Dr. Grossi's Blog
Everyone has had the experience of watching a film such as Indiana Jones surrounded by snakes or of Dr. No where a spider crawls up James Bond arm or of someone cutting themselves and of putting oneself in the other's shoes and experiencing their feelings. We size up friends, acquaintances, and learn from others by using this social skill. How is this accomplished?
In 1992 Giacomo Rizzolatti and colleagues were studying macaque monkeys by implanting electrodes in their ventral premotor cortex used to control hand and mouth movements. Serendipitously as a member of the team reached for his own lunch he noticed that the monkey's neurons began to fire in the premotor cortex,i.e., the same firing pattern when the monkey made the same hand movement. Yet, the monkey was just sitting there. This was the initial discovery of mirror neurons - neurons that fire when a certain action is performed and also when that action is observed.
This is an extraordinarily important discovery. More recent studies have broadened the findings that neurons mirror movement to neural activity mirrors intentions, sensations, and emotions. Abnormalities of the mirror system are found in autistic individuals who are impaired in the social fields - understanding and empathizing with others. Might this also yield insight into other disorders with social impairment or even provide a new theory of the development of language?
The human frontal region is homologous to the F5 region Rizzolatti et.al. studied in the macaque monkeys. He has postulated that mirror neurons in this area could improve the imitation of hand and mouth movements used in communication. This is important in an infants' acquisition of language. Iacoboni and colleagues at UCLA have shown that listening to speech activates those neurons used to produce speech. Additional work by both groups has shown a different pattern of mirror response depending on the intention of the action such as grasping food to eat versus grasping food to place in a container. It was also shown that this pattern was identical when the monkeys observed the actions. This suggests that mirror neurons take into account the context in predicting the next action.
Iacoboni and colleagues have also demonstrated that certain areas of the frontal cortex are activated when looking at or making emotional facial expressions. Other investigators, Keysers and colleagues, put masked subjects into a fMRI scanner and exposed them to noxious odors and they found that the insula was activated. This same area was activated when subjects were shown pictures of people displaying the emotion of disgust.
All of these observations are central to developing more complete ideas about empathy, imitation, language development, and the actions and emotions of others.
Alternative medicine includes medical practices and products that are outside the ambit of standard Western medical concepts and practice. Most of these treatments are readily available and commonly used because many people prefer these treatments to standard treatment. I plan to discuss commonly used supplements to antidepressant or mood stabilizing treatment.
The four most commonly used supplements are:
- Omega-3 fatty acids
- St. John's wort
- SAMe (S-adenosyl-L-methionine)
St. John's Wort (Hypericum perforatum extract) has been used extensively in Europe and has been exhaustively studied both as a stand alone antidepressant as well as an add on to conventional antidepressants. Probably the best studies were placebo-controlled with a large n. Those did not show St. John's wort separating from placebo. It also acts as an inducer of Cytochrome P450 3A4 isoenzyme system and thus has an impact on other concomitantly used medications especially oral contraceptives, hormone replacement therapy, retrovirals and more. In addition, there is evidence suggesting that sunlight promotes cataract formation. Therefore, anyone taking St. John's wort should not use light treatment for depression. I therefore do not recommend its use because of lack of efficacy in moderate to severe depressions and because of its many interactions.
SAMe (S-adenosyl-L-methionine) has been studied and has been found to be effective as an antidepressant but the studies are not generally considered to be definitive because of small n, unstable preparations and most comparisons against older antidepressants. Theoretically this should work because as a donor of methyl groups, it should increase the supply of the neurotransmitters dopamine, serotonin, and norepinephrine. Most side effects are gastrointestinal but anxiety and insomnia have been reported. This was tried in the office in the past without mixed results. A new study in the August 2010 issue of the American Journal of Psychiatry by Papakostas and colleagues report on its adjunctive use in the treatment of 73 patients with major depression. They found that response was more likely with adjunctive SAMe than placebo and remission was more likely as well. I think we will try it again as a adjunct.
Folate and related compounds have been demonstrated to be effective as adjuvant in the treatment of major depression. There are some polymorphisms in about 15% of the population which impair the methylation process and in those individuals methylfolate is the more effective agent.
The practice of psychiatry is both art and science. The true romance of the masterful psychiatrist is the skilled application of both art and science to the problems of his/her patients in order to resolve them. While my prior blogs were on the science side of the ledger, this and a number of following blogs will have entries on both sides of the ledger and will span the pre-scientific and the post scientific era, before and during the Age of Enlightenment in which we live.
In the early sixteenth century the Protestant Reformation was challenging Catholic dogma and authority. Questions regarding the meaning of scripture or knowing and understanding many phenomena became acute. It was an age of intense uncertainty. Newton, Leibnitz, Gallileo, Locke, Darwin, Boyle, and Mendel had not been born and their insights into the workings of the world were unknown. Into this uncertain environment where witchcraft, astrology, and superstition prevailed, came Michel de Montaigne in 1533. He looked at the world with profound philosophical skepticism expressed mostly in his influential book Essays written in an anecdotal, pungent, frank and personal style which appealed to William Shakespeare who was born in 1564 and who studied the Essays when he was a young man. Indeed Montaigne is almost quoted in The Tempest.
Shakespeare wrote his long poems in the early 1590s and his plays thereafter until 1612. Othello was written in 1602 and best exemplifies what has become known in the skeptical philosophical tradition as the problem of the other minds. As usual, Shakespeare's insights have continuing relevance even today and are often described as "timeless works". Simply stated we can observe others' behavior but we can only infer what is in their mind. Epistemological problems arise out of this basic cognitive structure. In a later blog I will attempt to connect the insights offered by the naturalist William Shakespeare to theory of mind coined by Premack and Woodruff in their paper on chimpanzees. I hope also to present some connections to linguistic origins and development and present relevant insights from ethology, and neurophysiology.
First, the play! For those who would like to refresh your recall of the plot go to Othello. On the surface it is a story of marriage, jealousy, betrayal, villainy, manipulation, race and murder. Under the surface however is an even more primitive story that is terrifying in its implications. I have an undisclosed, private part and a public observable part as does the other. To know the undisclosed intentions and thoughts of the other requires an inference that they are honorable and can be trusted. Iago is acutely aware of this discrepancy and the resident power for deception that is inherent. Language itself expands the possibilities for concealment because language can be used to obfuscate and mislead rather than to reveal and disclose. The human solution that has evolved is trust which is the basis of forming beliefs in others and is the basis of social interactions. Shakespeare states the issue through Iago when Othello asks Iago "By heaven, I'll know thy thoughts." and Iago responds "You cannot, if my heart were in your hand; Nor shall not whilst 'tis in my custody." In short, even if a person has access to the heart of a person, he does not have access to his mind because it is in his custody. He is foreshadowing the secrecy of his mind that will allow him to manipulate and control the feelings and thoughts of others and is thus the source of power. He will use this power to level the playing field with the general, Othello.
The stage for revenge is set out early in the play during the conversation between Iago and Roderigo. Iago reveals that he hates the Moor because he was passed up for a promotion in favor of Cassio who has mere book knowledge of war whereas Iago has proved himself in battle. He is insulted that his cognitive abilities and understanding of war have not been appreciated by Othello and thus he must be punished and shown to be inferior to Iago in this mental battle ahead. He will have an external honest and dutiful self and an internal, undisclosed, lying, scheming, and evil self. Roderigo and Iago rouse Brabanzio, Desdemona's father, a Venetian Senator, by shouting that his daughter is "covered with a Barbary horse" and his "daughter and the Moor are now making the beast with two backs". (two pungent metaphors both primitive and animalistic and bestial). Iago goes on to say that I must show out a flag and sign of love, Which is indeed "but sign." It is all for appearance sake.
Brabanzio goes to Othello and reveals that he has been deceived by his daughter. Later Iago cleverly reminds the trusting Othello of this fact before he suggests that Desdemona has been unfaithful. He brings Cassio into suspicion and there is an internal battle in Othello's mind for what he should believe about his wife. He then demands "ocular proof" to end his uncertainty and settle his doubt. Iago then responds that he slept in a bed with Cassio and Cassio muttered Desdemona's name. Then Iago lures Cassio into giving Bianca, a courtesan in love with Cassio, Desdemona's handkerchief which was a gift from Othello. Othello interprets this as a gift from Desdemona to her lover Cassio. Othello's jealousy (the green-eyed monster) has taken over his reason and he declares "I will chop her into messes." Jealousy distorts our reasoning and lowers the bar for convincing evidence needed to form belief.
Just as people in a psychiatric practice are highly individualized in terms of their presentation as well as their response to verbal and psychopharmacological interventions, each character in the play is sharply different that the other characters. What is even more important is the depth of error in reading the other characters. Othello cannot distinguish reality from what seems to be reality. He accepts Iago at face value. Desdemona sees Othello as trusting and not jealous. Othello sees Desdemona as unfaithful and lying whereas she is honest and faithful. Emilia, Iago's wife, is completely taken in by her husband until the end. These examples of interpersonal ignorance or psychological misjudgment are the direct result of the cognitive structural problem which I have been referring to as the problem of the other minds.