Biochemical Principles 10.13.11 Orchids 5HTT alleles

5HTT Allele Group must pick one question and respond by 8 AM Thursday 10.13.11

1. Why do you think that Kevin’s health care and education before the move to Worcester failed to recognize him as an orchid child? If genetic testing in early childhood had found Kevin to have the S/S or S/L allele for the serotonin-transporter gene, how might that have changed (for better or worse) his story?

2. The number of children with autism is reported to be increasing in the U.S., and is widely characterized as an epidemic. The short allele of serotonin-transporter gene has also been found to be involved in autism. How might that finding change the way that we interpret the reported increase in autism? How might it change the way that we understand, diagnose, and treat autism?

3. The Orchid hypothesis questions the idea of “bad genes”. What does this hypothesis imply for people having knowledge of their own genotype or that of their children?  How much involvement should people have in “changing” their own genes, and how could such involvement, including germ-line gene therapy, modify stress reactivity?


4. Do you know an orchid child? What resilience characteristics, internal and external, made the difference in how he or she ended up thriving?  How do you hypothesize that such characteristics affected stress reactivity and cortisol levels?

Orchid Goup pick one of these four questions and respond by 8AM Thurs 10.13.11

5. This study raises the possibility that searching for direct genetic links in mental illnesses has thus far been a far less productive avenue than expected. Given this, should mental illness awareness be taught from a young age as part of an effort to prevent depression? How would this play into a larger scheme to reduce adverse experiences, especially in children? Do you think it would be advisable to test infants for this allele? If so, what do you think we should do if we find that an infant has it. If not, why not?

6. Similarly to the ACE study, this paper focused on the quantity of stressful life events rather than the quality/intensity of them. It is also noted that there is conflicting evidence of a direct linkage between the 5-HTTPLR and depression.  Since we are discussing these stressors in relation to uncontrollable genetic factors rather than the voluntary risky behaviors in the ACE study, do you think the quantity vs. quality aspect is significant in this case?  If not, what are some other factors that should be taken into account to attain more conclusive results?

7. Refer to graph A-D on Page 388. What factors do you think account for the fact that at 0 number of stressful life events, there is a weaker correlation with self reported depressive symptoms, probably of major depressive episode, probability of suicide ideation/attempt, and informant reports of depression for the s/s genotype than for the l/l genotypes?

8. Inheritance of one or both alleles of the short variant of the 5-HTT gene results in greater increases in plasma concentration of adrenocorticotropic hormone (ACTH) in response to stress. Given the known interactions and downstream effects of ACTH on the HPA axis, what impact might short 5-HTT alleles have on cortisol production, HPA axis feedback mechanisms? How might a short 5-HTT individual react to chronic stress compared to a long allele individual? What might have been the evolutionary advantage of more sensitive reactions to stressful stimuli?

FOR CLASS DISCUSSION DON'T RESPOND TO THIS QUESTION :  This study, and those that we have read previously (ACE, etc), have emphasized the Environmental factor in the G x E equation presented in this article. They have discussed the influence of such factors on the exhibition of risk factors and physical/ mental health disparities, and have discussed alterations in the environment as potential methods of treatment and prevention. To what extent does the genetic component offer a means of treatment and prevention? With the advancement of genetic engineering, is the identification and replacement of alleles such as the 5-HTT short allele in human zygotes a moral, ethical, or even plausible solution to mental illnesses like depression? 

This two week segment will be done a bit differently.  Each of you will choose one of two papers and prepare a discussion question to be deposited in the drop box by Thursday 10.7.11 at 5 PM.  We will select or combine questions and post three questions for each questions on this site by Saturday at 5 PM.  Post a response to a question on the other paper by Thursday 10.13.11 at 8 AM.  That evening's discussion will be lead by the two groups.