Tag Archives: MAOA

Bouncing off a current in philosophy of biology that wants to make claims about causal contributions

This post bounces off a current in philosophy of biology that wants to make claims about specific causal contributions of different factors, especially with respect to genes and heritability.
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50 whys to look for genes: 15. Personalize medical treatment

Personalized medicine … in its simplest form, involves the use of genetic information to predict which patients with a given condition (e.g., heart arrhythmia) will benefit from a particular drug treatment (e.g., beta blockers). More ambitiously, personalized medicine promises to inform people of their heightened vulnerability (or resistance) to specific environmental, dietary, therapeutic, and other factors early enough that they can adjust their exposure and risky behaviors accordingly.

Complications

[T]he path to personalized medicine will involve a phase in which large numbers of people are treated according to their group membership. Moreover, this phase may not be a passing one.

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50 whys to look for genes: 14. Specific genes have effects on psychology that depend on upbringing

A 2002 Science article reports on antisocial behavior in adults in relation to the activity of monoamine oxidase typeA (MAOA) and childhood maltreatment; MAOA deficiency is a strong predictor of aggressive behavior only when the child has also been maltreated (Caspi et al. 2002).

Complications
“Some meta-analyses have cast doubt on the generality of the Caspi and Moffitt results (Risch et al. 2009; see Morris et al. 2007).”
However, “in order to illustrate the approach and to raise pertinent issues, the discussion that follows uses the 2002 study. The issues raised apply to the overall research program of examining interaction between measured genetic and environmental factors even if these particular 2002-3 results turn out not to be widely replicated.” Continue reading

The path to personalized medicine may run through social stereotyping

For a gene in which the effect depends on the environmental condition, what kinds of medical conditions would receive the necessary investment in pharmaceutical and sociological research, screening, and preventative treatment/monitoring to address the conjunction of genetic and environmental factors involved?

Recall the example of MAOA levels as a predictor of adult antisocial behavior, in which a misclassification problem arises:

Within each category [high or low MAOA level] people show a range of anti-social behaviors. It turns out that, among children who experienced probable or severe maltreatment, the ranges overlap, that is, some of the high MAOA individuals ended up with higher anti-social behavior scores than some of the low MAOA individuals.

However,

once the resources are invested to screen children for MAOA levels, attention would be focused on all low MAOA children. Indeed, how could this stereotyping be avoided if we do not know from a childhood MAOA assessment whether any particular individual is one who would go on, after maltreatment, to be an antisocial adult? Additional research would be needed to identify other characteristics that differentiate among the low MAOA children (and perhaps help predict who among the high MAOA children are also vulnerable). If that research were successful, additional resources would have to be invested to customize the way that parents, teachers, doctors, social workers treated the different low and high MAOA children and to educate everyone not to treat children according to their MAOA group membership…

Now consider the original question about investment in research, screening, and preventative treatment/monitoring for some less charged condition, say, some specific adult disease.  Some well-organized parental advocacy groups may secure funding to address the prenatal diagnosis and post-natal treatment of rare debilitating genetic disorders (such as PKU). However, public and corporate policy would more likely focus on conditions for which the number of vulnerable people times the average benefit of ameliorating the effect of the genetic difference would be large. In such cases, if the MAOA case is any guide, if the effect of the genetic difference depends on identified social or environmental factors, and if variability within the groups that have on-average high and low vulnerability produces a problem of misclassification, pressure would arise for researchers to differentiate among individuals within the groups. Until distinguishing characteristics were found, parents, teachers, doctors, social workers, insurance companies, policy makers, friends, and the individuals themselves could do no better than treat individuals according to their group membership. If the additional research were not conducted or not successful, or if the cost of differentiating among individuals were too high, we might never get beyond treating individuals according to their group membership.

The scenario speaks to the prospect of personalized medicine. In its simplest form, this involves the use of genetic information to predict which patients with a given condition (e.g., heart arythmia) will benefit from a particular drug treatment (e.g., beta blockers). More ambitiously, personalized medicine promises to inform people of their heightened vulnerability (or resistance) to specific environmental, dietary, therapeutic, and other factors early enough to adjust their exposure and risky behaviors accordingly. If the MAOA analogy holds, the path to personalized medicine will, ironically, pass through a phase in which large numbers of people are treated according to their group membership. Moreover, this phase may not be a passing one: What social conditions—or assumptions about control—can ensure that the information and resources needed to move beyond it are forthcoming?

Adapted from P. Taylor, “Infrastructure and Scaffolding: Interpretation and Change of Research Involving Human Genetic Information,” Science as Culture, 18(4):435-459, 2009

MAOA: Interventions through and in social infrastructure implied by knowledge about gene by environment interaction

In 2002 Avi Caspi, Terrie Moffitt and colleagues published two articles in Science that examined psychological traits in relation to measured genetic and environmental factors.  In one of them they reported on anti-social behavior in adults in relation to the activity of monoamine oxidase typeA (MAOA) and childhood maltreatment (Caspi et al. 2002). They summarized their results in figure 1.   For people who experienced severe childhood maltreatment and have low MAOA activity, the average antisocial behavior was higher than if they had only one of the conditions and much higher than if they experienced low or no childhood maltreatment together with high MAOA activity.   In other words, MAOA deficiency was a strong predictor of aggressive behavior only when the child had also been maltreated.

The authors conclude that their results ‘could inform the development of future pharmacological treatments’ (Caspi et al. 2002, 853).   In the context of research on childhood experiences in relation to adult behavior, the implication of their conclusion is that, if low MAOA children could be identified, prophylatic drug treatment could reduce their propensity to anti-social behavior as adults.  Or, to be more precise, such treatment could reduce their vulnerability to childhood maltreatment precipitating undesired adult outcomes.  An easy rejoinder would be that, if childhood maltreatment could be identified and stopped early, this action could reduce their vulnerability to low MAOA levels leading to undesired adult outcomes.  Indeed, eliminating childhood maltreatment would seem to be unconditionally positive, while prophylatic drug treatment may have sideeffects, and some of these may not emerge till later in life.  The rejoinder is too easy, however.  The social infrastructure needed to detect and prevent childhood maltreatment would intrude into many households, require surveillance, monitoring, and intervention by state agencies, divert government budgets from other needs, and so on.  The specific outcome may be positive, but the means are not unconditionally positive to all.  How would decisions about investment in the social infrastructure be decided?  How would individuals decide where to engage with that social infrastructure once it is established?

Once the issue of social infrastructure is brought into the picture, more significant problems emerge with the idea of early detection and intervention on the basis of MAOA status.  Notice that the points plotted in Figure 1 are the averages for the respective categories of people.  Within each category people show a range of anti-social behaviors.  It turns out that, among children who experienced probable or severe maltreatment, the ranges overlap, that is, some of the high MAOA individuals ended up with higher anti-social behavior scores than some of the low MAOA individuals.  The potential for misclassifying people as ones who may end up antisocial is not eliminated by adjusting what counts as antisocial.  If we count as antisocial only those individuals whose score exceeds some value that is higher than the upper limit of the range for high MAOA individuals, this increases the numbers of low MAOA individuals who do not end up counting as antisocial.  If we lower the cutoff score, many high MAOA individuals end up with behavior classified as antisocial (Figure 2).  Indeed, playing around with the cutoff score, the best that can be achieved with Caspi et al’s data is a little more than one-third of children correctly classified on the basis of their MAOA status (i.e., low MAOA ending up counting as antisocial and high MAOA ending up not).

The issue of misclassification is especially troubling because, once the resources are invested to screen children for MAOA levels, attention would be focused on all low MAOA children.  Indeed, how could this stereotyping be avoided if we do not know from a childhood MAOA assessment whether any particular individual is one who would go on, after maltreatment, to be an antisocial adult?  Additional research would be needed to identify other characteristics that differentiate among the low MAOA children (and perhaps help predict who among the high MAOA children are also vulnerable).  If that research were successful, additional resources would have to be invested to customize the way that parents, teachers, doctors, social workers treated the different low and high MAOA children and to educate everyone not to treat children according to their MAOA group membership.  Just as in the case of PKU, the meaning of new genetic knowledge (in this case in combination with environmental knowledge) is contingent on the presence or absence of social infrastructure; the positive benefits depend on extensive social reconstruction.

Another excerpt from P. Taylor, “Infrastructure and Scaffolding: Interpretation and Change of Research Involving Human Genetic Information,” Science as Culture, 18(4):435-459, 2009