Monday, August 24, 2009

Drug Treatments for Autism: A Quick & Dirty History

A propos of this post at the New Republic, I've decided to do a timeline of all the different drug regimens that have been proposed --- and tested, usually on children --- as potential treatments for autism.

Autism, you were probably already aware, first came into existence as a diagnostic category in 1943, with Leo Kanner's paper "Autistic Disturbances of Affective Contact" in the journal Nervous Child*.

Kanner himself was convinced that his subjects' shared pattern of atypical development was a) a separate phenomenon from "childhood schizophrenia":
The combination of extreme autism ["autism" used here to refer only to that aloofness which makes up part of the developmental pattern being described, not --- yet --- as a name for the overall pattern itself], obsessiveness, stereotypy, and echolalia brings the total picture into relationship with some of the basic schizophrenic phenomena. ... But in spite of the remarkable similarities, the condition differs in many respects from all other known instances of childhood schizophrenia.

First of all, even in cases with the earliest recorded onset of schizophrenia, ... the histories specifically emphasize a more or less gradual change in the patients' behavior. The children in our group have all shown their extreme aloneness from the beginning of life, not responding to anything that comes to them from the outside world. ...

Second, our children are able to establish and maintain an excellent, purposeful, and "intelligent" relationship to objects that do not threaten to interfere with their aloneness, but are from the start anxiously and tensely impervious to people, with whom for a long time they do not have any kind of direct affective contact.
and b) inborn:
One other fact stands out prominently. In the whole group, there are very few really warmhearted fathers and mothers. For the most part, the parents, grandparents, and collaterals [???] are persons strongly preoccupied with abstractions of a scientific, literary, or artistic nature, and limited in genuine interest in people. ... The question arises whether or to what extent this fact has contributed to the condition of the children. The children's aloneness from the beginning of life makes it difficult to attribute the whole picture exclusively to the type of the early parental relations with our patients.

We must, then, assume that these children have come into the world with innate inability to form the usual, biologically provided affective contact with people, just as other children come into the world with innate physical or intellectual handicaps. ... [H]ere we seem to have pure-culture examples of inborn autistic disturbances of affective contact.
Disregarding Kanner's conclusions**, most psychiatrists of the time regarded autism (and schizophrenia, which was still seen as a closely related phenomenon) as a psychological response to family dynamics. Bruno Bettelheim, in particular, popularized the idea of the "refrigerator mother," which was to dominate both lay and professional understanding of autism through the 1950s, and into the '60s and '70s. By the '60s, however, some competing hypotheses had sprung up: There was Bernard Rimland's book Infantile Autism: The Syndrome and Its Implications for a Neural Theory of Behavior, which argued that autism, whether innate or not***, arose from biological rather than psychological causes, and there was Ole Ivar Lovaas, who pioneered the behavioral approach to autism --- i.e., it doesn't matter what causes it, as long as autistic children can be trained to emulate nonautistic ones.

At the same time, a number of drug therapies were being investigated, though with none too precise an idea of the mechanisms involved (see this 1942 article on the use of the powerful stimulant benzedrine in "neurotic" children displaying such eclectic symptoms as depression, "sexual tension," fear, anxiety, aggression, and "hyperkinesis"). The first drug treatment I'm aware of being proposed and tested specifically for autism is LSD (of all things!).

Here, from a 1962 study of the effects of LSD (and a similar compound, methysergide) on fourteen six- to ten-year-old children diagnosed with schizophrenia (but referred to in the article also as "autistic"), is the rationale:
[W]ith awareness of the current interest in LSD-25 as a therapeutic agent because of its psychotomimetic ["psychosis-mimicking," for you English speakers] properties, it occurred to us that LSD might be effective in breaking through the autistic defense, in chronically regressed, retarded, mute, and withdrawn children.
The theoretical interest in LSD as a serotonin inhibitor, with consideration of the possibility that serotonin is in some way related to schizophrenia, further justified this endeavor. Also, since LSD is an autonomic nervous system stimulant, it could be of particular value in treating schizophrenic children, in whom general tissue tone, especially the tone of the vascular system, and the pattern of the autonomic nervous system functions are impaired.
Since this first experiment with LSD was deemed a success, this avenue of research was pursued farther: another 1962 study of LSD in twelve "autistic schizophrenic" children; a larger study of "disturbed" children --- some autistic, some not; some verbal, some not --- coauthored by one of the authors of the study I quoted above; a pair of experiments on a set of very young autistic twin boys combining LSD dosage with a behavioral regime; and two reviews detailing a dozen or so other smallish studies were all published during the mid-1960s.

What was next? Well, in 1979 the Estonian-born neuroscientist Jaak Panksepp published "A Neurochemical Theory of Autism," in which he suggested that --- due to behavioral similarities between autistic children and animals dosed with morphine --- autism may be the external manifestation of an overactive endogenous-opioid system, and thus treatable with opiate antagonists like naltrexone or naloxone.
We recognized that much of the behaviour induced by low doses of narcotics was similar to the major symptoms of those autistic children who suffered disturbances of affective contact, as described by Kanner. Specifically, opiate-elicited symptoms corresponding to those observed in autistic children are as follows: (1) the opiate-treated animal does not appear to appreciate fully physical pain; (2) it does not cry as readily and spontaneously as normal animals; (3) it clings poorly; (4) it does not have a strong desire for social companionship; (5) it can show unusual learning effects characterized by extreme persistence of behaviour in the absence of external rewards (akin to the insistence on sameness by autistic children). The list of similarities suggests that the underlying neurochemical imbalance in autistic children may be excessive, or unusual, activity in their own endogenous brain opiate systems. Such a brain disturbance may block psychosocial development at its earliest stages - leading to failures in language acquisition and other idiosyncrasies in learning.
The opioid-excess theory, particularly its prediction that opiate antagonists would lead to more prosocial behavior in autistic patients, was tested in many, many small clinical trials throughout the 1980s and 1990s. Results of these have been uneven --- some found improvement, some found only modest, patchy improvement (particularly for decreasing self-injurious behaviors), some found no differences, and some actually found that patients taking naltrexone fared significantly worse than those on placebo. Overall, I'd call it a wash.

From the 1990s on, two trends have emerged as the dominant ones in pharmaceutical treatment of autism: antidepressants (specifically, SSRIs) and atypical antipsychotics. Here, too, effectiveness has been spotty, and the antipsychotics particularly can give rise to some truly nasty side effects. The rationale has shifted from seeking to correct any perceived underlying cause of autism (researchers are pretty sure they don't yet know what that would be) to trying to ameliorate some of the less pleasant things often associated with autism: anxiety, depression, obsessive-compulsive behaviors, self-injury, social withdrawal, hyperactivity, aggression and mood lability, among others.

(I also like how the thinking on serotonin's involvement in autism seems to have come full circle --- since the 1960s, higher levels of blood serotonin have been observed off and on in autistic people, and during the era of LSD experimentation, it was supposed that one of the ways LSD might act in a beneficial way for people with autism might be to tamp down this apparent overactivity of serotonin. Now, the approach toward serotonin is to make it more available for use in the brain, not less).

... Well, I guess I lied about the "quick" part of this Quick & Dirty History. Oh well. You win some, you lose some.

*Yes, I think that's a hilarious title for a medical journal.

**It must be pointed out that, even though he clearly states his belief that autism is probably innate, and biological, in origin, and though he often pooh-poohed Freudian notions of psychosexual development, Kanner was pretty ambiguous about this in his public pronouncements. He must have thought the interpersonal style of the autistic children's parents had some relevance, for he saw fit to emphasize it in this 1960 interview in Time magazine:

[T]here is one type of child to whom even Dr. Kanner cannot get close. All too often this child is the offspring of highly organized, professional parents, cold and rational --- the type that Dr. Kanner describes as "just happening to defrost enough to produce a child." The youngster is unable, because of regression or a failure in emotional development, to establish normal relations with his parents or other people.

Kanner then went on to write a second paper in 1949, "Problems of nosology and psychodynamics in early childhood autism," which did posit a role for "a genuine lack of maternal warmth" in causing autism. He seems to have been very much on the fence about the whole refrigerator-mother thing, evolving from believing autism to be innate, to suspecting maybe a chilly mother-child relationship might also be in play, to reiterating that autism is innate and hotly denying he ever suggested mothers might be to blame.

***Rimland later espoused the belief that vaccines could cause autism, so he clearly did not believe strongly that autism had to be genetic and inborn.

Tuesday, August 11, 2009

Also, an Update

I think my computer is dead. Since adding some new music to my iTunes library, I have been unable to turn it on. Every time I do, it goes straight to the Blue Screen of Death.

I suspect I exhausted its hard-drive capacity. I do that sometimes, since I keep the things for years and years and years (my last computer, six years old, had ninety-five percent of its disk space in use!), and now, especially, since I have my extensive music collection stored in there.

(I hate how technology reproduces itself; you get one new thing, and sooner or later you find you have to get a lot more stuff to support it. Example: my CD player, which I had for ten years, quit working a couple years ago, so I got an iPod to replace it. Okay. So now all my CDs go onto my computer, where they can be in my iTunes Library. But, oh no! It turns out I had a ton of music. And now my friends can give me music more easily, in the form of giant file transfers. So now I am eating up disk space like a cyber-Galactus, when previously all I had required of a computer was that it allow me to write, surf the Internet and play old computer games. Nothing fancy. Now it seems I need, if not a massively more sophisticated computer, an external hard drive or two).

Anyway, that is why you haven't seen any new posts on this blog in a while.

Comparing Feminist Dystopias

In this post from two months ago, Red Megaera* says:
What I'd really like to see is a feminist dystopian novel about the creeping incursion of pornography into everyday life and its dangerous impact on women's freedom and autonomy. Margaret Atwood's acclaimed novel The Handmaid's Tale published in 1985 was written partly as a critique of Catharine MacKinnon and Andrea Dworkin's Antipornography Civil Rights Ordinance which proposed to treat pornography as a violation of women's civil rights, and allowed women harmed by pornography to seek damages through a lawsuit in civil court. It also stands as a critique of radical feminism in general, particularly its analyses of intercourse and patriarchal beauty practices. Atwood's Gilead is a dystopian society in which alliances between radical feminists, religious fundamentalists and other social conservatives have led to the overthrow of the United States government by a repressive, totalitarian society. The implications for women are horrendous. The Handmaid's Tale is a wonderful piece of literature, but I'm not sure about its politics. I've always thought it would be far more instructive at this time, in this culture to write a radical feminist dystopian novel which critiqued pornography, cosmetic surgery and the mass media. Heaven knows you don't have to look far for inspiration. ... [W]hat are totalitarian theocracy and capitalist patriarchy if not different sides of the same coin?
Since my copy of The Handmaid's Tale is being lent out at the moment, I won't be able to quote from it --- and I remember next to nothing of the final chapter, with the future academics discussing the hows and whys of Gilead's coming into existence, so it may be that Atwood mentions a role for radical feminism there --- but I have read it multiple times**, and had a rather different view of it than Megaera has.

I don't really see a critique of radical feminism in The Handmaid's Tale because I don't remember any representation of radical feminism in that book at all. I saw plenty of examples of women collaborating with patriarchy, though: Serena Joy, former televangelist and wife of the Commander, who preached submission and domesticity for women but finds herself miserable living that life herself; the Aunts, whose job it is to prepare fertile women for their new lives as Handmaids, and who often use their power over other women to vent their own considerable frustrations; the unknown partner each Handmaid must have to carry out her everyday errands --- neither woman can trust the other, so each feels compelled to put on a show of religious piety and righteous patriotism, which of course feeds the other's reluctance to confide in her; and Janine/Ofwarren, the one character in the book who really does believe in Gilead, and in the rightness of her place in it.

There is one passage where I can see the critique Megaera is talking about --- the idea that radical feminists, in seeking to eliminate sexual exploitation and oppression of women, are easy prey for the far more powerful religious conservatives who seek to eliminate women's sexual freedom --- where Aunt Lydia is trying to convince her charges to see the bright side of their new situation by contrasting "freedom to" (go where you please, wear what you please, have sex with whom you please) with "freedom from" (rape, street harrassment, abduction, murder). This is, of course, a fundamentally conservative analysis of violence against women: by existing in public, women make themselves prey to predatory men; therefore, every woman should belong to one particular man, who will protect her from all the others.

So perhaps the absence of radical-feminist ideas or social reforms --- even in perverted form --- reflect the likely outcome of a radical feminist/social conservative alliance, which would be the complete annihilation of the radical-feminist element. Indeed, those women who cannot or will not adapt to the new regime are exiled from it, to the radiation-contaminated "Colonies."

The whole structure of Gilead also depends on a practice to which radical feminists are opposed: prostitution. Men's loyalty is assured by bribing them with women --- they get a wife once they've advanced a certain distance up the ranks, and if they reach a particularly high status, they also get a Handmaid, to assure that they have issue. Additionally, there are clandestine houses of ill repute, called Jezebel's, where high-status men can go to meet, drink with, and bed those "loose" women who were too rowdy to become Handmaids but were not cast off to the Colonies.

So, while Gilead is certainly a feminist dystopia, predicated as it is on the reproductive enslavement of women, it's not necessarily what Red Megaera has in mind as a radical feminist dystopia, although I'm willing to give it a lot more credit in that regard due to the regime's tacit acceptance of, and reliance on, prostitution.

I do know of another feminist dystopia that might fit the bill more closely, though: in Sheri S. Tepper's Beauty, the time-traveling heroine discovers a horrible future that starts coming into being in the 1990s. That future is gray, ugly, cramped and overcrowded, with a centralized authority crowding hordes of people together into hivelike apartment complexes to free up the biggest possible expanse of ground on which to grow food for them all. Everything is strictly utilitarian and barely adequate for ensuring everyone's mere survival, to say nothing of making them happy. The people change with their environment; they become mean, jumpy, quick to anger, afraid of each other, small-minded and nihilistic.

While Tepper makes it clear that what leads human society down this path is a complex, deep-rooted and pervasive network of cultural trends (see the passage quoted in this post), she does draw special attention to growing societal misogyny as part of the process. Aesthetic degradation is the other important indicator for her --- beauty, both natural and man-made, is vanishing from the world --- and both of these themes show up in the superabundance of really violent, gory pornography in her dystopia, and in the lead-up to it. One of the characters Beauty meets on her first trip into the late twentieth century is a novelist, Barrymore Grimes, whose work she can barely stand to read but who is wildly popular in his own time.

That's probably the most striking way in which Tepper's dystopian vision differs from Atwood's --- rather than be tightly (if hypocritically) regulated and harnessed for the benefit of a totalitarian state, the desire of men to exploit women sexually is given a free rein. While the people in Tepper's dystopia may be losing almost all of their other freedoms, they retain the freedom to do whatever they want sexually, which really means the men retain the freedom to do whatever they want to the women. Other than that, their visions are surprisingly similar, given the huge differences in style and substance between their books. Like Tepper, Atwood sets her dystopia on a ruined, poisoned Earth; both writers critique the reproductive enslavement of women --- Atwood explicitly, and Tepper by making overpopulation, which she links to society's restriction of women to the reproductive role, and its denial of her right to self-determination even within that role, the driving force behind her dystopia; and both blame religion for its role in upholding said exploitation.

*Because I'm a Greek-mythology geek, I pay special attention to bloggers who take their pseudonyms from that canon. I've noticed two radical-feminist bloggers using the names of Furies --- the aforementioned Megaera and Allecto. If anyone has seen the third Fury, Tisiphone, anywhere around the Internet, I'd appreciate a link.

**Four or five, maybe? Definitely more than three, but not a huge number of times. (The most-read book by me is probably Dune, which I've read maybe seven or eight times).