The modern day interest in neurobiology owes a lot to Eric Kandel and his 1979 New England Journal of Medicine article "Psychotherapy and The Single Synapse." The focus of that article was on the application of his basic science research on plasticity to the psychotherapy situation. Plasticity was a relatively new concept at the time with the initial description of long-term potentiation (LTP) in 1973. Kandel's basic argument was that nervous systems of varying complexity are designed to change with the experience of the organism. The interesting part of his article is that it starts out with his experience as a psychiatric resident and the tension between the psychotherapists and the biological psychiatrists as they were called when I encountered the same dynamic in psychiatric training over twenty years later. It is an important consideration because people outside of the field often have a skewed perspective of what makes up the training of a psychiatrist and this tension has been present for as long as I can remember - with articulate faculty on both sides. He discusses this from the perspective of a parent discipline and an "antidiscipline" or one that is narrower in scope than the parent discipline and invigorates but does not displace it. Neurobiology being the antidiscipline to psychiatry. Molecular biology being the antidiscipline to cell biology and so on. At the experimental level Kandel uses habituation and sensitization experiments on the sea snail to illustrate that "dramatic and enduring" changes in neural transmission occur with changes in plasticity. He develops the theme that the functional-organic pathology based on gross or microscopic brain lesions is a false dichotomy. Profound changes in networks of neurons can occur with no change in the numbers of neurons involved. The mind is a function of the brain, but as Kandel later stated we do not have to think that all human behavior can be broken down to a specific biological level.
Getting back to the issue of addiction as a disease as opposed to something else offers a unique look at the plasticity concept and how it applies to brain problems. I looked at all of the papers in the Frontiers series and briefly describe the details in the table below. I would encourage reading the actual details in the papers since they are all freely accessible online and my one or two sentence summaries do not capture the complexity of some of these arguments. (click to enlarge)
There was a striking lack of the term "plasticity" in all of these papers. It only surface in the paper on choice by Heyman in the following sentences: "First, most drug addicts quit. Thus, drug induced plasticity does not prevent quitting." That is a restricted view of plasticity. First, it does not speak to the fact that plastic changes even if they appear to be long term can be reversed. Second, it treats plasticity as a linear process when it is likely that the brain processes involved in recovery and in all of the other mechanisms cited by these authors as being more important in the recovery process are plasticity based. The articles in general have the tone of polemics. There is certainly nothing wrong with that. As I have written on this blog, science is a dynamic process and part of that is an argument about theories over time. The argument about the neurobiology of addiction seems to get hung up on both the disease concept and morality. There can certainly be important neurobiology with or without disease. That neurobiology is there whether or not medication, social processes, or psychotherapy influences it. At least two of the authors equate neurobiological disease as the "no fault" condition and suggest that a biology based model is more blameless than one that suggests that addicts do have choices and respond to contingencies. I think moral interpretations of a mental illness or addiction have less meaning if we are accurately describing the process. It is much more than biology being no-fault and consciousness capable of decisions implying a moral judgment. Plasticity mediated mechanisms gets us a lot closer to the science of how the brain works and away from the primitive interpretations of the 19th and 20th centuries.
Plasticity is the best paradigm for describing addiction and the recovery process. Processes involving plasticity are all testable and the theory is falsifiable. The most significant obstacle to the application of brain plasticity as a central process is the old functional-organic dichotomy where organic implied a neuroanatomical brain lesion. It has been known from habituation and sensitization experiments like those described by Kandel in his 1979 paper that "dramatic and enduring" changes in neural transmission, do not require brain lesions or other abnormal anatomical features. A recent paper (3) proposing that maladaptive NMDA-mediated synaptic plasticity as a unifying theory for tardive dyskinesia is a good example of plasticity mediated illness.
There is no reason to believe that addiction and recovery may not be mediated by the same mechanisms.
George Dawson, MD, DFAPA
1: Kandel ER. Psychotherapy and the single synapse. The impact of psychiatric thought on neurobiologic research. N Engl J Med. 1979 Nov 8;301(19):1028-37. PubMed PMID: 40128.
2: Alternate Models of Addiction. Frontiers in Psychiatry.
3. Teo JT, Edwards MJ, Bhatia K. Tardive dyskinesia is caused by maladaptive synaptic plasticity: a hypothesis. Mov Disord. 2012 Sep 1;27(10):1205-15. doi: 10.1002/mds.25107. Epub 2012 Aug 1. Review. PubMed PMID: 22865512
