X-Message-Number: 12905 Date: Mon, 06 Dec 1999 20:48:30 -0500 From: Jan Coetzee <> Subject: Serotonin Midlife Crisis Serotonin Responsible for the Midlife Crisis by Laura Spinney One of the most common receptors for the neurotransmitter serotonin starts to vanish from the human brain at the age of 20, and continues to decline into old age at a rate of about 15 per cent per decade. The finding, presented at the 29th annual meeting of the Society for Neuroscience in Miami, could explain why depression is most commonly diagnosed in middle age, but hardest to treat among the elderly. The serotonergic system of the brain regulates mood and appetite. Around 14 serotonin (5-HT) receptors have been identified to date, and the most widely distributed of these is 5-HT2A. In the past, animal studies and post mortem examinations of humans have suggested that the aging process may be accompanied by a reduction in these receptors in certain regions of the brain. To find out exactly how age affects their density, and perhaps throw some light on the biochemical basis of depression, Mark Mintun of Washington University Medical School in St Louis, Missouri and his colleagues used positron emission tomography (PET) to scan the brains of 21 healthy men and women between the ages of 20 and 70. The volunteers were drawn from the healthy controls of a larger study on depression in mid- and later life, so none of them suffered from depression or had any family history of the condition. The subjects were injected intravenously with a radioactively labeled substance called altanserin, which has a high affinity for 5-HT2A receptors. They then had a 90-minute PET scan. Mintun's team paid particular attention to the uptake of altanserin in five regions, including the cerebellum, which has a very low density of 5-HT2A receptors, and the occipital cortex, where they are plentiful. They found no age-related changes in the cerebellum, but in the prefrontal cortex, hippocampus, occipital and anterior cingulate cortices the drop in 5-HT2A density was dramatic. "What's exciting about this is that a very important aspect of growing older is actually occurring in midlife," says Mintun. Interestingly, one particular area, the gyrus rectus, showed a rounding off, or stabilizing, of the decline at the latter end of the age spectrum, among the 70-year-olds. According to him, that fits with an intriguing finding from other recent studies that the density of 5-HT2A receptors may even begin to increase again among the very old. The question now is: what is the function of those receptors? And the answer could have crucial implications for the treatment of depression. Serotonin is known to be involved in depression, but the specific receptors that mediate the effect are not known. Depression in the elderly is hard to treat but is that because the serotonergic system underpinning it has become obsolete, and therefore unresponsive to treatment with anti-depressant drugs designed to block the reuptake of serotonin? Or is the system operating at maximum capacity? If the latter were the case, says Mintun, the decline in receptors may simply be the brain's way of compensating for elevated levels of serotonin. "The most we can say now is that the system doesn't hold much in reserve," he says. For more information email Mark Mintun Editor's choice links Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction. Meltzer CC, Smith G, Price JC, Reynolds CF 3rd, Mathis CA, Greer P, Lopresti B, Mintun MA, Pollock BG, Ben-Eliezer D, Cantwell MN, Kaye W, DeKosky ST Brain Res 1998 Nov 30 813:1 167-71 [MEDLINE], [full MEDLINE], [related records], [full text] Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=12905