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]
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