse the behavior. Just because a child was abused by a parent, does that justify the child's murder of the parent?

It is also interesting to see how questions we are tackling with science (how much of addictive behavior is automated?) are directly applicable to social institutions of the legal system. I was not aware that even if someone was not mentally challenged or psychotic, they could be found innocent of a crime because of a psychological condition such as abuse. Of course, their past contains factors that make the resulting crime more likely, but it doesn't make it any more acceptable.

Is it possible to have one's "head just go," where the impulses of the limbic system just override the prefrontal cortex in a healthy individual? Can a stimulus be so overpowering that one's better judgment doesn't even have a chance to have a say? Even if this were the case in the most extreme instant, many other mini-versions of this instance shape a person's life and behavioral tendencies. If every other chance to inhibit an anger or violent response was ignored, then it seems like the final instant where no inhibition was even possible is morally unjustified because of the pattern of poor decisions that preceded it.

In the case of addiction, I'm not sure that people who promote the brain disease model ever stated that free will was entirely out of the question. Otherwise, how would people ever remain abstinent? If they had absolutely no control against it, then every single person would relapse, and although it is a smaller number, it seems some people are successful in controlling their addictions. I think the disease model helps addicts and treaters understand how difficult it IS to stop, and in this understanding comes less blame, guilt, hopelessness etc., optimizing the state of mind needed to be ready and committed to stop. But it also does not take away responsibility. Now you have the knowledge just how difficult quitting is, and it is up to you to combat that difficulty.

How Effective is Alcoholism Treatment in the U.S. Summary - Matt

How Effective is Alcoholism Treatment in the United States?
Miller, Walters, & Bennett 2001

Overview: This study combined data from 7 large studies to assess in general how effective alcoholism treatment is in the U.S. The study did not attempt to compare the efficacy of various styles of treatment to one another.

Basic Findings: 1 in 4 participants stayed abstinent during the first year following treatment. 1 in 10 participants used alcohol moderately, without experiencing alcohol-related problems. The rest of the participants improved from pre-treatment status. They abstained from alcohol on 3 out of 4 days and decreased their drinking by 87%. In addition, alcohol related problems fell by 60% in this group.

Basic Conclusions: About 1/3 of participants were symptom free for a year following treatment. The other 2/3 of participants reduced their drinking and experienced fewer alcohol related problems. Studies that dichotomize treatment outcomes into abstained vs. did not abstain do not account for the improved functioning of participants who drink moderately after treatment. These types of studies paint a bleaker picture of treatment outcomes than is truly merited.

Intro: It is important to know how effective alcohol treatment is. Lawmakers, funding agencies, insurance companies, and individuals dealing with alcoholism often request this information. It can be difficult to determine effectiveness of treatment in general since studies differ in their definitions and measurements of treatment “success”. Some studies inflate success rates by excluding participants with a poor prognosis, not accounting for participants who drop out of the study, and using a short time period post-treatment to reevaluate alcoholism status.

Past studies addressing the issue of alcoholism treatment efficacy have been conducted.
Emrick (1974) found that 1/3 of participants abstain completely while 1/3 exhibit improvement post treatment. This work included studies with a short follow-up period. Costello et al. (1977) found an average “success” rate of 26% in outcome studies which used a 1-year follow-up period and accounted for lost cases.

Method: Alcoholism treatment studies were included in this meta-analysis if they met the following criteria: They were multi-site. They evaluated non-brief treatments for alcohol use disorders. They reported a quantitative measure of drinking outcomes. The follow-up period was at least 1 year. Follow-up data was available for at least 60% of the participants after 1 year. Seven studies including 8,389 participants were identified which met these criteria.

Results: 24% of participants were continuously abstinent for 12 months or more. 10% of participants drank moderately without alcohol-related problems or dependence. Participants who drank after treatment averaged one drinking day per 4-day period and increased their days of abstinence by 128%. These drinking participants reduced their “drinks per drinking day” by 57%. On average, participants decreased their drinking-related problems by about 60%.

Discussion: All of the studies included in this meta-analysis investigated treatment outcomes in the U.S. One should be cautious in generalizing these results to treatments outside of the U.S.

In order to facilitate future meta-analyses, outcome studies should report frequency of drinking, quantity of drinking, and the percent of participants that are totally abstinent.

These results are encouraging and support the “rule of thirds”. About 1/3 of participants remit from disorder for at least 1 year post-treatment while another third demonstrate considerable improvement.


Chiauzzi response - Kris

In the Chiauzzi article, the authors address the idea that behavior is a better predictor of addiction than personality traits, using the example of antisocial behavior v. antisocial personality disorder. They also implied that treatment should be individualized to address these behaviors. I was a bit surprised that they didn’t discuss how using behavior rather than traits would improve individualization of treatment. It seems to me that the real benefit of using behavior to predict addiction lies in the ability to correctly predict more cases of addiction, as more people would display antisocial behaviors than would show severe enough symptoms to qualify for a diagnosis of antisocial personality disorder. While I agree that improved prediction of addiction is a good thing, I also think that focusing treatment on changing these behaviors may reduce one the benefits of a trait model of addictive personality – namely, an understanding of the underlying biological predispositions toward addiction. Antisocial behavior and antisocial personality disorder are likely to have similar underlying biological causes, and these biological predispositions should not be ignored during the course of treatment.

Chiauzzi Taboo Topics overview; questions - Sarah

Big Picture: The article claims that the views of addiction in the health care system and in society contain many inaccurate beliefs that are not founded in empirical research. The authors argue that persistence of these beliefs is harmful to treatment of addiction, and there is a need to be more receptive to other ideas about addiction treatment. They support their claim by touching on 11 topics that oppose the traditional views of addiction and explaining how these counter-examples are supported by research.

1) Minnesota Model not empirically supported – The authors point out a study by Miller and Hester (1986) that did not find support for key components of this model, and then cite numerous studies that found support for other treatment models.

2) AA not necessary to maintain abstinence – No conclusions can be drawn about causality (whether AA increases abstinence or those most likely to abstain are more committed to AA) because of lack of research. Also, certain people are not a good fit for AA (severely depressed, non-religious).

3) Spontaneous remission – many addicted people remit on their own, without undergoing treatment. This is contrary to most disease models of addiction, in that disease supposedly should not remit without treatment. The authors point to maturing out of addiction after adolescence as an example of this scenario.

4) Using labels – The authors cite evidence that accepting the alcoholic label is not necessary for successful treatment, and also reference literature that describes stigma associated with labels (lower self-image, expectancy, etc.)

5) Self-report information – The conventional model includes denial as an important component of addiction, and the authors argue here that most alcoholics are not lying (and often may appear to be because of cognitive deficits) and treating them as though they are could hurt therapeutic alliance.

6) Addictive personality – The authors claim that specific behavior better predicts addiction than personality styles, contrary to popular belief.

7) Cue exposure – Exposure to drug cues in therapy is rarely done, but the authors cite evidence that using cue exposure can help treatment.

8) Motivation models – The authors argue that current models of motivation to abstain focus too much on client motivation and ignore the effects of therapist and treatment facilities on motivation. They also propose considering Prochaska’s stages of change into a model of addiction treatment.

9) Smoking cessation – Most programs do not require smoking cessation as part of treatment, and the authors argue that smoking cessation does not harm treatment of other addictions and should be implemented because of risks related to smoking.

10) Addiction concept – The authors point out that “addiction” is an overused term.

11) Codependency – The authors criticize labeling significant others and family of addicts as “codependent,” since this conceptualization has little support.

Some thoughts: 1) How can we help adolescents with their addictions, since they are most likely to react negatively to accepting a label (the first step of AA) and many of them actually might mature out of addiction? Do we just wait and see?
2) So many AA ideas are well-known in the general population – hitting rock bottom, accepting the label, belief in a higher power – and this could discourage some addicts from seeking treatment, since they may believe that is the only treatment available. This can be seen with Knapp, and her ideas about what AA meant. How do we reach these people and get them into treatment earlier?

Tuesday, April 25, 2006

Josh - One Nation Under Therapy

One thing that I thought was interesting about this chapter was the discussion of free will vs determinism, and the idea that it is irrelevant to the practical matters of how to deal with criminal offenders and drug addicts. In particular, the idea that society needs to approach certain behaviors (such as criminal behaviors) punitively, because the threat of punishment appeals directly to the inhibitory systems of the brain. If you believe in absolute free will, then it makes sense that, the more unnappealing you make something (by increasing the negative consequences), the less likely someone would be to freely choose it. If you believe in absolute determinism, the likelihood of an individual engaging in a specific behavior would be related to internal mechanisms and the environment. Increasing inhibitory environmental consequences would lead to less people engaging in that behavior.

But there is more to it than this. If an alcoholic has a basic attention or cognitive control problem, would the above mechanism actually effect behavior? Perhaps weaker cognitive control means that inhibitory cues exhibit a weaker effect on behavior in alcoholics than controls; likewise, moderate acute alcohol use could produce this effect, perhaps compounding the problems of those predisposed to alcoholism.

It is possible, then, that the strongest way to prevent addiction or to facilitate abstinence would be to establish an aversive response as the prepotent response to alcohol. It seems like that would be nearly impossible; it is a legal drug, so a punitive measure does not seem feasible. Once someone has become a chronic user, while he or she may be experiencing a myriad of negative consequences, it would be incredibly difficult to establish a prepotent response to not use the drug.

One thing that this paper pretty much ignores is related to the allostasis idea. Can this theory be dealt with in the framework of this chapter? Sommers and Satel do mention that "researchers have noted that self-reported craving does not necessarily correlate with a greater chance of actually using cocaine". They state this as support of personal responsibility, but this use could just as easily be due to something like allostasis, or some other mechanism yet to be discovered.

Sommers and Satel also talk about how two people can use drugs, one who will use drugs, love it, and immediately want more, and one who will use, love it, and never use again. They say "this is not a matter of brain physiology". I understand the point they are trying to make, but there is nothing to say that the difference between someone who uses and wants more and someone who uses and does not is not related to some pre-existing brain difference.

I also thought I'd pass along some drug-related stories I've seen recently, if anyone is interested.

This is about heroin addicts who are specifically seeking out a variety of drugs that is killing people, because it is supposed to cause such a potent high:
Yahoo news article

This article is about drugs used to treat narcolepsy being considered for the treatment of cocaine addiction:
Yahoo news article

This article is about Pete Doherty, whom the article calls "the most famous junkie in Great Britain".
Rolling Stone article


Dopamine and Glucocorticoids

The experimental evidence reviewed in Piazza and Le Moal reveals that basal levels and post stress levels of glucocorticoids (GC) predict the extent of self-administration of drug. I recall reading elsewhere that alcohol itself actually causes a rise in GC in humans. Would it be reasonable to predict that level of the rise in GC caused by the alcohol itself (controlling for basal GC levels and post-stress GC levels) would also independently relate to future alcohol consumption? Does this GC rise in response to alcohol perhaps suggest that a reasonable conceptualization of alcohol is that of a stressor itself?

It is interesting to conceptualize self-administration of drug as an experience of a stressor or challenge (at least on a physiological level) that ends up working out well (being followed by dopamine release) for the organism. Physiological challenge (drug) followed by relief or pleasure (dopamine) afterward would understandably be a very reinforcing sequence, even when it isn't preceded by negative affect. From this perspective, the reinforcing interaction of glucocorticoids and dopamine makes intuitive sense.

The message of the Piazza paper, that is, that an individual-centered approach explains as much or more than a drug-centered approach, would be endorsed by the men I heard at the AA meeting I attended. The men referred several times to how fundamentally different they were from other drinkers. They mentioned that they "knew others drank without the goal to get f***ed up," but that they "always drank with that intention." Specifically, two individuals mentioned that they pretended to select their beverages of choice on taste (dark German beers in one case, varieties of scotch in the other) but they acknowledged they were really always choosing them off the shelves based on the percentage alcohol content. They believed they were different fundamentally from other people they knew in their response to alcohol.

Why is the corticosterone and vulnerability to drugs link broken in inbred strains? Has metyrapone (the GC inhibitor) been used in human studies to reduce vulnerability to drug dependence?


Schatzberg Talk - jahn

i went to alen schatzberg's (sp?) talk today. he also (in piazza paper) said that rats tend to self administer glucocorticoids - which he couldn't explain.

he was looking at glucocorticoid antagonist effects on alleviating symptoms of psychotic depression. when asked about the mechanisms that might underly the effects he suggested dopamine (even mentioned Piazza) however, he was not sure that this was direct effect of gluc. on dopamine and further they have not been able to replicate the piazza results in their lab. if you are interested in this topic see Flores(sp?), Belenoff (sp?) and Young - with Schatzberg as a coauthor. i am very bad at spelling names sorry.

Monday, April 24, 2006

Josh - Krueger, etc

I share some of the concerns that Drew raised about the way in which externalizing was discussed in the Krueger et al paper.

Random thoughts regarding this paper:

I wonder what it would like like if you used each of the component scales of the constraint scale individually. Specifically, I wonder if harm avoidance would be more completely explained by externalizing, whereas traditionalism might be related to the additive genetic effects that they see for constraint. (I'm not sure where control would fall, I'd have to look at the items and look more carefully at what exactly that scale measured).

Is there a problem with using the measures that they use in this paper, to bring together antisociality and substance abuse? Are there items on the DSM-III-R for the assessment of antisociality that are directly related to substance use; does it make sense to separate them when it is abundantly clear that the covariance between substance abuse and antisociality is very high?

It seems to me intuitive that disinhibitory personality would be related to substance abuse and antisociality. One thing that this made me think of though, is what exactly externalizing is. Krueger et al describe it as "a broad, latent factor linking substance dependence and antisocial behavior disorders". This description makes externalizing sound like basically the covariance between these two things. I believe that personality features/steady traits would be the most intuitive manifestation of this covariance. Indeed, the items they use to assess antisociality are in part derived from the DSM criteria for antisocial PERSONALITY disorder. I'm not sure, again, what those were in DSM-III-R, but now it includes things like reckless disregard for the safety of self/others, which can be related to drug or alcohol use and probably to harm avoidance, impulsivity, irresponsibility, and lack of remorse. Those seem to be the types of things that could be more causally related to antisociality and substance abuse.

I hope this has been at least somewhat coherent, although I fear that it has not. I need to get some sleep.


Sunday, April 23, 2006

Piazza response - Helen

I found the evidence for the relationship between stress, glucocorticoids, and dopaminergic neurons really exciting and compelling. It elucidates a likely causal mechanism of why addicts are driven to use more when under stress. It also can explain different pathways by which people become addicted - people who are more stimulus seeking and have a natural large dopamine response to drug, people who may have less of a biological risk but continuously take high doses for whatever reason, people who are continuously stressed may find it more rewarding than if they were not stressed, etc.

What is still a little unclear to me is how increased motor response relates to stress and dopamine. Why would those things be connected? I guess increased dopamine in general would increase the "wanting" mechanism as well as motor activity in the basal ganglia, so an increased dopamine response could be indexed by an increased motor response.

I am also a little unclear about the exact role of corticosterone. It is reinforcing in itself because it is released to combat a stress response. If corticosterone is reinforcing itself, why does it intensify the reinforcing properties of drug? If corticosterone combats the stress response, what are the hormones that compose the stress response? Perhaps the intensified reinforcing properties of drug are more directly related to the immediate stress hormones than the response stress hormone. Perhaps someone who is more knowledgeable about stress can clear this up for me.

The higher D1 receptor concentration that is associated with a greater dopamine response in HR rats seems to be one target of treatment to decrease drug self-administration. Have Piazza & Le Moal attempted to block the D1 receptor to see if it decreases drug self-administration? Is it even close to feasible to do something similar in humans? I know L-Dopa is used to increase dopamine in humans. Is there another way to decrease dopamine in the human brain so that drug wanting or reward properties could be decreased? Or else corticosterone can be the target because suppression of corticosterone decreases dopaminergic response to stress in HR rats. However, how much would suppressing the stress and dopaminergic responses negatively alter response systems that they are designed to facilitate? It seems there would be harmful side effects as a trade off for less drug use. Would decreasing dopamine responses change wanting or liking or both?


I attended an AA meeting just before class last Thursday, and I have to say it was really difficult. The meeting began with just 3 middle-aged men and me around a small table. I felt very awkward, but they were all very kind and open to me being there just to observe. About midway through, a 20-something girl came in, and although I clearly had no chance to blend in by then, it was nice to have someone my age there.

My main impression was just how open people were. The session was a "first step," and everyone was brutally honest about their past drug use, and about why they came to AA and why they've stayed. The most memorable revelation for me was when one man said that Madison was a great place to be in recovery because there are so many drunks here. That seemed counterintuitive to me, what with all we've been learning about attention and environmental cues. BUT, he went on to say that Madison having so many drunks means that we've also got many alcoholics in recovery, and within those people, many are happy and have been successful abstainers for years, if not decades. I couldn't help but think about our last 741 course again, and about how believing you can change in therapy is one of the best predictors of success.

Finally, I was grateful to have a younger person at the meeting, because she showed the same issues, disastrous past, and current resolve the older guys did...this really brought home to me just how strong my alcoholic stereotype is. Just like Knapp says, I expect an alcoholic to be an old bum with a paper bag. Accordingly, I expect a recovering alcoholic to be older, more damaged...maybe in my mind the "breaking point" before recovery that Knapp describes is associated with a specific age. To step out onto the ledge even further, is the way we think about alcohol and alcoholism as a society causing more people to lose control? To think, "I'm not there yet?" And relatedly, is there some cognitive reason why younger people might be less likely to think that way...and therefore perhaps less likely to benefit from a program like AA?

Kreuger outline, questions--Kirkland

Kreuger, et al., 2002.

Take home point:

In a large (~1000) sample of twins, a single “externalizing factor” was found to be related to substance use, antisocial behavior, and disinhibited personality. The EXT factor had both genetic and environmental components. Authors present data supporting a spectrum of externalizing disorders sharing common risk factors, and possessing more specific, differentiating risk factors.

1. Past research suggests that externalizing disorders are related
2. Twin and adoption studies suggest genetic components to overlap between substance use and antisocial personality, as well as to overlap of other externalizing disorders and traits (ADHD, sensation-seeking)
3. Past research also suggests unique etiological factors that contribute to different externalizing disorders.
4. Disinhibited personality, including impulsivity and sensation-seeking, has been linked to externalizing.
a. Researchers sought to identify whether or not disinhibited personality would also
contain the EXT factor.

1.Twins and parent came to lab
2. Diagnosed, MPQ used as a personality measure
3. Used SEM to determine structure of externalizing and disinhibition (constraint)
a. Used 3 different models, with different levels of constraint on structure

1. Types of correlations
Cross-twin within-trait
Cross-twin cross-trait
2. Although all disorders more prevalent in males, structure similar
3. As expected from this, sex-invariant SEMs fit better than sex-variant
4. Odds of 150:1 that sex-invariant, common-pathway model fits best
a. G, shared E, nonshared E effects are mediated by a latent factor
b. Latent factor represents shared variance among phenotypes
c. Also allows for unique etiological contributions to each disorder
5. Additive genetic effects = 81% of EXT variance
a. Remaining variance nonshared E
6. All variables loaded on EXT (at different levels)
7. Specific G and E effects contribute to each disorder/phenotype

1. How do we translate this research into research on specific G and E CAUSES of both specific disorders and general risk for externalizing? What I’m most stuck on is how we measure EXT alone.
2. When fitting a model including adolescent antisocial behavior, what will be the implications of adolescent-limited vs. persistent antisocial behavior (i.e., Moffitt & Caspi)? Could not measuring these differences potentially affect model fit?
a. This is especially interesting in terms of the finding that unique shared E effects are
relatedto conduct disorder. Are the CD kids the only ones later marked as antisocial
3. If nonshared E effects less reliably account for variance with multiple measurements, are the “facets” of Ext really as clear as they seem here?

Jahn - Piazza, Externalizing Model, TV

I find it interesting that there is some common genetic factor that seems to solidify in late adolescents. There is a similar pattern of emergence of depression in adolescents. What is critical about this time, puberty, prefrontal maturation, unique portion of social development? Could a non-shared environmental factor that the authors discuss be friends (as suggested in Piazza)? I think it would be interesting to look at the contribution of social group to this dynamic. Can rats/mice assert peer pressure?

Has anyone looked at how informing individuals of the high genetic heritability or the “biologic makeup” of the externalizing factor and the risk of developing drug and alcohol use might limit substance abuse?

I am glad we are reading the Piazza paper. I was wondering when we would discuss the stress system and the development of addiction. I found it interesting that drug use followed social stress interactions in rats. I also found it interesting that use was not related to physical violence. How is social stress different from physical stress?

I haven't watched TV all week. My reading has increased and I finally went for some real runs this week. But now i am going to see a movie and even though I am on the moderation method I am feeling a little guilty for loosing some potentially productive time. Oh well... i can let you know how American Dreams is tomorrow morning.

Krueger and Frey Knapp - Deb

I would have liked to have seen some specific measurements of cognitive control in the Krueger sample of externalizers. What exactly is the externalizing factor that they show is so important? Disinhibition only accounts for a portion. Related to this; what is the relationship between cognitive control and constraint? Some very basic questions have been answered but it seems like there is still a lot of picking around to do is this data to come to some sharper conclusions, and, as they mention many different additional studies to be done (gene specific studies). The fact that disinhibitory personality traits such as impulsivity measured as early as at 3yrs of age can predict adult alcohol dependence and criminal behavior stunned me. I know that we are going to be talking about treatment next week, but something this reliable and early has great intervention implications. How could we integrate this information, along with current treatment procedures, and the finding that shared environmental factors may be more important earlier in life to development of these behaviors into a treatment strategy?

Knapp complements Frey in that she seems to convey the reasons behind the need to drink, the motivating psychology and logic behind her choices, while he conveys with brutal force the actual act of drinking and addiction in of itself. When I read Frey I felt it in my gut, very visceral in its impact. Knapp takes me on a cerebral tour guided by affect, I feel her in my head and heart.

seek wix post - Drew

Kruger: They label externalizing, but they only measured variables that have to do with externilizing. Couldn't this "externalizing" variable be much broader? -- How do we dissociate the correlation of externalizing behavior with the outcome variables from an increased correlation between outcome variables. These two interpretations seem to represent different biological instantiations, but are mathematically identical.

Piazza: High/Low responding rats were selected based on their locomotor reactivity in response to novelty were more likely to administer drugs... Couldn't these both be related to the dopamine system? The one-liner that I latched onto in this article was the finding that dopamine cells left in-vitro with coticosterone cells for 15 days showed increased dopamine release.

Could it be that one useful function of the dopamine system is to be more responsive in times of stress? -- In times of no stress, there may an increased ability to try various behaviors and no particular hurry to latch on to any one behavior. In times of stress it may be more beneficial to stick to behaviors that are high-reward/low-punishment. In terms of error-responsiveness, it could be that it is helpful to be hyper responsive during a high-risk period of time.

Could this interpretation explain the findings in the Piazza paper? If we are hyper responsive in times of stress, we would see an increase in dopamine release in response to drug. We would see increases in relapse susceptibility and increases in novelty seeking exploratory behavior. Adrenalectimized rodents would demonstrate reduced sensitivity to stress under this model. Interestingly this model would also predict that at some point there would be no effect of low glucocorticoid
concentration on dopamine response, which is seen in the low responders...

Thats my 2-cents.

See you in class,
- Drew

week 6 (sharee)

I learned a new fact from the Piazza et al. (1996) paper. Mainly, the fact that “glucocorticoids have intrinsic reinforcing effects” (page 366) was completely new to me. It made me wonder what it is about glucocorticoids that produce this effect. Is it primarily their connections with dopamine? I guess it just put a different spin on the stress, glucocorticoids and dopamine relationship that other authors have presented. Previously, I had thought that the activation of the stress system led to negative affect type symptoms, and vulnerable individuals take drug in order to ‘deal’ with the stress (i.e. to dampen the stress felt). And this idea seemed to flow from the fact that when faced with a stressor, a rat will reinstate self-administration behavior after it has been extinguished. But Piazza reports that rats will self administer glucocorticoids to reach a plasma concentration similar to what would occur with an intense stressor. This observation suggests that the relationship between cortisol and dopamine is additive or complementary versus opposing.

AA Meeting, Kreuger Article, Evolution & Mental Disorders? - Matt

As far as the Alanon meeting goes, I think Josh gave a really good summary of how it all played out. Just as a refresher, the AA meeting we went to turned out to be an Alanon meeting for couples. There were maybe 10 husband and wife pairs ranging in age from about 45 to maybe 65. To me, it really felt more like group marital therapy than an intervention pointed at dealing with addiction. As Josh mentioned, the majority of the meeting consisted of talking about how parents should deal with their children. Several people focused on situations in which spouses disagree about how to enforce rules or discipline their children. I’m sure that this is a difficult topic for most parents but I wonder if it represents a bigger problem for couples with a history of substance dependence. One man said that when he was using alcohol he had childrearing disagreements with his wife and he eventually realized that since he was drunk most of the time, his opinions on childrearing didn’t really count. If the sober partner learns to ignore her spouse’s opinions over the years, it may be more difficult to compromise on childrearing practices once the alcoholic partner quits using. Like Josh said, people emphasized how important it is for parents to be consistent in their discipline, to negotiate rules that both partners feel comfortable with, and to stick to those rules no matter what. I think this is probably a really good thing and if this philosophy comes from the AA handbook, way to go AA! Another thing that was interesting about the meeting was that there was no real expert leading the discussion. Members trade off responsibility for starting and ending the meeting week to week. This was just a bunch of average couples sitting around trying to help each other out. This may reflect the idea that recovered addicts are the real experts when it comes to dealing with addiction.

Reading the Krueger article made me think about how far we are from accurately characterizing the development of psychopathology. I think that this was mainly due to the fact that this article considered very broad constructs (genetic and environmental influences) in relation to several psychological disorders.

So the basic finding was that the broad dimension of externalizing is largely accounted for by genetic influences while the more narrow constructs of conduct disorder, alcohol dependence etc. are largely accounted for by environmental influences. This finding has daunting implications since our field cannot get very specific about what sorts of environments correlate with specific mental disorders. Oftentimes, environmental risk factors correlate with both internalizing and externalizing disorders. I think that we will have to develop much more sophisticated techniques for measuring environmental influences in order to determine what aspects of the environment differentially predict various types of mental problems. Also, there is the complication of determining how particular genetic influences interact with particular environmental influences in the development of psychopathology.

This hierarchical model of psychopathology also made me think about the evolution of species as an analogy for the development of mental disorders. So you start out with one species of bird. Birds of this species eventually find themselves in different environments. Over the generations the birds adapt to different environmental challenges by developing different beaks for finding different types of food etc. etc. As the birds face multiple environmental challenges and adapt in multiple ways, new species of birds evolve. In the case of psychopathology, you start out with a genetic predisposition toward the development of externalizing problems. People with this common liability find themselves in different environments. These different environments present an assortment of unique challenges to the organism. Perhaps the child in a physically violent family learns to express his genetic liability via outward aggression while the child in a substance abusing family learns to express his liability via drug use. Over the lifespan, various mental disorders evolve in different people who share a common genetic predisposition. Characterizing these environmental influences which shape the expression of genetic liability seems like a very difficult task.

Hope that made sense.

Piazza reaction - Kris

I thought the Piazza and Le Moal article was a good review of the relationship between stess, dopamine, and drug abuse. This got me thinking about the role that early neonatal factors, specifically maternal care, may play in the development of propensity to self-administer drugs.
Increased maternal care is associated with reduced stress reactivity in the offspring and can overcome the increased reactivity caused by prenatal stress, suggesting that increased maternal care should also reduce self-administration in the offspring. This also brings up the role of maternal care in generating HR v. LR offspring. Dams that are more stress reactive tend to have more reactive offspring, but it isn’t clear how much of this effect is genetic v. epigenetic, as stress reactive dams provide less maternal care and maternal care is associated with permanent changes to the CRF response system. The implications this may hold for humans include the possibility that the increased probability of an addict’s offspring developing addiction problems themselves may not be entirely due to genetic predisposition, but may also be influenced by parenting.
There is also evidence suggesting that maternal care can alter the mesolimbic dopamine pathway. Individual variation in maternal care can alter the development of social play in the offspring. As this behavior is dependent upon the central amygdala and appropriate levels of dopamine activity during development, this suggests that maternal care can influence the development of regions important for reward. Additionally, a study that I’m currently working on suggests that maternal care can alter dopamine activity within restricted brain regions, including the central amygdala. The ability of maternal care to alter both the dopamine system and the stress response system suggests that the ability of maternal care to alter development of “addictive personality” needs to be investigated.

Saturday, April 22, 2006

Krueger, Piazza reactions - Sarah

I enjoyed reading about the individual difference factors that may predispose an individual to addiction – since telling people I’m in this class, almost all have asked me to explain why some people get addicted and others don’t. I think it’s an important question and it’s nice to start to get a few answers.

The Krueger et al. article suggested that an underlying latent externalizing factor connects substance dependence, conduct disorder, antisocial behavior, and so on, and that this underlying factor seems to be largely genetic. This made me think about the grant proposal from a few weeks ago that proposed a genetically transmitted weakness of cognitive control in children of alcoholics. Based on Krueger, et al, would this mean that individuals with other externalizing disorders would also have this weak cognitive control? Could it be that weak cognitive control is actually the “externalizing” factor?

Also, Krueger, et al. emphasized a model where the different diagnoses would have different unique factors in addition to the uniting externalizing factor. It seems like exposure to alcohol early on and alcohol use in the family would be an important unique environmental factor that would push an individual towards alcohol abuse as opposed to other externalizing disorders.

On a different note, the Piazza paper suggested that personality differences (in this case, HR and LR rodents) are associated with differential response to drug in administration and relapse. They also mention that individuals can be more vulnerable to drug addiction under conditions of high stress, separate from those personality differences. I thought this was particularly interesting – under enough stress, would any individual become addicted? Is there a difference between chronic stress and acute stress in promoting drug addiction? Does chronic stress create a new set point (allostasis) for corticosterone and that is what makes drug addiction more likely?