Genetics and environment: Interaction in a different key

In previous posts, I wrote about PANDAS, the streptococcus related autoimmune disorder which involves obsessions, compulsions and perhaps more broad anxiety and movement problems. Discussion has been vigorous about the role of pathogens in creating mood and mental health issues.
Genetics as an influence is another biological factor often considered as a causal factor in mental health and behavior. Today, Brain Blogger discusses the influence of genetics and depression in a post with the provocative title, “Stressed by his short allele.” Brain Blogger is an interesting read in that he attempts to bring neurological research to a lay audience in a magazine format.
Regarding depression, stress and genetics, BB writes:

Individual differences in the genetic makeup of the serotonin system have been shown to increase one’s vulnerability to depression, anxiety and other psychiatric conditions, particularly if individuals are exposed to stressful events in their lives. Studies are showing that certain people (those that have the short allele of the serotonin transporter gene) have a greater biological reactivity to stressful events, including a larger hormonal response to stress and a greater brain reactivity to threat. In other words, both the hormonal and brain systems (amygdala) involved in fear and anxiety are more active in response to stress in those individuals who have a certain genetic makeup (short allele). This genetic difference may also account for individual differences in personality; those people who have a short allele for the serotonin transporter have been suggested to exhibit more “anxious” personality traits. This means our differences in gene function may bias our brains and our personalities to create a tendency to be more “negative,” “anxious” or reactive to stress.

Bringing together the PANDAS research with the observations regarding short serotonin gene alleles, one can envision several scenarios. A child with a stubby allele gets strep throat. This child is unfortunate in that the antibodies created to seek and destroy the strep bacteria find and bind with dopamine receptors in the basal ganglia. At that point, the cells designed to kill strep bacteria which are supposed to be hooked up with strep antibodies find this unholy alliance of strep antibody and dopamine receptors and launch their holy war of immunity. Dopamine cells fall in friendly fire thus sending the dopamine-serotonin balance into disarray. This child, being completely unaware of this of course, begins to feel nervous and irritable (mood change). This creates stress in the family and parents who may also have stubby alleles get stressed too. As BB notes, the short-allele brain already primed to be more reactive in the event of stress (the illness itself, the mood change and reaction of parents and sibs) goes into full fledged alert, generating lots of chemicals which basically provide that child with thoughts suggesting something is wrong here (anxiety and depression).
We can also imagine a child with a full sized allele going through the same thing. When the dopamine-serotonin balance is disrupted via an autoimmune disorder, one may see the typical rapid onset of PANDAS symptoms but these will likely not turn into a chronic problem. Furthermore, it is possible that the symptoms will be less intense or that the child will be more easily soothed with even modest parental inputs, thus preventing an escalation of panic.
Active readers will probably imagine a few hundred more scenarios.
I recently spoke with Susan Swedo at the NIMH who provided invaluable information regarding PANDAS. She agreed with me that we are at the beginning of this line of research and thinking. There is no doubt that psychological trauma is stressful and thus impacts mental health. However, the mechanisms of extended impact may be much different than psychodynamic theorists imagine.
The more of this kind of information we can get to patients the better in my view. It is helpful for people to understand the tricks their brain is playing on them when they get the intuition that they must engage in a compulsive action in order to relieve anxiety. Or when everything is really going well and they constantly fear the worst. Our active, monitoring minds play tricks on us and we are learning more about how those tricks are constructed in part via pathogens in the environment interacting with a genetically prepared host.