Tuesday, July 8, 2008

Trait-like anxious temperament in primates

Richard Davidson and company have published a new paper:

Fox AS, Shelton SE, Oakes TR, Davidson RJ, Kalin NH. Trait-like brain activity during adolescence predicts anxious temperament in primates. PLoS ONE. 2008. I hope someone will look it over and answer a couple of questions for me.

The authors’ begin with this:
[D]ata now demonstrate that children with this disposition [shy children, or those with anxious temperament] are at increased risk to develop anxiety, depression, and comorbid substance abuse. Additional key features of anxious temperament are that it appears at a young age, it is a stable characteristic of individuals, and even in non-threatening environments it is associated with increased psychic anxiety and somatic tension… To understand the neural underpinnings of anxious temperament, we performed imaging studies with 18-fluoro-deoxyglucose (FDG) high-resolution Positron Emission Tomography (PET) in young rhesus monkeys. Rhesus monkeys were used because they provide a well validated model of anxious temperament for studies that cannot be performed in human children.
1. Why couldn’t the neural underpinnings of anxious temperament have been studied in humans? In other words, what was done in this study that isn’t done in humans that absolutely had to be done to answer the question?

A little online research shows that FDG is used in human brain imaging studies, and that children have been routinely used in studies that intentionally place them in emotionally stressful conditions.

2. Why monkeys?

The authors’ write:
Young rhesus monkeys are ideal for this work because numerous studies validate their use in modeling childhood anxious temperament.
But anxious temperament seems to have been studied in rats (Ray J, Hansen S. Temperamental development in the rat: the first year. Dev Psychobiol. 2005) and mice (Calatayud F, Coubard S, Belzung C. Emotional reactivity in mice may not be inherited but influenced by parents. Physiol Behav. 2004).

People who experiment on a particular species do so habitually, not because that species is the best suited for a particular study, but because it is the species they use. It appears that there are many vivisectors who claim that rats are important models of human emotional reactivity and study rats’ amygdales, orbitofrontal cortexes, and hippocampuses. It doesn’t appear that any of the brain regions under study in this paper aren’t also being studied in rats.

Let me be clear: I don’t think rats should be used in harmful or frightening experiments either. But the University of Wisconsin, Madison’s spokespersons on these matters say that the campus oversight committees are committed to the 3Rs. Here's a powerpoint from them. Coincidentally, the issue of the appropriateness of phylogenic order (species) was the subject of an article in the July 2008 issue of Lab Animal: “Deciding which animals to use” (293-295). In that article, USDA is clear: “The principle investigator must consider alternatives (e.g., replacement with a species of a lower phylogenic order ...)”. I suspect that the oversight committee failed again to do its job.

3. Why did they use venipuncture to sample cortisol levels?

The authors state that they expected the monkeys they used to be anxious under all conditions. Anxiety is trait-like in these monkeys. Yet, they write:
To minimize the effects of handling and injection, animals were adapted to all procedures associated with the handling and injection (with the exception of inserting the syringe) 5-days a week for up to 21 days prior to scanning.
But scientists studying human children don’t use this method:
[T]he Trier Social Stress Test (TSST), was administered to 30 adolescents with major depressive disorder and 25 healthy adolescent volunteers. Cortisol concentrations were measured in saliva samples collected before and after the stressor. Rao U, Hammen C, Ortiz LR, Chen LA, Poland RE. (Effects of Early and Recent Adverse Experiences on Adrenal Response to Psychosocial Stress in Depressed Adolescents. Biol Psychiatry. 2008.)
Vertebrates’ brains are highly interconnected complex systems; mental and emotional functioning are part and parcel of the feedback and parallel processing made possible by this interconnectivity. This isn’t news.

4. So why was the publication of this paper hyped by the UW?

It can’t be the long-known fact that some young monkeys with an anxious temperament don't grow out of it, in spite of the headline: ONCE A SHY MONKEY, ALWAYS A SHY MONKEY? NEW STUDY SHOWS PERSISTENCE OF ANXIETY. The authors seem to have known this for at least a decade. See: Kalin NH, Larson C, Shelton SE, Davidson RJ. Asymmetric frontal brain activity, cortisol, and behavior associated with fearful temperament in rhesus monkeys. Behav Neurosci. 1998.

I hope one of the many “anonymous” visitors here will take the time to answer these questions for me.

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