Posted by SLS on July 13, 2004, at 9:06:40
In reply to Re: question for chemist » linkadge, posted by chemist on July 12, 2004, at 20:31:45
Hi Chemist.
> as for the kindling hypothesis, i am a believer.
I like the kindling hypothesis for mania. Intuitively, it makes sense. To experience mania or watch someone else in a manic state, it is easy to imagine an electrical storm of overly excitable neurons occurring in the brain. In depression, however, with the global reduction of activity throughout most of the cerebral cortex and certain areas of the limbic system, it is a bit harder to conceptualize. However, there are some circuits in the brain that are overactive in depression. Perhaps therein lies the substrate for a kindling model of depression, although one could make a case that these overactive regions are the result of depression rather than its cause. Being depressed is extraordinarily stressful, and places great demands on the individual to maintain psychosocial function. It would not be surprising if those circuits in the amygdala and thalamus involved in the stress response to these demands, including the production of fear and anxiety, were to be working overtime. They might not necessarily be areas subject to kindling.
I think it is more complicated than simply a series of repeated exposures to stimuli. There is most probably a convergence of biological events superimposed upon genetic and epigenetic vulnerabilities that leads to a dysregulation of circuits within the system. It might be necessary, for example, for the hippocampus to be bathed in cortisol chronically as the result of a defect in a feedback loop failing to shut down the normal reaction to stress. I guess one can argue that this is the result of kindling in areas afferent to neuroendocrine links to the adrenal glands, but it could also be due to an exhaustion of the cellular machinery necessary to regulate gene transcription. There are some who suggest that people who develop depression are born with enlarged amygdalas. There are some people with bipolar disorder for whom there doesn't seem to be any precipitating environmental factors. I don't know how such things are determined, though.
I don't know. Sometimes I just don't give a damn.
- Scott
poster:SLS
thread:365438
URL: http://www.dr-bob.org/babble/20040712/msgs/365614.html