Drug use memories and relapse: Can medication provide addiction help?

Originally posted on allaboutaddiction.com:

About a year ago, while sitting in a lecture on learning and memory, the idea that certain drugs can affect the emotional responses to memory long after the memory itself has been formed came up. As someone interested in addiction research, the implication for treatment immediately came up in my head:

Could we reduce the effect of triggers by giving people a pill?

In one word – Yes! But, the answer is not, in fact, that simple. Even in the studies already done in PTSD patients, the memories have to be re-triggered and the drug given at exactly the right time to be effective. In fact, in humans, some of the best work has been done in PTSD patients immediately after the traumatic event.

Addiction help through relapse prevention

Still, a recent study in animals suggests that the theory is sound. By interfering with the activity of a neurotransmitter important in the formation of memories, researchers were able to stop animals trained to self-administer cocaine from doing so. The animals, which had been trained to push a lever for cocaine when a light went on, reduced, or even stopped responding after a single dose of a substance that blocked memory formation. Essentially, the researchers prevented the animals from relapse. Again, this only worked if the drug was given while the light (as in the drug-trigger) was presented at the same time.

More recent studies, using repeated doses of the drug propranolol, have been shown to have an even more promising effect. Check out my coverage of that research here.

Given the powerful role of triggers in relapse, this avenue of research has some promising possibilities for future treatment of drug addiction.

Perils in obtaining a Ph.D.

I was struck by the recent article by Louis Menand in this issue’s Harvard Magazine. Essentially, for many academic fields the length of time to obtain a Ph.D. and the potential prospects for finding a tenure-track academic job is enough to make one who desires further academic inquiry to question whether the Ph.D. is the best next step. Additionally, the 6-9 years in takes to receive the Ph.D. involves heavy inquiry into a small area of one’s discipline. This quote from the article was particularly powerful:

“Doctoral education is the horse that the university is riding to the mall. People are taught—more accurately, people are socialized, since the process selects for other attributes in addition to scholarly ability—to become expert in a field of specialized study; and then, at the end of a long, expensive, and highly single-minded process of credentialization, they are asked to perform tasks for which they have had no training whatsoever: to teach their fields to non-specialists, to connect what they teach to issues that students are likely to confront in the world outside the university, to be interdisciplinary, to write for a general audience, to justify their work to people outside their discipline and outside the academy. If we want professors to be better at these things, then we ought to train them differently.”

brain mapping disorders

An ever growing number of studies feature brain mapping to illustrate structural differences in the brain based on grouping those with and without a given disorder. Techniques such as structural magnetic resonance imaging (MRI) can aid in researchers understanding of differences in shape and volume of various brain regions. Group differences are often found, yet there is wide variability in the structure and volume within any group. One potential contribution is the current methods for defining disorder (see Problems with the DSM). Psychiatric/psychological disorders denote important functional differences between individuals, yet what technically counts as a disorder or not is flawed and often arbitrarily defined. For example, children may receive a diagnosis of ADHD if they meet criteria for 6 or more inattention OR hyperactive/impulsive symptoms. This means that one child could be diagnosed with ADHD who has 6 inattention and 0 hyperactive symptoms, whereas a child with 5 inattention and 5 hyperactive symptoms would not meet criteria. I hesitate to think that this is a perfect system. Yet, interestingly, there are MRI findings that differentiate ADHD from non-ADHD groups. Notably, any one child may not “fit” with their group, as these differences only appear at the group level.

I wonder, is it useful to use group data to make conclusions that may affect those at the individual level? And, perhaps the problems with our current psychological tools in honing in on the disorder are what causes the lack of consistency between groups in the MRI findings. Perhaps the use of biological measures to help to define the lines for what is and is not “disorder” will better aid in the identification and treatment of problems in functioning. An approach using differences in the brain that may be associated with specific functions or impairments in those functions to locate disease related endophenotypes is a promising future area of research.

Healthcare savings and alcohol and drug abuse treatment: Saving lives and money

From allaboutaddiction:

A recent paper put out by an initiative called Closing the Addiction Treatment Gap (CATG) talks about some of the cost savings benefits that go along with alcohol and drug abuse treatment. The numbers refer to current treatment methods, success rates, etc., so the savings should only go up as we become more successful and introduce longer, more chronic treatment methods (as I discussed here).

• 2.3 Million hospital stays in 2004 we directly related to substance disorders.
• Total medical costs were reduced 26 percent among patients that received addiction treatment.
• Brief counseling alone allowed for a reduction of 20 percent in emergency department visits and 37 percent in days of hospitalization among a group of high-risk alcoholics.
• Addiction contributes directly to many off our most pressing health issues: heart disease,
  cancer and stroke.
• In one study, outpatient addiction treatment reduced total medical costs by 26%, inpatient health-care costs by 35%, and emergency room by 36% !!!

You can find the rest of the report on CATG’s website, but I think you’ll agree that alcohol and drug abuse treatment needs to be part of the discussion in our ongoing health-care debate. We can save billions of dollars and millions of life every year by making appropriate, effective, addiction treatment part of the reality of ongoing health care in America.

It’s the responsible thing to do. It’s the right thing to do.

More money more problems? Rich teens, drugs, and other mental health issues

From allaboutaddiction.com:

Teens raised in affluent homes display the highest rates of depression, anxiety, and substance abuse according to a recent article in Monitor on Psychology, the APA’s monthly magazine.

One of our recent posts dealt with some of the issues unique to teens and drugs. In addition to the issues we’d already mentioned, the article named a number of reasons for the high prevalence of mental-health issues among affluent teens. Among them were an increasingly narcissistic society, overbearing parents, and an common attitude of perfectionism.

Each of these reasons are likely contributors to the prevalence of mental health issues among upper-middle-class (and above) teens. Still, as far as I’m concerned, the main take home message of the article is this:

Money truly doesn’t buy happiness.

While we often focus on the lower socioeconomic strata, these recent findings, indicate that being financially stable offers little in the way of protection from some of the most common psychological difficulties.

Thankfully, the researchers cited in the article made some very simple suggestions to parents:

• Give children clear responsibilities to help around the house.
• Take part in community service (to unite the family and reduce narcissism).
• Reduce TV watching (especially of reality TV shows that glorify celebrity and excess).
• Monitor internet use.
• Stop obsessing about perfect grades and focus instead on the joy of learning for its own sake.

I couldn’t agree more with these recommnedations. Having taught a number of classes myself, I have withnessed the ridiculous inflation in students’ expectations of top grades. I think it’s time we turned attention back to the family and reintroduce some of the basic skills that many addicts find themselves learning much too late… Often in recovery.

The Ethics of Neuroenhancement

A recent issue of the New Yorker featured a wide-ranging and engagingly written review of the current controversy over the ethics of neuroenhancement. Neuroenhancement refers to the growing trend of off-label use of psychiatric drugs by men and women of all ages and backgrounds for the purpose of boosting their brain power and ability to get things done. In an anonymous survey of scientists and academics that appeared in the journal Nature in 2007, about one in every five of respondents reported off-label use of Ritalin, Adderall, or the anti-narcoleptic drug Provigil (known generically as modafinil) to increase their productivity and focus. The New Yorker article, written by Margaret Talbot, is one of the most comprehensive reports on this trend to appear in a major news publication, and I strongly encourage readers with interest in this subject to read the original article in full.

Prior to reading Talbot’s article, I was unaware of the possibility that neuroenhancers are most often used to overcome cognitive or motivational deficits, but the more I think about it the more sense it seems to make. Support for this claim can be found in the New Yorker article, which argues that most neuroenhancers in college are underachievers (note, however, that this is based mainly on anecdotal evidence). So it may be true that students who take Adderall in college are gaining an unfair advantage, but this advantage may only be relative to other underachievers. Specifically, non-enhancing underachievers may receive sub-normal grades while those who take neuroenhancers may obtain grades that are closer to average. Further, recent empirical findings suggest that drugs such as Adderall and Ritalin may benefit less cognitively sharp people to a greater extent than they benefit more intelligent folks.

One interviewee in the New Yorker article raises the specter of parents who might force their children to take neuroenhancers so as to increase their competitive advantage in the academic arena and therefore their ability to get into the best colleges. This is a valid and important concern, but there is a world of difference between parents forcing their children to take neuroenhancers for non-clinical purposes and adults choosing to do so of their own free will. In any case, such abuses are already possible, as parents may push for psychiatrists to diagnose their children with ADHD so that a prescription for a neuroenhancer may be obtained.

As technology and culture continue to co-evolve in the new millennium, the public debate over the benefits and drawbacks of neuroenhancement will likely become increasingly central to how we view ourselves as individuals and as a society. Neuroenhancement offers the potential for tremendous increases in productivity across occupational and professional domains, but it also raises questions about our core ethical values and what it means to be truly meritocratic. The jury is still out on many of these questions. What do you think?

Self-Control is important, and teachable to some extent

Self-control or behavioral disinhibition has been implicated in a number of psychiatric disorders, including Attention-Deficit/Hyperactivity Disorder (ADHD). It may be a mediating factor responsible for the lowered academic performance found among many children with ADHD.

The ability to inhibit responses may predict academic performance even better than IQ. This New Yorker article reviews studies of self-regulation and how “will power” may be a trainable trait that makes a difference in our social, academic, and financial domains.

One example of how animal research can help humans

Human and animal studies have found that brains go through substantial
synaptic pruning during childhood, removing approximately half of all synapses until puberty. While the pruning of synapses is a natural process, some researchers have theorized that schizophrenia arises from excessive pruning (Siekmeier & Hoffman, 2002). Presuming schizophrenia is a disorder of disruptions in neural connectivity caused by excessive pruning, then efforts to prevent the onset of psychosis and other symptoms of schizophrenia should being prior to adolescence. Identification of likely prodromes should therefore occur as early as possible in development.

Identifying the areas of the brain and specific neurotransmitters that play a role in pruning, in particular pruning likely specific to schizophrenia is an important step to keep those areas from being pruned unnecessarily. One possible prevention strategy could be to stimulate glutamate receptors on pyramidal neurons during childhood or before the heightened rate of pruning. Great care would need to be taken to be sure that only areas with excessive synaptic pruning be targeted. Animal studies could help to locate which agonist will bind to the correct receptors. Some early research is encouraging, as a study on amphibians found that after chronic NMDA treatment, changes in the magnitude of NMDA currents were detected in glutamatergic synaptic currents (Hickmott & Constantive-Paton, 1997). It will likely take many years to be confident that the introduction of pharmacological treatments to prevent unnecessary pruning will have benefits that outweigh the risks.

Animal research can and has helped to identify novel treatments for a number of diseases. For more information on how to support humane animal research go to http://www.ucla-pro-test.org/

References

Hickmott, P. W., & Constantine-Paton, M. (1997). Experimental down-regulation of the NMDA channel associated with synapse pruning. The Journal of Neurophysiology, 78, 1096-1107.

Siekmeier, P. J., Hoffman, R. E. (2002). Enhanced semantic priming in schizophrenia: a computer model based on excessive pruning of local connections in association cortex. British Journal of Psychiatry, 180, 345-350.

Disclose or not? The catch 22 of mental illness

A recent report published by SAMHSA addresses the issue of self-disclosure regarding mental illness.

Research has already shown that the more familiar people are with others who have different form of mental illness, the more their attitudes regarding mental illness will improve.

The problem is that in the process, those who self-disclose fear being ostracized, losing their jobs, and suffering other similar consequences.

Still, the report found that those who do self-disclose often experience relief and find that it improves their relationships.

Obviously, the process requires careful timing. Also, a progression of self-disclosure, from a small group of trusted friends on, is suggested.

For the full report, go here: “Self-disclosure and its impact on individuals who receive mental health services.”

Social Defeat may play a causal role in schizophrenia

Some ethnic minority groups have higher rates of schizophrenia than the general population. My first thought was that the differences were genetic. Current research has found a strong genetic component to schizophrenia, and given that different ethnic groups may have different rates of high risk genotypes, the genetic variation between groups may be in part responsible for the different rates. However, when these groups (often recent immigrants) were compared with those from the broader population of their own national/ethnic origin, there was no evidence of these groups being more genetically “at-risk.” Additional work found that those who had chosen to migrate were not likely different in the degree to which they were genetically predisposed to schizophrenia. There are separate fronts in the battle to understand mental disorder, with many pushing to further ‘biologize’ psychiatric disorders. One danger of over-biologizing is the removal of consideration of other causal explanations. While it may not be the schizophregenic mother that is responsible for the development of schizophrenia in her child, the social environment in which we live and interact likely plays at least a partial role in the development of serious psychopathology, even one as genetically-influenced as schizophrenia.

Research on the epidemiology of schizophrenia has found that risk for the disorder increases among nonwhites as their neighborhood composition becomes more white (Halpern, 1993). The repeated findings that minority members are at greater risk depending on the social environment in which they live means that environment may influence the onset, course, and possible origin of schizophrenia (Luhrmann, 2007). This effect has been explained by the experience of “social defeat,” which had been used in animal research to term the effect when one animal becomes physically dominant over another. In rats, social defeat appears to increase dopaminergic activity in the mesolimbic dopamine system pathway, which has been found to be associated with positive symptoms in schizophrenia in humans (Tidey & Miczek, 1996).

Most gene x environment research in psychological research has focused on objectively traumatic events (e.g. combat exposure, child sexual or physical abuse), yet the introduction of more subtle environmental “events,” such as discrimination, provides a new avenue of analysis that should be incorporated in the integrative models of psychopathology.

References

Halpern, D. (1993). Minorities and Mental Health. Social Science and Medicine, 36, 597–607.

Luhrmann, T. M. (2007). Social defeat and the culture of chronicity: Or, why does schizophrenia do so well over there and so badly over here? Culture, Medicine and Psychiatry, 31, 135–172.

Tidey, J., & Miczek, K. (1996). Social defeat stress selectively alters mesocorticolimbic dopamine release: An in vivo microdialysis study. Brain Research, 721, 140-149.