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On the Brain and Behaviour, Part III

Monday Musings for Monday June 17, 2013

Volume III, No. 22/125


Brain  and  Behaviour,  Part   3

Thinking  About  Thinking,  Episteme,  Chrestomathy

Twenty  First  Century , The  Age  of  Mind

By Assad Meymandi, MD, PhD, DLFAPA*

Editor’s Note: This is part III of a four part series on Brain and Behaviour. Part I, June 3, 2013, the general topography and physiology of the brain was discussed,  Monday June 10, the topic of Epigentics was explored.  Today we examine the relationship between psychoanalysis and biology.  Next week we will review some of the books about the subject to enhance our understanding of what lies in the future of neuroscience.

In preparing for this essay, obviously I was drawn to psychoanalytic literature of the late 19th and early 20th century. But the further I dug, the more it became obvious that psychoanalysis did NOT start with Freud. Many of Freud’s teachers and predecessors had expounded on the theory of unconscious. Plato, Shake­speare, Kant, Schopenhauer, Nietzsche have all dealt with and expounded on the possibility of the unconscious, the soul and metaphysics. Yes, I was taken all the way back to Aristotle, a student and rival of Plato, whose writings are so very organized and detailed, making the reader feel like they are biting into stone. Aristotle had a lot to say about psyche (soul), God, ether and metaphysical phenomena. Psychoanalysis thrived in the first 60-70 years of the 20th century, but experts fear the threatened demise of the field.  What is the answer? The answer lies with uniting psychoanalysis with biological sciences. Let me elaborate:

In a recent discussion with an academic colleague who was identifying the twentieth century’s greatest achievement as the discovery of the atomic bomb, I argued rather forcefully that the contribution of the twentieth century was advancement of Father Gregor Mendel’s genetics through the discovery and understanding of RNA and DNA by James Watson and Francis Crick in 1953. They were awarded Nobel Prize for Medicine or Physiology in 1962. We celebrated at the University of North Carolina and Research Triangle Park, in 2003, the 50th anniversary of the discovery by having Dr. James Watson amongst us. The understanding of DNA and subsequent expansion of the knowledge and advancement of human genome project which was completed in 2003 by Dr. Craig Venter, Director, The Institute for Genomic Research, in my opinion, was the greatest achievement of the 20th century.

Now, facing the 21st century, with wars going on every corner of the globe, humans killing humans for a few pieces of mud prized as land, the need for understanding human behavior makes psychoanalytic research more urgent.  And I believe we have the opportunity to develop further understanding of ourselves, the new science, the science of mind, provides us with a powerful instrument for further development of the field. If the 20th century was known for the discovery of DNA, genomics and epigenetics, the 21st century will be known for the discovery and understanding of the science of mind. And the promise of establishing such a discipline rests with espousing psychoanalysis with biological sciences, neuroscience and neurobiology. Of course, the concept of scientific understanding of mind is not new. Sigmund Freud in “Beyond the Pleasure Principle” wrote an increase in plasma ACTH and glucocorticoid is a response to stress as adults. Thus, differences in an infant’s interactions with his/her mother–differences that fall in the range of naturally occurring individual differences in maternal care– are crucial risk factors for an individual’s future response to stress. In the same book he further elaborated, “The deficiencies in our description would probably vanish if we were already in a position to replace the psychological terms with physiological or chemical ones….we may expect [physiology-and-chemistry] to give the most surprising information and we cannot guess what answers it will return in a few dozen years of questions we have put to it. They may be of a kind that will blow away the whole of our artificial structure of hypothesis…” Further reference: in his classic paper “On Narcissism” he wrote, “We must recollect that all of our provisional ideas in psychology will presumably one day be based on an organic substructure.” On the cusp of 21st century, we really need a contemporary Freud to orchestrate the disparate parts of the symphony of life, psychoanalysis, biological sciences, genomics, neurosciences and neurobiology to produce the rich symphony of better understanding mind and ultimately life.  Well, we do have a few contemporary Freuds, one is Eric R.Kandel whose most recent book, “The Science of the Mind”, we reviewed in this space. Dr. Kandel who is a Nobel Laureate psychiatrist and professor at Columbia University insists that to save psychoanalysis and pump vigorous life into this elegant field, we need to bring about fusion of the two disciplines of psychoanalysis and biology. Otherwise, there is a wide spread concern about viability of psychoanalysis as a scientific discipline. For example, Jonathan Lear. Others have argued that psychoanalysis and psychoanalytic literature from Freud to Hartmann to Erickson to Winnicott, will be read as a modern philosophical or poetic text alongside Plato, Aristotle, Shake­speare, Kant, Schopenhauer, Nietzsche, and Proust (the literature I went through for preparation of this essay). On the other hand, if the field aspires, as I believe most psychoanalysts do aspire, to be an evolving, active contributor to an emerging science of the mind, then psychoanalysis will survive. There is no doubt that psychoanalysts could and did make many useful and original contributions to our understanding of the mind simply by listening to patients. We must at last acknowledge that at this point in the modern study of mind, clinical observation of individual patients, in a context like “the psychoanalytic situation that is so susceptible to observer bias is not a sufficient basis for a science of mind. Psychoanalysis research is depleted from opportunities to add more knowledge,” so say the late Kurt Robert Eissler (1908-1999) and Hartvig Dahl (1924-2007). Marshall Edelson in his book “Hypothesis and Evidence” offers a persuasive argument that the holy marriage between psychoanalysis and biology must take place: “we must bring psychoanalysis and biology together.”

Psychoanalysis is based on the concept that individuals are unaware of the many factors that cause their behaviors and emotions. These unconscious factors have the potential to produce unhappiness, which in turn is expressed through a score of distinguishable symptoms including disturbing personality traits, difficulty in relating to others, or disturbances in self-esteem or general disposition. As I have suggested earlier, most biologists believe that the mind will be to the twenty-first century what the gene was to the twentieth century. I have briefly discussed how the biological sciences in general and cognitive neuroscience in particular may contribute to a deeper understanding of a number of key issues in psychoanalysis.

As things stand now, psychoanalysis is falling behind biology. Psychoanalysis and biology must marry to reinvigorate the exploration of the mind. I should say at the outset that although we have the outlines of what could evolve into a meaningful biological foundation for psychoanalysis, we are very much at the beginning. We do not yet have an intellectually satisfactory biological understanding of any complex mental processes. In the next century, biology is likely to make deep contributions to the understanding of mental processes by delineating the biological basis for the various unconscious mental processes, for psychic determinism, for the role of unconscious mental processes in psychopathology, and for the therapeutic effect of psychoanalysis.  Biology has the potential to enlighten these deep mysteries at their core.

We have seen that one point of convergence between biology and psychoanalysis is the relevance of procedural memory for early moral development, for aspects of transference, and for moments of meaning in psychoanalytic therapy. We have considered a second point of convergence in examining the relationship between the associative characteristic of classical conditioning and psychological determinacy. Here, I want to illustrate a third point of convergence: that between Pavlovian fear conditioning, a form of procedural memory mediated by the amygdala, signal anxiety, and post-traumatic stress syndrome. Psychoanalysis and cognitive neuroscience would accomplish two goals, one conceptual and the other experimental. We must recollect that all of our provisional ideas in psychology will presumably one day be based on an organic substructure.

The American psychologist best known for his maternal-separation and social isolation experiments on rhesus monkeys, Abraham Maslow, demonstrated the importance of care-giving and companionship in social and cognitive development. He conducted most of his research at the University of Wisconsin-Madison. As an aside, the etymology of the word companionship comes from Latin for bread—PAIN—nutrition.  Another psychologist, Hans Selye, had pointed out as early as 1936 that humans and experimental animals respond to stressful experiences by activating their hypothalamic-pituitary-adrenal (HPA) axis. The end product of the HPA system is the release of glucocorticoid hormones by the adrenal gland.

The prefrontal association cortex has two major functions: it integrates sensory information, and it links it to planned movement. Because the prefrontal cortex mediates these two functions, it is thought to be one of the anatomical substrates of goal-directed action in long-term planning and judgment. Patients with damaged prefrontal association areas have difficulty in achieving realistic goals. As a result, they often achieve little in life, and their behavior suggests that their ability to plan and organize everyday activities is diminished.

What To Do?  What is Next?

For one thing, we must transcend territorial imperative, and learn to speak each other’s language– neuroscientists the language of psychoanalysts, and psychoanalysts the language of neuroscience. For many years both the Association for Psychoanalytic Medicine at Columbia and the New York Psychoanalytic Institute, to use but two examples, have instituted neuropsychoanalytic centers that address interests common to psychoanalysis and neuroscience, including consciousness, unconscious processing, autobiographical memory, dreaming, affect, motivation, infantile mental development, psychopharmacology, and the etiology and treatment of mental illness. The prospectus of the New York Psychoanalytic Institute now reads as follows: “The explosion of new insights into numerous problems of vital interest to psychoanalysis needs to be integrated in meaningful ways with the older concepts and methods as do the burgeoning research technologies and pharmacological treatments. Similarly neuroscientists exploring the complex problems of human subjectivity for the first time have much to learn from a century of analytic inquiry make a significant fraction of psychoanalysts technically competent in cognitive neuroscience and eager to test their own ideas with new methods.” The challenge for psychoanalysts is to become active participants in the difficult joint attempt of biology and psychology, including psychoanalysis, to understand the mind. If this transformation in the intellectual climate of psychoanalysis is to occur, as I believe it must, the psychoanalytic institutes themselves must change from being vocational schools- guilds, as it were- to being centers of research and scholarship.

We have precedence, the Carnegie Foundation commissioned Abraham Flexner to study medical education in the United States. The Flexner Report, which was completed in 1910, emphasized that medicine is a science- based profession and requires a structure education in both basic science and its application to clinical medicine. To promote a quality education, the Flexner Report recommended limiting the medical schools in this country to those that were integral to a university. As a consequence of this report, many inadequate schools were closed, and credentialed standards for the training and practice of medicine were established. To return to its former vigor and contribute importantly to our future understanding of mind, psychoanalysis needs to examine and restructure the intellectual context in which its scholarly work is done and to develop a more critical way of training the psychoanalysts of the future. Thus, what psychoanalysis may need, if it is to survive as an intellectual force into the twenty- first century, is something akin to a Flexner Report for the psychoanalytic institutes.


*The writer is Adjunct Professor of Psychiatry, University of North Carolina School of Medicine at Chapel Hill, Distinguished Life fellow American Psychiatric Association, and Founding Editor and Editor-in Chief, Wake County Physician Magazine(1995-2012). He serves as a Visiting Scholar and lecturer on Medicine, the Arts and Humanities at his alma mater the George Washington University School of Medicine and Health.

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On Epigenetics and the Epigenome

Monday Musings for Monday June 10, 2013

Volume III, No. 21/124


Epigenetics and the Bible—Brain and Behaviour Part II

By Assad Meymandi, MD, PhD, DLFAPA*

This is a follow up—Part II–on last week’s “MM” devoted to Brain and Behaviour. Today we discuss the related important topic of epigenetics.

It seems a bit odd to start a discussion of cutting edge, up to the minute, science of epigenetic with an ancient Biblical story: Genesis chapters 41 through 47 talks about the Egyptian Pharaoh’s dream of “seven years of plenty and seven years of famine…”   Well, here is the relevance of the Old Testament to this cutting edge 21st century science:

Actually, there is a place in northern Sweden called Norrbotten sparsely populated, six people per square mile that has offered astonishing epidemiologic and scientific data which have given birth to the science of epigenetics. In 19th century Norrbotten there were literally seven years of famine followed by good harvest and abundance of food.  For instance, 1800, 1812, 1821, 1836, and 1856 (the year of potato famine in Ireland) were years of total crop failure and famine for the people of Norrbotten. But in 1801, 1822, 1828, 1844, and 1863, there was excellent harvest and abundance of food.  Scientists of renowned Karolinska Institute have taken the painstaking work of tracing the effect of this famine and feast to see how it affected the lives of the children.  With these studies, they have established “life conditions could affect your health not only when you were a fetus but well into adulthood”, concluding that “Parents’ experiences early in their own lives change the traits they passed to their offspring.” The result of the study is that the years parents were well fed; their children grew up to be healthier and physically bigger offspring.

In 1967, when the writer was director of Cumberland county Mental Health Center, applying for a grant for the Head Start program, I used a study by Karolinska Institute which was published in the Acta Physiologica Scandinavica, and Lancet, demonstrating that fetus and fetal central nervous system (CNS) exposed to excess secretion of maternal catecholamines and its metabolites, especially metanephrines, vinyl mandellic acid, and 3-methoxy 5-hydroxy methyl glycol (MHPG) produces babies that are more irritable, scrawny, cranky, susceptible to Attention Deficit Hyperactive Disorder (ADHD), and prone to anxiety, phobia and social maladjustment. The project titled “Intrauterine Head Start” was funded and our findings were published. So, the knowledge of environmental influence on fetus is not new. What is new is the epidemiologic studies from Norrbotten in defiance of Darwin’s assertion in his seminal work “On the Origin of Species”, 154 years old coming November 2013 (I will have another ‘MM’ in November marking the anniversary of this seminal work), that evolution takes place over millions of years. The Norrbotten studies suggest that evolution and environmental influence affect genes in one or two generations. It does not take millions of years. This is heretical. Suddenly, we have evidence that Darwin was wrong! It takes only 25 to 75 years, one to three generations, and not millennia for evolution of genes to take place.

 What is epigenetics?

The exciting science of epigenetics as the name implies is “the study of changes in gene activity that does not involve alteration to the genetic code but gets passed down to successive generations…” It is very much like a switch on the outside of the genetic circuits and genome that influences the behaviors of a gene. The very word epi means above explains that this activity while not an integral part of an organism’s genetic code, from outside or above influences the gene’s activities.  In essence it is like a switch that may turn on or off the activity of a gene.

In Utero Cell Differentiation

A cell in the kidney and the cell in the brain, a neuron, have the exact same DNA. The nascent cell can differentiate only when crucial epigenetic processes turn on or turn off the right gene in utero. This is why studies of identical twins show why one sibling develops asthma or bipolar disorder, even schizophrenia while the other is perfectly normal. The studies from Norrbotten clearly show that because of epigenetic switch you can pass down epigenetic changes in a single generation.

There are several epigenetic drugs on the market. 5-Aza-cytidine (produced by Celgene Corporation is an example of an epigenetic drug that prolongs the life of patients afflicted by severe myelodysplastic syndromes, MDs). By turning a switch that is outside of the genome sitting on DNA, one enhances (turns the gene on) or inhibits (turns the gene off) of DNA’s activities. Cutting edge science is after discovering how to enhance the activities of the good genes and how to silence and discourage the activities of the bad genes. The task is not very difficult.  To chemically turn on the good switch is to introduce a methyl group (CH3) to the side chain of DNA, a very simple procedure. Or vice- versa, remove demethylate (take the methyl, CH3 group off) the compound and suppress the activities of the bad genes. In recent years FDA has approved three other epigenetic drugs that are thought to stimulate tumor suppressing genes. It is hoped that we will find drugs that turn off expression of genes of many diseases including cancer, Alzheimer’s, autism, and schizophrenia, even alcoholism.

In the case of Alzheimer’s disease, where blobs of starch like gunk or amyloids are deposited in the brain interfering with transmission of messages in nerve cells (neurons) causing dementia, by using the instrument and knowledge of epigenomics, it is conceivable to find the switch (the epigenome) that turns off the dumping of amyloid in the neural synaptic clefts. Currently, the National Institute of Health is investing heavily in better understanding and codifying epigenomics. The Human Genome project completed in March 2000 found that the human genome contains approximately 25,000 genes. Private enterprise, and Craig Venter, who won the Nobel Prize in Medicine or Physiology in 2005 bested government bureaucracy and completed the project ahead of the government by two years. We had Venter’s book reviewed in this space a few years ago. Now we need a massive project to identify the epigenome and compile the human epigenomic book. The number of epigenomes far exceeds 25,000 and the cost of completing the project will cost hundreds of billions of dollars. Besides, it will cause a bad case of Darwinitis. We will keep you posted as the science of epigenomics further develops.


*The writer is Adjunct Professor of Psychiatry, University of North Carolina School of Medicine at Chapel Hill, Distinguished Life fellow American Psychiatric Association, and Founding Editor and Editor-in-Chief, Wake County Physician Magazine (1995-2012). He serves as a Visiting Scholar and lecturer on Medicine, the Arts and Humanities at his alma mater the George Washington University School of Medicine and Health.

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