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Dr. Bob is Robert Hsiung, MD,
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Posted by jrbecker on June 19, 2003, at 11:40:55
Depression May Be Intracellular Rather Than Related To Serotonergic Or Noradrenergic Post-Synaptic Receptor Changes
JAMA 2003;289:3134.
06/19/2003 10:16:50 AM
By Martha KerrPatients with depression show decreased metabolism of norepinephrine and serotonin in multiple cortical areas, researchers with Emory University in Atlanta, Georgia, report. Rather than post-synaptic changes, which many antidepressive agents target, the changes may be intracellular. Patients on selective serotonin reuptake inhibitors (SSRIs) who have a tryptophan depletion-induced return of depressive symptoms have a markedly slow metabolism in various cortical areas. This was demonstrated by Dr. J. Douglas Brennon and others using positron emission tomography (PET) with fluorodeoxyglucose. In their previous work, the Emory team showed that these patients have a sharp drop in metabolism in the orbitofrontal cortex, the dorsolateral prefrontal cortex and the thalamus. When they began to take norepinephrine reuptake inhibitors (NRIs) instead of SSRIs, depressive symptoms returned as norepinephrine and dopamine levels were depleted using alpha-methylparatyrosine (AMPT). Dr. Brennon and colleagues presented their current findings with PET in 18 patients with depression in remission with NRI treatment. At the start of the study, patients were begun on desipramine until a clinical response occurred. They then received AMPT orally in 5 1-gm doses over a 28- hour period followed by placebo in the form of diphenhydramine hydrochloride given in 5 50-mg doses over 28 hours. The Atlanta team reports that AMPT-induced depressive symptoms occurred in 11 of the 18 patients. Decreased brain metabolism in specific areas was observed in this group, with the greatest effect seen in the orbitofrontal and dorsolateral prefrontal cortex and the thalamus. The investigators say that an increased resting metabolism in the prefrontal and limbic areas were predictive of an increased risk of return of symptoms of depression. Dr. Brennon points out that these areas of the brain "receive important noradrenergic innervation and are involved in a functional circuit with the thalamus." The researchers explain that disruption of the serotonin or norepinephrine neurotransmitter systems appears to lead to depression in individuals with depression in remission, but that this phenomenon does not occur in healthy individuals without depression or in depressive patients currently experiencing depression. "This is primarily related to a ceiling effect, whereby the patients with depression have a limit in the degree to which they can develop additional symptoms of depression." Dr. Brennon and associates conclude that "the fact that depressive symptoms can recur with serotonergic or noradrenergic depletion suggests that this may not be secondary to a change in the post-synaptic receptor in vulnerable patients but rather a common alteration in an intracellular process in specific brain areas, including orbitofrontal cortex."
Posted by Squiggles on June 19, 2003, at 12:52:09
In reply to JAMA: Depression's cause may be intracellular, posted by jrbecker on June 19, 2003, at 11:40:55
Kraeplin would be smiling in his grave
if reading this - though i doubt that
is what he meant by manic depression being
a "metabolic disorder" -- probably meant
hormonal rather than brain?Squiggles
Posted by johnj on June 22, 2003, at 13:33:20
In reply to JAMA: Depression's cause may be intracellular, posted by jrbecker on June 19, 2003, at 11:40:55
this is a little less scientific manner? I find myself a little confused. Probably due to my inability to follow the whole thread. Thank you
johnj
This is the end of the thread.
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