Posted by chemist on July 13, 2004, at 9:36:32
In reply to Re: question for chemist, posted by SLS on July 13, 2004, at 9:06:40
> 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.
>
>
> - Scotthi scott.....i must say i omitted the side of the kindling hypothesis you mention, as do goodwin and jamison, who point out the same things you do. in citing kraepelin (1921), g&J give more than a nod to it: ``We must regard all alleged injuries as possibly sparks for the discharge of individual attacks, but that the real cause of the malady must be sought in permanent internal changes, which at least very often, perhaps always, are innate... Unfortunately, the powerlessness of our efforts to cure must only too often convince us that the attacks of manic-depressive insanity may be to an astonishing degree independent of external influences (pp. 180-181)'' g&j follow this quote with their observation that ``However, the independence from external influences appears to develop over time...It was, in fact, Kraepelin who first noted that precipitating events play an important role in the onset of the first few episodes, but then, as the illness unfolds, the process driving the onset of new episodes seems to become more autonomous, with stressful events contributing little or nothing.'' and so on...perhaps my (revised) position can best be summed up in another gem from g&j: ``Early precipitating events, rather than merely influencing the timing of an episode, may actually activate the preexisting vulnerability, thereby making the individual more vulnerable to the next episode.'' anyhow, like you, sometime i don't care why, but more ``how can we address this?''.....anyhow, thanks for the food for thought, i do enjoy your posts. all the best to you, chemist
poster:chemist
thread:365438
URL: http://www.dr-bob.org/babble/20040712/msgs/365621.html