On 25 Mar 2008 at 10:40, Bourgeois, Dr. Martin wrote:

> Here's the abstract of the Caspi study I mentioned, published in Science in 
> 2003:
> 
> In a prospective-longitudinal study of a representative birth cohort,
> we tested why stressful experiences lead to depression in some people
> but not in others. A functional polymorphism in the promoter region of
> the serotonin transporter (5-HTT) gene was found to moderate the
> influence of stressful life events on depression. Individuals with one
> or two copies of the short allele of the 5-HTT promoter polymorphism
> exhibited more depressive symptoms, diagnosable depression, and
> suicidality in relation to stressful life events than individuals
> homozygous for the long allele. This epidemiological study thus
> provides evidence of a gene-by-environment interaction, in which an
> individual's response to environmental insults is moderated by his or
> her genetic makeup. 
> 
> Influence of life stress on depression: Moderation by a polymorphism in the 
> 5-HTT gene.
> Caspi, A. et al> Science. Vol 301(5631), Jul 2003, pp. 386-389
>

OK, I seem to be taking a beating on this one, and perhaps I deserve it, 
as I have discovered that my thinking on the matter is muddled. Yet in my 
own defense, I should say that I asked Mike for examples. I didn't say 
there weren't any (although, truth be told, I thought there were only a 
few good ones).

Martin's cite is a good one. I've tried to clarify the issue by dipping, 
once again, into Judy Harris' book _No Two Alike_. I find there that she 
agrees that certain kinds of gene-environment interaction do occur quite 
commonly (see around p. 58), as per her example of the child with musical 
genes who is born into a musical environment and becomes a Mozart, but a 
child without those musical genes born into the same family who grows up 
to have no facility for music.  Then she mentions the Caspi study, 
describing it as showing that a child with genes predisposing to 
depression brought up in a stressful environment becomes depressed, but 
not a child who lacks those genes.

She calls this a "sensitivity" type of interaction, because there are 
always main effects as well--that is children with musical genes become 
more musical overall than children without; children with depression 
genes become more depressed overall. 

She has no problem with the sensitivity type of interaction. Referring to 
a talk by a critic of her theory, she says "Maccoby had hit upon the 
three areas--IQ, criminal behavior, and mental illness--where reliable 
interactions have been demonstrated. None of these interactions, however, 
are found in the absence of main effects". (p. 59)

It's the claims for a gene-environment interaction effect in the absence 
of a main effect (which, she says, would disconfirm her theory)  that get 
her goat.  These claims are often thrown at her, she says, but when she 
goes in search of them, they disappear. She calls them "vaporware". My 
muddle comes in in not sufficiently appreciating the difference between 
the two types of interaction, at least when I'm left without a minder. 
Like Barbie, I have to say "This stuff is hard!"

The study I thought I was going to receive from this list is another   
she classifies as a sensitivity type of gene-environment interaction.  It 
was also the work of Caspi et al in Science, this time in 2002.  Harris 
describes it as finding that a particular gene which produces low amounts 
of the enzyme MAOA increases antisocial behaviour in adulthood, but only 
if the kids were maltreated as children. She deconstructs it, but you'll 
have to check her book to see what her criticisms are. But with the 
advantage of writing two years later than her, I know something she 
didn't. A major attempt to confirm this finding has failed (Hulzinga et 
al (2006). In a review of the research area, Morris et al (2007) had this 
to say about it:

"Replication attempts have yielded mixed results; some studies have 
reached similar conclusions, another reported a "non-significant trend" 
toward the Caspi conclusions, and yet others completely failed to 
replicate the findings, including the gene-environment interaction. 
Moreover...at least two studies found a contradictory _inverse_ 
relationship." [references omitted]. 

So it remains to be seen how the later Caspi work on the 5-HTT 
interaction fares. In the meantime, I'm going to work hard on my 
understanding of sensitivity and non-sensitivity type of interactions.

On one point, I stand firm.  I disagree with Joan Warmbold that orphanage 
studies overwhelmingly show that bad rearing early in life causes bad 
outcomes. These studies are hopelessly confounded by the fact that the 
children constitutionally least prepared to do well (either through fetal 
and early life malnutrition and disease, or genes for low IQ) are the 
most likely to end up in an orphanage, and the least likely to leave it. 
I once praised these studies, but I see now that they are quasi-
experimental, and not to be trusted.

As it happens, a study (Nelson, 2007) was just published on Romanian 
institutionalized kids. What makes it unique is that the kids were, 
believe it or not, _randomized_ to either institutional or foster care, 
making this a true experimental study.  Foster care kids did better 
cognitively. But the children were only  4-5 years old when assessed, and 
the differences may fade with time, as they often do. 

I'd like to stay and chat longer but family matters call. So I'll concede 
the last word to Mike and to Martin and to Joan, if they want to take it. 
I'll remain as defenseless as that poor goalie who got pounded by the son 
of hockey coach Patrick Roy last night.  

Stephen

References

Nelson, C. (2007). Cognitive recovery in socially deprived young 
children: the Bucharest Early Intervention Project. Science. 2007 Dec 
21;318(5858):1937-40.

Morris, C. et al (2007). Deconstructing violence. GeneWatch, 20, No. 2 
March-April

Caspi, A. et al (2002). Role of genotype in the cycle of violence in 
maltreated children. Science, 297, 851-854.

Caspi, A. et al (2003). Influence of life stress on depression: 
modulation by a polymorphism in the 5-HTT gene. Science, 301, 386-389.

Hulzinga, D. et al (2006). Childhood maltreatment, subsequent antisocial 
behaviour, and the role of monoamine oxidase A genotype. Biological 
Psychiatry, 60, 677-83. ["Conclusions: findings from this general 
population sample could not confirm the hypothesis that MAOA moderates 
the relationship between adolescent maltreatment and adoilescent or adult 
antisocila behavior"]











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Stephen L. Black, Ph.D.          
Professor of Psychology, Emeritus   
Bishop's University      e-mail:  [EMAIL PROTECTED]
2600 College St.
Sherbrooke QC  J1M 1Z7
Canada

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