Monday, March 26, 2007

First Birthday

March 26 is the first anniversary of Just Noticeable Differences. I was shocked to see that the year went so fast. Now that I'm approaching 60, time just flies by.

It has been an interesting year. Blogging has been more difficult than I thought. I had forgotten (or repressed) the experience of writer's block from when I was writing my dissertation. Fortunately, unlike my dissertation, I can get up and leave the computer until my brain reconnects.

Blogging has been very rewarding; it's helped me met some interesting people. The attention I've gotten from readers has been gratifying and a bit surprising. One reason I had named myself Free Operant was because I wasn't sure I was going to get any readers. As a result, I thought, most of what I was writing would be free operants. I'm happy to find out that some people have indeed been reading what I write. Thank you all.

One interesting thing I've found in this year. Blogging anonymously has its own set of limitations, some positive and some negative. On the positive side, I realized it isn't fair for me to attack people from behind a shield of anonymity. I've tried to eliminate snarkiness when responding to people who write under their own name. I may disagree with them, but I should do it respectfully. Their reputation is out there and mine isn't. I think that limitation has made me a better writer. It's easier to be snarky than to be respectful and still disagree.

On the negative side, I also decided that I would create a wall between my real person and Free Operant. Free Operant will never comment on what I do under my real name, and I will never comment on Free Operant under my real name. This is proving frustrating because I am working on another project under my real name that I can't reference.

Finally, even with my anonymity, I would love to discuss events that have happened in therapy, but I can't. A recent article addressed that particular pitfall for medical doctors who blog. I think confidentiality is too critical to come even close to breaching it. Before I ever wrote my first post, I decided to put up a "fence around the law," to use a Talmudic phrase, and never write about anything that ever happened in therapy. There was one point where I was going to post a comment on another blog about an event occurring 30 years ago in therapy. I didn't. It killed me because it was hysterically funny, but I didn't post it.

Overall, it's been a good year. I look forward to many more.

Saturday, March 17, 2007

A Passover Story

We are coming up on Passover, which is a joyous time of year. I thought it would be fun to break away from the serious stuff and post this story, which I wrote last year.

* * *

Passover is a family holiday, where, over a sumptuous meal, we read the story of the exodus from Egypt. It is a very happy time and most Jews have very good memories of family seders.

The text of the story is contained in a book called the Haggadah. Along with the text, the Haggadah also contains commentaries and prayers. It used to be, the only Haggadah you could find was distributed by Maxwell House Coffee. It contained the traditional Hebrew text, along side of a translation written in King James English. Today, there are many different versions available, written with new text and translation into modern English.

The modern Haggadahs written by non-orthodox movements have eliminated a small section from the traditional text. It contains an interplay between three Rabbis, Rabbi Akiva, Rabbi Eleazar, and Rabbi Yose (pronounced, “Yo-say”), in which they recount the number of plagues visited on the Egyptians.

In Exodus we are told there were ten plagues, but through Talmudic logic and deduction, Rabbi Yose concluded there were fifty plagues visited on the Egyptians at the Red Sea. Rabbi Eleazar deduced there were forty plagues visited on the Egyptians in Egypt, and two hundred plagues visited on the Egyptians at the Red Sea. Rabbi Akiva deduced that in Egypt there were fifty plagues, and at the Red Sea there were two hundred and fifty plagues.

For years, I read this as Talmudic pilpul (hairsplitting), and was not sorry to see it go in our current Haggadah. However, I've come to realize that the Haggadah doesn't tell the full story, and I think there's an important message in this commentary.

In the Jewish tradition of the Midrash, I've taken liberties and fleshed out the story. I've interspersed the traditional text in the story below, signified by boldface. The entire text from the traditional Hagaddah is there. But first, we start with some background.


Rabbi Akiva was the dominant thinker of his day. He was not only a great Rabbi, but he was also a leader in the resistance against the Romans. He was later martyred by them in a particularly gruesome manner. So, Rabbi Akiva was not your typical locked-in-the-Yeshiva Rabbi. He was a very smart and very tough guy. Rabbi Eleazar was a contemporary of Akiva's. Not as brilliant, but no slouch, either. Rabbi Yose was one of Rabbi Akiva's students, conceivably one of his best.

In those days, there were no Haggadahs and the recounting of the Exodus was spontaneous. Everybody did it differently. Being invited to a seder with Rabbi Akiva would have been a great honor. The learned, the wealthy, and the powerful would all have been there. His seder would have been a great event, with everyone hanging on Akiva's words as he told the story of the Exodus in his own way.

The Scene

Rabbi Yose was thrilled to be invited to Akiva's seder, and wanted to impress him with his intellect. He spent weeks thinking about the Exodus, studying the Torah, trying to find something there to impress Akiva. On the night of the seder, he was ready.

There were many people present at Akiva's seder. The table was set, and the master expounded on the Exodus with incredible brilliance. Rabbi Yose was in awe of him and almost forgot what he prepared.

It is traditional at the seder to drink four cups of wine, which always adds to the merriment. Akiva seemed bent on blurring the distinction between a cup and a barrel. As the seder wore on, Akiva began to nod off. There was a lull, and Yose realized that this was the best chance he was going to have. He hoped he could wake up Akiva by speaking loudly. Raising his voice, he asked,

How can we say that the Egyptians were smitten with ten plagues in Egypt, and in the Red Sea, fifty plagues?” The room was silent. He hoped Akiva was listening. He continued,

Of Egypt, it is said the magicians told Pharaoh, 'This is the finger of God.' But of the sea, it is said, 'And Israel saw the mighty hand with which God smote the Egyptians, and believed in God and believed in Moses, God's servant.' If one finger smote the Egyptians with ten plagues in Egypt, it may be deduced that in the Red Sea they were smitten with fifty plagues.”

The others at the seder were awestruck. They applauded and cheered. They congratulated Rabbi Yose for his insight.

Except for Rabbi Akiva, who was snoring quietly.

Except for Rabbi Eleazar, who was thinking, “Pretty clever, Junior, but not clever enough. Time to put you in your place.” Rabbi Eleazar thought for a moment more. Then he said,

How can we say that every plague, which The Most Holy, blessed be the One, brought upon the Egyptians actually consisted of four different plagues? Because it is said God was angry at the Egyptians, sending them wrath, indignation, trouble, and a band of evil angels. Wrath is one; indignation is two, trouble is three, and a band of evil angels is four. Hence, we can deduce that while in Egypt they were smitten with forty plagues, and in the Red Sea, two hundred plagues.”

The onlookers at the seder applauded more. They knew they were watching a rabbinical smackdown in progress and wanted to hear how Rabbi Yose would respond. Unfortunately, Rabbi Yose's mind had gone blank and he was thinking that discretion was the better part of valor. He was about to concede gracefully, happy that Rabbi Akiva was asleep. Then came a snuffle and a snort from the head of the table.

Rabbi Akiva opened his eyes and said, “How can we say that each plague which The Most Holy, blessed be the One, brought upon the Egyptians in Egypt consisted of five plagues? Because, it is said, “God sent against the Egyptians the fierceness of God's anger, wrath, indignation, trouble, and a band of evil angels. The fierceness of God's anger is one, wrath is two, indignation is three, trouble is four, and a band of evil angels is five. Hence, we deduce that while in Egypt, the Egyptians were smitten with fifty plagues, and in the Red Sea, two hundred fifty plagues.

All of the onlookers exploded into cheers and applause. Rabbi Eleazar and Rabbi Yose looked at each other, shrugged their shoulders, raised their glasses to Rabbi Akiva, and both took a long drink of wine. Rabbi Akiva took another drink of wine and slowly slid under the table.

The Moral

The Haggadah says that all who recount the story of the Exodus are worthy of praise. This story teaches that no recounting is complete without joy, humor, and some friendly competition.

Saturday, March 03, 2007

Father's Age and Serious Mental Illness

I have recently been corresponding with a reader concerning paternal age and schizophrenia. Schizophrenia is a serious mental illness where the individual suffers from delusions and hallucinations. Thought processes are often disturbed. (It is not a "split personality.") Schizophrenia is widely considered to be a neurobiological disorder, caused by a combination of genetics, the prenatal environment, and environmental stressors.

Surprisingly, the New York Times, which is becoming my favorite psychological journal, also devoted an article to the issue, entitled, It Seems the Fertility Clock Ticks for Men, Too. The article summarizes research on the relationship between the father's age and the risk of birth defects:

Geneticists have been aware for decades that the risk of certain rare birth defects increases with the father’s age. One of the most studied of these conditions is a form of dwarfism called achondroplasia, but the list also includes neurofibromatosis, the connective-tissues disorder Marfan syndrome, skull and facial abnormalities like Apert syndrome, and many other diseases and abnormalities.

“We have counseled for quite a long time that as paternal age increases, there is an increased frequency in new mutations,” said Dr. Joe Leigh Simpson, president-elect of the American College of Medical Genetics.
Both autism and schizophrenia have been tied to paternal age, dating back to research published in 2001. In an interview with Medscape, Dr. Dolores Malaspina described her research, also cited in the New Y0rk Times article. (Also check here, here, and here.) Malaspina and her colleagues performed several large-scale studies of demographic data collected in Israel both through the public health system and the Israeli Army. She stated:
We found that paternal age explained over a quarter of the risk for schizophrenia in the population. At the time, people were skeptical. But the findings have been replicated many times now, and not a single study has failed to find this strong relationship between father's age and the risk for schizophrenia. And at this point, other explanations for the relationship have been ruled out, including social factors in the family, prenatal care, and parental psychiatric ailments. There simply seems to be a relationship between paternal age and schizophrenia risk.
Malaspina described the proposed mechanism for this risk:
When Penrose found that paternal age predicted new human genetic diseases, he proposed the Copy Error Theory. He said that each time the spermatozoa are copied there's an opportunity for a new mutation. Sperm cells divide every 16 days after puberty, so the DNA in the sperm of a 20-year-old father has been copied 100 times, but sperm DNA from a 50-year-old father has been copied more than 800 times.
Think of sperm replication as a copy machine. Each time the a copier makes a copy, slight imperfections are created. If you copy the original each time, you never notice a change. But, if you make a copy of a copy, of a copy, of a copy, ad nauseum, you get the familiar spots, streaks, and fading. Human sperm is created from copies of previous generations of sperm, not from copies of an original template in the individual. The DNA in the sperm of a 20 year old has been copied 100 times, while the sperm DNA from a 50 year old has been copied more than 800 times.

Evolutionarily, this is advantageous because it provides for more variation in the offspring. But, with increased variation, comes the risk of negative, as well as positive, traits being transmitted. These include mental retardation and mental illnesses, notably schizophrenia and autism.

The Times cites critics of this research who argue the truism that correlation does not prove causality. That argument is certainly true, but there is more to the research than just correlation:

First, it is also a truism that, to show a cause and effect relationship, the cause must precede the effect. In the case of paternal age that is certainly the case. Paternal age obviously precedes conception.

Second, other explanations must be ruled out. Malaspina and her colleagues controlled for a number of environmental variables, including an adverse fetal environment, maternal age, and psychosocial stressors. Of course, we can never rule out all possible explanations, so we can only rely on a preponderance of evidence. But overall, the evidence favors paternal age.

Third, to argue causality, there must be a plausible mechanism moving from cause to effect. Copy error theory is certainly plausible. It is consistent with known biological processes.

Finally, to argue for causality, there has to be a convergence of data which is consistent with the explanation. Malaspina presents the following data:
  1. The risk of schizophrenia rises with age, from .007% for fathers under 25; to 1% for fathers 30 -35, and 2-3 % for fathers 50 and older;
  2. The risk factors are consistent across world cultures;
  3. It's consistent with the data on other genetic diseases, as I mentioned above; and
  4. Inbred mice show increasing behavioral disturbances with increasing paternal age.
All of this said, it is important to note that increased paternal age increases risk of schizophrenia, autism, and other genetic diseases, but there are other causes as well. Advanced paternal age is neither necessary nor sufficient for the development of schizophrenia. It is a significant risk factor, and one that can be avoided.

Malaspina argues against warning older men away from having children:
I would personally not discourage anyone from having a child at any age. People weigh their own risks. For the offspring of older fathers, the risk of schizophrenia is about 3%. That means that 97% of the offspring do not have schizophrenia. Other cognitive diseases linked to paternal age include mental retardation of unknown etiology and Alzheimer's disease, and there is a strong relationship between paternal age and autism.
I'm not sure I would completely agree with her. Given this data, I would urge an older man to think twice about parenthood, as I would urge an older woman to think twice. Having a family member with schizophrenia, autism, mental retardation, or other disorder can be a terrible burden for both parents and siblings.

According to one study, about a third of patients with schizophrenia make a full recovery. About one third make a partial recovery, where medication works effectively to manage their symptoms. The remaining one third remain very seriously ill. So, the risks of having an impaired child are small, but the cost can be tremendous, and should not be taken lightly.